Practical cardiovascular medicine 9781119233367, 1119233364, 9781119233503, 111923350X, 9781119233534, 1119233534

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Practical Cardiovascular Medicine

Practical Cardiovascular Medicine

Elias B. Hanna, MD

Associate Professor of Medicine Associate Program Director of Cardiovascular Disease Fellowship Associate Program Director of Interventional Cardiology Fellowship Louisiana State University School of Medicine University Medical Center New Orleans, Louisiana, USA

This edition first published 2017 © 2017 by John Wiley & Sons Ltd Registered Office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial Offices 9600 Garsington Road, Oxford, OX4 2DQ, UK The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030‐5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley‐blackwell. The right of Elias B. Hanna to be identified as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by health science practitioners for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging‐in‐Publication Data Names: Hanna, Elias B., author. Title: Practical cardiovascular medicine / Elias B. Hanna. Description: Chichester, West Sussex ; Hoboken, NJ : John Wiley & Sons Inc., 2017. | Includes bibliographical references and index. Identifiers: LCCN 2016055802| ISBN 9781119233367 (pbk.) | ISBN 9781119233497 (epub) Subjects: | MESH: Cardiovascular Diseases Classification: LCC RC667 | NLM WG 120 | DDC 616.1–dc23 LC record available at https://lccn.loc.gov/2016055802 A catalog record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Cover image: Science Photo Library - PIXOLOGICSTUDIO/Gettyimages Cover design: Wiley Set in 8.5/10.5pt Frutiger Light by SPi Global, Pondicherry, India

10 9 8 7 6 5 4 3 2 1

To my mother Marie, my sister Eliana, and my beautiful niece Clara and nephew Marc‐Elias, the constant light in my life To my mentors and my fellows, and to all those who share my love for cardiology

Contents

Preface, xix Abbreviations, xx PART 1.  Coronary Artery Disease, 1 1.  Non‐ST‐Segment Elevation Acute Coronary Syndrome, 1 I. Types of acute coronary syndrome (ACS),  1 II. Mechanisms of ACS,  2 III. ECG, cardiac biomarkers, and echocardiography in ACS,  3 IV. Approach to chest pain, likelihood of ACS, risk stratification of ACS,  4 V. Management of high‐risk NSTE‐ACS,  6 VI. General procedural management after coronary angiography: PCI, CABG, or medical therapy only,  9 VII. Management of low‐risk NSTE‐ACS and low‐probability NSTE‐ACS,  11 VIII. Discharge medications,  11 IX. Prognosis, 12 Appendix 1.  Complex angiographic disease, moderate disease,  13 Appendix 2.  Women and ACS, elderly patients and ACS, CKD,  14 Appendix 3.  Bleeding, transfusion, prior warfarin therapy, gastrointestinal bleed,  15 Appendix 4.  Antiplatelet and anticoagulant therapy,  16 Appendix 5.  Differences between plaque rupture, plaque erosion, and spontaneous coronary dissection,  19 Appendix 6.  Harmful effects of NSAIDs and cyclooxygenase‐2 inhibitors in CAD,  19 Questions and answers,  19 References, 25 2. ST‐Segment Elevation Myocardial Infarction, 30 1.  Definition, reperfusion, and general management,  31 I. Definition, 31 II. Timing of reperfusion,  31 III. ECG phases of STEMI,  32 IV. STEMI diagnostic tips and clinical vignettes,  32 V. Specific case of new or presumably new LBBB,  33 VI. Reperfusion strategies: fibrinolytics, primary PCI, and combined fibrinolytics–PCI,  34 VII. Coronary angiography and PCI later than 24 hours after presentation: role of stress testing,  37 VIII. Angiographic findings, PCI, and cellular reperfusion; multivessel disease in STEMI,  38 IX. Antithrombotic therapies in STEMI,  39 X. Other acute therapies,  40 XI. Risk stratification,  41 XII. LV remodeling and infarct expansion after MI,  41 XIII. Discharge, EF improvement, ICD,  41 2. STEMI complications, 42 I. Cardiogenic shock,  42 II. Mechanical complications,  45 III. Recurrent infarction and ischemia,  47 IV. Tachyarrhythmias, 47 V. Bradyarrhythmias, bundle branch blocks, fascicular blocks,  49 VI. LV aneurysm and LV pseudoaneurysm,  50 VII. Pericardial complications,  51 VIII. LV thrombus and thromboembolic complications,  51 IX. Early and late mortality after STEMI,  52 Appendix 1.  Out‐of‐hospital cardiac arrest: role of early coronary angiography and therapeutic hypothermia,  52 Questions and answers,  54 References, 59 3. Stable CAD and Approach to Chronic Chest Pain, 65 I. Causes of angina; pathophysiology of coronary flow,  65 II. Diagnostic approach,  66 vii

viii  Contents

III. Silent myocardial ischemia,  68 IV. Medical therapy: antiplatelet therapy to prevent cardiovascular events,  70 V. Medical therapy: antianginal therapy,  70 VI. Medical therapy: treatment of risk factors,  72 VII. Indications for revascularization,  72 VIII. CABG, 73 IX. PCI, 73 X. PCI vs. medical therapy,  74 XI. PCI vs. CABG in multivessel disease,  75 XII. High‐surgical‐risk patients,  76 XIII. Role of complete functional revascularization,  76 XIV. Hybrid CABG–PCI,  77 XV. Enhanced external counterpulsation (EECP),  77 XVI. Mortality in CAD,  77 Appendix 1. Note on outcomes with various surgical grafts,  77 Appendix 2. Coronary vasospasm (variant angina, Prinzmetal angina),  79 Appendix 3. Women with chest pain and normal coronary arteries,  81 Appendix 4. Myocardial bridging,  81 Appendix 5. Coronary collaterals, chronic total occlusion,  82 Appendix 6. Hibernation, stunning, ischemic preconditioning,  82 Questions and answers,  83 References, 87

PART 2.  Heart Failure (Chronic and Acute Heart Failure, Specific Cardiomyopathies, and Pathophysiology), 93 4. Heart Failure, 93 Definition, types, causes, and diagnosis of heart failure,  94 1.  Definition and types of heart failure,  94 I. Heart failure is diagnosed clinically, not by echocardiography,  94 II. After HF is defined clinically, echocardiography is used to differentiate the three major types of HF,  95 III. Two additional types of HF,  96 2.  Causes of heart failure,  97 I. Systolic HF (or HF with reduced EF),  97 II. HF with preserved EF,  98 III. Right HF,  100 3. Diagnostic tests, 100 I. Echocardiography, 100 II. BNP, 100 III. ECG, 101 IV. Coronary angiography and other ischemic workup,  101 V. Diastolic stress testing,  102 VI. Endomyocardial biopsy,  102 VII. Cardiac MRI,  102 Chronic treatment of heart failure,  102 1.  Treatment of systolic heart failure,  102 I. Treat the underlying etiology,  102 II. Value of revascularization in ischemic cardiomyopathy: STICH trial,  102 III. Subsets of patients who are likely to benefit from revascularization: role of viability testing and ischemic testing,  103 IV. Drugs that affect survival,  105 V. Specifics of drugs that affect survival,  106 VI. Drugs that improve symptoms and morbidity,  110 VII. Devices, 112 VIII. Other therapeutic measures,  113 IX. Prognosis, 113 2. Treatment of HFpEF, 114 Acute heart failure and acutely decompensated heart failure,  115 I. Triggers of acute decompensation,  116 II. Profiles of acute HF: congestion without low cardiac output, congestion with low cardiac output,  116 III. Treatment of acute HF: diagnosis and treatment of triggers,  117 IV. Treatment of acute HF: diuretics, cardiorenal syndrome, aggressive decongestion, ultrafiltration,  118 V. Treatment of acute HF: vasodilators,  121 VI. Treatment of acute HF: IV inotropic agents (dobutamine, milrinone, dopamine),  122

Contents  ix

VII. In‐hospital and pre‐discharge use of ACE‐Is and β‐blockers, 122 VIII. Treatment of acute HF: O2, non‐invasive ventilatory support (CPAP, BiPAP), intubation,  123 IX. Summary: keys to the treatment of acute HF,  123 X. Discharge, 124 XI. Inability of severe HF to tolerate vasodilatation or hemodialysis,  124 XII. Outpatient monitoring of HF and prevention of hospitalization,  124 Appendix 1. Management of isolated or predominant RV failure,  125 Questions and answers,  127 References, 135 5. Additional Heart Failure Topics, 142 1. Specific cardiomyopathies, 142 I. Specific dilated cardiomyopathies,  142 II. Specific infiltrative restrictive cardiomyopathies,  145 2.  Advanced heart failure: heart transplant and ventricular assist devices (VADs),  146 I. Stages of HF,  146 II. Cardiac transplantation,  146 III. Left ventricular assist devices (LVADs),  147 3.  Pathophysiology of heart failure and hemodynamic aspects,  149 I. LV diastolic pressure in normal conditions and in HF (whether systolic or diastolic),  149 II. Definition of afterload,  149 III. Cardiac output, relation to preload and afterload,  150 IV. LV pressure–volume relationship in systolic versus diastolic failure: therapeutic implications,  151 V. Decompensated LV failure: role of heart rate,  152 VI. Mechanisms of exercise intolerance in HF,  153 VII. Pressure–volume (PV) loops (advanced reading),  153 VIII. Additional features of HF with preserved EF,  153 IX. High‐output HF,  154 References, 155 PART 3.  Valvular Disorders, 157 6. Valvular Disorders, 157 1. Mitral regurgitation, 158 I. Mechanisms of mitral regurgitation,  158 II. Specifics of various causes of mitral regurgitation,  158 III. Assessment of MR severity,  164 IV. Natural history and pathophysiology of organic MR,  164 V. Treatment of organic (primary) MR,  165 VI. Treatment of secondary MR (ischemic and non‐ischemic functional MR),  166 VII. Treatment of acute severe MR related to acute MI,  167 VIII. Percutaneous mitral valve repair using the Mitraclip device,  167 2. Mitral stenosis, 167 I. Etiology and natural history,  167 II. Diagnosis, 168 III. Treatment, 171 3. Aortic insufficiency, 173 I. Etiology, 173 II. Pathophysiology and hemodynamics,  174 III. Diagnosis, 176 IV. Natural history and symptoms,  176 V. Treatment, 176 4. Aortic stenosis, 178 I. Etiology, 178 II. Laboratory diagnosis and severity,  179 III. Low‐gradient AS with aortic valve area (AVA) ≤1 cm2 and low EF 5 ng/ml), the worse the prognosis.20 Also, an e­ levated troponin associated with elevated CK‐MB signifies a larger MI and a worse short‐term prognosis than an isolated rise in troponin. CK‐MB and troponin peak at ~12–24 hours and 24 hours, respectively. CK and CK‐MB elevations last 2–3 days. Troponin elevation lasts 7–10 days; minor troponin elevation, however, usually resolves within 2–3 days. In acutely reperfused infarcts (STEMI or NSTEMI), those markers peak earlier (e.g., 12–18 hours) and sometimes peak to higher values than if not reperfused, but decline faster. Hence, the total amount of biomarkers released, meaning the area under the curve, is much smaller, and the troponin elevation resolves more quickly (e.g., 4–5 days). The area under the curve, rather than the actual biomarker peak, correlates with the infarct size. Troponin I or T is much more sensitive and specific than CK‐MB. Frequently, NSTEMI is characterized by an elevated troponin and a normal CK‐MB, and typically CK‐MB only rises when troponin exceeds 0.5 ng/ml. To be considered cardiac‐specific, an elevated CK‐MB must be accompanied by an elevated troponin; the ratio CK‐MB/CK is typically >2.5% in MI, but even this ratio is not specific for MI. When increased, CK‐MB usually rises earlier than troponin, and thus an elevated CK‐MB with a normal troponin and normal CK may imply an early MI (as long as troponin eventually rises). Overall, CK‐MB testing is not recommended on a routine basis but has two potential values: (i) in patients with marked troponin elevation and subacute symptom onset, CK‐MB helps diagnose the age of the infarct (a normal CK‐MB implies that MI is several days old); (ii) CK‐MB elevation implies a larger MI. Cardiac biomarkers, if negative, are repeated at least once 3–6 hours after admission or pain onset. If positive, they may be repeated every 8 hours until they trend down, to assess the area under the curve/infarct size.* * A new generation of high‐sensitivity troponin assays (hs‐troponin) has a much lower detection cutoff (detection cutoff = 0.003 ng/ml vs. 0.01 ng/ml for the older generation; MI cutoff = 0.03 ng/ ml for both generations). If hs‐troponin is lower than the detection cutoff on presentation or lower than the MI cutoff 3 hours later, MI can be ruled out with a very high negative predictive value >99.4%.4 The positive predictive value of these low values, however, is 75% at best, and is improved by seeking a significant rise or fall pattern.

4  Part 1.  Coronary Artery Disease

In patients with a recent infarction (a few days earlier), the diagnosis of reinfarction relies on: • CK or CK‐MB elevation, as they normalize faster than troponin, or • Change in the downward trend of troponin (reincrease >20% beyond the nadir)1 In the post‐PCI context, MI is diagnosed by a troponin elevation >5× normal, along with prolonged chest pain >20 min, ischemic ST changes or Q waves, new wall motion abnormality, or angiographic evidence of procedural complications.1 In patients with elevated baseline cardiac markers that are stable or falling, post‐PCI MI is diagnosed by ≥50% reincrease of the downward trending troponin (rather than 20% for spontaneous reinfarction). Note that spontaneous NSTEMI carries a much stronger prognostic value than post‐PCI NSTEMI, despite the often mild biomarker elevation in the former (threefold higher mortality). In fact, in spontaneous NSTEMI, the adverse outcome is related not just to the minor myocardial injury but to the ruptured plaques that carry a high future risk of large infarctions. This is not the case in the controlled post‐PCI MI.21,22 Along with data suggesting that only marked CK‐MB elevation carries a prognostic value after PCI, an expert document has proposed the use of CK‐MB ≥10× normal to define post‐PCI MI, rather than the mild troponin rise.22 In the post‐CABG context, MI is diagnosed by a troponin or CK‐MB elevation >10× normal, associated with new Q wave or LBBB, or new wall motion abnormality.1 In randomized trials recruiting patients with high‐risk non‐ST‐segment elevation ACS, only ~60–70% of patients had a positive troponin; the remaining patients had unstable angina. However, with the current generation of high‐sensitivity troponin, unstable angina is becoming a rare entity. In fact, in patients with a serially negative troponin, ACS is unlikely.7 This is particularly true in cases of serially undetectable troponin (20% of the inner myocardial thickness (70, diabetesb In the absence of the above features, the following suggests a low ACS likelihood (the 3 Ps) Chest pain that is Positional or reproduced with certain chest/arm movements Pleuritic pain (↑ with inspiration or cough: suggests pleural or pericardial pain, or costochondritis) Palpable pain localized at a fingertip area and fully reproduced with palpationc Pain >30–60 min with consistently negative markers. Very brief pain 5%), may be better served with multivessel PCI. Thus, in the era of an aging population with comorbidities, multivessel complex PCI still has a role. A heart team discussion is warranted for these patients. In addition to the high surgical risk patients, patients with small vessels and diffuse distal disease that is severe or calcified may not have appropriate distal targets for CABG and may not be candidates for CABG, especially when the LAD cannot be grafted. They may undergo PCI of focal, critical, proximal disease. A third reason that may preclude CABG is the lack of conduits, in particular venous conduits in patients with large varicose veins and venous insufficiency. The use of LIMA necessitates surgical entry into the pleural cavity, with a high risk of pleural effusion and deterioration of pulmonary function in patients with severe lung disease.

XIII.  Role of complete functional revascularization Complete revascularization is defined as revascularization of all functionally significant stenoses in vessels ≥1.5 mm supplying viable territories. However, this has been defined differently across studies, and some based it on angiographic disease >50–70% rather than on ­functionally significant disease, or on achieving revascularization of the three major epicardial vessels (as opposed to all branches).81 CABG generally achieves more complete revascularization than PCI, as it is less affected by lesion complexity (e.g., CTO) (67% vs. 53% in SYNTAX patients).82 In most registries and post‐hoc analyses, only incomplete revascularization with PCI was associated with impaired outcomes (New York and ARTS registries).83,84 This adverse outcome may be related to the residual disease itself or to the fact that residual disease is a marker of more extensive and aggressive atherosclerosis even across the revascularized arteries, which explains why incomplete revascularization is more unfavorable after PCI than CABG. In fact, the intense pursuit of complete revascularization may not, by itself, improve outcomes. In two analyses of CABG patients, incomplete revascularization of a small/poor target RCA or LCx in patients receiving LIMA‐to‐ LAD graft did not adversely affect long‐term outcomes; in fact, too aggressive revascularization of >1 non‐LAD vessel may be associated with worse outcomes.85,86 This is called “reasonable” incomplete revascularization. This reasonable revascularization concept fits with the functional revascularization concept where only large and ischemic territories are revascularized. Incomplete revascularization usually has a worse connotation with PCI than with CABG, as (i) PCI is a suboptimal therapy for extensive disease, and (ii) PCI more frequently omits large, otherwise graftable vessels because of technical challenge, such as CTO.

Table 3.5  Variables analyzed in surgical risk scores (STS and EuroSCORE). 1. Underlying patient‐related factors and comorbidities (i) age (the risk doubles with every 10 yr >60); (ii) women (~50% higher risk than men); (iii) moderate or severe COPD; (iv) severe CKD; (v) prior disabling stroke or neurological illness; (vi) carotid disease, PAD 2. Underlying EF–HF (i) EF (3 months old and a low PCI success rate. This fine bridging network is sometimes confused with intra‐CTO microchannels (functional CTO), yet the two entities have radically opposite implications: the former implies a low PCI success rate, while the latter implies a high PCI success rate. After successful PCI of a CTO, a considerable fraction (50%) of the collateral function is immediately reduced through spasm and is non‐recruitable should acute reocclusion occur.125 The patient may have a stable CTO for years; however, if a CTO is recanalized with PCI then acutely reoccludes, an acute MI will ensue, even if reocclusion occurs as early as a few hours or days after recanalization. This is due to: (i) early loss of collateral flow (spasm early on, anatomic involution later on), (ii) distal embolization from the upstream thrombosis, which occludes the microcirculation and any patent collaterals (similar to early SVG thrombosis). Yet sometimes, when reocclusion occurs early, collateral flow may be quickly recruited and may limit MI size.

Appendix 6. Hibernation, stunning, ischemic preconditioning Hibernation is chronic impairment of the myocardial function that results from a severe, persistent coronary stenosis; the myocardium downregulates its function and its metabolism to survive and remains viable. Chronic ischemia may, however, lead to irreversible fibrosis. The myocardial segment has reduced nuclear uptake at rest and with stress, but preserved metabolic uptake on PET study. Stunning is transient myocardial dysfunction occurring after a severe, transient episode of ischemia. Ischemia resolves and leaves a viable myocardium that will recover in time. This is the case of an acutely occluded artery that is opened with PCI or fibrinolytics (acute MI), exertional ischemia that occurs at stress and resolves at rest, or ischemia induced by cardiac surgery or PCI. Some myocardium is necrotic already, some is stunned; only time will show. As opposed to hibernation, the artery is now open and there is no persistent ischemia, hence the stunned myocardium does not remain dysfunctional. In the post‐MI and post‐cardiac surgery cases, temporary support with inotropes or IABP is sometimes needed until the myocardium recovers, provided there is no ongoing ischemia. Unlike hibernation, the nuclear uptake is usually normal at rest. Repetitive stunning (exertional ischemia) can lead to persistent dysfunction and hibernation. Recovery of function occurs 1–6 months after revascularization (faster with stunning, days to 1 month). See Chapter  4 for viability evaluation. In a patient with active chest pain and severe CAD, the myocardial dysfunction is usually an actively ischemic dysfunction, rather than hibernation or stunning.

Ischemic preconditioning is the phenomenon whereby brief exposure to ischemia preconditions the heart and makes it more resilient to a later, prolonged and severe ischemia. In fact, ischemia stimulates protective myocyte receptors, such as adenosine receptors and G‐protein receptors (protein kinase C). There are two windows of protection: the first starts within a few minutes of the brief ischemia and lasts a few hours; the second occurs at 24 hours and lasts 96 hours. This is partly why patients with pre‐infarct angina suffer from smaller

Chapter 3.  Stable CAD and Approach to Chronic Chest Pain  83

infarcts and have better outcomes. Also, patients with severe pre‐existing disease have already formed mature collaterals, which attenuate the infarct size.

Q u esti o ns and   answers Question 1. A 67‐year‐old man with a history of HTN and diabetes presents with exertional chest pain CCS III for 3–4 months. Chest pain is relieved with rest and with his wife’s NTG. He has left lower extremity claudication. On exam, distal left lower extremity pulses are not palpable. ECG shows LVH with 0.5 mm ST‐segment depression. What is the most appropriate next step? A. Coronary angiography B. Exercise stress ECG C. Exercise stress SPECT D. Adenosine SPECT Question 2. A 67‐year‐old man with a history of LAD stent placed 2 years ago presents with mild angina on heavy exertion (CCS I). He is on atenolol, amlodipine, aspirin, and atorvastatin. BP 110/65, pulse 58 bpm. Exercise stress test result: 8 min on a Bruce protocol, mild angina occurred, DTS score +4. Nuclear perfusion shows a small area of apical–lateral ischemia, with a summed stress score of +3. Coronary angiography shows 80% proximal LCx stenosis, 30% mid‐LAD, 40% mid‐RCA. What is the next step? A. PCI of LCx. No need for FFR since the lesion is angiographically significant B. PCI of LCx. No need for FFR since the stress test is positive C. FFR of LCx. Stent if FFR 2 blocks). He receives aspirin and a statin. A nuclear stress test shows moderate anterior ischemia, and coronary angiography shows 80% proximal LAD stenosis and 75% mid‐RCA and mid‐ LCx stenoses. What is the next step? A. Medical therapy B. PCI C. CABG Question 6. A 76‐year‐old man presents with chest pain on heavy activity (walking >2 blocks). He receives aspirin and a statin. A nuclear stress test shows severe anterior ischemia with summed stress score of +8, and coronary angiography shows 80% proximal LAD stenosis. What is the next step? A. Medical therapy B. PCI C. CABG D. B or C Question 7. A 47‐year‐old executive man, asymptomatic, is starting an exercise program at the gym. He is asymptomatic during daily activities. A stress test is ordered by his family physician. He exercises for 5 minutes and develops 1.5 mm ST depression without chest pain. Nuclear images show a large anterior and anterolateral reversible defect, with a normal EF and no TID. A. Because he is asymptomatic, there is no need for coronary angiography since there is no need for revascularization. Just initiate medical therapy B. Perform coronary angiography, but only revascularize if left main or three‐vessel CAD is present C. Perform coronary angiography, but only revascularize if left main, three‐vessel CAD, or one‐ or two‐vessel CAD involving the proximal LAD is found. If isolated mid‐LAD stenosis is found, start intense medical therapy and repeat stress test before going for PCI D. Perform coronary angiography, but only revascularize if left main, three‐vessel CAD, or one‐ or two‐vessel CAD involving the proximal LAD is found. Do not revascularize if isolated mid‐LAD stenosis is found Question 8. A 56‐year‐old man presents with angina walking up one flight of stairs or less (= CCS III). He is not receiving any antianginal therapy. His nuclear stress test shows severe inferior ischemia. His angiogram shows CTO of the RCA with features that make it favorable for PCI (non‐calcified, ~2 cm long). True or false: PCI is not appropriate, as the patient is not receiving maximal antianginal therapy Question 9. A 46‐year‐old diabetic woman, smoker, who also has dyslipidemia and whose diabetes is not insulin‐dependent, presents with a typical exertional angina CCS III. ECG shows LVH without ST changes. She has no arterial bruits and peripheral pulses are normal. What is the most appropriate next step?

84  Part 1.  Coronary Artery Disease

A. Coronary angiography B. Exercise stress ECG C. Exercise stress SPECT, as the patient cannot receive stress ECG with the baseline LVH D. Exercise stress SPECT, because it is more appropriate for this patient’s presentation E. Adenosine SPECT Question 10. A 50‐year‐old female, smoker, presents with chest pain that occurs with exertion, but not consistently, and sometimes occurs at rest. Each episode lasts ~45 minutes. BP = 160/95, HR = 78. She undergoes a treadmill nuclear stress testing. She walks for 5 minutes, does not report any chest pain, and no ST abnormality is seen. Her nuclear images show a large reversible anterior defect with a summed stress score of +10. The patient prefers to try medical therapy first if deemed appropriate by the physician. What is her Duke Treadmill Score? What is the most appropriate next step? A. Start aspirin, statin, β‐blockers and amlodipine. Coronary angiography is not indicated, as her risk of cardiac events is 5% per year C. Start amlodipine, since the likely diagnosis is vasospasm Question 11. A 65‐year‐old diabetic patient is planning to undergo elective cholecystectomy. He has mild dyspnea on exertion (>4 METs) but no angina. He undergoes preoperative testing with a nuclear SPECT, which shows severe inferior ischemia and preserved EF. Coronary angiography shows CTO of the RCA with angiographic features favorable for PCI. What is the next step? A. Aggressive medical regimen. Revascularization is not indicated. His surgical risk is intermediate but revascularization will not improve this B. Aggressive medical regimen. Revascularization is not indicated. His surgical risk is low C. Aggressive medical regimen and PCI of the RCA with BMS D. Aggressive medical regimen and PCI of the RCA with DES Question 12. A 58‐year‐old woman has exertional chest pain (and some episodes of pain with mental stress). While undergoing treadmill stress ECG, she develops severe chest pain, inferior ST‐segment elevation, and multiple runs of non‐sustained VT. The pain and ST elevation resolve at 5 minutes of recovery. Coronary angiography is performed and shows a smooth 80% stenosis of the mid‐RCA, which improves to a mild, 25% stenosis with NTG. What is the prognosis and what is the treatment? A. Even in the absence of obstructive CAD, her risk of unstable angina/MI/VT is ~20% at several years of follow‐up. She must be placed on amlodipine and statin B. In the absence of obstructive CAD, her risk of unstable angina/MI/VT is low (40% risk of severe CAD (age, sex, diabetes, typical angina).13 Also, PAD predicts severe CAD. He has not only a high probability of CAD, but a high probability of severe CAD. The severity of his angina is another indicator of the need for invasive angiography with possible revascularization. Answer 2. D. This is a typical COURAGE patient with mild angina, good functional capacity, and low‐risk stress test. For this patient, medical therapy is as good as PCI + medical therapy. If the stress test is high‐risk (≥10% ischemia), or angina is severe despite medical therapy, COURAGE nuclear and functional substudies would support PCI (PCI would be superior to medical therapy for reduction of angina and reduction of ischemic burden). Also, a large retrospective analysis suggested improved survival when revascularization is performed for high‐risk ischemia on nuclear imaging.16 FFR is not necessary, since ischemia has already been proven by nuclear imaging.

86  Part 1.  Coronary Artery Disease

Answer 3. A. A patient with mild angina and mild/moderate ischemia is appropriately treated with medical therapy only. The MASS trial showed that for isolated LAD disease >80%, there was no difference in mortality between CABG vs. angioplasty vs. medical therapy, although angina was reduced with angioplasty and more so with CABG. The LAD disease addressed in the MASS trial was proximal LAD disease. Answer 4. A. Again, a patient with mild angina, mild/moderate ischemia and no severe functional limitation is appropriately treated with medical therapy only (typical COURAGE patient). A proximal LAD with mild/moderate rather than severe ischemia may be initially treated conservatively according to the ACC appropriateness criteria. While revascularization with either CABG or PCI may be performed, the value of this strategy in patients with no severe ischemia, no severe or refractory angina, and isolated proximal LAD disease (no two‐ or three‐vessel CAD) is questionable. The appropriateness criteria puts it in an “uncertain” category. If the mild angina persists despite two antianginal drugs, revascularization becomes appropriate. Answer 5. C. As opposed to Questions 3 and 4, the patient has three‐vessel CAD (>70%). According to the ACC appropriateness criteria, even if angina is mild and only moderate ischemia is induced on non‐invasive testing, revascularization is justified for three‐vessel CAD or two‐vessel CAD with proximal LAD involvement, particularly because the stress test may underestimate the true severity of ischemia. Nuclear defects being comparative to the best segment, the LCx and RCA may appear to be normally perfused when, in fact, they are ischemic but less ischemic than the LAD. FFR may be warranted in the absence of a high‐risk stress test result, and will allow adequate assessment of RCA and LCx. Answer 6. D. A patient with severely positive stress test is appropriate for revascularization even if angina is mild and antianginal therapy has not been initiated. A meta‐analysis of early trials of CABG vs. medical therapy suggests that survival with CABG is superior to medical therapy in proximal LAD disease, even single‐vessel LAD (as long as LAD stenosis is definitely significant, typically with high‐risk ischemia). A meta‐analysis of randomized data of CABG vs. PCI suggests no mortality difference in isolated proximal LAD disease. Thus, revascularization with CABG or PCI, if technically feasible, is appropriate for this patient. Answer 7. C. Asymptomatic patients qualify for revascularization if the stress test is high‐risk despite maximal medical therapy, or high‐risk along with proximal LAD, left main, or three‐vessel CAD. This is supported by data from the ACIP trial (trial of revascularization of asymptomatic patients with ischemia) and old CABG vs. medical therapy trials. Answer 8. False. PCI of CTO is appropriate as long as stress test is high‐risk and angina is either severe or refractory. He qualifies for PCI by the fact that his angina is severe and the CTO has favorable PCI features, even if he is not on maximal antianginal therapy. Being appropriate does not mean it is necessary, and one may alternatively maximize antianginal therapy and proceed with PCI only if angina persists. Answer 9. D. Despite being a young woman 80%) for the diagnosis of elevated right‐ but also left‐sided filling pressures (PCWP).2–4 B. Low‐output findings (also known as “cold” signs) correlate with a more advanced HF stage: • Severe fatigue. • Since the pulse pressure corresponds to stroke volume, a narrow pulse pressure (85% sensitivity and specificity).1 Occasionally, severe arterial noncompliance prevents pulse pressure from narrowing. • Pulsus alternans, which refers to an every‐other‐beat variation in pulse intensity. This is different from pulsus paradoxus, seen in tamponade. • Cold, clammy extremities. • Compensatory tachycardia. • Renal failure, hyponatremia, poor response to diuretics. • At an advanced stage: impaired mentation, drowsiness, central hypoventilation with Cheyne–Stokes pattern (hyperpnea alternating with hypopnea/apnea). • Abdominal pain may result from functional bowel ischemia or from liver distension. The functional capacity of HF patients is classified into four classes (NYHA class I: no limitation, can jog or carry > 24 lb up a flight of stairs; class II: can walk more than a flight of stairs or a block without symptoms, but symptoms occur with heavy weight carrying or walking two blocks; IIIA: symptoms with walking one block; IIIB symptoms with mild activities, such as dressing, showering, short walking; IV: symptoms at rest). This functional classification applies to patients at their most stable cardiac status, outside of HF exacerbations. Frequent HF hospitalizations, however, usually imply a worse functional class and a poor prognosis.

II. After HF is defined clinically, echocardiography is used to differentiate the three major types of HF A.  HF secondary to LV systolic dysfunction, where EF is reduced (≤40%) In order to improve the stroke volume, the LV cavity dilates, but may be of normal size in acute systolic HF (acute MI, acute valvular regurgitation, acute myocarditis). B.  HF secondary to LV diastolic dysfunction, where EF is normal (≥50%), sometimes supranormal, and LV is generally of normal size, sometimes small Diastolic HF is also called HF with normal or preserved EF (HFpEF), and this constitutes 40–50% of all HF presentations. In order to make a diagnosis of HFpEF, two other diagnoses have to be ruled out: 1.  Transient, ischemic LV systolic dysfunction. HFpEF is best defined when the echo is performed within 72 hours of HF presentation and ACS is ruled out. 2.  Dynamic ischemic MR in patients with off/on or persistent inferior wall dysfunction. HFpEF is diagnosed when the following three features are present (ESC) (Figure 4.1):7 1.  Clinical HF 2.  Normal EF and normal or only mildly increased LV volume 3.  Invasive, echocardiographic, or BNP evidence of elevated LVEDP or LA pressure, or diastolic dysfunction The following mechanisms are incriminated (see detailed discussion in Chapter 5): 1.  Abnormal diastolic function: (i) LV does not relax well (reduced active relaxation or tau index), and (ii) LV is not “elastic” enough to further distend after relaxation and accept the diastolic filling (increased diastolic stiffness or beta index). This limited LV filling results in a backward rise of PCWP despite a normal LV volume, and a forward drop of stroke volume. 2.  Other mechanisms are found in many patients with HFpEF. Thus, HFpEF does not always equate with diastolic HF: • Impaired contractility. A normal EF does not necessarily imply normal contractility. EF being equal to stroke volume divided by end‐diastolic volume, EF is affected by contractility but also by changes in loading conditions. For the same contractility, a reduction in preload reduces the EF denominator and thus improves EF; a reduction in afterload increases stroke volume and thus improves EF. • Increased arterial stiffness, which leads to exaggerated exertional hypertension. • Pulmonary vascular stiffness with a rise in PA pressure disproportionate to LA pressure. • Very small and stiff LV cavity that cannot distend in diastole, sometimes with cavity obliteration in systole and LVOT obstruction. • Volume overload conditions, with a stretch of a normal LV, or only mildly abnormal LV, beyond its compliance point (e.g., end‐stage renal disease). • Chronotropic incompetence, seen in ~50% of patients, may be secondary to HF but may also be a contributor to exercise intolerance.

96  Part 2.  Heart Failure

Symptoms and signs of HF

Normal LV EF and normal or mildly dilated LV size OR Cath criteria: -LVEDP> 16 mmHg -PCWP> 12 mmHg

OR E/E’>14

BNP>200 pg/ml

+ E/E’ 9–14 Or low E’ Or PA pressure>35 Or B-bump on M-mode of mitral valve Or LA enlargement, LVH, or AF

HFpEF Figure 4.1  Diagnosis of HFpEF by catheterization, echo, or BNP features, according to ESC criteria.7 A normal or mildly dilated LV is defined as LV end‐ diastolic volume 65 years), diabetes (30–50% of diastolic HF patients have diabetes), obesity (30–50%), female sex, renal failure, and AF. B.  CAD (ischemia without infarction) Relaxation being an active process, CAD may contribute to diastolic dysfunction. In fact, in patients with CAD, a rise in LVEDP (diastolic stiffening) is an early hemodynamic manifestation of angina induced by pacing or exercise.14 As importantly, CAD may lead to transient LV systolic failure or dynamic ischemic MR that is mislabeled as diastolic failure, and thus, CAD needs to be considered in all heart failure cases that are labeled diastolic failure. Overall, CAD is a less common etiology of HFpEF than HF with reduced EF, but is still considered the underlying etiology of HFpEF in 25–45% of patients in large HFpEF trials.15,16 As with systolic HF, significant, usually multivessel CAD must be present to be considered the underlying mechanism of HFpEF. C.  Hypertrophic cardiomyopathy D.  Restrictive cardiomyopathy (RCM) RCM is characterized by:17,18 a.  LV is small and stiff with severe diastolic failure. Unlike in dilated cardiomyopathy, the LV cavity is small. Systolic function is relatively preserved and becomes progressively impaired at an advanced stage, yet the LV remains small. The RV may also be stiff and small or may be dilated; RV dilatation/RV systolic dysfunction is common at an advanced stage and is a poor prognostic sign. 19 b.  As in any decompensated ventricular failure, LA and RA are markedly dilated and functional TR and MR, sometimes severe, may be seen. c.  The myocardial thickness is normal or near‐normal in idiopathic restrictive cardiomyopathy but is increased in infiltrative restrictive cardiomyopathies, particularly amyloidosis, where it may reach levels seen with hypertrophic cardiomyopathy (>20 mm) and may occasionally be asymmetric.18 As opposed to hypertrophic or hypertensive cardiomyopathy, the increase in thickness is due to myocardial infiltration rather than myocardial hypertrophy, explaining the discrepancy between the low voltage on the ECG on the one hand and the thick myocardium on echocardiography on the other hand. As opposed to hypertensive cardiomyopathy, the thickening frequently involves both ventricles, not just the LV. Moreover, amyloidosis has the following echo characteristics: a small pericardial effusion, valvular thickening, and a granular, “sparkling” myocardial texture. The sparkles are bright echo spots corresponding to amyloid deposits; note that the heterogeneous texture of HCM may simulate the sparkled texture of amyloidosis.20 d.  On ECG, two findings are common with the thick amyloid cardiomyopathy, corresponding to replacement of the myocardium by the amyloid material: pseudo‐Q waves and low QRS voltage, or at least a QRS voltage that is disproportionate to the thickness of the myocardium. LVH voltage criteria are never seen in the limb leads in amyloidosis. Hypertensive cardiomyopathy may have the same echocardiographic features and severely restrictive filling as RCM, especially in the elderly. Hypertensive cardiomyopathy is sometimes labeled restrictive cardiomyopathy, but is better labeled “restrictive process” (“restrictive process” accounts for the pathophysiology, regardless of the underlying etiology). In a patient with a thick myocardium and severely restrictive filling/HF, three diagnoses are considered: (i) hypertensive cardiomyopathy, (ii) hypertrophic cardiomyopathy, (iii) infiltrative cardiomyopathy. ECG and MRI help with the differential diagnosis.

Chapter 4.  Heart Failure  99

In addition to echocardiography, right and left heart catheterization may be performed in a patient with suspected RCM to confirm the severe elevation of filling pressures and differentiate it from constrictive pericarditis. MRI and endomyocardial biopsy may be needed to diagnose the etiology of infiltrative cardiomyopathy.

Causes of RCM: • Idiopathic, primary RCM (rarely familial). ~50% of RCMs are idiopathic. • Infiltrative disease, most commonly amyloidosis, but also hemochromatosis, sarcoidosis, and hypereosinophilic syndrome. • Scleroderma. • Radiation heart disease, which leads to a combination of RCM, constrictive pericarditis, valvular heart disease (AS/AI, MR, TR), CAD, and pulmonary fibrosis. All these develop 5–30 years after radiation exposure. E.  Constrictive pericarditis Constrictive pericarditis mimics the presentation of RCM and RV failure.

Obstructive sleep apnea not only worsens right HF but also left HF. The deep negative intrathoracic pressure increases the LV transmural pressure (= LV pressure minus surrounding pressure), and thus increases the LV wall tension (= afterload), an opposite effect to positive‐pressure mechanical ventilation. Venous return is also increased, which distends the RV and creates RV–LV ventricular interdependence, further reducing LV flow. In addition, the episodes of hypoxia lead to sympathetic activation and systemic and pulmonary vasoconstriction, and thus both left and right HF and ischemia.21 While a normal individual may recover from these effects quickly upon apnea termination, recovery is delayed in patients with underlying HF. LV filling pressure, LV diastolic function, but also LVEF and myocardial ischemia are affected by sleep apnea.

Tachycardia decompensates any compensated LV failure, whether systolic or diastolic, by reducing the diastolic time provided for the slow LV filling. On Doppler, an impaired relaxation pattern with a reversed E/A ratio and a slow E flow at rest becomes a high E/A ratio with a narrow and brief E flow during tachycardia (Figure 4.2). Once LV failure is decompensated, tachycardia should not be immediately reversed; at this point, the diastolic filling (E wave) is brief and impeded by the quick rise of LV diastolic pressure. Prolonging diastole will not increase diastolic filling; it is rather tachycardia that improves cardiac output and LV filling by providing more cardiac cycles. Only in compensated failure, a controlled heart rate (60–80 bpm) may allow better diastolic filling. A newly diagnosed tachyarrhythmia at a rate > 105–110 bpm, coinciding with a new HF diagnosis, suggests the possibility of tachycardia‐mediated cardiomyopathy. This is the case in 25–50% of new‐onset atrial arrhythmias associated with a new‐onset HF and warrants aggressive rate and possibly rhythm control, after treating HF decompensation.22–24

A E

E HF decompensation for any reason, Including tachycardia A L

Compensated HF: -Small E (impaired early filling) -Large A Slowing heart rate may improve LV filling as it allows more E and A flow

Decompensated HF: E wave is tall because of high LA pressure, but narrow because of quick LA-LV pressure equalization. Atrial kick cannot push too much flow against the high LV diastolic pressure Slowing heart rate does not improve LV filling, as LV filling can only occur briefly during E wave. At this point, a faster heart rate improves LV filling by providing more cardiac cycles per min.

Figure 4.2  Change of LV filling pattern between compensated and decompensated HF. The E and A waves correspond to the transmitral flow in diastole. The L wave is a marker of elevated LA pressure which attempts to push flow throughout diastole.

100  Part 2.  Heart Failure

III. Right HF Left HF is the most common cause of right HF. Overall, there are three mechanisms of RV failure, including isolated RV failure: a.  Pressure overload: pulmonary hypertension secondary to left heart disease, lung disease, PE, or pulmonary vascular disease. b.  Volume overload: ASD, tricuspid or pulmonic regurgitation. TR is often functional and secondary to RV failure but exaggerates its progression through the extra volume load. Conversely, primary TR may be a cause of an otherwise unexplained RV failure. In the absence of severe pulmonary hypertension, TR and especially PR are usually well tolerated for years before leading to RV failure. The adult RV is more tolerant of volume overload than pressure overload. c.  Intrinsic RV dysfunction: ARVD or RV infarct. Acute myocarditis, tachycardia‐mediated cardiomyopathy, and idiopathic, HIV, or alcoholic cardiomyopathy usually lead to RV and LV involvement, but one may be more predominantly involved than the other.

In any patient presenting with right heart failure, do not overlook the possibility of pericardial processes, the great mimickers of right heart failure. Tamponade mimics acute right heart failure, while constrictive pericarditis mimics chronic right heart failure. Moreover, restrictive cardiomyopathy, a form of biventricular failure, frequently presents clinically as a predominant right heart failure.

3.  Diagnostic tests I. Echocardiography As mentioned under Definition, HF is a clinical diagnosis. The severity of HF is assessed using the NYHA functional classification. Echocardiography is done to differentiate the three major categories of HF based on the assessment of EF, valvular function, diastolic dysfunction (low E’), and LA pressure (elevated E/E’):

A normal EF suggests diastolic dysfunction or transient systolic dysfunction (as in ischemia). One should look for specific signs of diastolic dysfunction such as reduced mitral tissue Doppler E’ (E’ corresponds to myocardial recoil in diastole). A normal E’ is very unusual in diastolic or systolic HF.13 Patients with diastolic HF usually have signs of elevated LA pressure if they are in active HF (elevated E/E’ ratio > 14), or signs of stage 1, compensated diastolic dysfunction if they are not in HF (low E’  400–500 pg/ml (or NT‐pro‐BNP > 1200 pg/ml) is highly suggestive of acute left HF in a patient with acute dyspnea. It correlates with increased LVEDP; however, the exact BNP value does not correlate with the exact degree of LVEDP rise. For a given filling pressure, dilated ventricles secrete more peptide because of the greater wall stress/stretch and chamber mass. This explains why BNP is higher in LV systolic than in LV diastolic failure, and how it may be high despite a normal LVEDP. Also, several factors such as age, sex, and renal failure contribute to the absolute BNP levels. B. BNP  60 mmHg with exercise).

E

A F

Normal E F

MS (a)

(b)

(c)

(d)

Figure 6.7  (a) Long‐axis view in diastole. See the hockeystick shape of the anterior leaflet (arrow), the tip of which looks attached to the stiff posterior leaflet (line), with no diastolic opening. In fact, both leaflets are tied together by the commissural fusion. (b) M‐mode across the mitral valve. The E–F slope is flattened and the posterior leaflet is dragged towards the anterior leaflet (arrowhead). (c) Commissural fusion on the mitral short‐axis view (arrow). Commissural calcium is seen (arrowhead). Rather than oval, the mitral opening has a “fish mouth” shape. (d) Apical four‐chamber view shows severe chordal thickening extending to the papillary muscles (arrows). The mitral leaflets are thickened, and the thickening and immobility extend beyond the edges into the body of the leaflets. The Wilkins score is 10 (leaflet thickness = 2, calcium = 2, leaflet mobility = 2, chordal thickening = 4).

Chapter 6.  Valvular Disorders  169

d.  Commissural fusion ± commissural calcium are seen on the mitral short‐axis view and lead to a “fish mouth” shape of the mitral orifice (Figure 6.7). e.  Since it is easy to align the Doppler beam with the mitral inflow on the apical views, the echocardiographic determination of the ­transmitral gradient is highly accurate. However, the estimation of the mitral valve area (MVA) using one of the four echo methods (mitral inflow pressure half‐time, continuity equation, PISA method, and planimetry) may be subject to measurement errors, and thus MVA is ­better assessed with invasive hemodynamics. MVA is a better determinant of MS severity than the mitral gradient. In fact, transmitral pressure gradient being proportional to the square of the transmitral flow per second, tachycardia or a high‐output state (e.g., anemia, heavy vasodilator use, sepsis) may convert an anatomically mild MS into a hemodynamically severe MS with a severely increased transmitral gradient. Hence, in any echo or invasive study of MS, it is always important to report the heart rate. Heart rate reduction and diuresis may be appropriate first‐line therapies in an anatomically mild MS, which underlines the importance of invasive assessment of cardiac output and MVA in selective cases. Overall, invasive hemodynamics are valuable for the assessment of MS whenever there is discrepancy between the echocardiographic MVA and transmitral gradient; and whenever it is not clear whether the patient’s symptoms or pulmonary hypertension are purely secondary to MS, or rather secondary to mild MS + high‐output state and tachycardia, mild MS + LV diastolic dysfunction, or intrinsic pulmonary arterial hypertension. The invasive calculation of MVA and cardiac output is invaluable in these cases, and is often performed in patients whose echocardiographic MVA is in the mild or moderate range. Another case scenario: a patient with severe diastolic dysfunction and mild/moderate MS (MVA > 1.5 cm2) may have severe LVEDP elevation with a PCWP that is only slightly larger than LVEDP, implying a more dominant role of LV dysfunction in the patient’s symptomatology. Stress testing may be performed: a disproportionate rise of PCWP and transmitral gradient in comparison to LVEDP implies significant MS.

B. Catheterization Simultaneous LA–LV pressures should be obtained, and, ideally, LA pressure should be directly measured through a trans‐septal puncture. PCWP is often used as a surrogate of LA pressure and PCWP–LV simultaneous recordings are often used to assess MS (Figure 6.8). Three pitfalls attend the use of PCWP and lead to overestimation of the transmitral gradient: • PCWP tracing is delayed by 50–150 ms in comparison to LA pressure tracing. • PCWP is more damped than LA pressure with less deep and steep Y descent. • The obtained PCWP may not be a true PCWP and may rather be a damped PA pressure or a hybrid PA–PCWP. True PCWP has well‐defined A and V waves with the following characteristics: (1) as opposed to the systolic PA pressure, the V wave of PCWP peaks after the T wave and its peak intersects the LV descent; (2) if a diastolic segment is well seen between pressure peaks, it is horizontal or upsloping in PCWP vs.

LV LV Diastolic gradient of MS

LA or PCWP

30

v

PCWP

a

V

A

20

10

Systole

Diastole

0

No LV A wave

1 sec Figure 6.8  Two examples of mitral stenosis with a diastolic pressure gradient between PCWP and LV at a heart rate of 60 bpm (dark filled areas). Due to phase delay, the tracing of PCWP has been shifted to the left so that the peak of the V wave almost intersects the LV downslope. There is no LA–LV diastasis, i.e., LA pressure remains higher than LV pressure throughout diastole, signifying severe MS. LA A wave is pronounced but LV A wave is reduced because of ventricular underfilling. With more severe MS, the LA pressure tracing is higher and the intersection between V wave and LV occurs earlier; this translates into an opening snap that is closer to S2.

170  Part 3.  Valvular Disorders

LV

LV LV

v LA

v

v PCWP

PCWP

a

a

LA-LV pressures in a patient with MR

PCWP-LV pressures in the same patient before shifting PCWP to the left

a

PCWP-LV pressures in the same patient after shifting PCWP to the left

Figure 6.9  False impression of MS resulting from the use of PCWP as a surrogate for LA pressure in a patient with severe MR. When LA–LV pressures are simultaneously recorded, an early diastolic gradient is seen between LA and LV and is quickly followed by diastasis. However, when PCWP–LV pressure recording is performed, the damped and prolonged Y descent creates the impression of a large pressure gradient and a lack of diastasis, even when PCWP is appropriately shifted to the left, thus creating the impression of MS. Also, in comparison to patients without concomitant MR, patients with combined MS and MR are more likely to have their transmitral gradient overestimated with the use of PCWP. Note that LV A wave is still present and prominent, arguing against severe MS. Reproduced with permission from Hanna EB. Mitral stenosis. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 101.

downsloping in damped PA pressure; (3) A wave is seen between V peaks on the PCWP tracing, whereas a dicrotic notch is seen on the PA tracing; (4) mean PCWP 15 mmHg; or if systolic PA pressure or PCWP increases to >60 mmHg or >25 mmHg, respectively, without a significant increase in LVEDP. A second condition where stress testing is helpful is asymptomatic severe MS. An exertional increase of systolic PA pressure to >60 mmHg or a severe increase in transmitral gradient signifies that the patient is likely limited functionally and will likely benefit from an intervention to avoid the consequences of prolonged pulmonary hypertension. Note that, similarly to exercise, the heavy use of vasodilators increases cardiac output and the mitral gradient. Also, passive leg raising increases venous return and the mitral gradient. In fact, passive leg raising is routinely performed during echo assessment of MS. Dobutamine may also be used.

III. Treatment A.  Medical therapy • Diuretics and β‐blockers often produce substantial symptomatic improvement. β‐Blockers increase diastolic time, allowing more time for LA emptying. A heart rate of 60 bpm should be targeted. Medical therapy is not usually indicated as a standalone therapy, as even patients with class II symptoms have impaired long‐term outcomes without mechanical relief of MS. Standalone medical therapy may, however, be used in select patients with class II symptoms: ○○ Patients with class II symptoms who do not have appropriate morphological features for percutaneous mitral balloon valvotomy (PMBV). Class II symptoms are not severe enough to warrant surgery. ○○ Patients who improve after PMBV but have residual symptoms. ○○ Patients with mild/moderate MS that is symptomatic because of hemodynamic disturbances (tachycardia, high cardiac output). ○○ Sedentary, elderly patients with mild symptoms on exertion.47 This includes senile MS. • Treatment of AF: β‐blockers and/or digoxin are used for rate control. Rhythm control may be attempted after a new onset of AF, but repeated DC cardioversions should be avoided in light of the associated stroke risk and the fact that, over time, rhythm control is difficult to achieve in MS. The yearly risk of stroke with the AF–MS combination is 10–15% per year, implying a critical role of warfarin therapy. Note the effect of β‐blockers on the transmitral gradient (Figure 6.10). The reduction of PCWP and transmitral gradient with a longer diastole makes β‐blocker therapy important in decompensated MS with pulmonary edema. A similar benefit of β‐blockade is seen when pulmonary edema is related to HOCM. No other case of decompensated left heart failure, whether systolic or diastolic, is acutely served by β‐blockers.

B. Indications for percutaneous or surgical therapy A mechanical intervention is indicated for select patients with severe (≤1.5 cm2) or very severe MS (≤1 cm2):12 • Symptoms class II–IV for PMBV or III–IV for MV surgery (class I indication). • Asymptomatic patient with moderate pulmonary hypertension qualifies for PMBV (systolic PA pressure >50 mmHg at rest, >60 mmHg with exertion) (class I indication in older guidelines). Pulmonary hypertension more readily indicates mechanical correction in MS than MR, as pulmonary hypertension of MS more quickly progresses to precapillary pulmonary hypertension and RV failure. • Asymptomatic patient with very severe MS (≤1 cm2) qualifies for PMBV, as the patient likely has unnoticed functional decline and will develop progressive pulmonary hypertension (class IIa). • Asymptomatic patient with AF. PMBV may be performed, but the strength of this recommendation is weak (IIb), as PMBV has not been universally successful in preventing or reverting rheumatic AF (≠ MV replacement for MR).47 Also, as explained above, symptomatic patients with moderate MS (MVA 1.5–2 cm2) and moderate gradient at rest need to be assessed with stress testing. A severe increase in transmitral gradient without a significant change in LVEDP implies that MS is hemodynamically significant and may benefit from PMBV (class IIb). On the other hand, patients with moderate anatomic MS who have a severe

172  Part 3.  Valvular Disorders

LV v LA 20

a

x

0 mmHg Figure 6.10  β‐blockers slow the heart rate and allow more LA emptying, which ultimately reduces LA pressure, V and A waves. The slope of the PCWP descent is unchanged (arrows); however, a longer diastole allows a longer duration of emptying and approximation of LA and LV pressures. Diastasis may be achieved if MS is not very severe. The height of LA pressure ↓ after several long R–R cycles as LA volume ↓. Reproduced with permission from Hanna EB. Mitral stenosis. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 107.

gradient at rest need to be invasively assessed and treated for associated hemodynamic disturbances: tachycardia, high‐output state (e.g., anemia, vasodilator therapy). In the absence of those hemodynamic disturbances, moderate MS may be the cause of the severe gradient and the severe pulmonary hypertension and may warrant PMBV (also, a valve area of 1.6 cm2 may imply severe MS when indexed for body size). For patients who are not PMBV candidates, mitral valve replacement is not usually considered unless symptoms are class III/IV, i.e., more severe than required for PMBV, as valve replacement has a higher operative mortality than PMBV. Patients with class II symptoms and a valve morphology that is not favorable for PMBV should undergo medical therapy with 6‐month follow‐ups rather than surgery. Yet, those patients with severe pulmonary hypertension and MVA 70 years of age, MVA and symptoms improved in most patients, even those with Wilkins score >8; half of patients with Wilkins score >8 had improvement of MVA to >1.2 cm2, and most patients, even those with scores >10, had some improvement of valve area and functional class with PMBV.49 Also, while moderate 2+ MR predicts a 4× higher failure rate, it does not prohibit PMBV.43,48 In the original Wilkins paper, no patient with moderate MR developed severe MR after PMBV.43 In a large PMBV series, ~6.5% of patients had moderate baseline MR.48 Balance Wilkins score with the degree of MR (Wilkins score of 10 without any MR may be as amenable to PMBV as Wilkins score of 8 with mild‐to‐moderate MR). Thus, while a surgical approach is advisable in most patients with high scores, PMBV may still be beneficial in patients with an intermediate (9–11) or even high score, or patients with 2+ moderate MR when serious comorbidities are present or the surgical risk is high.48–50 Hence, the ACC guidelines consider PMBV a reasonable therapy for patients with class III/IV symptoms and a valve morphology that is not favorable for PMBV if the surgical risk is high (class IIb indication).

Chapter 6.  Valvular Disorders  173

After a successful PMBV, restenosis occurs at a rate of ~20% at 10 years, more so in patients with a suboptimal early result and in those with unfavorable Wilkins score, which is associated not only with short‐term but also with long‐term failure.51,52 Overall, ~25% of patients require MV replacement within 5 years, whether for restenosis, progression of a suboptimal result, or progression of MR; this risk is higher in patients with an unfavorable early result or a high Wilkins score (up to 50%).48,52 Redo PMBV may be performed with a high success rate (~75%) in the presence of favorable echocardiographic features.51

Beside a young age  25 mmHg may develop reactive changes in the pulmonary arteriolar bed, severe increases in the pulmonary vascular resistance (PVR), as high as 25 Wood units, and very severe pulmonary arterial hypertension disproportionate to the PCWP. This may be associated with severe RV failure. Even at this stage, however, patients usually respond to correction of MS; the elimination of the passive postcapillary component of pulmonary hypertension results in an immediate drop in PA pressure, followed by a slow and gradual decline in the reactive and hypertrophic component.54–56 In fact, PA pressure and PVR decline towards normal over the course of several weeks to months. Therefore, invasive treatment is still warranted at the stage of severe pulmonary hypertension. In the majority of patients, an almost complete normalization of pulmonary hypertension is expected. Pulmonary vasodilators (endothelin antagonist, intravenous prostacyclin) may be temporarily used in the early postoperative period.

3 .  A o rt i c i n s u f f i c i e n c y I. Etiology A.  Acute AI a.  Endocarditis: the vegetation may perforate the leaflet(s) or prevent valvular coaptation. b.  Aortic dissection leads to AI through three potential mechanisms: (i) dilatation of the sinotubular junction; (ii) dissection extends into the leaflet attachment at the sinotubular junction, resulting in leaflet prolapse and eccentric AI; (iii) dissection flap prolapses through the aortic orifice and prevents leaflet coaptation. AI may also be pre‐existent, secondary to a bicuspid aortic valve. c.  Closed chest trauma may lacerate the aortic leaflet or its sinotubular insertion, causing it to prolapse. Being anterior, the aortic valve is the valve most commonly involved in chest trauma. B.  Chronic AI a.  Dilatation of the ascending aorta with secondary AI: this is the most common cause of severe AI. Dilatation of the ascending aorta may lead to dilatation of the junction between the aortic root and the sinuses of Valsalva, called the sinotubular junction, precluding the coaptation of the aortic leaflets (Figure 6.11). Rather than being secondary to AI or AS, aortic dilatation is a primary process that can cause AI or coexist with bicuspid aortic valve disease. While potentially causing AI, aortic dilatation is reciprocally worsened by the high stroke volume of AI; it is also worsened by the high post‐stenotic jet of AS (post‐stenotic dilatation). Causes of ascending aortic disorders: i.  Degenerative aortic dilatation, related to age and HTN, is the most common cause of ascending aortic dilatation. ii.  Cystic medial necrosis, which occurs in younger patients: (1) Marfan or Marfan fruste, (2) bicuspid aortic valve, (3) spondyloarthropathies.

174  Part 3.  Valvular Disorders

Sino-tubular junction S Ventricular septum

L

Fibrous anterior mitral annulus (aortic-mitral curtain)

Basal valvular hinge Normal aortic valvular apparatus

Aortic and sinotubular dilatation with secondary AI

Loose sino-tubular junction with cusp prolapse

Figure 6.11  Aortic leaflets and their relation to the ascending aorta. A normal valve apparatus consists of aortic tissue that extends from the sinotubular junction, forms local aortic dilatations called aortic root or sinuses of Valsalva (S), then touches the ventricle and suspends the aortic leaflets (L) (also called semilunar cusps). The sinuses of Valsalva are an extension of the aortic wall tissue. The sinotubular junction, rich in elastic tissue, provides the main support for the sinuses. The coronary arteries originate from the sinuses of Valsalva or just above them. Two‐thirds of the circumference of the aortic valve is connected to the muscular ventricular septum, while the remaining one‐third is in fibrous continuity with the anterior mitral leaflet (fibrous trigone, close to the non‐coronary posterior cusp) (see Figure 6.1). At one point posteriorly, the aortic valve is in continuity with the interatrial septum. The annulus is a ring formed by the junction of the basal valvular hinges (leaflets’ insertion on the ventricle).

b.  Aortic valve disorders i. Bicuspid aortic valve is the most common valvular cause of severe AI. AI results from prolapse of a leaflet or incomplete closure of a thickened redundant valve. ii. Old, healed endocarditis. Subacute endocarditis may only be associated with mild or moderate AI early on, but progressive valvular deformity results from the healing process and leads to progressive AI (progressive widening of a perforation or progressive retraction of the scarred leaflet(s) with malcoaptation). iii. Idiopathic degeneration of the aortic valve with increased and disorganized collagen and elastic fibers. Anatomically, a mild degree of thickening/retraction, redundancy, or myxomatous degeneration may be seen. This was the most common cause of isolated AI in one study.57 iv. Rheumatic fever with fibrosis and retraction of the leaflets. Fibrosis and fusion of the commissures also leads to AS. The aortic valve is immobile and does not open or close (combined AS/AI). v. Prolapse of an aortic valve leaflet in the context of bicuspid aortic valve, endocarditis, trauma, or myxomatous degeneration. vi. Degeneration of a bioprosthesis.

II.  Pathophysiology and hemodynamics (Figure 6.12) A.  Acute AI In acute AI, LV is non‐compliant and LV volume is normal. Thus, the regurgitant volume leads to a severe increase in LVEDP and the aortic and LV diastolic pressures come close together (Figure 6.12). LV diastolic pressure exceeds LA pressure in mid‐ or late‐diastole (Figure 6.12), leading to a reverse LV–LA gradient and forcing the mitral valve to close prematurely (functional MS), a finding typical of decompensated AI.58,59 Since LV is not dilated, the stroke volume is reduced in acute AI. Therefore, in addition to the low DBP, SBP is usually low (e.g., BP 90/40 mmHg). As opposed to chronic AI, pulse pressure is only mildly widened, but this already suggests acute AI in a patient with acute heart failure, wherein the arterial pulse pressure is typically narrow. Tachycardia is an important compensatory response in acute AI as it increases the cardiac output and reduces the regurgitant time, and thus should be respected. B.  Chronic compensated AI In chronic compensated AI, LV volume increases, the total stroke volume increases, leading to a high pulse pressure (e.g., 160/60 mmHg), and the forward stroke volume is maintained. The LV is large and compliant in a way that it accommodates the regurgitant volume without an increase in LVEDP. The aortic and LV pressures do not approximate at the end of diastole; on Doppler, this corresponds to a gradual rather than steep drop of the regurgitant flow velocity with a pressure half‐time that is >250 ms, even if AI is severe. While a wide pulse pressure (>½ SBP or >60–80 mmHg) is a very sensitive finding in chronic severe AI, it is not a specific finding and may be seen in a poorly compliant aorta and in high‐output states with low afterload (patent ductus arteriosus, hyperthyroidism, anemia, fever, and arteriovenous fistula). The peripheral femoral pressure may get excessively amplified and may exceed the central systolic pressure by 50 mmHg or more. This is an exaggeration of a normal effect and is due to the hyperdynamic state and the excess of reflected waves in the periphery. These reflected waves may explain a second systolic pressure peak in the peripheral arteries and aorta (pulsus bisferiens). C.  Chronic decompensated AI In chronic decompensated AI, the LV function starts to decline, and EF decreases such that the forward stroke volume declines and the LV volume further increases. This leads to increased LVEDP despite good LV compliance. Similarly to acute AI, LV and aortic pressures approximate in end‐diastole.58,59 On Doppler, this corresponds to a steep drop of regurgitant flow velocity throughout diastole with a short pressure half‐time 60% of the aortic area (short‐axis view). The narrowest AI neck, measured at the aortic valve level and called vena contracta, is >6 mm (long‐axis view). Bicuspid AI jet may be eccentric and may thus be underestimated. • Holodiastolic flow reversal in the descending aorta (most important feature). • On the spectral Doppler, pressure half‐time of the regurgitant flow is 250 ms if AI is severe but chronic and compensated. Conversely, pressure half‐time may be 70 mm have the highest risk of progression to ­symptoms and/or LV dysfunction (10–20% per year). Conversely, symptomatic AI or AI with LV dysfunction has a mean survival rate of 2–3 years without surgical intervention: yearly mortality 5–10% if NYHA class II dyspnea, >10% if angina, >20% if class III–IV HF, wherein the mean survival is 1.5 years.60 AI symptoms appear late in the disease process, usually after LV has severely enlarged. Class II dyspnea appears earlier than angina and severe HF. Subendocardial coronary flow being driven by the gradient between aortic diastolic pressure and LVEDP, angina is often ­functional and related to the severe drop in aortic diastolic pressure and the increase in LVEDP. Moreover, O2 demands of the large LV are severely increased. Angina may be nocturnal rather than exertional, aggravated by bradycardia, wherein the aortic diastolic pressure decreases to very low levels. Diastolic reversal of coronary flow may be seen in severe cases. Palpitations may appear early on and are related to the ­ejection of a large LV volume, especially after a PVC; they are not, per se, an indication for surgery.

V. Treatment A.  Medical therapy Aortic valve surgery is the only effective therapy for severe AI that requires treatment. Vasodilators (ACE‐I, CCBs) may be useful for systolic HTN and are used as a temporizing measure preoperatively. Vasodilators, as well as β‐blockers, may be used in patients who are not undergoing surgery because of high risk (class IIa). By prolonging diastole, β‐blockers may aggravate symptoms, but if tolerated, they may prevent the deleterious LV dilatation and remodeling, according to one retrospective analysis. In severe asymptomatic AI with dilated LV and no indication for surgery, vasodilators may slow LV dilatation; however, a  ­randomized trial has disproved this theory, and thus vasodilators have a questionable value in severe asymptomatic AI (not

Chapter 6.  Valvular Disorders  177

­recommended).61 Also, it is important to avoid a harmful drop in DBP with these agents; a slightly increased SBP may be accepted if SBP reduction would come at the price of excessive DBP reduction (per guidelines). Mild exercise is allowed in asymptomatic severe AI. Athletic activity may be allowed in some cases, after performing stress testing for safety purposes; the long‐term effect of exercise on severe AI is, however, unknown. B. Indications for surgery Aortic valve surgery is indicated for severe AI with any of the following: • Symptoms (NYHA functional class ≥ II) • EF 50 mm (as compared to ≥ 40 mm for MR) or >25 mm/m2 of BSA • Asymptomatic severe AI while undergoing CABG or other cardiac/aortic surgery. AVR is also reasonable for moderate AI while undergoing cardiac/aortic surgery (class IIa indication) Similarly to LVESD, LVEDD correlates with AI volume overload but less strongly with LV systolic function. Surgery may be considered for LVEDD >65 mm, particularly when LV dilatation is rapidly progressive and the surgical risk is low (class IIb indication). In general, asymptomatic patients with less severely enlarged LV (LVESD 40–50 mm or LVEDD 55–65 mm) should be re‐evaluated by echo in 3 months then every 6–12 months if the LV dimensions are stable. If unstable, echo should be repeated every 3 months. AI is tolerated for a long period of time before symptoms develop. Even when symptoms develop, they are insidious in a way that the patient may not realize his functional limitation. Before considering AI asymptomatic, exercise testing is often warranted. Patients with advanced symptoms or LV dysfunction. As opposed to MR, LV function does not usually deteriorate postoperatively and is likely to improve even with markedly reduced EF.62 Early on in AI, the reduced EF is secondary to the high afterload rather than intrinsic dysfunction (afterload mismatch). AVR reduces regurgitant flow, which reduces LV wall stress/afterload and allows an improvement of EF, the earliest sign being a reduction of LV size. However, long‐term postoperative survival is significantly reduced, ~ in half, in patients with NYHA class III–IV symptoms or EF 18 months, severe (EF 40 years old, and 75% of bicuspid patients eventually develop severe AS over their lifetime (not all become severe AS).69,70 Bicuspid aortic valve is the most common cause of AS in patients 20 mmHg with exercise (ESC, class IIb). • Patients with associated CAD that requires CABG should undergo concomitant AVR. A recent Japanese registry suggested that, in very low‐surgical‐risk patients with severe AS, watchful waiting was associated with a significant increase in 5‐year mortality compared with initial AVR. This was driven by an increased rate of HF during the waiting period, including severe HF as first presentation, and a higher operative risk once AS was symptomatic.96 E.  MR associated with severe AS MR frequently coexists with severe AS and is often functional, secondary to LV and LA remodeling and the increased LV systolic pressure (>15% of AS patients have moderate or severe MR). MR often improves by ≥ 1 grade in 50–90% of patients after AVR, especially if functional and not severe. MR improves in two waves (immediate and late).97 Mitral annuloplasty repair is generally performed concomitantly to AVR if MR is severe, or moderate with pulmonary hypertension, LA enlargement/AF, or intrinsic mitral valve disease, and the surgical mortality is low.97 If the surgical mortality is intermediate or high, only AVR is generally performed. F.  Percutaneous aortic valvuloplasty Valvuloplasty, which consists of inflating a balloon across the aortic valve, is only a palliative therapy and is not effective over the long term. Valvuloplasty may be performed as a bridge to eventual AVR in patients with severe AS who are hemodynamically unstable with multiple organ failure. Once the patient is stabilized, surgical or transcutaneous AVR may be performed at a lower risk.

In early rheumatic MS, valvuloplasty is effective as it opens the fused but non‐calcified commissures. In calcific AS, the whole valve is calcified and the process is not limited to the commissures. Aortic valvuloplasty temporarily fractures the calcified framework of the valve, making it more flexible/pliable; also, it mildly tears the valve and opens the commissures. It is usually moderately effective and converts critical AS into severe AS, with a high risk of complications (>10%, including AI and stroke). Calcium quickly regrows and leads to recurrence of AS within 6–12 months.

Valvuloplasty may be used as a long‐term therapy in children or young adults with non‐calcified bicuspid AS wherein commissural fusion is the cause of stenosis, and where valvuloplasty produces small commissural tears. The results usually last 10–20 years, and most patients eventually require AVR later in adulthood. Moreover, there is an early and late risk of AI (~15% at 3–4 years). Valvuloplasty is indicated in children or young adults with a peak‐to‐peak or mean gradient >50 mmHg who are symptomatic, or asymptomatic with ST–T changes of LVH (class I), asymptomatic with a peak‐to‐peak gradient >60 mmHg (class I), or asymptomatic and planning pregnancy or athletic activity (class IIa). G.  Transcutaneous aortic valve replacement (TAVR) TAVR may be performed through a transfemoral, transaxillary, or transcaval approach. It may also be performed surgically through a transapical or direct ascending aortic approach. The valve is a balloon‐expandable valve (Edwards Sapien valve, Sapien 3 valve) or a self‐ expanding valve (Corevalve). In high‐surgical‐risk patients (STS score ≥ 8%), TAVR was associated with a postoperative mortality similar to

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that of surgical AVR (~6.5%). In inoperable, high‐risk patients, TAVR drastically reduced 1‐year mortality in comparison with conservative management (30% vs. 50% one‐year mortality) (PARTNER trial).98 The mean age in the PARTNER trial was 84 years (84 ± 7), functional class was mainly III–IV, and prior CABG, stroke, or advanced COPD was common; ~20% of patients had associated moderate or severe MR. Therefore TAVR was mainly applied to advanced‐stage, often octogenarian patients. Approximately 9% of patients had radiation heart disease and ~20% had extensively calcified aorta. The mean transaortic gradient was 43 ± 15 mmHg; in fact, the PARTNER trial included a significant proportion of patients with low‐flow/low‐gradient AS (with low EF [15%] or normal EF/paradoxical low gradient [14%]). Those demonstrated the highest mortality and the most drastic survival improvement with TAVR in comparison with conventional management, whether EF was reduced or not.99 The Corevalve trial of self‐expanding valve was even more impressive than the PARTNER trial. TAVR with Corevalve was associated with better 1‐year survival than surgical AVR, in intermediate and high‐surgical‐risk patients (most patients had STS score between 4 and 10, mean age was 83).100 Corevalve impinges on the AV nodal area, hence the frequent need for permanent pacing (~20%). The PARTNER 2A trial used a lower‐profile, newer balloon expandable valve (Sapien) in intermediate‐surgical‐risk patients with STS score 4–8%. It suggested a better 1‐year survival with transfemoral TAVR vs. surgical AVR, potentially expanding the use of TAVR to these lower‐risk patients.101 The transcutaneous valve consists of a thin stent frame that actually contains stentless bioprosthetic leaflets. Without the bulk of the sewing ring and the stented struts, the transcutaneous valve has a larger orifice area and less gradient than a surgical bioprosthesis (~0.4 cm2 larger), with less patient/prosthesis mismatch. TAVR is not typically used in patients with a clearly bicuspid valve, where the aortic opening is elliptical rather than circular, which prevents symmetrical apposition of the cylindrical prosthesis and allows paravalvular leaks. This is only a relative contraindication, particularly because in many critical AS cases, the tight residual orifice does not allow distinction between tricuspid and bicuspid valves. The use of TAVR in severe AI is limited by: (1) coexistent aortic root disease and large annular size, which increases the risk of dehiscence and persistent AI; (2) frequent lack of significant valvular calcifications, which serve as a fluoroscopic landmark for valve positioning and as an anchor at the lower part of the stent frame; (3) difficulty in positioning in a patient with regurgitant jet. TAVR is associated with a 5% rate of postoperative stroke. Moderate or severe paravalvular regurgitation is common (10%) and is associated with early and long‐term increase in mortality, particularly with the balloon‐expandable valves. Conversely, the Corevalve trial revealed that paravalvular AI improves at 1 year to less than mild in 75% of patients with moderate/severe AI, thanks to the sustained expansion of the self‐expanding frame.

5 .  T r i c u sp i d r e g u r g i tat i o n a n d   s t e n o s i s I. Etiology of tricuspid regurgitation (TR) A.  TR is often secondary to RV pressure or volume overload i.  PA pressure >55 mmHg or PVR >3 Wood units implies that TR is secondary to pulmonary hypertension:102 • LV dysfunction or left valvular disorders with pulmonary hypertension • Pulmonary arterial hypertension or lung disease with pulmonary hypertension The high RV pressure as well as the secondary RV dilatation, annular dilatation, and leaflet tethering lead to TR. As opposed to functional MR, annular dilatation is the more important factor in functional TR (the right papillary muscles are highly placed and less severely tether the tricuspid leaflets). The tricuspid annulus is very dynamic and may considerably “shrink” with volume unloading. ii.  PA pressure  35–40 mm on TTE (or > 21 mm/m2). Tricuspid annular dilatation is an ongoing progressive process that results in more annular dilatation, such that an initially mild TR may progress over time and become the primary driver of RV failure. When the primary process is degenerative MR, < 20% are left with significant residual TR or late TR after correction of MR (vs. > 50% in MS or ischemic MR, several years after surgery).104 Therefore, adjunctive tricuspid annuloplasty is reasonable in severe TR, or mild/moderate TR with severe annular dilatation, and is associated with improved functional capacity and reduced long‐term risk of TR and HF (yet questionable survival benefit).104 In general, tricuspid annuloplasty concomitant to mitral surgery does not significantly increase the surgical risk and pump time, whereas reoperation for severe progressive TR after mitral surgery is associated with a high mortality of 10–25%, further justifying early, concomitant surgery.12

III. Treatment of TR A.  Medical therapy of RV pressure or volume overload This includes diuretics, treatment of LV failure, lung disease, or pulmonary arterial hypertension. B. Surgical indications a.  Severe and symptomatic primary TR (fatigue, dyspnea, right HF with edema/ascites) (class IIa). Perform tricuspid repair with an ­annuloplasty ring (preferably) or tricuspid valve replacement with a bioprosthetic valve. A bioprosthesis is preferred to a mechanical ­prosthesis because of the high thrombotic risk on the right side, where the closing pressure is low. Also, a bioprosthetic valve lasts longer in a low‐pressure system (i.e., tricuspid, or, even better, pulmonic position). b.  Severe primary TR with progressive RV dilatation or dysfunction, even if asymptomatic (class IIb). c.  In a patient undergoing mitral valve surgery, tricuspid valve surgery should be performed if secondary severe TR is present (class I). Tricuspid annuloplasty is preferred to replacement. Tricuspid annuloplasty should also be performed for mild or moderate TR associated with annular dilatation >40 mm or prior right HF,12 as annular dilatation and TR may continue to progress after mitral surgery even if pulmonary pressure is eventually reduced (class IIa); this is particularly true if baseline PA pressure is not severely elevated and does not appear to be the driver of TR. When measured intraoperatively on an arrested heart, annular dilatation >70 mm, rather than 40 mm, indicates repair. d.  If the mitral valve is amenable to PMBV, PMBV may be performed and TR reassessed. If the mitral valve is treated surgically, TR is concomitantly repaired to avoid the risk of progressive TR and a second surgery.12 There are two types of tricuspid annuloplasty: (1) ring annuloplasty; (2) suture annuloplasty, which consists of a single suture tied circumferentially around the posterior and anterior aspects of the annulus (de Vega). A ring has more sustained long‐term efficacy than a suture, lasting >5 years, but requires more surgical time (~30 minutes). De Vega annuloplasty usually requires 80 mmHg, and moderate when the peak‐to‐peak gradient is >40 mmHg. The gradient in PS, particularly mild or moderate PS, usually remains stable over the long‐term follow‐up. Severe PS is usually symptomatic

188  Part 3.  Valvular Disorders

and is treated with percutaneous balloon valvotomy with excellent long‐term result (no recurrence over >20 years follow‐up). Most patients with moderate PS eventually develop symptoms during a 25‐year follow‐up and require valvotomy.106 In the ACC guidelines, percutaneous valvotomy is indicated for symptomatic PS with a peak‐to‐peak gradient >30 mmHg, or asymptomatic PS with a peak‐to‐peak gradient >40 mmHg. Moderate‐to‐severe pulmonary regurgitation may subsequently be seen in up to 20% of patients, but is not usually clinically significant; 40 mmHg can participate in low‐intensity competitive sports or can be referred for intervention. Two to four weeks after valvuloplasty, asymptomatic athletes with no more than mild residual PS and normal ventricular function can participate in all competitive sports.107 Patients with PS have a hypertrophied RVOT. Following percutaneous valvuloplasty, the reduction in RV afterload reduces RV volume and may cause a dynamic obstruction across the hypertrophied RVOT and a residual gradient that is actually an intraventricular gradient. This gradient should not be confused with a persistent transpulmonic gradient, and the diagnosis is confirmed on a slow PA‐to‐RV pressure pullback. The RVOT obstruction may be severe (“suicide RV”) and is initially treated with fluids, β‐blockers, and calcium channel blockers. This gradient resolves gradually.

II.  Pulmonic regurgitation (PR) The most common cause of PR is pulmonary hypertension, which leads to a secondary form of PR. This is classically seen with MS. Primary PR may be seen decades after surgical therapy of tetralogy of Fallot, valvotomy for PS, or after Ross procedure. It may also be seen with endocarditis and carcinoid syndrome. When associated with pulmonary hypertension, PR leads to Graham Steell’s PR murmur, which is a diastolic murmur similar to AI, except that it is only heard at the left second intercostal space and increases with inspiration. Isolated PR is seldom severe enough to require any specific therapy, particularly when secondary to pulmonary hypertension. Valve replacement may be required for severe PR related to endocarditis or surgical correction of tetralogy of Fallot if symptomatic RV failure ensues. Note that the RV usually tolerates PR for years, sometimes decades, before it fails. RV size tends to normalize and functional status improves when pulmonic valve replacement is performed for PR late after tetralogy of Fallot repair. However, RV function may not fully recover once marked enlargement and systolic dysfunction are evident.108 Therefore, many experts recommend valve replacement in asymptomatic severe PR with RV dilatation/dysfunction.

7 .   M i x e d va lv u l a r d i s e a s e ; r a d i at i o n h e a rt d i s e a s e I.  Mixed single‐valve disease In mixed moderate or severe stenosis and moderate or severe regurgitation of the same valve, i.e., MS + MR or AS + AI, one lesion usually predominates over the other (stenosis or regurgitation) and the pathophysiology resembles the dominant lesion. However, the non‐­dominant lesion worsens the effect and the symptomatology of the dominant lesion, and these patients are more prone to elevate PCWP and develop pulmonary edema than patients with isolated stenosis or regurgitation. Since the flow across the valve is increased, the transvalvular gradient is increased in comparison to valvular stenosis without regurgitation. This leads to overestimation of the anatomic severity of the stenosis when assessed by gradient. The gradient, however, correlates with the physiologic consequences of the mixed stenosis–­ regurgitation and properly correlates with the overall disease severity. The valvular area is unchanged when calculated by Doppler echocardiography (continuity equation for AS or MS, or pressure half‐time for MS). The valvular area may be underestimated, i.e., the stenosis may appear more severe, if Gorlin’s equation is used with the net forward cardiac output rather than the total output across the valve. In moderate mixed disease in a symptomatic patient, a hemodynamic study is useful in addressing the selective impact of valvular vs. myocardial disease. If mixed mitral disease is the cause of the patient’s symptoms, PCWP and PA pressure will rise with exercise disproportionately to LVEDP. If mixed aortic valve disease is the cause of the patient’s symptoms, LV and aortic end‐diastolic pressures are approximated, the dicrotic notch is attenuated, the LV–aortic gradient is in the severe range even if the valve area is not, and an anacrotic notch may be seen.

II.  Multiple valvular involvement (combined stenosis or regurgitation of two different valves) Multiple valvular involvement may be caused by: rheumatic disease (MS with AI or AS, MR with AI), radiation, endocarditis, severe AS or AI with functional MR, myxomatous degeneration of both aortic and mitral valve, or AI due to aortic dilatation and MR due to MVP in patients with connective tissue disorders. Functional TR may occur secondarily to severe mitral disease. Moderate or severe multiple valvular disease is poorly tolerated. One valvular lesion may mask the hemodynamic manifestation of the other. The proximal lesion tends to mask the severity of the more distal lesion by reducing the flow across the distal lesion, whereas the distal lesion tends to exacerbate the hemodynamic effect of the proximal lesion because of increased backward volume and/or pressure. In general, the clinical effect of the proximal lesion is more prominent than that of the distal lesion. In severe MR or MS associated with AS, AS worsens the hemodynamic effects of MS or MR and may worsen the severity of MR (from moderate to severe). In combined AS and MR, the LV is exposed to both pressure and volume overload in systole. Aortic stenosis does not affect the assessment of severity of mitral valve disease, except that MVA may be falsely increased when calculated using the echocardiographic pressure half‐time. On the other hand, the severity of AS may be underestimated by gradient assessment as a result of the low cardiac output, but may be overestimated by AVA assessment (low‐flow/low‐gradient pseudo‐severe AS). If surgery is indicated for the mitral valve, consider anatomic assessment of the severity of AS during surgery (palpation of the aortic valve) to make a decision about concomitant aortic valve replacement. When MS is associated with mild AS and mitral balloon valvuloplasty is planned, reassess the aortic valve after treatment of MS. In severe MS with AI, the hemodynamic effect of MS is exacerbated. In order to allow transmitral flow, LA pressure has to increase in parallel to the increase in LV diastolic pressure. On the other hand, the hemodynamic effect of AI is reduced. Overall, the patient has a higher LA

Chapter 6.  Valvular Disorders  189

pressure than a patient with isolated MS, but less LV dilatation and less elevated LVEDP than a patient with isolated AI. The severity assessment of MS or AI by catheterization and of AI by echo Doppler are not affected; MVA calculated by Doppler pressure half‐time is falsely increased. Combined MR–AI is the most poorly tolerated combination. The LV gets a double volume load in diastole and is more severely enlarged than with either lesion alone. MR is aggravated, and the regurgitant MR volume is more severely increased than with isolated MR. LV and LA filling pressures and volumes are more severely increased than with each lesion alone. The combination does not affect the echocardiographic or invasive assessment of either lesion. MR may be functional, secondary to LV dilatation; AVR alone often improves functional MR, but MV annuloplasty is usually warranted. In combined severe AS–moderate‐to‐severe MR, MR is often functional, related to the LV pressure overload, and often improves after aortic valve surgery. MR is worsened by AS, and AS severity may be underestimated by gradient assessment because of the low flow ­secondary to MR. If MR is severe, these patients often undergo mitral valve repair along with aortic valve replacement; if MR is moderate, mitral repair may be warranted when MR is organic rather than functional or when the surgical risk is low.

III. Radiation heart disease Radiation heart disease leads to calcification of the cardiac valves and fibrous skeleton, with cardiac abnormalities becoming evident over 5–10 years, sometimes decades, after radiation. The pericardium is the cardiac structure that is most sensitive to radiation and is the most common site of clinical involvement (constrictive pericarditis). The aortic valve is the valve most commonly affected, the combination of AS and AI being the most common radiation‐induced valvular disease. MR is also common (second in frequency), followed by TR. The early process consists of fibrosis of the aortic and mitral annuli with subsequent valvular retraction and regurgitation. This is followed by progressive thickening and calcification of the valves but also the cardiac skeleton and mitroaortic curtain.109 As opposed to rheumatic disease, the mitral base is involved but the mitral leaflets’ tips and commissures are spared. In addition, radiation leads to: (1) ostial or diffuse CAD, mainly involving the left main, ostial RCA, or LAD (anterior); (2) myocardial fibrosis with restrictive cardiomyopathy and sometimes LV ­systolic dysfunction (usually mild); and (3) heavily calcified porcelain aorta. All this complicates the valvular surgery and limits its efficacy. The severe calcifications limit the size of the aortic prosthesis that can be implanted. In addition, interstitial lung disease, recurrent pleural effusions, and impaired skin and sternal healing complicate the operation.12 While senile mitral annular calcifications are usually posterior, anterior mitral annular calcifications on the long‐axis view always suggest radiation heart disease. This corresponds to calcification of the mitroaortic intervalvular fibrosa.

8 .   P r o s t h e t i c va lv e s I. Bioprosthesis A bioprosthesis can be a porcine trileaflet valve or a bovine pericardial trileaflet valve, with three components: ring, struts (both mounted over a stent frame), and leaflets arising from the struts. The leaflets, per se, do not contain any metal. Less commonly, stentless porcine or homograft valves are used: they have a thin ring and thin struts and are only available for the aortic position. The percutaneous aortic prosthesis consists of leaflets mounted inside a thin stent frame without bulky struts; the leaflets are stentless (Figures 6.16, 6.17). Prosthetic leaflets Stentless prosthetic leaflets

Struts Stent frame

Ring Bioprosthetic valve with its 3 components

Percutaneous bioprosthetic aortic valve Metallic leaflet

Metallic leaflets

Bileaflet tilting disk

Hinges

Hinges

Ring

Ring

Single leaflet tilting disk

Mechanical prosthesis with its 3 components Figure 6.16  Prosthetic valves. Surgical bioprostheses typically have a metallic stent frame that extends from the sewing ring to each strut. Stentless bioprostheses have very thin rings and struts without any metal.

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Figure 6.17  Bioprosthetic valve as seen on fluoroscopy. The ring and the three struts (arrowheads) are mounted over a metallic stent frame, which explains their visualization on fluoroscopy. The leaflets, per se, do not contain any metal and are not visualized.

One‐third of bioprostheses degenerate in 10–15 years. Scarring/calcification and tears/perforations occur over time. Leaflet fibrosis and calcification may lead to stenosis but also regurgitation from leaflet retraction. Cuspal tears and perforations lead to regurgitation. A bioprosthesis degenerates more quickly in younger patients (1 CAD risk factor. The presence of CAD dictates a combined CABG + valvular surgery. Beside being an appropriate therapy for CAD, CABG reduces the risk of postoperative infarction and LV failure. Coronary angiography may be forgone in emergent valvular surgery (acute regurgitation, endocarditis, aortic dissection). • A hemodynamic study of AS or MS and a hemodynamic and angiographic study of MR or AI can help define the severity of the valvular disorder. This invasive valvular assessment is indicated if the echo data are inconclusive or if there is discrepancy between the echo and the clinical findings. F. Endocarditis prophylaxis • Not routinely indicated for native valvular disease of any severity. • Only indicated in patients with high‐risk cardiac conditions who are undergoing an invasive gingival, dental, or respiratory procedure: ○○ Prosthetic valve or history of valvular repair using a prosthetic material. ○○ History of infective endocarditis. ○○ Unrepaired cyanotic congenital heart disease, partially repaired congenital heart disease with persistent defects adjacent to a prosthetic material, or in the first 6 months after full repair of any congenital heart disease. ○○ Transplant valvulopathy. G.  Follow‐up echo • Q6–12 months for severe valvular disease without symptoms and without surgical indication (more spaced for MS: Q1 year for very severe MS, Q1–2 years for severe MS) • Q1–2 years for moderate valvular disease without symptoms and without surgical indication (more spaced for MS: Q3–5 years for moderate MS) • Q3–5 years for mild valvular disease H. Surgical mortality • CABG: ~1–5% • Redo CABG: ~10% • AVR: ~3–4%; 1–2% in low‐risk patients, up to 8% in patients with low EF • AVR + CABG: 6% • AVR in octogenarians: ~6–9% (6.4% in PARTNER trial), increases to 18% if AVR + multivessel CABG • MVR: ~6%; MV repair: ~1–3% (half the mortality of MVR) • MVR in patients >70 years old: 14% • MVR + CABG: 11% (mainly due to the higher baseline comorbidity of these patients; the risk is related to CAD rather than CABG itself and is potentially higher if CAD is left untreated) • AVR + aortic aneurysm repair: 9% • Multiple valve replacement: 9% • Redo valve replacement: 5–15% (depending on age and comorbidities) I.  Volume and pressure overload with valvular disease • MR leads to an increase in LV preload. LV afterload is initially reduced because of the low‐pressure leak. However, at an advanced stage, LV afterload (= wall stress) increases because of LV dilatation. • AS leads to an increase in LV pressure afterload. • AI leads to an increase in preload but also a severe increase in afterload from the LV dilatation and the increased pulse pressure. This increase in preload, volume afterload, and pressure afterload explains the massive LV dilatation and the ensuing progressive rise in LV afterload. LV has eccentric hypertrophy. In comparison with AS, AI is associated with the highest afterload and the highest LV mass. • In MS, HF results from mitral obstruction without any LV abnormality, unless intrinsic LV disease coexists. • All severe valvular disorders lead to HF before LV systolic function is grossly affected.

Questions and answers Question 1. A 69‐year‐old woman presents with acute HF and severe HTN (SBP 180 mmHg). Echocardiography shows normal LVEF, AS with a mean gradient of 27 mmHg and AVA of 0.9 cm2, and moderate MR. If this is severe AS, what can explain the paradoxically low gradient? A. Hypertension at the time of the study, particularly if concentric LV hypertrophy is present. In this case, the stroke volume is reduced because of double afterload (HTN and AS), and the small LV cavity B. MR, which reduces forward cardiac output C. Truly severe AS with false measurement of aortic gradient (Doppler beam not parallel to aortic flow) D. All of the above

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Question 2. If the patient in Question 1 actually has moderate AS, what could explain the low AVA calculation? A. Echocardiographic error in measurement (underestimation of LVOT diameter leads to a falsely low AVA) B. Pressure recovery phenomenon in a patient with a small tubular aorta (true gradient is smaller and true AVA is larger) C. The AVA is truly 0.6 cm2/m2, implying a truly moderate AS D. All of the above Question 3. In the above patient, how can one make a diagnosis of severe AS vs. moderate AS? A. Try to obtain aortic gradient in multiple views, including right parasternal view, and try to be coaxial to the aortic flow. Ensure proper echo measurement of LVOT at the aortic annulus (early systole) B. Measure aortic gradient after control of HTN C. Measure stroke volume index and valvuloarterial impedance. A stroke volume index >35 ml/m2 or a high LVOT velocity >1 m/s suggest that the stroke volume is preserved, ruling out low‐output low‐gradient AS and suggesting moderate AS. D. Invasive measurements are frequently required to measure cardiac output, true gradient and AVA, especially after control of HTN E. Dobutamine testing F. A through D Question 4. A patient has dyspnea on exertion and a mid‐systolic murmur with absent A2. Echo shows AS with calcified aortic valve, a mean gradient of 48 mmHg and AVA 1.1 cm2. No AI is present. Is AS severe? A. AS is severe. When the gradient is >40 mmHg on echo, AS is usually severe even if AVA >1 cm2 B. AS is severe. AVA may be over‐calculated in a patient with a septal hypertrophy and a high LVOT velocity C. AS may be moderate, but this is unlikely. A pressure recovery phenomenon may falsely exaggerate the gradient and is suggested by a small aortic diameter  AI > MR B. AI > AS > MR C. AS > MR > AI Question 15. A 55‐year‐old man presents with HF. He has a history of mechanical bileaflet AVR performed 5 years previously. An echo is performed and shows a transaortic gradient of 30 mmHg and a peak velocity of 3.5 m/s, without a significant AI. Hemoglobin is 13 g/dl. What is the most likely cause of the gradient across the valve? A. Normal gradient across a normally functioning valve B. Patient/prosthesis mismatch C. High flow state D. Pressure recovery E. Valvular obstruction, further suggested if metallic S2 is muffled Question 16. If the patient in Question 15 is presenting with atypical chest pain or a non‐cardiac complaint rather than HF, what would the diagnosis be? A. Normal gradient across a normally functioning valve B. Patient/prosthesis mismatch C. High flow state D. Pressure recovery E. Valvular obstruction, further suggested if metallic S2 is muffled Question 17. If the patient in Question 15 is presenting with HF, but a review of a postoperative echo shows a similarly increased velocity and gradient across the prosthetic valve, what would the diagnosis be? A. Normal gradient across a normally functioning valve B. Patient/prosthesis mismatch C. High flow state D. Pressure recovery E. Valvular obstruction, further suggested if metallic S2 is muffled Question 18. What is the next step for the patient in Question 15? A. TEE B. Cinefluoroscopy C. A and B D. No further workup, as the cause is benign Question 19. A 60‐year‐old patient presents with shock and pulmonary edema. He is intubated and requires vasopressor support. He has a history of mechanical MVR 5 years previously. An echo shows a large gradient across the prosthetic valve (35 mmHg). On fluoroscopy, one mechanical leaflet is totally immobile, while the other one has restricted motion. INR is 1. What is the next step in management? A. Thrombolytic therapy B. Valvular surgery C. Anticoagulation with heparin

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Question 20. Which of the following patients with severe MR does not have an indication for mitral valve surgery? A. LV end‐systolic diameter 40 mm B. LVEF 60% C. Recently diagnosed HF with LVEF 20% and severe MR D. LVEF 45% Question 21. Answer each option as true or false: A. S3 and S4 are present in MS B. Persistently split S2 suggests RV failure C. Loud P2 (= loud S2 split) suggests pulmonary hypertension D. Absent A2 with midsystolic murmur suggests severe AS E. A loud S1 characterizes MS or a short PR interval F. A short S2‐opening snap interval implies severe MS G. A wide pulse pressure with a diastolic murmur implies severe AI H. A high JVP that peaks simultaneously with the pulse suggests TR I. HOCM murmur changes in an opposite direction to preload and afterload Question 22. A 55‐year‐old man with a history of radiation for lymphoma 20 years ago presents with hypoxia and peripheral edema. On exam, he has lung crackles, an elevated JVP with a high V wave peaking along with the pulse, and a pulsatile liver. He has a holosystolic murmur at the LLSB that increases with inspiration. A holosystolic murmur is also heard at the apex and radiates to the axilla. At the RUSB and LUSB, a mid‐systolic murmur is heard. An early, decrescendo diastolic murmur is heard at the LUSB. S2 is normal. Carotid upstroke is weak. RV heave is present. PMI is not enlarged. BP is 105/75 mmHg. What abnormalities does this patient have? (multiple choices) A. Severe TR, severe MR, severe AS B. Severe TR, moderate MR, severe AS C. Severe TR, severe MR, moderate AS and moderate AI D. On echo, AS gradient will seem less severe because of MR and TR. Conversely, MR severity is exaggerated by AS and AI. AI does not affect the severity assessment of MR E. Restrictive cardiomyopathy is likely present Question 23. Once symptoms arise in severe AS, AI, or MR, what is the mean survival without surgical correction? A. 1 year B. 2–3 years C. 5 years Question 24. A patient with a mechanical aortic prosthesis presents with hypotension. Echo is performed and shows increased velocity across the aortic valve (Figure 6.18). Is it cardiogenic shock? What is the cause of the elevated aortic valve velocity?

Figure 6.18 

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Question 25. A 44‐year‐old obese, hypertensive woman presents with dyspnea on exertion. On exam, she has a diastolic rumble and a loud S1. Echo shows LA dilatation with typical MS. The mean gradient at rest is 6 mmHg (heart rate 85 bpm) and the MVA is calculated as 1.7 cm2 by PHT method. Systolic PA pressure is ~35 mmHg at rest. The valve is pliable, not heaviliy calcified, with a Wilkins score of 7. With exercise testing, the gradient increases to 12 mmHg and systolic PA pressure increases to 45–50 mmHg. What is the next step? A. MV replacement B. Percutaneous mitral balloon valvuloplasty C. Diuretic therapy D. β‐Blocker therapy and clinical follow‐up in 6–12 months Question 26. A 47‐year‐old man has a history of bicuspid aortic valve with AI. He is active and asymptomatic with excellent functional capacity. A surveillance echo shows severe AI, LVEF 50%, LVESD 52 mm, and LVEDD 68 mm. Note that LV dimensions have increased by ~4 mm over the last 6 months. The aortic root size is 46 mm. What is the next step? A. AVR + ascending aortic replacement B. AVR C. Continue surveillance D. Exercise testing Question 27. A 70‐year‐old woman presents with severe dyspnea. She is found to have AF at a rate of 110 bpm, BP 110/70, and pulmonary edema. Echo shows normal LV systolic function, mitral thickening, biatrial enlargement, and mild RV dilatation. After rate control,

Figure 6.19 

diuresis, and cardioversion, a hemodynamic study is performed (Figure 6.19). What is the diagnosis? A. Severe MR B. Severe MS C. LV diastolic dysfunction and restrictive cardiomyopathy Question 28. A 70‐year‐old woman presents with progressive dyspnea. She is severely hypertensive (BP 180/95 mmHg). Echo shows normal LVEF, biatrial enlargement, and mild MR. A hemodynamic study is performed (Figure 6.20). What is the diagnosis and what is the next step? A. Severe MR (underestimated by echo) B. Severe MS C. Severe LV diastolic dysfunction and restrictive process from severe HTN

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50

25

V

A

LVEDP

0

Figure 6.20 

Question 29. A 67‐year‐old man has end‐stage renal disease. He presents with pulmonary edema, SBP 85 mmHg, and two episodes of syncope over the last 3 weeks. On exam, 3/6 midsystolic murmur is heard throughout the precordial area, with absent A2, and delayed and narrow carotid pulse. ECG shows anterloateral Q waves. Echo performed 2.5 years previously showed mild AS with AVA >2 cm2. A. Ischemic HF. AS is unlikely, as AVA declines by 0.12 cm2/year and it takes >5 years to progress from mild AS to severe AS B. Combination of ischemic HF and severe AS. AS may progress faster in end‐stage renal disease Question 30.  In the prior patient (Question 29), echo shows severe AS and EF 25%, and coronary angiography shows a totally occluded LAD without significant anterior wall viability on thallium testing. Attempts to perform hemodialysis and ultrafiltration are impeded by the occurrence of severe hypotension during hemodialysis. His surgical STS score for AVR is 14%. What is the best management option? A. Perform CABG + AVR urgently B. Perform hemodialysis with the support of norepinephrine. Perform CABG + AVR once pulmonary edema has resolved C. Perform hemodialysis with the support of norepinephrine. Perform TAVR once pulmonary edema has resolved Question 31. Which of the following statements is incorrect? A. MR is associated with reduced afterload early on, then LV dilatation and increased afterload later on B. AI is associated with a rise in preload and afterload C. AI is associated with more rise in afterload than AS D. In MR, the earliest EF reduction reflects intrinsic LV dysfunction and may be irreversible E. In AI and AS, the earliest EF reduction reflects afterload mismatch rather than intrinsic LV dysfunction and is reversible with AVR F. In acute AI, pulse pressure is severely widened and peripheral systolic pressure is much higher than central aortic pressure Question 32. The valve shown in Figure 6.21 is seen on fluoroscopy. What type of valve is it? A. Surgical bioprosthesis B. Transcutaneous bioprosthesis C. Mechanical prosthesis (St. Jude) D. Mechanical prosthesis (single‐leaflet tilting disk) Question 33. A 67‐year‐old man has dyspnea on exertion. On exam, a mid‐systolic murmur is heard, A2 is absent, and pulsus parvus and tardus is present. His echo shows a mean aortic gradient of 1 cm2. What is the diagnosis and what is the next step? A. AS is moderate. No need for further workup B. AS is probably severe. Cardiac catheterization and invasive AVA calculation are indicated Question 34. A 67‐year‐old man has dyspnea on exertion. He has a loud holosystolic apical murmur with S3. Echo shows a small eccentric MR jet. What is the diagnosis and what is the next step? A. MR is mild or moderate. No further workup is needed B. MR is likely severe. Perform TEE

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Figure 6.21 

Question 35. A 60‐year‐old man is asymptomatic. He has a mild end‐systolic murmur at the apex without S3. Echo is performed and shows mitral valve prolapse with severe MR by jet area and ERO. LA size is normal. What is the diagnosis? A. Severe MR from mitral valve prolapse B. Mild‐to‐moderate end‐systolic MR from mitral valve prolapse Question 36. A 60‐year‐old man has dyspnea on exertion, with holodiastolic murmur at the base, enlarged PMI, and wide pulse pressure. Echo shows a bicuspid aortic valve with mild‐to‐moderate AI jet. AI pressure half‐time is 320 ms. LV is enlarged. What is the diagnosis? A. Severe AI. Further testing is needed (TEE, invasive aortogram) B. Mild‐to‐moderate AI Question 37. A 68‐year‐old hypertensive woman has dyspnea on exertion and a long diastolic murmur at the apex extending into end‐ diastole. Echo shows a rheumatic mitral valve with transmitral pressure gradient of 12 mmHg at rest and systolic PA pressure of 55 mmHg (heart rate of 70 bpm). The mitral valve area is calculated at 1.7 cm2. A. MS is severe B. MS is mild/moderate anatomically, and the gradient is exaggerated because of a high cardiac output Question 38. A 72‐year‐old man with a bioprosthetic mitral valve is presenting with dyspnea on exertion and a holosystolic apical murmur. Echo shows thickened prosthetic leaflets, mild mitral regurgitation, and a peak E velocity of 2.4 m/s. What is the diagnosis? A. Prosthetic valve obstruction B. Prosthetic valve regurgitation C. Normally functioning mitral prosthesis Question 39. A 67‐year‐old woman has mild dyspnea on exertion. On exam, he has a mid‐systolic murmur with a well‐heard A2 and a preserved carotid upstroke. His echo shows a mean aortic gradient of 38 mmHg and an aortic valve area of 0.9 cm2. What is the diagnosis, and what is the next step? A. AS is severe. No need for further work‐up B. AS is likely moderate. Cardiac catheterization is indicated Answer 1. D. Answer 2. D. Answer 3. F. The indexed AVA in this patient is calculated at 0.45 cm2/m2. The stroke volume index is calculated at 25 ml/m2, suggestive of low flow. After control of HTN, the flow increased and the aortic gradient increased to 39 mmHg, confirming the effect of low flow on her gradient. Thus, she has a paradoxical low‐flow, low‐gradient severe AS related to severe HTN. In patients with normal EF and paradoxical low‐gradient AS, the reduction in flow is secondary to the high afterload and the small underfilled ventricular cavity rather than impaired contractility. In this setting, dobutamine testing is not a suitable way of increasing cardiac output. Answer 4. D. Echo rarely overestimates aortic valve gradient. It rather frequently underestimates the gradient. If the aortic valve is calcified and poorly mobile on echo imaging, a high gradient implies severe AS, even if AVA is calculated as >1 cm2. An exaggeration of LVOT velocity or diameter may exaggerate the calculated AVA: AVA = LVOT area × LVOT velocity/aortic valve velocity.

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Answer 5. A. The patient has low‐gradient AS related to poor EF. The low gradient here is likely related to poor flow rather than errors in echo measurements. Dobutamine testing is appropriate. The stroke volume rose >20%, implying proper contractile (or flow) reserve. The gradient rose >10 mmHg to >30 mmHg, and the AVA remained 1.2 cm2. Answer 6. A. In truly severe AS, LVOT velocity increases with dobutamine, but aortic velocity increases similarly or further. DI, which is LVOT velocity/aortic velocity, remains unchanged or declines. In pseudo‐severe AS, the aortic velocity increases less than LVOT (→ DI increases). Answer 7. B. In light of the low‐gradient/low‐EF AS and the prior cardiac surgery, the surgical mortality is elevated, at least 8%. Formal STS score calculation should be performed and the patient referred for TAVR. In the PARTNER trial, patients with a low‐gradient AS derived the largest mortality benefit from TAVR, as compared to conservative management. Answer 8. E. The patient has ischemic MR due to an akinetic inferior wall. The presentation is HF, rather than acute ischemia; the inferior wall akinesis is a steady, persistent abnormality rather than an off/on ischemia and does not have a high likelihood of fully reversing with revascularization. As a result, MR only has a 50% chance of improving with revascularization. CABG along with mitral surgery is indicated in a patient with multivessel CAD and severe MR. The inferior wall akinesis is steady but ischemic MR is dynamic and may improve with diuresis and improvement of preload and afterload. However, MR easily reverses back to severe with a reversal of loading conditions, such as exercise or supine position (night), further attesting to the need for mitral surgery. Answer 9. C. Anterior wall akinesis, per se, does not produce enough leaflet tethering and MR. Anterior MI may, however, lead to global remodeling with posterolateral and apical tethering of the papillary muscles and leaflets. This leads to ischemic MR, which may be centrally or posteriorly directed. Answer 10. A. As opposed to Question 8, where the patient had a chronic persistent dysfunction of the inferior wall with HF presentation, this patient is having acute, fleeting ischemic dysfunction of the inferior wall with MR. The dynamic MR is dictated by ischemia, not just loading conditions. It is expected that this MR will reverse with revascularization of the acute RCA lesion. MV surgery is not immediately required here. Answer 11. F. All these tests are reasonable in the asymptomatic patient with severe MR. On stress testing, if the patient develops severe dyspnea that persists into late recovery, or if her functional capacity is below expected (14.7 – [0.13 × age]), she is unlikely to be NYHA class I and MV surgery is reasonable. If the prolapse is limited to P2 cusp, MV repair is likely to be successful and durable, and is reasonable even in an asymptomatic patient (class IIa). Elevated BNP, pulmonary hypertension, or elevated PCWP suggests that MR is starting to have hemodynamic repercussions and implies a high risk of HF and symptomatic deterioration, as well as an impairment of long‐term outcomes; MV surgery is reasonable. Answer 12. B. MVA is a better determinant of MS severity than the mitral gradient. In fact, transmitral pressure gradient being proportional to the square of the diastolic mitral flow, tachycardia or a high‐output state may convert an anatomically mild MS into a hemodynamically severe MS with a severely increased transmitral gradient. Invasive hemodynamics are valuable for the assessment of MS whenever there is discrepancy between the echocardiographic MVA and transmitral gradient; and whenever it is not clear whether the patient’s symptoms or pulmonary hypertension are purely secondary to MS, or rather secondary to mild MS + high‐output state and tachycardia. Answer 13. A. The cardiac output is markedly increased because of anemia and the heart rate is increased, both of which converted an anatomically mild MS (valve area 2 cm2) into a hemodynamically severe MS, with a high gradient and lack of diastasis. Anemia should be corrected, the heart rate should be reduced to 55–60 bpm with β‐blockade, and a small dose of diuretic may be administered. PA pressure and transmitral gradient should be assessed afterward. Once exacerbating factors are treated, valvuloplasty is considered for mild MS (MVA >1.5 cm2) only if the patient remains symptomatic with exertional increase in PA pressure and transmitral gradient (>15 mmHg) (class IIb). Answer 14. A. In AS and AI patients with LV dysfunction, the low EF is usually related to the high afterload rather than an intrinsic LV dysfunction (afterload mismatch). Thus, valvular surgery improves afterload and EF. This is not the case in MR: (1) afterload is usually reduced in MR, and thus the low EF is often due to intrinsic myocardial dysfunction; (2) MV surgery may disrupt the subvalvular apparatus and LV geometry, further reducing EF. Answer 15. E. The five listed causes are the main causes of a high gradient across a prosthetic valve. The severity (>3 m/s) makes normal gradient less likely (not option A). The fact that he is presenting with HF implies a need to rule out valvular obstruction. Answer 16. B or D. C is unlikely in the absence of anemia or sepsis. Answer 17. B or D. Answer 18. C. The next step consists of assessing the leaflet structure and excursion. This is done by using both TEE and fluoroscopy. If the structure and excursion are normal, PPM or pressure recovery is the cause of the valvular gradient. Answer 19. A. The mitral obstruction is the cause of shock in this patient. The differential diagnosis includes thrombus or pannus formation. The acuity of onset and the normal INR are suggestive of thrombus. TEE may be performed to show the large thrombus but is not mandatory at this point. Patients with large prosthetic thrombosis or functional class III–IV should undergo surgical replacement or thrombolytic therapy if surgery is deemed high‐risk. Surgery is high‐risk in a patient with shock requiring multiple vasopressors. Serial echocardiograms need to be performed to document a reduction of gradient. Fluoroscopy may document improvement of disk mobility. Answer 20. C. MR that occurs with a very low EF is likely a functional MR (unless a longstanding history of severe symptomatic MR precedes HF and low EF). Surgery is not first‐line therapy for functional MR, particularly functional MR from a non‐ischemic cardiomyopathy. Surgery is indicated in patients with MR and secondary LV dysfunction, manifested as EF ≤ 60%.

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Answer 21. A is false (S3 and S4 cannot be present in MS). All the remaining statements are true. Answer 22. C, D, and E. The patient has clinical signs of severe TR. He has MR that is likely severe, as he has pulmonary edema. AS is not severe by the fact that S2 is not attenuated. The weak carotid pulse is due to the low‐output state from the combined valvular disease rather than severe AS. AI is unlikely to be severe as the pulse pressure is narrow; however, a concomitant MR, TR, and cardiomyopathy may attenuate the total stroke volume and the pulse pressure of severe AI. PMI is not enlarged, strongly arguing against severe AI, especially AI ­combined with MR, where LV would be severely dilated. In combined mitral and aortic valvular disease, the aortic disease exaggerates the severity of the mitral disease and the rise in LA pressure. Conversely, the mitral disease reduces AS gradient and leads to underestimation of true AS severity. Despite MR and moderate AS/AI, LV is not enlarged by PMI. This suggests a concomitant restrictive cardiomyopathy from radiation. Answer 23. B. Answer 24. First, ensure the tracing obtained is truly an aortic tracing rather than MR. It is a true aortic tracing by the fact that is starts some time after the peak of the electrocardiographic R wave (this is opposite to MR, which starts exactly at the peak of R, i.e., at the isovolumic contraction). Second, address why the velocity is increased. The contour of the transaortic envelope is round and symmetrical, consistent with AS. However, within this envelope, there is another envelope that is late‐peaking and consistent with an increased LVOT velocity (“whiter” envelope). Thus, the aortic velocity is ~4 m/s, but the LVOT velocity is ~2 m/s, implying a dimensionless index of ~0.5 (>0.3), which is not consistent with severe valvular or prosthetic obstruction. In addition, by using the true Bernoulli equation, the peak gradient across the prosthesis is not in the severe range: gradient = 4 (Vaortic valve2 – VLVOT2) rather than 4 Vaortic valve2. The velocity across the prosthesis is likely mildly increased at baseline (e.g., some degree of patient/prosthesis mismatch), and is now worsened by the increased LV velocity (hypercontractile state from sepsis, hypovolemia, or fever). Answer 25. D. This patient has mild MS by MVA (>1.5 cm2). For this MVA, intervention is only considered if the mean gradient increases to >15 mmHg with stress or PA pressure increases to >60 mmHg with stress, after ruling out tachycardia or a high‐output state as a cause of the high gradient. In this patient, obesity or diastolic LV dysfunction may be the cause of dyspnea. It is reasonable to perform heart catheterization and verify that MVA is truly in the mild/moderate range. Heart catheterization will also allow a diagnosis of LV diastolic dysfunction (LVEDP rises with stress more than the transmitral gradient does). Answer 26. A. EF is still above the surgical cutoff (EF 50 mm and LVEDD >65 mm are class II indications for surgery. This is even more worrisome when progressive LV dilatation is noted. Answer 27. B. This tracing represents simultaneous PCWP–LV pressure recording. Despite a rate of 60–75 bpm (in this case 62 bpm), there is a lack of PCWP and LV diastasis at end‐diastole, which suggests severe MS. Also, PCWP A wave is prominent while LV A wave is attenuated, which further suggests MS. V wave is prominent; this does not necessarily imply MR and is common in MS. Answer 28. A. This tracing represents simultaneous PCWP–LV pressure recording. Note the very large V wave (~47 mmHg), which mainly suggests severe MR, but may also be seen with severe LV failure. One may get the false impression of a gradient between PCWP and LV in diastole. Yet note that, when using PCWP as a surrogate of LA pressure, a large V wave exaggerates the transmitral gradient and may falsely suggest MS. In fact, the large V wave of PCWP has a slower downslope than the V wave of LA pressure, which exaggerates the space between PCWP and LV. Severe MR may have been missed on TTE for various reasons: (1) dynamic functional MR from hypertensive cardiomyopathy and severe LA enlargement (MR may have been milder at the time of the echo and got worsened by HTN); (2) extremely eccentric MR, such as MR related to MVP, underestimated on many TTE views. Answer 29. B. The exam suggests severe AS, and ECG suggests anterior infarct. It is true that AVA only declines by 0.12 cm2/year and mean gradient only increases by 7 mmHg per year, but those are only average numbers. Progression is faster in renal patients and in those with heavy valvular calcifications. Answer 30. C. While decongestion improves cardiac output, quick fluid removal during dialysis (2–3 liters in 3 hours) exceeds plasma refill time and creates transient reduction of intravascular volume. In patients with limited cardiac output reserve, the LV cannot increase its stroke volume and EF to fill the empty circulation. BP will precipitously drop during dialysis. Norepinephrine may be used to constrict the empty ­circulation and maintain BP during dialysis; in hypotensive patients, norepinephrine does not increase afterload untowardly as it only raises the SBP to 90–100 mmHg. In order to reduce perioperative complications, it is important to properly decongest the patient before a cardiac ­intervention. Considering his STS surgical risk score of ≥ 8%, TAVR is an acceptable alternative to surgical AVR. While non‐viability does not p ­ reclude a benefit from CABG revascularization (STICH trial), non‐viability associated with Q waves further reduces the likelihood of benefit. Answer 31. F. Pulse pressure is severely widened when the stroke volume is markedly increased, as in chronic AI, where the LV is dilated, not acute AI. In AI, the early EF reduction reflects a reduction of stroke volume from the high afterload (stroke volume is the EF numerator). Answer 32. A. The leaflets are not visualized (bioprosthetic leaflets). The metallic ring and struts of a bioprosthesis are seen on this image. Answer 33. B. The echo findings should always be analyzed in the context of the physical exam. Since the exam suggests severe AS, echo may have underestimated the gradient because of poor alignment of the Doppler beam with the transaortic flow. Answer 34. B. The exam suggests severe MR. On color Doppler, an eccentric MR (mitral valve prolapse) jet occupies a smaller area of the LA than a central jet of similar severity; MR may be underestimated. E velocity should remain elevated at >1.2 m/s and remains a hint to severe MR.

206  Part 3.  Valvular Disorders

Answer 35. B. The color assessment of MR, whether by color jet area or color PISA calculation, assumes that MR occurs throughout systole. Inherently, an end‐systolic MR that looks severe by color and PISA may only be mild or moderate when one accounts for the fact that it only occurs at the end of systole. The auscultation (end‐systolic rather than holosystolic murmur, no S3), and the normal LA size suggest that MR is overestimated by color. Also, color M‐mode across the mitral valve shows that MR is limited to a portion of systole. LA size cannot be normal in chronic severe MR. Answer 36. A. In a patient with a bicuspid aortic valve, AI may be eccentric and may appear mild by color Doppler. Pressure half‐time is typically 250 ms in chronic compensated AI. The physical exam and the enlarged LV suggest severe AI. Holodiastolic flow reversal of the descending aorta on the suprasternal view would confirm severe AI. Answer 37. A. MS is severe, as suggested by physical exam and by the high transmitral gradient and PA pressure despite a heart rate of 1.9 m/s, especially if >2.2 m/s) is abnormal and suggests prosthetic obstruction but also, as implied by exam, regurgitation across the prosthesis. Regurgitation is underestimated because prosthetic struts lead to acoustic shadowing into the LA. Answer 39. B. While echo suggests severe AS, the auscultation suggests mild‐to‐moderate AS, In light of the physical exam, this is likely moderate AS with pressure recovery exaggerating the gradient and falsely reducing the calculated AVA.

References MR 1. O’Gara P, Sugeng L, Lang R, et al. The role of imaging in chronic degenerative mitral regurgitation. J Am Coll Cardiol 2008; 1: 221–37. 2. Carpentier A, Adams DH, Filsoufi F. Carpentier’s Reconstructive Valve Surgery. Maryland Heights, MO: Saunders, 2010. 3. Anyanwu AC, Adams DH. Etiologic classification of degenerative mitral valve disease: Barlow’s disease and fibroelastic deficiency. Semin Thorac Cardiovasc Surg 2007; 19: 90–6. 4. Kumanohoso T, Otsuji Y, Yoshifuku S, et al. Mechanism of higher incidence of ischemic mitral regurgitation in patients with inferior myocardial infarction: quantitative analysis of left ventricular and mitral valve geometry in 103 patients with prior myocardial infarction. J Thorac Cardiovasc Surg 2003; 125: 135–43. 5. Yiu SF, Enriquez‐Sarano M, Tribouilloy C, et al. Determinants of the degree of functional mitral regurgitation in patients with systolic left ventricular dysfunction: a quantitative clinical study. Circulation 2000; 102: 1400–6. 6. Piérard LA, Lancellotti P. The role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary edema. N Engl J Med 2004; 351: 1627–34. 7. Watanabe N, Ogasawara Y, Yamaura Y, et al. Mitral annulus flattens in ischemic mitral regurgitation: geometric differences between inferior and anterior myocardial infarction: a real‐time 3‐dimensional echocardiographic study. Circulation 2005; 112: I458–62. 8. Lancellotti P, Troisfontaines P, Toussaint AC, Pierard LA. Prognostic importance of exercise‐induced changes in mitral regurgitation in patients with chronic ischemic left ventricular dysfunction. Circulation 2003; 108: 1713–17. 9. Otsuji Y, Handshumacher MD, Liel‐Cohen N, et al. Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three‐dimensional echocardiographic studies in models of acute and chronic progressive regurgitation. J Am Coll Cardiol 2001; 37: 641–8. 10. Agricola E, Oppizzi M, Pisani M, et  al. Ischemic mitral regurgitation: mechanisms and echocardiographic classification. Eur J Echocardiogr 2008; 9: 207–21.

Survival in asymptomatic severe MR 11. Enriquez‐Sarano M, Avierinos JF, Messika‐Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med 2005; 352: 875–83.

Guidelines 12. Nishimura RA, Otto CM, Bonow RO, et al. 2014 ACC/AHA guideline for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63: 2438–88.

AF and pulmonary hypertension as indication for MV surgery 13. Ghoreishi M, Evans CF, DeFilippi CR, et al. Pulmonary hypertension adversely affects short‐ and long‐term survival after mitral valve operation for mitral regurgitation: implications for timing of surgery. J Thorac Cardiovasc Surg 2011; 142: 1439–52. 14. Grigioni F, Avierinos JF, Ling LH, et al. Atrial fibrillation complicating the course of degenerative mitral regurgitation: determinants and long‐term outcome. J Am Coll Cardiol 2002; 40: 84–92.

AF 85%), like TRAMI, only had 2.5% periprocedural mortality. 37. Franzen O, van der Heyden J, Baldus S, et al. MitraClip therapy in patients with endstage systolic heart failure. Eur J Heart Fail. 2011; 13: 569–76. 38. Auricchio A, Scillinger W, Meyer S, et al. Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by mitraclip improves symptoms and promotes reverse remodeling. J Am Coll Cardiol 2011: 58: 2183–9.

MS 39. Olesen KH. The natural history of 271 patients with mitral stenosis under medical treatment. Br Heart J 1962; 24: 349–57. 40. Horstkotte D, Niehues R, Strauer BE. Pathomorphological aspects, aetiology, and natural history of acquired mitral valve stenosis. Eur Heart J 1991; 12 (suppl): 55–60. 41. Bittrick J, D’Cruz IA, Wall BM, et al. Differences and similarities between patients with and without end‐stage renal disease, with regard to location of intracardiac calcification. Echocardiography 2002 Jan; 19: 1–6. 42. Lange RA, Moore DM, Ciggaroa RG, Hillis LD. Use of pulmonary capillary wedge pressure to assess severity of mitral stenosis: is true left atrial pressure needed in this condition? J Am Coll Cardiol 1989; 13: 825. 43. Wilkins GT, Weyman AE, Abascal VM, Block PC, Palacios IF. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilation. Br Heart J 1988; 60: 299–308. 44. Schwammenthal E, Vered Z, Agranat O, et al. Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: an exercise echocardiographic study Circulation 2000; 102: 2378–84. 45. Picano E, Pibarot P, Lancelotti P, et al. The emerging role of exercise testing and stress echocardiography in valvular heart disease. J Am Coll Cardiol 2009; 54: 2251–60. 46. Leavitt JI, Coats MH, Falk RH, et al. Effects of exercise on transmitral gradient and pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study. J Am Coll Cardiol 1991; 17: 1520–6. 47. Carabello BA. Modern management of mitral stenosis. Circulation 2005; 112: 432–7.

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Wilkins score and PMBV results 48. Palacios IF, Sanchez PL, Harrell LC, et al. Which patients benefit from percutaneous mitral balloon valvuloplasty? Prevalvuloplasty and postvalvuloplasty variables that predict long‐term outcomes. Circulation 2002; 105; 1465–71. 49. Sutaria N, Elder AT, Shaw TRD. Long term outcome of percutaneous mitral balloon valvotomy in patients aged 70 and over. Heart 2000; 83: 433–8. 50. Reid CL, Otto CM, Davis KB, et al. Influence of mitral valve morphology on mitral balloon commissurotomy: immediate and six‐month results from the NHLBI Balloon Valvuloplasty Registry. Am Heart J 1992; 124: 657–65. 51. Pathan AZ, Mahdi NA, Leon MN, et al. Is redo percutaneous mitral balloon valvuloplasty (PMV) indicated in patients with post‐PMV mitral restenosis? J Am Coll Cardiol 1999; 34: 49–54. 52. Cohen DJ, Kuntz RE, Gordon SPF. Predictors of long‐term outcome after percutaneous mitral valvuloplasty. N Engl J Med 1992; 327: 1329–35. 53. Abreu Filho CAC, Lisboa LA, Dallan LA, et al. Effectiveness of the maze procedure using cooled‐tip radiofrequency ablation in patients with permanent atrial fibrillation and rheumatic mitral valve disease. Circulation 2005; 112: I20–5. 54. Levine MJ, Weinstein JS, Diver DJ, et al. Progressive improvement in pulmonary vascular resistance following percutaneous mitral valvuloplasty. Circulation 1989; 79: 1061–7. 55. Dev V, Shrivastava S. Time course of changes in pulmonary vascular resistance and the mechanism of regression of pulmonary arterial hypertension after balloon mitral valvuloplasty. Am J Cardiol 1991; 67: 439–42. 56. Vincens JJ, Temizer D, Post JR, Edmunds LH, Herrmann HC. Long‐term outcome of cardiac surgery in patients with mitral stenosis and severe pulmonary hypertension. Circulation 1995; 92: II137–42.

AI 57. Lakier JB, Copans H, Rosman HS, et al.Idiopathic degenration of the aortic valve: a common cause of isolated aortic regurgitation. J Am Coll Cardiol 1985; 5: 347–57. 58. Hanna EB. Aortic insufficiency. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012. 59. Carabello BA. Progress in mitral and aortic regurgitation. Curr Probl Cardiol 2003; 28: 553–82. 60. Dujardin KS, Enriquez‐Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice: a long‐term follow‐up study. Circulation 1999; 99: 1851–7. 61. Evangelista A, Tornos P, Sambola A, Permanyer‐Miralda G, Soler‐Soler J. Long‐term vasodilator therapy in patients with severe aortic regurgitation. N Engl J Med 2005; 353: 1342–9. 62. Chaliki HP, Mohty D, Avierinos J, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. J Am Coll Cardiol 2002; 106: 2687–93. 63. Klodas E, Enriquez‐Sarano M, Tajik AJ, et al. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symptoms. J Am Coll Cardiol 1997; 30: 746–52. 64. Bonow DO, Rosing DR, Maron BJ, et al. Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of the duration of preoperative left ventricular dysfunction. Circulation 1984; 70: 570–9. 65. Kallenbach K, Karck M, Pak D, et al. Decade of aortic valve sparing reimplantation. Are we pushing the limits too far? Circulation 2005; 112: I253–9. Reoperation with sparing, good long‐term result. 66. Shimizu H, Yozu R. Valve‐sparing aortic root replacement. Ann Thorac Cardiovasc Surg 2011; 17: 330–6. 67. Borger MA, Preston M, Ivanov J et al. Should the ascending aorta be replaced more frequently in patients with bicuspid aortic valve disease? J Thorac Cardiovasc Surg 2004; 128: 677–83.

AS 68. Huntington K, Hunter AG, Chan KL. A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve. J Am Coll Cardiol. 1997; 30: 1809–12. 69. Lewin MB, Otto, CM. The bicuspid aortic valve. Adverse outcomes from infancy to old age. Circulation 2005; 11: 832–4. 70. Fenoglio JJ, McAllister HA, DeCastro CM, et al. Congenital bicuspid aortic valve after age 20. Am J Cardiol 1977; 39: 164–9. 27% of patients >70 had a normally functioning bicuspid aortic valve. 71. Ward C. Clinical significance of the bicuspid aortic valve. Heart 2000; 83: 81–5. 72. Seiler C, Jenni R. Severe aortic stenosis without left ventricular hypertrophy: prevalence, predictors, and short‐term follow up after aortic valve replacement. Heart 1996; 76: 250–5. 73. Nishimura RA, Grantham JA, Connolly HM, et al. Low‐output, low‐gradient aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory. Circulation 2002; 106: 809–13. 74. Picano E, Pibarot P, Lancellotti P, et al. The emerging role of exercise testing and stress echocardiography in valvular heart disease. J Am Coll Cardiol 2009; 54: 2251–60. 75. Monin JL, Quere JP, Monchi M, et al. Low‐gradient aortic stenosis: operative risk stratification and predictors for long‐term outcome: a multicenter study using dobutamine stress hemodynamics Circulation 2003; 108: 319–24. 76. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low‐flow, low‐gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007; 115: 2856–64. 77. Barasch E, Fan D, Chukwu EO, et al. Severe isolated aortic stenosis with normal left ventricular systolic function and low transvalvular gradients: pathophysiologic and prognostic insights. J Heart Valve Dis 2008; 17: 81–8. 78. Dumesnil JG, Pibarot P, Carabello B. Paradoxical low flow and/or low gradient severe aortic stenosis despite preserved left ventricular ejection fraction: implications for diagnosis and treatment. Eur Heart J 2010; 31: 281–9. 79. Cramariuc D, Cioffi G, Rieck AE, et al. Low flow aortic stenosis in asymptomatic patients. Valvular‐arterial impedance and systolic function from the SEAS substudy. JACC Cardiovasc Imaging 2009; 2: 390–9. 80. Hachicha Z, Dumesnil JG, Pibarot P. Usefulness of the valvulo‐arterial impedance to predict adverse outcome in asymptomatic aortic stenosis. J Am Coll Cardiol 2009; 54: 1003–11. 81. Briand M, Dumesnil JG, Kadem L, et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic ­stenosis: implications for diagnosis and treatment. J Am Coll Cardiol 2005; 46: 291–8.

Chapter 6.  Valvular Disorders  209

82. Ozkan A, Hachamovitch R, Kapadia SR, Tuzcu EM, Marwick TH. Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation 2013; 128: 622–31. 83. Eleid M, Sorajja P, Michelena HI, et al. Flow‐gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation 2013; 128: 1781–9. In this Mayo Clinic paper, normal‐flow low gradient AVA 1.3:1, and more specifically >1.5:1, but it may be symmetric and diffuse, involving the posterior wall in 10–20% of the cases (= concentric hypertrophy).1–3 One report suggests that the posterior wall is involved in cases of diffuse hypertrophy,3 while another report suggests that posterobasal wall involvement is very unusual even when hypertrophy is diffuse.4 Either way, the posterior wall is the site least frequently thickened in HCM. Hypertrophy most often involves two or more myocardial ­segments in an asymmetric and sometimes “bumpy” fashion, but may involve only one segment. Severe LVOT obstruction leads to severe afterload elevation that may result in a global LV hypertrophy with time; hence, septal reduction not only reduces septal thickness but also the LV thickness at distant segments. C.  LVOT obstruction When obstructive, HCM is called hypertrophic obstructive cardiomyopathy (HOCM) and is usually characterized by septal hypertrophy that narrows the left ventricular outflow tract (LVOT). The increased velocity across the LVOT draws the anterior mitral leaflet and its chordae during systole, which further narrows the LVOT and creates LVOT obstruction. This process is called systolic anterior motion (SAM) of the anterior leaflet (both the leaflet edge and chordae). A significant obstruction is characterized by a resting gradient >30 mmHg or a gradient >50 mmHg with provocative maneuvers (peak instantaneous gradient).1,2 Only 30% of patients with hypertrophic cardiomyopathy have a resting gradient, while 45% have a gradient with provocative maneuvers; the remaining patients have non‐obstructive hypertrophic cardiomyopathy.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

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The gradient is within the LV, i.e., pressure is elevated throughout the LV body and a portion of the LVOT then drops at one point in the LVOT rather than across the aortic valve. On echo‐Doppler, the velocity is increased across the point of LVOT obstruction and is decreased proximal to this point (LV inflow and mid‐LV cavity) and distal to this point (aortic valve) (Figure 7.1). Mild or moderate MR is usually seen and is associated with SAM of the mitral valve. In up to 10% of HOCM cases, the hypertrophy and the obstruction may be mid‐ventricular, as is the case with mid‐ventricular HOCM, apical HOCM, or HOCM with anterolateral papillary muscle inserting directly onto the mitral leaflet. The marked septal hypertrophy may also contribute to RV outflow tract obstruction, particularly in children with HOCM. LVOT obstruction is associated with more symptoms and a higher HF‐related mortality, but only a weak correlation with sudden death. D.  Causes of MR in HOCM; mitral valve abnormalities in HOCM MR is mainly related to SAM; it is directed posteriorly and peaks in mid and late systole (Figures 7.1–7.3).5–7 The severity of MR correlates with the severity of the LVOT gradient.5 MR may be severe (in ~10%) if the posterior leaflet is not elongated enough to meet with the “sucked” anterior leaflet. Severe MR with a relatively short posterior leaflet is expected to improve after myectomy, while severe MR despite an elongated posterior leaflet, or central or anteriorly directed MR, is concerning for a structural mitral abnormality.8 • Mitral valve abnormalities that aggravate SAM and LVOT obstruction. Structural valvular abnormalities are common (~20%) and may consist of: i.  Anterior leaflet elongation >30 mm, which provides extra slack and facilitates SAM and LVOT obstruction ii.  Central/anterior papillary muscle malposition (as opposed to anterolateral position) iii.  Chordal insertion at the base rather than the tip of the anterior leaflet

+

Ao

Ao + +++

LV +++

(a)

LV

+++

(b)

Figure 7.1  (a) Asymmetric septal hypertrophy with increased velocity across the LVOT (3 arrows). This increased systolic velocity creates a Venturi effect that pulls the anterior mitral leaflet (SAM) and creates LVOT obstruction as well as a posteriorly directed MR (blue arrow). Note the anatomic contiguity of the mitral and aortic valves. Pulsed‐wave Doppler should be used to sequentially interrogate the LV from apex up to the LVOT in order to confirm the anatomical level of obstruction. Note the normal velocity across the LV body, LVOT proximal to the obstruction and distal to it, and aorta (single arrows). (b) Pressure is increased throughout LV inflow, LV body, LVOT (+++), and drops beyond the LVOT obstruction (+). Even pressure at the mitral valve level (inflow tract pressure) is elevated.

Anterior leaflet SAM Chordal SAM

Large LA

Posterior MR

Figure 7.2  Parasternal long‐axis view of a patient with HOCM, showing SAM of the anterior leaflet tip. Not just the leaflet gets drawn to the septum, but also the chordae (chordal SAM).

Chapter 7.  Hypertrophic Cardiomyopathy  213

Anterior leaflet drawn towards the septum in systole septum

Figure 7.3  M‐mode of SAM. The star corresponds to the gap between the anterior and posterior leaflets in systole, leading to severe MR in this patient.

(ii) and (iii) lead to tenting of the anterior leaflet anteriorly, into the LVOT stream. All these abnormalities facilitate SAM and LVOT obstruction, even in patients with milder degrees of septal hypertrophy ≤ 18 mm. Papillary muscle insertion directly on the anterior leaflet, ­without chordae, may cause LVOT obstruction (as it directly abuts the septum with each beat) and anterior tethering/MR. • Mitral valve abnormalities that can cause a primary form of MR. Some primary valvular abnormalities can cause MR independent of SAM, and these are seen in 10–20% of HOCM:5 (i) extreme elongation and prolapse of the posterior mitral leaflet (~9% of operated HOCM);8 (ii) chordal rupture; (iii) papillary muscle insertion directly onto the anterior leaflet. This primary MR is characterized by a central or ­anteriorly directed jet that is usually holosystolic and is not expected to resolve with septal reduction.5,6 E.  Less common forms of HCM • Mid‐cavitary HCM consists of thickening of the mid‐portion of the LV, with associated apical thinning and aneurysm formation, simulating apical MI; the hypertrophy was probably more diffuse, but the apex infarcted as a result of the severe pressure rise and diffusely increased O2 demands that accompanied cavity obliteration. This form of HCM has a particularly unfavorable prognosis with a high risk of sudden death and LV thrombus. Mid‐cavitary HCM may also be due to anomalous basal position of the anterior papillary muscle that inserts directly onto the anterior leaflet. • Apical HCM is a common form of HCM in the Asian population, has a benign prognosis with 100 mmHg, even if asymptomatic), symptoms (NYHA II or III–IV), or functional limitation.13,14 A gradient 85% of predicted METs) does not impair long‐term survival.13 While LVOT obstruction is associated with ­HF‐related death, the specific relation of obstruction to sudden cardiac death (SCD) is significant but weak. The positive predictive value for sudden death is low.

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A large cohort analysis has shown that there are three modes of death in HCM: SCD (~50%, age 45 ± 20), progressive HF (~36%, age 56 ± 19), and AF‐related stroke. SCD, while a relatively more common cause of death in young patients 30% of systole), the more severe the obstruction. In addition, M‐mode of the aortic valve shows mid‐systolic closure due to the mid‐systolic obstruction. LA enlargement is universal in HCM (a normal LA size makes HCM unlikely).

Chapter 7.  Hypertrophic Cardiomyopathy  215

Anacrotic notch

Spike

Dome

HOCM

AS

Figure 7.4  HOCM hemodynamics. Note the early aortic pressure peaking (blue vertical arrow), the late LV pressure peaking (horizontal arrow), and the late gradient (gray area). The aortic pressure peaks in the first 80 ms of systole; then, LVOT obstruction worsens, the LV pressure tracing ”bends” then peaks in mid‐ to late systole while the aortic systolic pressure adopts a “dome” appearance (LV pressure bend, black arrowhead). This contrasts with AS, where the aortic pressure bends and peaks late while the LV pressure peaks early. As opposed to AS, the mean gradient in HOCM does not characterize the obstruction well, as it integrates the unobstructed early part of systole and under‐represents the LVOT obstruction. As opposed to AS, the peak‐to‐peak gradient approximates the peak instantaneous gradient in HOCM, and both those gradients are used to classify the severity of HOCM (≠ AS, where mean gradient is used).

PVC

LV

Aorta

HOCM

AS

Figure 7.5  Brockenbrough phenomenon after a premature beat in HOCM. Note the increase in pressure gradient (interrupted lines) but the reduction in aortic pulse pressure (double arrows) after a pause in HOCM, vs. the increase in pressure gradient with an increase in aortic pulse pressure in AS. Note the “spike and dome” appearance of the aortic pressure in HOCM, which becomes more pronounced with worsening obstruction (after the pause).

Pulsed‐wave Doppler interrogation reveals that the velocity is increased across one point in the LVOT, but is normal (~1 m/s) or low in the LV body and distally across the aortic valve. However, the velocity may also increase in the LV body when hypertrophy is generalized with cavity obliteration, even if the obstruction is mainly at the LVOT level. The LVOT gradient is late peaking, with a “dagger” shape on spectral Doppler. It is dynamic and may be unveiled or worsened by Valsalva maneuver, which should be performed in all cases of HCM (Figure 7.6). Aliasing typically occurs across the point of LVOT obstruction rather than the aortic valve. After localizing the site of obstruction with pulsed‐wave Doppler, continuous‐wave Doppler is required to capture the actual velocity. Cardiac MRI may be used to further delineate the LV geometry and thickness and mitral geometry when echo is inconclusive (class I recommendation).

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Figure 7.6  LVOT velocity in HOCM: late‐peaking dagger‐shape LVOT velocity (arrows). This is opposed to the parabolic, symmetrical AS Doppler. Occasionally, an older patient may have both AS and HOCM. The continuous‐wave Doppler will show two superimposed but distinct ejection envelopes (e.g., AS envelope within the HOCM envelope). Note the notch in early systole, before the LVOT envelope (stars). This notch corresponds to MR and is characteristic of LVOT interrogation in HOCM. In fact, in HOCM, MR is frequently captured on LVOT interrogation, as the mitral flow is in close proximity to the LVOT. Also, LVOT may be captured on MR interrogation.

VII.  Provocative maneuvers Patients without any gradient at rest may develop a significant gradient with maneuvers. The gradient increases with decreased preload (Valsalva maneuver, hypovolemia, nitroglycerin), decreased afterload (vasodilators), or increased inotropism (exercise, inotropic drugs such as dobutamine). Each of these changes results in closer approximation of the ventricular septum and anterior mitral leaflet during systole. For instance, a reduction in preload or afterload reduces LV volume and the high LV end‐systolic pressure that holds the LVOT walls apart. Also, when the heart rate rises or when the atrial systole is lost, as in atrial fibrillation, the gradient increases as a result of the reduced diastolic filling time (preload). While dobutamine increases the intraventricular gradient in patients with HOCM, dobutamine also induces a significant gradient in up to 20% of patients undergoing dobutamine echocardiography without suspected HOCM or even without LV hypertrophy.17,18 Dobutamine‐induced gradient does not necessarily imply exertional gradient and should not be used to diagnose HOCM. In fact, exercise increases myocardial contractility but also preload, which reduces cavity obliteration and the potential for intracavitary obstruction; dobutamine increases myocardial contractility but does not increase preload, and thus more readily creates intracavitary obstruction even in the absence of HOCM. Physiological maneuvers rather than pharmacological interventions should be used to assess provocable gradient (exercise, Valsalva).

VIII.  Genetic testing for diagnosis; screening of first‐degree relatives Genetic testing identifies definite pathogenic mutations in only 60–70% of HCM cases. While the genes affected in HCM are known, the actual nucleotides affected vary widely; some sequences represent definite pathogenic mutations of the gene, while others may represent normal variants. Therefore, a positive test definitely establishes the HCM genotype, but a negative test is unhelpful. Genetic testing of an index patient is indicated for family screening purposes. If the patient tests positive for a definite mutation, first‐ degree family members should be screened for that same mutation. The absence of this mutation excludes the risk of HCM occurrence in these relatives and is reassuring. A positive genotype with a negative phenotype in a family member indicates a considerable risk of developing HCM; routine ECG and echo follow‐up is performed throughout life. The risk of SCD is unclear, and decisions about athletic activities are individualized. Short of genetic testing, first‐degree relatives of HCM patients should undergo yearly ECG and echocardiograms starting in early adolescence and until the age of 21.19 Approximately 25% of those patients will develop HCM. Afterwards, they need to be screened every 5 years for the late development of HCM (more frequent interval in case of athletic activity or family history of SCD).

IX.  Differential diagnosis of LVOT obstruction The differential diagnosis of dynamic LVOT obstruction includes the following: 1.  Patients with hypertension and generalized or asymmetric LV hypertrophy may develop intracavitary LV obstruction, particularly in case of hypovolemia. LVOT obstruction and a true LVOT gradient, sometimes exceeding 100 mmHg, may be seen, with occasional SAM of the mitral valve. This is called “hypertensive hypertrophic cardiomyopathy” or “hypertensive obstructive cardiomyopathy,” and unlike HOCM, is not associated with myofibrillar disarray.20,21 • Similarities with HOCM. The invasive hemodynamics are similar to those of a typical HOCM (late‐peaking pressure gradient, Brockenbrough phenomenon). While hypertensive obstructive cardiomyopathy is typically symmetric,21 ~ 5% of all hypertensive patients have asymmetric septal hypertrophy and up to 34% of cases of severe hypertensive LV hypertrophy are asymmetric and predominantly septal (septal‐to‐posterior wall thickness >1.5), particularly in elderly patients with sigmoid septum, which further mimics HCM.22–24

Chapter 7.  Hypertrophic Cardiomyopathy  217

• Differences from HOCM. As opposed to HCM, the septal thickness in hypertensive cardiomyopathy does not usually exceed 20 mm,21 the hypertrophy does not have a bumpy heterogeneous morphology, SAM is less common,21 and there is usually a diffuse increase in velocity throughout the LV, including the mid‐cavity, directing the attention toward globally abnormal ejection hemodynamics. Occasionally, however, the septal thickness may be >20 mm (mean 21 mm in Topol et al.).20,22,25 Ancillary signs of severe HTN are ­typically present and help distinguish this entity from HOCM (aortic sclerosis, aortic dilatation, mitral annular calcification, nephropathy). This obstructive cardiomyopathy is more prevalent in the elderly female, particularly black female, in whom the LV cavity is small (Table 7.2).20,21

In a patient with systemic HTN, a diagnostic dilemma frequently arises in determining whether the markedly increased LV wall thickness is solely a reflection of HTN or, alternatively, whether it is a manifestation of a coexistent, genetically determined HCM.22 In addition, it is possible that some of these patients have a genetic HCM substrate that evolves into a HCM phenotype when exposed to longstanding HTN.21 Genetic testing, if positive, or a family history of HCM helps point towards genetic HCM. On the other hand, ancillary manifestations of HTN, such as aortic dilatation or nephropathy, support the diagnosis of chronic severe HTN. One study, however, has shown that hypertrophic cardiomyopathy with LVOT gradient in severely hypertensive patients is indistinguishable from hypertrophic cardiomyopathy in normotensive patients, with similar SAM rates, pressure gradient (frequently exceeding 100 mmHg), and septal thickness, implying that “hypertensive obstructive cardiomyopathy” may, in fact, be a genetic HOCM with coexistent HTN rather than a hypertensive cardiomyopathy.25

For practical purposes, LVH >15–20 mm with significant SAM and LVOT obstruction, in the absence of severe hypovolemia or sepsis, is pathophysiologically a HOCM, even in a hypertensive patient and even if hypertrophy is symmetric, and is managed as HOCM.25 In fact, a firm diagnosis of genetically determined HOCM is not always present in patients treated for the disease, even in HOCM studies and even when invasive therapies are used. This is related to the phenotypical overlap of HOCM and severe hypertensive cardiomyopathy and the limitations of genetic testing. Over 50% of patients in HOCM studies are hypertensive.

2.  Severe asymmetric septal hypertrophy with subaortic obstruction is also seen in ~10% of patients with severe AS and is unmasked after aortic valve replacement (septal thickness up to 22 mm).26 Doppler flow acceleration develops postoperatively and is attributed to LVOT obstruction and SAM in some series, while other series attribute it to the hyperdynamic small LV cavity that totally obliterates in systole. This obstruction is associated with postoperative hypotension, increased morbidity and mortality, and long‐term persistence of a gradient in some patients. It is mainly treated medically (β‐blockers, avoidance of inotropes, fluid resuscitation); a limited pre‐emptive myectomy has been selectively used in patients with septal bulge, with good results.27 3.  LVOT obstruction is frequently seen in patients receiving dobutamine regardless of the presence of LV hypertrophy and does not signify HOCM per se, as the obstruction may not be reproduced during exercise in most of these patients. It may also be seen in hospitalized patients with severe hypovolemia or sepsis and an empty, hypercontractile LV cavity, even if LVH is mild. 4.  A pattern of LVOT obstruction and mitral SAM may also be seen in patients with apical dyskinesis and hypercontractile LV base, as in large anteroapical infarction or takotsubo cardiomyopathy. Another form of subvalvular obstruction is subvalvular aortic stenosis that results from a discrete fibrous membrane or fibromuscular thickening within the outflow tract, just below the aortic valve (see Chapter 6). It leads to a fixed obstruction, the characteristics of dynamic LVOT obstruction being absent: no dagger‐shaped LV pressure, no spike‐and‐dome aortic pressure, and no Brockenbrough phenomenon. As opposed to HOCM, the gradient does not worsen with maneuvers such as Valsalva. Table 7.2  Differentiate LVOT obstruction of HOCM from hypertensive obstructive cardiomyopathy.

HOCM

Hypertensive obstructive cardiomyopathy

Invasive hemodynamics: late‐peaking gradient, Brockenbrough, gradient dynamic with maneuvers Gradient >100 mmHg SAM

+

+

Possible +

Septal thickness >20 mm Asymmetric septal hypertrophy >1.5:1

Frequent Common (but 10–20% concentric)

Genetics and family history of HCM or SCD Severe and chronic HTN, with other evidence of hypertensive disease (e.g., nephropathy, aortic dilatation) Hypovolemia

Frequently + ± HTN, sometimes severe, may coexist ±

Less common Less common The increase in velocity is more global, involving LVOT but also mid‐LV Rare Less common (but present in up to 1/3 of severe hypertensive hypertrophy) – + Common trigger of LVOT obstruction

218  Part 4. Hypertrophic Cardiomyopathy

X.  Differential diagnosis of severe LV hypertrophy Severe LV hypertrophy (septal thickness >15 mm, sometimes >20 mm) may be seen in hypertension or AS and may be asymmetric and/ or obstructive. In older patients, elongation of the aorta changes the angle of the aortic–septal junction and leads to a sigmoid septum. A sigmoid septum exaggerates the degree of asymmetric septal hypertrophy and may lead to LVOT obstruction (Figure 7.7). A severe increase in septal thickness may also be seen with infiltrative disorders such as amyloidosis; in this case, thickening of the valve leaflets and the interatrial septum is often seen, along with a pericardial effusion. The increase in LV thickness is related to infiltration rather than true hypertrophy and is usually diffuse but may be asymmetric and obstructive. The familial form of amyloidosis may be seen at a young age and is, therefore, more likely to simulate HCM than the AL amyloidosis occurring in the elderly. An ECG showing a disproportionately low voltage differentiates amyloidosis from HCM but is insensitive. Cardiac MRI and endomyocardial biopsy may ­distinguish hypertrophic from amyloid cardiomyopathy. While the septal thickness is usually >15 mm in HCM, it can be 12–15 mm in up to 15% of the patients, overlapping with the degree of wall thickening commonly found in hypertensive cardiomyopathy and occasionally found in normal athletes (Table 7.3). Hypertrophy can also be concentric in 10–20% of patients. In these cases, a mild hypertrophy that is otherwise unexplained in a young patient suggests HCM.

XI.  Treatment of symptoms A.  Chronic medical therapy (applies to HOCM and to the hypertensive obstructive cardiomyopathy) Medical therapy consists of agents that reduce inotropism and chronotropism: β‐blockers or non‐DHP CCBs. By reducing inotropism and the LV ejection speed, they reduce the mitral valve drag. By reducing the heart rate, they increase preload and diastolic filling time, and reduce functional ischemia. A third agent, disopyramide, may be used (class Ia antiarrhythmic drug with potent negative inotropic effect and mild vasoconstrictive effect).7 These drugs do not affect SCD. β‐Blocker therapy titrated to a heart rate of 60 bpm is the first‐line therapy. It mainly blunts the provocable gradient with little effect on the resting gradient, unless the patient has baseline tachycardia. Thus, it is mostly effective in patients who have a provocable gradient

septum

septum

Figure 7.7  In the elderly, elongation of the aorta sharpens the angle between the aorta and the septum (arrow) and leads to a sigmoid “stocky” septum. A mild septal hypertrophy is transformed into a more severe, discrete septal thickening (DUST: discrete upper septal thickening).

Table 7.3  Athlete’s heart vs. HOCM.

Septum thickness LV diastolic diameter LA enlargement LV filling (diastology) Family history LVH response to deconditioning (weeks) SAM

Athlete’s heart

HOCM

45 mm) None Normal None ↓ LVH No SAM

>15 mm, but can be less (gray zone) 50 mmHg despite proper medical therapy. Myectomy is the first‐line ablative therapy, unless the surgical risk is high. Moreover, in a patient with LBBB, alcohol septal ablation will lead to RBBB in 50–60% of the cases and thus complete AV block. Answer 3. C. The exam suggests HOCM and AS. The holosystolic dynamic murmur at the LLSB and apex is the combination of HOCM and its MR murmur. The murmur that radiates to the carotids is not characteristic of HOCM, and rather implies AS. The normal S2 and the normal carotid upstroke imply that AS is not severe. The echo confirms this diagnosis. The two envelopes within the LVOT CW Doppler correspond to the LVOT envelope (dagger‐shaped) and AS envelope (parabolic). The LVOT velocity is very high, implying severe HOCM obstruction rather than AS obstruction. The severity of the SAM and the gradient suggests HOCM rather than hypertensive cardiomyopathy. Answer 4. B. An end‐hole catheter is positioned in the LV and pulled back slowly across the LVOT and aortic valve, allowing the measurement of the LVOT gradient (between LV and LVOT) and the AS gradient (between LVOT and aorta). This study is performed and confirms the severity of the LVOT gradient (peak‐to‐peak 100 mmHg), and the rather mild AS gradient (peak‐to‐peak 18 mmHg, AVA 1.5 cm2 using Gorlin’s equation). Since most of the gradient is determined to be across the LVOT, simultaneous LV–aortic recording is subsequently performed using a double‐lumen pigtail catheter, and maneuvers are performed. Coronary angiography is necessary to see if a large proximal septal branch is available for alcohol septal ablation. Conversely, extensive CAD would favor CABG+ myectomy. TEE may be performed to calculate the AVA by planimetry and determine the severity of AS, but has a lower yield than catheterization. Answer 5. E. The MR is severe but posteriorly directed, suggesting it is purely related to SAM. Unless posterior leaflet prolapse is present (anterior or central jet), MR usually resolves with septal ablation. The patient has moderate AS by catheterization, and thus, if he is undergoing cardiac surgery, AVR would be reasonable (class IIa). Note that the AS gradient will increase once the LVOT obstruction is relieved (aortic flow will increase → gradient increases). Yet this non‐severe AS should not necessarily drive the choice between myectomy or alcohol septal ablation. Alcohol septal ablation is an acceptable option, especially in a patient >65 years old with a septal thickness 50 mmHg (rest or stress) and septal thickness >15 mm; thus, he qualifies for septal ablation. As opposed to the patient in Question 3, this patient has abnormalities of the posterior mitral leaflet and an anteriorly directed MR, implying a form of primary MR (this MR is not simply secondary to SAM). Septal reduction, per se, will not abolish MR Answer 8. E.

References 1. Maron BJ, McKenna WJ, Danielson GK, et  al. ACC/ESC expert consensus document on hypertrophic cardiomyopathy. J Am Coll Cardiol 2003; 42: 1687–713. 2. Wigle ED, Rakowski H, Kimball BP, et al. Hypertrophic cardiomyopathy: clinical spectrum and treatment. Circulation 1995; 92: 1680–92. 3. Shapiro LM, McKenna WJ. Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a two‐dimentional echocardiography study. J Am Coll Cardiol 1983; 2: 437–44. 4. Louie EK, Maron BJ. Hypertrophic cardiomyopathy with extreme increase in left ventricular wall thickness: functional and morphologic features and clinical significance. J Am Coll Cardiol 1986; 8: 57–65. 5. Yu EHC, Omran AS, Wigle ED, et al. Mitral regurgitation in hypertrophic obstructive cardiomyopathy: relationship to obstruction and relief with myectomy. J Am Coll Cardiol 2000; 36: 2219–25. 6. Grigg LE, Wigle ED, Williams WG, Daniel LB, Rakowski H. Transesophageal Doppler echocardiography in obstructive hypertrophic cardiomyopathy: clarification of pathophysiology and importance in intraoperative decision making. J Am Coll Cardiol 1992; 20: 42–52. 7. Fifer MA, Vlahakes GJ. Management of symptoms in hypertrophic cardiomyopathy. Circulation 2008; 117: 429–39. 8. Schwammenthal E, Nakatani S, He S, et al. Mechanism of mitral regurgitation in hypertrophic cardiomyopathy: mismatch of posterior to anterior leaflet length and mobility. Circulation 1998; 98: 856–65. 9. Maron BJ, Casey SA, Pollac LC, et al. Clinical course of hypertrophic cardiomyopathy in a regional United States cohort. JAMA 1999; 281: 650–5. 10. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287: 1308–20. 11. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003; 348: 295–303.

Chapter 7.  Hypertrophic Cardiomyopathy  223

12. Ommen SR, Maron BJ, Olivetto I, et al. Long‐term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005; 46: 470–6. 13. Sorajja P, Nishimura RA, Gersh BJ, et al. Outcome of mildly symptomatic or asymptomatic obstructive hypertrophic cardiomyopathy. A long‐term follow‐ up study. J Am Coll Cardiol 2009; 54: 234–41. In this study study of class I (60%) or class II patients, a severe resting gradient (peak velocity >4 m/s) was associated with a striking increase in mortality and HF. A less severe gradient was neutral on mortality. 14. Desai MY, Bhonsale A, Patel P, et al. Exercise echocardiography in asymptomatic HCM. Exercise capacity, and not LV outflow tract gradient predicts long‐ term outcomes. JACC Cardiovasc Imaging 2014; 7: 26–36. In this study of patients who are asymptomatic or minimally symptomatic, resting or stress LVOT gradient up to 100 mmHg did not appear to predict outcomes; rather, a limited exercise capacity on treadmill testing (65 (mean 75) and significant LVH with small cavity. Most of them had dagger‐shaped elevated velocity, mean septum 16 mm. SAM rare, ~like Ref. 20 22. Lewis J, Maron B. Diversity of patterns of hypertrophy in patients with systemic hypertension and marked left ventricular wall thickening. Am J Cardiol 1990; 65: 874–81. Thirty‐four percent of asymmetry in severe LVH in hypertensive patients, mean peak SBP 200, DBP 110. 23. Wicker P, Roudaut R, Haissaguere M, et al. Prevalence and significance of asymmetric septal hypertrophy in hypertension: An echocardiographic and clinical study. Eur Heart J 1983; 4 (suppl G): 1–5. 24. Kansal S, Roitman D, Sheffield LT. Interventricular septal thickness and left ventricular hypertrophy: an echocardiographic study. Circulation 1979; 60: 1058–65. 25. Karam R, Lever HM, Healy BP. Hypertensive hypertrophic cardiomyopathy or hypertrophic cardiomyopathy with hypertension? J Am Coll Cardiol 1989; 13: 580–4. A study of 78 patients with HOCM morphology (>15 mm with SAM and gradient at rest or exertion) and HTN vs. patients with HOCM morphology and no HTN: both have the same echo features, implying that HTN is not the main cause of the hypertrophy in those patients. 26. Aurigemma G, Battista S, Orsinelli D, et al. Abnormal left ventricular intracavitary flow acceleration in patients undergoing aortic valve replacement for aortic stenosis. Circulation 1992; 86: 926–36. 27. Kayalar N, Schaff HV, Daly RC, et al. Concomitant septal myectomy at the time of aortic valve replacement for severe aortic stenosis. Ann Thorac Surg 2010; 89: 459–64. 28. Stenson R, Flamm M, Harrison D, Hancock E. Hypertrophic subaortic stenosis. Clinical and hemodynamic effects of long‐term propranolol therapy. Am J Cardiol 1973; 31: 763–73. 29. Adelman A, Shah P, Gramiak R, Wigle E. Long‐term propranolol therapy in muscular subaortic stenosis. Br Heart J 1979; 32: 804–11. 30. Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005; 45: 1251–8. 31. Olivotto I, Cecchi F, Casey SA, et al. Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy. Circulation 2001; 104: 2517–24. 32. Maron BJ, Nishimura RA, McKenna WJ, et al. Assessment of permanent dual‐chamber pacing as a treatment for drug‐refractory symptomatic patients with obstructive hypertrophic cardiomyopathy: a randomized, double‐blind, crossover study (M‐PATHY). Circulation 1999; 99: 2927–33. 33. Nishimura RA, Trusty JM, Hayes DL, et al. Dual‐chamber pacing for hypertrophic cardiomyopathy: a randomized, double‐blind, crossover trial. J Am Coll Cardiol 1997; 29: 435–41. 34. Patel P, Dhillon A, Popovic ZB, et al. Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients without severe septal hypertrophy: implications of mitral valve and papillary muscle abnormalities assessed using cardiac magnetic resonance and echocardiography. Circ Cardiovasc Imaging 2015; 8: e003132. 35. Sorajja P, Valeti U, Nishimura RA, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2008; 118: 131–9. 36. Kwon DH, Kapadia SR, Tuzcu EM, et al. Long‐term outcomes in high‐risk symptomatic patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation. JACC Cardiovasc Interv 2008; 4: 432–8. 37. Sorraja P, Binder J, Nishimura RA. Predictors of an optimal clinical outcome with alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Cath Cardiovasc Interv 2013; 81: 58–67. 38. ten Cate FJ, Soliman OI, Michels M, et al. Long‐term outcome of alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: a word of caution. Circ Heart Fail 2010; 3: 362–9. Alcohol ablation of patients without ICD is associated with a significant increase in the long‐term risk of sudden death (~14% at 5 years). 39. Kovacic JC, Khanna D, Kaplish D, et al. Safety and efficacy of alcohol septal ablation in patients with symptomatic concentric left ventricular hypertrophy and outflow tract obstruction. J Invasive Cardiol 2010; 22: 586–91. 40. Veselka J, Tomasov P, Zemanek D. Mid‐term outcomes of alcohol septal ablation for obstructive hypertrophic cardiomyopathy in patients with sigmoid versus neutral ventricular septum. J Inv Cardiol 2012; 24: 636–40. 41. Naidu SS. Rethinking the selection criteria for alcohol septal ablation: is it time to push the envelope? J Inv Cardiol 2010; 22: 592–3. 42. Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverter defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 2007; 298: 405–12. 43. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000; 36: 2212–18. 44. Spirito P, Autore C, Rapezzi C, et al. Syncope and risk of sudden death in hypertrophic cardiomyopathy. Circulation 2009; 119: 1703–10.

Part 5  Arrhythmias and Electrophysiology 8 

Approach to Narrow and Wide QRS Complex Tachyarrhythmias

I. The unstable patient (shock, acute pulmonary edema)  225 II. Initial approach to any tachycardia  225 III. Approach to narrow QRS complex tachycardias  226 IV. Approach to wide QRS complex tachycardias  227 V. Features characteristic of VT, as opposed to SVT with aberrancy  228 VI. Features characteristic of SVT with pre‐excitation  232 VII. Role of adenosine in establishing a diagnosis  233 VIII. Differential diagnosis of a wide complex tachycardia on a one‐lead telemetry or Holter monitor strip  234 IX. Various notes  234 X. General management of SVT  234 XI. Non‐tachycardic wide complex rhythms  235 Questions and answers: practice ECGs of wide complex tachycardias  235

I.  The unstable patient (shock, acute pulmonary edema) In a hemodynamically unstable patient with supraventricular tachyarrhythmia (shock or severe HF), always ask yourself: did the tachyarrhythmia cause the shock or did the shock cause an increase in heart rate with a secondary SVT or AF? Typically, to attribute a shock to SVT or AF, the heart rate must be >150 bpm. In addition, clinical features suggestive of another primary process should be sought (sepsis, acute bleed/severe anemia, tamponade, massive PE); in these cases, tachycardia is not the isolated cause of the instability, it is rather the consequence. For example, in a patient with BP 75/50 mmHg and AF rate of 125 bpm, AF is likely secondary to the shock rather the cause of the shock. If a tachyarrhythmia faster than 150 bpm is assumed to be the cause of instability, emergent DC cardioversion should be performed.

II.  Initial approach to any tachycardia When analyzing a tachycardia, start by looking at three features: 1.  Narrow QRS vs. wide QRS (≥120 ms) (choose the lead where QRS is widest) 2.  Regular vs. irregular ventricular rate 3.  Look for P waves and their relationship with QRS complexes. P waves are usually seen as notches or deflections that fall over the ST–T segments and have a consistent morphology and timing, i.e., those deflections are regularly placed and can be marched out. Try to confirm that these deflections are P waves, rather than artifacts or parts of T wave, by analyzing multiple leads. Once P waves are found, their relationship with QRS complexes is analyzed. P waves are often best seen in lead II, which is generally parallel to the spread of atrial depolarization; and in the lead where T and QRS are smallest (opening up room to see the scattered P waves). In wide QRS tachycardia, analyze: (i) AV dissociation, and (ii) the number of P waves compared to the number of QRS complexes. In ­narrow QRS tachycardia, assess the length of the RP interval.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

225

226  Part 5.  Arrhythmias and Electrophysiology

III.  Approach to narrow QRS complex tachycardias (see Figures 8.1, 8.2) QRS width

Narrow complex tachycardia QRS30 ms, R‐to‐nadir of S >70 ms, or notched S descent in V1; or Q wave in V6. • RBBB with a wide R pattern in V1 instead of RSR’, R >R’ in V1, or monophasic R or QS in V6. RBBB with a left axis or with a rS pattern in V6 does not necessarily imply VT (could be RBBB + LAFB). While rS pattern in V6 is not typical of LBBB or RBBB, it may be seen with atypical LBBB (enlarged LV) or RBBB + LAFB. Deep Q in V6 (QS or Qr) implies VT. Left QRS axis may be seen with LBBB or RBBB + LAFB. Right QRS axis, on the other hand, is not typically seen with either LBBB or RBBB and usually implies VT.

230  Part 5.  Arrhythmias and Electrophysiology

P

P

*

P

P

*

*

P

Figure 8.8  Run of wide complex tachycardia on a telemetry strip: is it VT or SVT? 1.  See how it starts: the first wide complex is not preceded by any premature P wave and there is no deformation of the preceding T wave. This initial complex is a PVC, and the tachycardia has a morphology similar to this initial complex: this suggests that the tachycardia is VT. 2.  Look for P waves. Some notches are visible inside the wide complex run. Try to march them out with the preceding and following sinus P waves → they do march out at the same rate as the sinus P rate, independently of the wide complex rhythm and scattered inside it. Some P waves are hidden within QRSs and cannot be seen (marked with an asterisk [*]). The two visible P waves that are dissociated from the QRS complexes imply AV dissociation, characteristic of VT. 3.  The initial upslope of the wide QRS complex is slower and less steep than the upslope of the baseline QRS. This is suggestive of VT.

Figure 8.9  Wide complex tachycardia: VT or SVT? 1.  Look for P waves, i.e., look for scattered “blips” that: (a) have a consistent morphology and timing, and (b) can be marched out. Blips are seen in lead II (vertical arrows). These blips can be marched out (calipers) and have a consistent morphology; they are not part of the T wave, as they do not consistently fall on every T wave. They are also seen in other leads (I, V5, V6, arrows), further adding to the evidence that these are P waves, not artifacts or parts of T wave. They do not have a consistent relationship with the QRS complexes, and some of them fall inside the QRS complexes and are not seen (dashed arrows). Thus, P waves are dissociated from QRS complexes and are less numerous than QRS complexes. This is diagnostic of VT. The variable T‐wave morphology is usually a hint to the presence of P waves that are dissociated from QRS/T and falling variably over some T waves. 2.  Analyse QRS morphology. QRS has a LBBB‐like morphology in lead V2. However, there is a QR pattern in V5–V6, QS pattern in lead I, and right‐axis deviation (QRS negative in lead I), not consistent with LBBB. Besides, QRS has excessive notching, best seen in leads V1 and V3 (horizontal arrows). Thus, this is VT. 3.  Additional findings: • Wide QRS complexes of different morphology are scattered within the tachycardia (stars). Those may represent fusion complexes or PVCs. Being wide, they have no diagnostic value. • ST‐segment elevation, concordant with QRS, is seen in the anterolateral leads. This is concerning for STEMI.

Figure 8.10  Two short tachycardia runs. The tachycardia starts after a regularly occurring sinus P wave (bar) at a shorter PR interval (the bar marches out with the arrows). This is typical of a PVC, which occurs without disrupting the timing of the underlying sinus P waves. PAC would have started with a premature P wave. Thus, the tachycardia starts with a PVC and has the same morphology as the PVC. This is VT.

Chapter 8. Narrow and Wide QRS Complex Tachyarrhythmias  231

Figure 8.11  Wide complex, regular tachycardia, at a rate of ~135 bpm. QRS looks narrow in some leads; this is due to the fact that part of the QRS is isoelectric in those leads. That is why QRS should be measured in the lead where it is widest. QRS is wide (~140 ms) in lead V3 in particular. 1.  QRS looks like a typical LBBB in leads I, aVL, and V1. This suggests SVT with LBBB aberrancy. 2.  P waves are seen. A negative P wave is overlying the ST–T segment and another P wave is just preceding QRS (arrows); these deflections are recognized as P waves, as opposed to being fragments of T wave, by the fact that they have a consistent morphology and can be marched out. Thus, this tachycardia is an atrial tachyarrhythmia with 2:1 AV conduction, the atrial rate being 270. The atrial rate (>240) as well as the sawtooth shape seen in leads II and aVR and the lack of isoelectric baseline make the diagnosis atrial flutter. Final diagnosis: Atrial flutter with 2:1 AV conduction and wide QRS due to LBBB aberrancy.

R

# R1

R

# R2

R

# R3

R

# R4

R

Figure 8.12  The baseline rhythm is sinus, consisting of QRS complexes (R) preceded by sinus P waves. Outside these complexes, there are premature complexes occurring in a bigeminal pattern (R1, R2, R3, R4). These could be PVCs or PACs with aberrancy. Look for P waves preceding these complexes: there is a P wave before each complex, marked #. It is an inverted, non‐sinus P wave and occurs prematurely. This means that R1–R4 are PACs with aberrancy rather than PVCs. These PACs have aberrant conduction because they occur very prematurely, while the right bundle is still in its refractory period, which leads to RBBB morphology. Note that the aberrancy (QRS widening) is less pronounced when PAC is less premature. This is a form of Ashman’s phenomenon. R–R1 interval 40 ms. Normally, aVR consists of a sharp and deep negative deflection, sometimes preceded or followed by a small r wave (QS, rS, or Qr pattern).

VI.  Features characteristic of SVT with pre‐excitation Once a diagnosis of VT is made using the above criteria of VT vs. aberrant SVT, step back and consider the diagnosis of p ­ re‐ excited SVT before closing. Since the ventricular stimulation does not spread down from the His bundle, the QRS morphology of a ­pre‐excited SVT resembles the QRS morphology of VT, i.e., not a typical LBBB or RBBB morphology. The initial portion of QRS is slurred, but this is seen with VT as well (slow upslope) and does not help differentiate VT from pre‐excited SVT. Seeing the slurred delta wave on the baseline ECG is diagnostic of pre‐excitation; seeing it during tachycardia implies VT or pre‐excited SVT. The most typical SVT with pre‐excitation is AF with pre‐excitation. In this case, the wide tachycardia is irregular, implying AF rather than VT, with a differential diagnosis that includes AF with aberrancy. AF with pre‐excitation is diagnosed when AF has VT morphological features; or when AF is wide and polymorphic (QRS varies in height and width), bizarre looking, or very fast (>200 bpm) (Figure 8.13).

• When AF has the morphological features of VT or is too fast (>200 bpm), consider pre‐excited AF (WPW syndrome). • Also, as opposed to AF with aberrancy, where the QRS becomes more aberrant and wider after a shorter R–R interval (Ashman’s phenomenon), pre‐excitation may become more evident and the QRS may become wider after a longer R–R interval that allows recovery of the accessory pathway’s refractory period.

Figure 8.13  Very wide QRS complex tachycardia (particularly wide in lead I, ~200 ms), very fast (rate ~240 bpm), and grossly irregular. Because it is so fast, it may initially seem regular; but on careful assessment one sees that R–R intervals are grossly irregular, with some R–R intervals being half the size of other R–R intervals, without any particular pattern (irregularly irregular) (double arrows). Differential diagnosis: 1.  VT: VT is usually regular or slightly irregular, not grossly irregular. However, it may be grossly irregular in case of polymorphic VT, which is a very fast VT that quickly degenerates into VF. This could be the case here. 2.  Being irregular, this tachycardia is likely AF with wide QRS complexes. AF is wide in the case of (a) aberrancy, or (b) accessory pathway (WPW). Aberrancy is unlikely because QRS morphology does not fit with a typical RBBB or LBBB. In fact, QRSs are too wide and polymorphic, with some complexes being ~200 ms wide (arrow). Thus, this is AF with VT features, implying AF with conduction over an accessory pathway. Note that QRS gets wider when the R–R interval increases (stars), which is consistent with pre‐excitation rather than aberrancy.

Chapter 8. Narrow and Wide QRS Complex Tachyarrhythmias  233

A regular SVT with pre‐excitation is less common than AF with pre‐excitation (e.g., antidromic AVRT, atrial tachycardia with pre‐excitation). Since the QRS morphology simulates VT, other features help differentiate VT from SVT with pre‐excitation: • AV dissociation or QRS complexes outnumbering P waves (→ VT). • A predominantly negative QRS complex in leads V4–V6 implies ventricular activity originating close to the apex, and thus VT rather than pre‐excitation, as the accessory pathway cannot be apical. For the same reason, negative monophasic concordance in all precordial leads can only be VT, not pre‐excitation. Positive monophasic concordance may be seen in pre‐excitation from a left posterior or lateral accessory pathway. Acutely, AF or any other SVT with pre‐excitation is treated as VT. The administration of AV nodal blocking agents that are typically used for AF, particularly calcium channel blockers or digoxin, may shorten the accessory pathway’s refractory period and allow more atrial activity to conduct over the accessory pathway, thus leading to a faster rate. Give procainamide if the patient is stable, then perform DC cardioversion if the arrhythmia does not respond or if the patient is unstable. Table 8.1 summarizes the approach to wide QRS complex tachycardias.

VII.  Role of adenosine in establishing a diagnosis Adenosine may help differentiate various types of SVT. AVNRT, AVRT, SNRT, and a subgroup of atrial tachycardias often totally break with adenosine, but they may remain unchanged or may slightly and transiently slow down if the slow pathway (AVNRT) or the AV node (AVRT) is slowed rather than blocked. Atrial flutter and most subgroups of atrial tachycardia usually do not break but develop AV block with adenosine, which slows the QRS rate and allows one to see and assess the hidden P waves and make the diagnosis (Figure 8.14). AV block during tachycardia (e.g., 2:1 conduction) excludes AVRT and makes AVNRT less likely. The AVRT loop is dependent on both the atrial and ­ventricular myocardium; thus, a drop of atrial or ventricular activity leads to cessation of the arrhythmia. VT is not affected by adenosine (except idiopathic VT). While potentially helpful in distinguishing SVT from VT, adenosine IV or verapamil or diltiazem IV should be avoided in wide complex tachycardias of uncertain diagnosis, because these should be presumed VT and treated as such. Diltiazem, verapamil, or adenosine are vasodilators that can lead to hemodynamic collapse in case of VT, in which the patient’s systemic pressure is merely maintained by vasoconstriction. They can also lead to rate acceleration and VF in case of WPW (i.e.,

Table 8.1  Summary of the approach to wide QRS complex tachycardia. (1) VT vs. (2) SVT (including AF) with aberrancy vs. (3) SVT (especially AF) with pre‐excitation 1. VT is the most likely diagnosis (>80%), especially if history of heart disease. Features that further support VT: • P waves are seen scattered within QRS complexes or ST–T segments and are unrelated to QRS complexes (AV dissociation); and/or number of P waves 160 ms if the baseline QRS is narrow. • Tachycardia similar in morphology to a prior PVC. • Tachycardia starts with a PVC rather than a premature P wave and has the same morphology as the PVC. • The initial portion of the wide QRS is wide, slurred or slow, sometimes with a notched descent. Conversely, the presence of a narrow initial deflection q or r (qR or rS, with narrow q or r 90% cure rate, obviating the need for long‐term anticoagulation

Table 8.3  Management of focal atrial tachycardia. 1. Rate control (same protocol as AF and atrial flutter) 2. Rhythm control a. Adenosine, β‐blockers, diltiazem: all may slow down atrial tachycardia or convert it to sinus rhythm. Antiarrhythmic drugs are used as second‐line agents b. Digoxin is not usually used, because it can cause atrial tachycardia c. DC cardioversion may not be successful, as many atrial tachycardias are caused by enhanced automaticity rather than reentry. DC cardioversion is only attempted if the patient is unstable 3. Anticoagulation is not usually necessary for atrial tachycardia per se, but may be necessary in an older patient whose atrial tachycardia frequently coexists with AF

Figure 8.15  Two types of QRS complexes are seen: (1) narrow complexes preceded by sinus P waves; (2) wide complexes that seem to be preceded by sinus P waves (arrows) but are, in reality, coming too close to the P waves and dissociated from them, with a variable PR interval (ventricular complexes). The wide complex rate is close to the sinus rate, which makes those wide complexes fall around the sinus P waves. Whenever the sinus rate accelerates, P waves get conducted; when the sinus rate slows down, the wide rhythm expresses itself. The wide complex rhythm is an accelerated idioventricular rhythm, an automatic ventricular rhythm that competes with the sinus rhythm (rate ~65 bpm). The dissociation between P and QRS during those beats is isorhythmic AV dissociation.

B.  AVNRT, AVRT Convert with: vagal maneuvers, adenosine 6–12 mg IV (first‐line therapy if no asthma), metoprolol 5 mg IV, diltiazem 20 mg IV. C.  Focal atrial tachycardia (Table 8.3) Always remember to seek an underlying cause of the tachycardia and treat it. This alone may control the rate ± the rhythm: • HF decompensation, hypovolemia, acute bleed, sepsis, PE, hypoxia, hyperthyroidism

XI.  Non‐tachycardic wide complex rhythms (see Figures 8.15, 8.16, 8.17) QUESTIONS AND ANSWERS: Practice ECGs of wide complex tachycardias Review every ECG and attempt to make a diagnosis of SVT vs. VT (Figures 8.18–8.25).

Figure 8.16  Again, two types of QRS complexes are seen: (1) narrow complexes preceded by a sinus P wave; (2) wide complexes preceded by the same sinus P wave (best seen in V2–V6). These wide complexes are not premature, hence they are not PVCs. They may represent an idioventricular rhythm similar to Figure 8.15; however, the P and QRS relationship remains constant throughout those beats. This intermittent widening of the QRS may represent intermittent bundle branch block or intermittent pre‐excitation. The lack of a change in rate argues against bundle branch block. The morphology of the wide QRS favors pre‐excitation. A positive delta wave with a short PR interval is seen on the wide complexes in leads V5–V6 and I, while a negative delta wave (pseudo‐Q wave) is seen in the inferior leads. This intermittent conduction across the accessory pathway implies a long refractory period and an inability to consistently conduct even at a normal rate (good prognosis).

Figure 8.17  Alternation between wide and narrow QRS complexes. Both QRS complexes are occurring regularly after the regular sinus P waves (arrows), with a constant P–QRS relationship. The P–P interval and PR intervals are constant. The morphology suggests intermittent LBBB. Diagnosis: sinus rhythm with alternating LBBB.

II

V2

V5 V6

Figure 8.18  A run of wide complex tachycardia. It is irregular, but this does not necessarily imply AF. In a short run of VT or at the onset of VT, VT may be irregular. 1.  See how it starts: tachycardia starts after a regularly occurring sinus P wave (blue arrows), at a shorter PR interval (bars). This implies that it starts with a PVC, a beat that does not interrupt the regularly occurring sinus P wave. The tachycardia has the same morphology as this PVC; thus, the tachycardia is VT. 2.  Look for P waves: two P waves are seen within the tachycardia, in leads II, V5, V6 (black arrows). The first P wave has a similar morphology to the sinus P wave and comes at an interval that is equal to the sinus P–P interval. The second P wave falls at twice the sinus P–P interval. Another sinus P wave is expected to fall in between and is hidden in the QRS complex (dashed arrow). Those P waves fall around the QRS and ST–T segments at their own rate and are dissociated from QRS, implying VT. 3.  Look at the QRS morphology. The QRS has a QS morphology in V5–V6, which is not seen with LBBB or RBBB, and is pathognomonic of VT. Final diagnosis: VT.

Chapter 8. Narrow and Wide QRS Complex Tachyarrhythmias  237

Figure 8.19  Regular wide complex tachycardia, QRS width ~180 ms (lead II). 1.  QRS morphology is consistent with a typical LBBB in leads V1–V6. 2.  Look for P waves in all leads. One can identify inverted blips that have a consistent morphology and timing and that can be marched out in lead II (arrows), and in leads III and aVF. They occur after every third QRS, and have a consistent relationship with QRS. Thus, there is AV association, with three QRS complexes for every P wave. Since the number of QRS complexes >number of P waves, this is VT. The P waves are retrograde P waves, secondary to a 3:1 ventriculoatrial conduction.

Figure 8.20  Wide complex tachycardia, regular, at a rate of ~155 bpm. The QRS is widest in lead aVF (~140 ms). 1.  P waves are not seen. One cannot comment on AV dissociation. 2.  QRS morphology. There is monophasic negative QRS concordance in V1–V6, with a QS pattern, pathognomonic for a VT that originates apically (likely from an apical MI scar). The axis is northwest (QRS negative in leads I and aVF), which is also suggestive of VT. QRS has a lot of notching, particularly seen in the inferior leads and in lead V1, also characteristic of VT. A large dominant R wave is seen in lead aVR, also characteristic of VT. Wide complexes of a different morphology are scattered in the tachycardia (arrows). The first three are likely fusion complexes, whereas the fourth is very wide and is likely a PVC from another focus.

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Figure 8.21  This is the baseline ECG of the patient in Figure 8.20. It shows an anterior MI pattern; however, the QS pattern does not extend all the way to V6 and the axis is normal. Note the morphology of QRS in lead II, and see how the three different‐looking complexes in Figure 8.20 are fusion between this narrow QRS and the VT’s QRS.

Figure 8.22  Wide complex tachycardia on telemetry or Holter monitoring. Is it SVT or VT? 1.  See how it starts. The first complex is not preceded by a P wave or a deformation of the T wave, and thus is a PVC. The tachycardia starts with a PVC and has a morphology similar to the PVC → VT. 2.  Look for AV dissociation: scattered notches are visible on the T waves (blue dots), and can be marched out (blue calipers). They are at equal distance from each other, and this distance is the same as the distance between two sinus P waves (marked by the last caliper). They are dissociated from QRS complexes. These are sinus P waves that keep marching through the tachycardia without any relation to it → VT. Deformation of a T wave is usually a hint to a hidden P wave. 3.  There are three narrower complexes scattered within the tachycardia (arrows). They start similarly to the tachycardia’s QRS and end similarly to the sinus beat’s QRS, suggesting fusion complexes in a patient with VT. 4.  The tachycardia is irregular. This does not necessarily imply AF, as any SVT or VT may be irregular at its onset (the first 20 beats). Conclusion: VT.

Chapter 8. Narrow and Wide QRS Complex Tachyarrhythmias  239

Figure 8.23  Run of wide complex tachycardia. Is it VT or SVT? 1.  Look at how it starts. The first QRS of the tachycardia is preceded by a P wave (first arrow) that is premature in comparison to the sinus P waves (caliper); thus the first QRS is a PAC with aberrancy. A tachycardia that starts with a PAC and has a morphology identical to the PAC is SVT. 2.  Throughout the tachycardia, one sees P waves (arrows) having a consistent 1:1 association with QRS. AV association does not prove the tachycardia is SVT, as it may also occur in up to 25% of VT. 3.  What are the complexes in the area marked by the rectangle? Three wide complexes are preceded by sinus P waves with the same PR interval as the sinus rhythm. These are sinus beats conducted with aberrancy (LBBB aberrancy, QRS being negative in II). The patient probably has intermittent, rate‐related LBBB. In fact, the sinus rhythm is a bit faster at the time of these three complexes. This proves that the left bundle is prone to rate‐related block. The wide complex tachycardia is SVT having the same LBBB aberrancy. 4.  Look at how the tachycardia ends (box). There is no P wave at the end; the tachycardia ends with a QRS complex. A presumed VT with 1:1 VA conduction usually ends with the retrograde P wave; thus, in this case, the lack of P wave at the end argues against VT. So this is SVT. The next question is: what type of SVT? Is it AVNRT, AVRT, or atrial tachycardia? 1.  Look at the RP interval. RP interval being over half the RR interval, this is a long RP tachycardia. The diagnosis includes atrial tachycardia vs. atypical AVNRT vs. SNRT. 2.  The fact that the first P wave (PAC) marches out with the subsequent P waves means that each one of these P waves originates, like the PAC, from the same atrial focus and conducts antegradely. This favors automatic atrial tachycardia. The fact that the tachycardia ends with a QRS is also consistent with this diagnosis.

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Figure 8.24  The baseline rhythm is AF and the baseline QRS is marked by lines. Runs of wide complexes are seen. In a patient with baseline AF, are the wide complex runs VT or aberrant runs of AF? 1. Use the rhythm strip with a different set of criteria, focused on Ashman’s phenomenon: a. Does the wide run follow the Ashman rule, meaning it occurs after a long–short sequence? The first run (cross) starts after an interval that is not too short (first caliper), as there is, on the same ECG, a “longer–shorter” sequence without aberrancy (the sequence of the first two complexes, underlined). This argues against aberrancy. The second run (second caliper) starts after a long R–R interval. This again argues against aberrancy. b. Two complexes of intermediate morphology are seen (dots). These complexes are fusion complexes, further supporting VT (the complex starts similarly to the ventricular complex, and ends as a summation between the ventricular complex and the baseline QRS). c. If the coupling interval of the wide complexes was constant (timing of onset in relation to the normally conducted complex), it would have further supported VT (this is not the case here). 2.  Use the 12‐lead ECG to analyze the morphology of the wide complexes (i.e., the complexes that are not marked by a line or a dot on the rhythm strip) (e.g., Brugada criteria): • The wide QRS complex morphology does not fit with a typical LBBB or RBBB; it is close to LBBB in V4–V5, but the R wave of the RS complex in lead V2 is wide (>30 ms), and QRS is negative in leads I and aVL, arguing against LBBB; the right‐axis deviation of the wide complexes also argues against typical LBBB. This is VT. • The onset/initial part of QRS is more slurred than its later part (leads II, aVF, and V3–V5), which implies VT. • The notch on the descending limb of QS in leads aVR and aVL is consistent with VT. Final diagnosis: AF with two runs of VT.

Chapter 8. Narrow and Wide QRS Complex Tachyarrhythmias  241

Figure 8.25  Baseline sinus rhythm with LBBB morphology. Two runs of wide complex tachycardia are seen (horizontal lines). Are these runs VT or SVT with aberrancy? • Look at how the run starts. It starts with a P wave that occurs prematurely and deforms the preceding T wave, giving it a peaked appearance (first arrow), thus a PAC. The QRS of the tachycardia has the same morphology as this aberrant PAC. Thus, this is SVT. • The morphology is similar to the baseline QRS morphology. A tachycardia that keeps the same bundle branch block morphology as the baseline is SVT. • Look for P waves and for AV dissociation: there are notches after each QRS, likely P waves, associated with QRS in a 1:1 fashion (arrows). These notches are evident when the tachycardia’s QRS morphology is compared to the baseline QRS. This 1:1 AV association implies SVT or VT with retrograde VA conduction (not here). The fact that the tachycardia ends with a QRS and no P wave argues against VT with 1:1 VA conduction. This is SVT. What type of SVT is it? It is a short RP tachycardia, which could fit with AVNRT, AVRT, or atrial tachycardia. The P wave of the initial complex (PAC, first arrow) keeps marching out with the subsequent P waves, arguing that each one of these P waves is, like the first P wave, coming from the same atrial focus and conducting antegradely to the ventricles. Thus, the tachycardia is likely an automatic atrial tachycardia. Also, the upright P morphology in lead II indicates that the P wave is not a retrograde P wave, and thus the tachycardia is unlikely to be AVNRT or AVRT, which favors atrial tachycardia. The tachycardia ends with a QRS, as no P notch is seen at the last QRS complex. It is consistent with automatic atrial tachycardia, wherein the P vanishes as the automatic focus becomes quiescent. Final diagnosis: sinus rhythm with LBBB, runs of a wide complex atrial tachycardia.

Further reading Brugada P, Brugada J, Mont L, et  al. A new approach to the differential diagnosis of a regular tachycardia with a wide complex. Circulation 1991; 83: 1649–59. Strickberger SA, Man KC, Daoud EG, et al. Adenosine‐induced atrial arrhythmia: a prospective analysis. Ann Intern Med 1997;127: 417–22. Adenosine causes transient AF in 12% of patients after SVT therapy: transient AF lasts 5–20 minutes, but requires DCCV in 1/3 of those cases. ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005; 112 (suppl 24): IV1–203. Vereckei A, Duray G, Szenazi G, et al. Application of a new algorithm in the differential diagnosis of wide QRS complex tachycardia. Eur Heart J 2007; 28: 589–600.

9 

Ventricular Arrhythmias: Types and Management, Sudden Cardiac Death

I. Premature ventricular complexes  242 II. Ventricular tachycardia (VT)  243 III. Polymorphic ventricular tachycardia  246 IV. Congenital long QT syndrome (LQT)  248 V. Indications for ICD implantation  249 VI. Specific VTs that should be considered in the absence of obvious heart disease  251 VII. Causes of sudden cardiac death (SCD)  253 Questions and answers  254

I.  Premature ventricular complexes In the absence of heart disease, premature ventricular complexes (PVCs) are generally benign and do not clearly portend an increased risk of sudden or cardiac death, regardless of their frequency (>1 per minute) or pattern (e.g., couplets). Frequent PVCs are relatively common in an apparently healthy population (prevalence 1–4% at mean age of ~50). Benign PVCs generally occur at rest and improve with exercise; yet some idiopathic PVCs are triggered by exercise. Recent data suggest that a high PVC burden, exceeding 0.5 % of all QRS complexes, is associated with twice the risk of HF at 15‐year follow‐up, although no causal relationship is established. Very frequent PVCs (>5–10% burden) warrant echo ± stress test to assess for heart disease. Even in the absence of underlying heart disease, very frequent PVCs may lead to a form of tachycardia‐mediated cardiomyopathy. Among patients referred for PVC ablation, ~40% of those with PVC burden > 10% have reduced EF; EF fully normalizes with PVC ablation.1,2 In patients with heart disease, frequent or complex PVCs or non‐sustained VT portend an increase in mortality independently of other baseline variables, according to most post‐MI studies. However, targeted therapy of PVCs or non‐sustained VT is not indicated. In fact, the use of class I antiarrhythmic drugs (AADs) to suppress PVCs worsens outcomes (as a result of the proarrhythmic side effects of AADs) and should be avoided in patients with underlying heart disease (CAST trial: in patients with a history of MI and normal or low EF, PVC suppression with class I AADs increases mortality).3 β‐Blockers are the safest treatment for symptomatic PVCs and PVCs occurring in the context of structural heart disease. PVCs that originate from the same focus have a monomorphic appearance and may be treated with catheter ablation if the patient has refractory symptoms. In the particular case of frequent PVCs (>5–10% burden on 24‐hour Holter) with LV systolic dysfunction, there are three possible diagnoses: (1) ischemia causing both PVCs and LV dysfunction; (2) LV dysfunction causing PVCs; (3) frequent PVCs causing a form of tachycardia‐mediated cardiomyopathy. Once ischemia is ruled out, it is reasonable to suppress PVCs using amiodarone or catheter ablation and see if EF improves. In fact, EF substantially improves in over 80% of these patients.4,5

How to differentiate PVC from PAC with aberrancy PVC is a wide premature complex with ST–T changes opposite in direction to QRS. A PVC does not affect the sinus P waves, which keep marching through the PVC at approximately the same rate. Therefore a sinus P wave falls within the PVC and distorts it, or precedes the PVC at a PR interval shorter than baseline; a wide premature complex preceded by a sinus P wave at a shorter PR interval is a PVC. This also means that the PVC does not reset the sinus node. Hence the R–R interval between the complex before and the one after the PVC is equal to twice the regular R–R interval, and it looks like there is a pause after the PVC. PVC may, however, be interpolated between two normal QRS complexes, not affecting at all the sinus‐conducted QRS complexes.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

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Chapter 9.  Ventricular Arrhythmias  243

PAC with aberrancy (functional bundle branch block) mimics a PVC.* PAC, however, starts with a premature P wave of a different shape than the sinus P wave (may fall in the T wave and manifest as a change in the preceding T‐wave morphology: deformity, peaking). PAC often conducts retrogradely to the sinus node and resets it, making it fire after the PAC at a rate close to baseline. Thus, the interval after a PAC is not a fully compensatory pause and is only slightly longer than the baseline R–R interval. The R–R interval between the complex before and the one after the PAC is less than twice the normal R–R interval. PAC with aberrancy is often of RBBB morphology. Interpolated PACs are possible but unusual, and may occur when the sinus node is not reset by the PAC. While frequent PVCs are considered benign in patients with no identifiable heart disease, frequent PACs are associated with an increased risk of AF, stroke, and death in patients 55–75 years of age (prolonged rhythm monitoring may be warranted to detect periods of AF).

P

P

PVC

P

PVC

P

P

P

PVC

P

P

PVC

Figure 9.1  Wide premature complexes with a different morphology than the baseline QRS, and with prominent ST–T changes opposite to QRS, occurring in a trigeminal pattern. These are typically PVCs, but could be PACs with bundle branch block (aberrancy). They fall after normally occurring, non‐premature P waves with a shorter PR interval than the sinus beats, which is typical of PVCs. Sinus P waves keep marching out through the PVCs.

• Frequent PVCs = PVCs > 30 per hour or > 1 per minute. • Very frequent PVCs with a risk of tachycardia‐mediated cardiomyopathy: total PVC burden > 5–10% of the total QRS complexes, or > 20,000 PVCs per day. • Complex PVCs = polymorphic PVCs, or couplets or triplets of PVCs. • Bigeminy means the alternation of one sinus beat with one PVC; trigeminy means the occurrence of one PVC after every two sinus beats (Figure 9.1). This is different from couplet (two PVCs in a row), or triplet (three PVCs in a row). • Ventricular parasystole corresponds to an automatic ventricular focus that fires at a regular rate (~30–60 per minute), independently of the basic sinus or supraventricular rhythm and uninhibited by this rhythm (the parasystolic focus is protected by an entrance block). This focus impulse propagates to the ventricles whenever they are not in their refractory period. Parasystole manifests as PVCs that have no fixed relationship with the baseline QRS (non‐fixed coupling), with interectopic intervals that are a multiple of the shortest interectopic interval. Fusion complexes are particularly common. Parasystole may be seen in the presence or absence of heart disease and does not affect prognosis. Even frequent parasystolic PVCs are benign, per se. In contrast to ventricular parasystole, typical PVCs are due to a reentrant circuit that is initiated by the supraventricular rhythm, and thus show fixed‐interval coupling. • Site of origin of the PVC (PVC looks away, i.e., looks negative, from where it originates): (i) right vs. left: right ventricular origin → LBBB morphology left ventricular origin → RBBB morphology (ii) anterior vs. inferior: anterior origin → QRS (+) in the inferior leads (vertical axis) inferior origin → QRS (–) in the inferior leads (left axis) (iii) basal vs. apical: basal origin → QRS complex is upright in all precordial leads, and (–) in I-aVL (if lateral origin) apical origin → QRS complex is negative in all precordial leads

II.  Ventricular tachycardia (VT) (Figure 9.2) A. Types • Sustained VT = VT lasting > 30 seconds or VT associated with hemodynamic compromise (such as syncope/presyncope) • Non‐sustained VT: at least three consecutive ventricular beats, with a total VT duration  100 bpm. A ventricular rhythm slower than 100 bpm is accelerated idioventricular rhythm (AIVR); a ventricular rhythm slower than 40 bpm is a ventricular escape rhythm.

* PVC and PAC with aberrancy are wide, but may be narrow if the PVC or the aberrancy originates high in the septum close to the His bundle. They will, however, look different than the baseline QRS. In case of a wide baseline QRS, a PAC with aberrancy is wider than the baseline, with the same bundle branch block morphology as the baseline; a QRS narrower than baseline is diagnostic of PVC.

244  Part 5. Arrhythmias and Electrophysiology

Figure 9.2  Tachycardia that seems narrow but has a different morphology than the native QRS and is associated with secondary ST/T abnormalities → VT or SVT with aberrancy. To differentiate, see how the tachycardia starts. It does not start after a premature P wave, but rather starts after a regularly occurring sinus P wave (third arrow) with a shorter PR interval than regularly: this means it starts with a PVC. It has the same morphology as this PVC → the tachycardia is VT. Also, one can regularly march out sinus P waves scattered within the tachycardia and dissociated from the QRS complexes, which is diagnostic of VT. These P waves are marked by arrows. One P wave falls within a QRS (marked by an interrupted line).

B.  Causes of sustained VT Sustained VT is typically secondary to an underlying heart disease: • Acute or chronic ischemia. Acute ischemia typically leads to polymorphic VT, whereas a prior ischemic scar/old infarct leads to monomorphic VT. Occasionally, a scar may lead to polymorphic VT. • Any cardiomyopathy, especially with EF  450 ms in men. In the absence of reversible metabolic, drug, or ischemic causes, LQT syndrome is suspected, particularly if QTc > 480 ms. Up to 10% of normal individuals have QTc that is mildly prolonged (up to 480 ms), and 10–15% of patients with long QT syndrome have normal baseline QTc (mainly 400–460 ms).15 Furthermore, 24‐hour ambulatory monitoring of QTc has shown that the QTc of healthy individuals varies throughout the day by an average of 76 ms and may reach 480–490 ms at night or in the early morning.16 In patients with QTc prolongation, rule out the transient causes (e.g., drugs) and perform an echo to rule out underlying cardiomyopathy (any cardiomyopathy may prolong QT). If QTc > 480–500 ms without any reversible cause, the diagnosis of LQT is virtually established. In patients with borderline QTc prolongation of 450–480 ms, further testing may need to be performed, particularly in case of syncope or family history of sudden death: a further prolongation of QTc with exercise testing (measurement performed a few minutes into recovery, as the heart rate slows down), epinephrine infusion, Valsalva, standing, or post‐PVC implies LQT1. In normal individuals, QTc is reduced with exercise or epinephrine infusion.17 In addition, the presence of macroscopic T wave alternans supports the diagnosis of LQT. Other supportive features: syncope with borderline QTc prolongation, family history of LQT or sudden death, familial screening with ECG (marked prolongation of QTc in a family member may confirm the diagnosis in the index patient). QT interval is best measured in the lead that shows a distinct T‐wave termination with the best separation of T and U waves.18 The QT interval may be artificially shortened in some leads, because an isoelectric segment may be recorded at the beginning of the QRS complex or at the end of the T wave in those leads. On the other hand, QT is often longest in leads V2–V3, but those leads show the least separation between the T wave and the normal U wave and may therefore overestimate the length of the QT interval. Leads I, aVR, and aVL do not have the normal diastolic U wave but do not always show a distinct T wave. Thus, QT interval is often best measured in leads II and V5 or V6.

T

U

U

Hypokalemia: ST depressed, T flat, U prominent

Hypocalcemia, long QT 3, and sometimes LQT 1: ST prolonged, T narrow Ischemic long QT: usually along with deep T inversion

LQT 1

LQT 2 (~similar to hypokalemia)

Figure 9.7  Typical ST–T morphologies in hypokalemia, hypocalcemia, and congenital long QT syndromes (LQT). In hypokalemia, ST segment is depressed and U wave is large while T wave is flattened. In hypocalcemia and LQT3, QT interval is prolonged as a result of ST‐segment prolongation and, as opposed to other congenital LQT or QT prolongation secondary to drugs, there is no significant widening of the T wave. In LQT1, T wave is wide and ample without ST‐segment depression, similar to Figure 9.5. In LQT2, T wave is wide and notched (double hump). LQT1 may have a morphology similar to LQT3 and is actually the most common LQT with this morphology. In all long QT cases, particularly congenital LQT, the T wave may become notched after a pause, the notch representing the early afterdepolarization (EAD) wave that triggers TdP.

Chapter 9.  Ventricular Arrhythmias  249

Table 9.1  Risk of sudden death and cardiac events in patients with long QT syndrome before the age of 40. LQT1

LQT2 or LQT3

Risk of sudden death before the age of 40

10% Same risk in men and womena

20% Highest risk if woman LQT2 or man LQT3 (~25%)

Risk of sudden death or syncope before the age of 40 Highest risk when QTc > 500 ms, regardless of LQT type (70 % risk)

30%

~50%

Data from Priori et al. (2003).19 a  Same risk in men and women in reference 19, higher risk in female in reference 20, where only adult patients were considered. QTc shortens with adult age in men (testosterone effect), and adult men are thus at lower risk of sudden death than women. Overall, the yearly risk of sudden death averages  500 ms, or LQTS 2 or 3, the latter two being less responsive to β‐blockade and having a high residual risk of cardiac events despite β‐blockade (class IIb recommendation).

V.  Indications for ICD implantation A.  Secondary prevention ICD is indicated for sustained VT secondary to any structural heart disease, regardless of EF (AVID, CIDS trials),25,26 except: • Polymorphic VT or VF occurring the first 48 hours after a large MI or STEMI. • Polymorphic VT secondary to active ischemia that can be treated with revascularization. The revascularization is urgent in this context. In addition, ICD is not indicated for patients with sustained monomorphic VT, no structural heart disease, and no specific channelopathy/ electrical disease (idiopathic monomorphic VT). VT occurring in a patient with CAD but without acute MI or with only low‐level troponin elevation qualifies for ICD regardless of EF and of the potential for complete revascularization (for the most part).27 Outside acute MI, polymorphic VT with low EF and monomorphic VT usually signal an underlying scar and are unlikely to be affected by revascularization.28

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B.  Primary prevention means ICD implantation in a patient without a history of sustained VT or sudden death It is indicated in ischemic or non‐ischemic cardiomyopathy if EF is ≤ 35% and the patient is symptomatic, NYHA functional class II or III, despite optimal medical therapy (ACC class I recommendation). The following waiting periods are required before implanting the ICD: • >40 days after acute MI. • > 3 months after revascularization for acute or chronic ischemia that did not lead to acute MI. • > 3 months of guideline‐directed medical therapy for non‐ischemic cardiomyopathy. This ensures the cardiomyopathy is not reversible before proceeding with ICD implantation (appropriateness criteria 2013).27 Note that, in ischemic cardiomyopathy with EF ≤ 30%, ICD is indicated even if the functional class is I, i.e., if the patient is asymptomatic (class I recommendation). Also, in ischemic cardiomyopathy, ICD is indicated if EF is 36–40%, NSVT is present, and VT is inducible on EP study (class I recommendation). Those recommendations are based on the MADIT II and SCD‐HeFT trials*.11,29 The absolute yearly reduction in mortality was 3.5% in MADIT II, and 2% in SCD‐HeFT. In these two trials, the survival curves of ICD therapy and placebo progressively diverged with time; however, in both trials, the curves did not begin to diverge until 9–12 months, indicating that the benefit from ICD as a primary prevention therapy is a long‐term benefit that is seen in patients healthy enough to survive several years. The yearly number needed to treat (NNT) to prevent one death is 25 in the MADIT II trial.** While the risk of sudden death is highest in the first 40 days after MI, ICD implantation is not beneficial during this time frame. One hypothesis is that, during this early period, patients at highest risk of VT/VF are patients with large infarctions and severe heart failure who may eventually succumb to pump failure even if resuscitated from VF (DINAMIT, IRIS trials).31,32 Thus, ICD simply converts arrhythmic death into pump failure death or pulseless electrical activity (PEA) in many of those patients and does not prevent the eventual mortality. Also, the untoward effects of the periprocedural stress of ICD implantation may hinder the benefit. Building on this data, an analysis of the MADIT II trial has suggested that the benefit of ICD is mainly seen in patients whose MI is older than 1.5 years; while sudden death is highest in the early MI period, pump failure death, HF events, and recurrent acute coronary events are also highest during this period, reducing the effect of ICD on the overall mortality.33 ICD is mainly effective in patients who have been stable for a prolonged duration after their MI, wherein the risk of isolated arrhythmic death from the arrhythmogenic scar becomes a relatively bigger concern. The sickest patients with the highest risk of sudden death (e.g., class IV HF, recent MI, recurrent HF hospitalizations) also have a high risk of death related to pump failure and comorbidities. Preventing sudden death may not prevent the ultimate death, but rather converts it from sudden death to pump failure death or death related to comorbidities (e.g., MI, stroke, CKD). In fact, recent data suggest that old patients (>65 years old) with ≥ 3 HF hospitalizations have a high mortality despite ICD placement, showing once more that ICD is mostly useful in stable patients, even though stable patients have a lower absolute sudden death risk.34 The highest‐risk patients in the MADIT II trial, such as those with advanced renal failure, did not benefit from ICD.30 The 3‐month wait time after revascularization is derived from MADIT II, which excluded patients who received revascularization in the prior 3 months. The CABG‐PATCH trial further supports this concept: patients with EF  30 mm). Note: Wearable, external cardioverter defibrillator (Lifevest) A Lifevest may be temporarily used in patients who are at high risk of sudden death yet do not have an ICD indication. This includes patients with a newly diagnosed non‐ischemic cardiomyopathy, in whom EF frequently improves, and patients in the first 40 days after MI. In the WEAR‐IT registry, the latter groups received a Lifevest for up to 3 months; 1.1% of the patients, mainly ischemic cardiomyopathy patients, * MADIT II: ischemic cardiomyopathy > 40 days post‐MI, LVEF ≤ 30%, NYHA class I–III, 75% of patients had their MI > 1.5 years prior to randomization (median of ~5 years). SCD‐HeFT trial: ischemic or non‐ischemic cardiomyopathy, LVEF ≤ 35%, NYHA class II or III, placebo vs. amiodarone vs. ICD. ** MADIT II identified high‐risk criteria that, combined with reduced EF, increase the likelihood of benefit from an ICD in primary prevention: AF, QRS > 120 ms, functional class II–III, mild renal failure, age > 70 years old. On the other hand, very high‐risk patients with advanced renal failure, ≥ 3 high‐risk features, or functional class IV seem less likely to benefit (U curve); ICD reduces their sudden death but does not reduce their ultimate death (pump failure, comorbidities).30

Chapter 9.  Ventricular Arrhythmias  251

had a sustained VT/VF that was prolonged, unstable, and treated by Lifevest, with all of those VT/VF patients eventually surviving to the end of follow‐up (they did not die of PEA or pump failure).36 Another registry analysis has shown that Lifevest is associated with a dramatic mortality reduction in the first 3 months after PCI and after CABG in the setting of low EF, the first 3 months representing the highest risk period of sudden death (Cleveland Clinic registry).37 Eventually, beyond the first 3 months, the risk of sudden death declines and EF improves to > 35% in 40% of patients.36 Only 40% of patients require ICD implantation at the end of 3 months.36,37 While these data support the use of Lifevest in ischemic cardiomyopathy, there are no randomized data addressing it.

VI.  Specific VTs that should be considered in the absence of obvious heart disease A.  Brugada syndrome A Brugada pattern is defined by two ECG characteristics: • ST elevation in V1–V3, typically coved and gradually descending. Less specifically, ST elevation may have a saddleback shape (Figure 9.8). • True RBBB or pseudo‐RBBB. In pseudo‐RBBB, rSR’ is seen in V1–V3 but the QRS is normal in the lateral leads. PR interval is frequently prolonged. There are three types of Brugada patterns: • Type 1: coved ST elevation ≥ 2 mm at the J point in ≥ 2 of the leads V1–V3, with T‐wave inversion • Type 2: saddleback ST elevation > 1 mm with upright or biphasic T wave • Type 3: coved ST  45%). What is the diagnosis? A. ARVD B. Brugada syndrome C. Idiopathic RVOT VT D. Myocarditis Question 4. What is the next step? A. High dose of metoprolol, or sotalol. If this fails, switch to amiodarone and consider VT ablation B. ICD C. Genetic testing for the purpose of diagnosing the disease in his children D. All of the above Question 5. A 55‐year‐old woman presents with syncope. She had diarrhea for a week and her potassium is 3 mEq/l and calcium and magnesium are low. She has the ECG shown in Figure 9.5. What is the most likely underlying diagnosis? A. Electrolyte abnormalities B. Acute ischemia C. Drug effect D. Congenital long QT syndrome 1 E. Congenital long QT syndrome 2 Question 6. Which statement is incorrect? A. VT with twisting QRS polarity is called TdP even if baseline QTc is normal B. Bradycardia may elicit polymorphic VT even in the absence of a prolonged QTc (bradycardia‐induced VT) C. LQT1 and 2 are due to a loss of function (of K channel), while LQT3 is due to a gain of function (of Na channel) D. Brugada syndrome is due to a loss of function of Na channel, while LQT3 is due to a gain of function of this same channel E. If QTc > 480–500 ms without any reversible cause, the diagnosis of long QT syndrome is likely F. In patients with borderline QTc 450–480 ms, further testing may need to be performed (e.g., effect of exercise or epinephrine on QTc) G. In patients with QTc 430–450 ms who have syncope or a family history of sudden death, further testing may need to be performed Question 7. A 30‐year‐old man who grew up in Mexico presents with syncope during basketball exercise. ECG and echo are normal. Stress testing reveals a monomorphic VT which appears to be originating from the LV inferolateral wall (QRS upright in V1, negative in the inferior leads and lateral leads I-aVL). Coronary arteries are normal on angiography. What is the next step? A. Ablation for idiopathic LV VT B. Cardiac MRI

Chapter 9.  Ventricular Arrhythmias  255

Question 8. Cardiac MRI is performed in the patient of Question 7. It shows a large inferolateral scar. In addition, the patient develops a complete RBBB on his ECG a few months later. What is the diagnosis? A. Sarcoidosis B. Chagas disease C. ARVD D. Giant‐cell myocarditis E. Some genetic cardiomyopathies (mutation of desmosomal genes) F. A or B Question 9. A patient experiences anterior MI and undergoes LAD PCI. His post‐MI LVEF is 25%. Which of the following is true? A. His highest risk of sudden death is in the first 40 days after MI. ICD is indicated in the first 40 days B. His highest risk of sudden death is in the first 40 days after MI. But ICD implantation is not beneficial in the first 40 days. ICD is indicated at ≥40 days. Lifevest may be used in the first 40 days C. His highest risk of sudden death is in the first year (risk equally spread throughout the year). ICD is indicated at ≥40 days Question 10. A patient has LVEF 30% and is found to have severe LAD and RCA disease for which he undergoes PCI. Is the following statement true or false? The first 3 months after PCI constitute the highest‐risk period of sudden death, yet ICD is only indicated beyond those 3 months (if EF remains ≤ 35%). Question 11. A 40‐year‐old man has had daily palpitations described as “skipped beats” for 4 months, mostly at rest but also during emotional stress. He never had sustained palpitations or syncope. He is active and cycles 30 minutes every day without cardiac symptoms. ECGs capture frequent PVCs, of the same morphology (Figure 9.9). His baseline sinus rate is ~65 bpm. Echo is normal. What is the first‐line therapy? A. Metoprolol B. Flecainide C. Verapamil D. Catheter ablation

I V1 II III

V6

Figure 9.9 

Answer 1. B. In patients with unsuspected cardiac disease, palpitations frequently correspond to non‐arrhythmic awareness of one’s heart beat (anxiety, stress) or to benign premature complexes. However, this patient has two worrisome elements in his history: (i) palpitations are sustained and associated with true near‐syncope (in the absence of a myriad of functional complaints), and (ii) a fast pulse is documented. The ECG has borderline findings that, in an asymptomatic patient, may be considered normal (QRS being  10%, the risk of HF is ~35%. In those without or with minimal PVCs, the risk is ~20%.

Prevalence of tachycardia‐mediated cardimyopathy in patients with a high PVC burden Baman TS, Lange DC, Ilg KJ, et al. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm 2010; 7: 865–9. Prevalence of reduced EF is ~33%, more so if PVC burden > 10%.

The prognostic value of PACs Beneci Z, Intzilakis T, Nielsen OW, et al. Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke. Circulation 2010; 121: 1904–11. In patients 55–75 years old, frequent PACs (>30/hour) are associated with a threefold increase in stroke risk.

10  Atrial Fibrillation

I. Predisposing factors  258 II. Types of AF  259 III. General therapy of AF  259 IV. Management of a patient who acutely presents with symptomatic AF  261 V. Peri‐cardioversion management and long‐term management after the acute presentation  262 VI. Decisions about long‐term anticoagulation, role of clopidogrel, role of triple therapy  262 VII. Special situation: atrial fibrillation and heart failure  264 VIII. Special situation: atrial fibrillation with borderline blood pressure  265 Appendix 1. Antiarrhythmic drug therapy (indications and examples)  265 Appendix 2. Catheter ablation of atrial fibrillation, surgical ablation, AV nodal ablation  267 Appendix 3. INR follow‐up in patients receiving warfarin; new anticoagulants  268 Appendix 4. Bridging anticoagulation in patients undergoing procedures and receiving warfarin  270 Appendix 5. Management of elevated INR values  270 Appendix 6. A common special situation: AF and symptomatic pauses (sinus or AF pauses) or bradycardia  271 Appendix 7. DC cardioversion in patients with a slow ventricular response  271 Appendix 8. AF occurring post‐cardiac surgery and AF related to acute transient triggers  271 Appendix 9. Brief asymptomatic runs of AF seen on telemetry or device interrogation  272 Questions and answers  272

Atrial fibrillation (AF) is the most common sustained arrhythmia that requires treatment, with an estimated prevalence in the United States of 2.3 million in 2001.1 Its prevalence increases with age, hypertension, and heart failure: 3–4% of patients aged 65–75 have AF and 10% of patients aged 80 years or older have AF; 4% of patients with heart failure (HF) functional class I and 50% of patients with functional class IV have AF.2 On the other hand, HF is present in 34% of AF patients.3 AF is typically initiated by one or more premature atrial complexes, often originating around the pulmonary veins, or by atrial tachycardia or atrial flutter.

I.  Predisposing factors (see Table 10.1) Hypertension is the most common factor associated with AF on a population basis; coronary artery disease (CAD) and HF are the most common associated features in hospital series.4 Between 30% and 45% of paroxysmal AF cases, and 20–25% of persistent AF cases, are “lone AF,” i.e., AF that occurs in patients younger than 65 years without underlying heart or lung disease and without hypertension.5 Even in the case of lone AF, there are structural atrial abnormalities and some degree of atrial dilatation and dysfunction, as well as an increased prevalence of high‐normal blood pressure (i.e., systolic pressure 130–140 mmHg), that are contributive to AF.6,7 As they age, however, patients with lone AF may develop hypertension or heart disease that contributes to the progression of AF. The most frequent histopathological feature of AF is atrial fibrosis, which may precede the onset of AF. Atrial dilatation is present in over 50% of patients with AF, with a mean left atrial diameter of ~40 ± 8 mm in the Canadian Registry of non‐valvular AF; atrial dilatation is less prevalent in patients with non‐recurrent AF and lone AF.7 Atrial dilatation may be not only a cause but also a consequence of AF, as evidenced by the fact that the left atrial size further increases with time, over months to years, in patients with persistent AF.8,9 On the other hand, left atrial size decreases after AF cardioversion.10,11. Atrial electrical remodeling, i.e., progressive shortening of the effective refractory period, further explains how prolonged AF makes restoring and maintaining sinus rhythm less likely (“AF begets AF”).2 AF requires a trigger that initiates the arrhythmia and a substrate that sustains it. The most common triggers are premature atrial beats originating from the pulmonary veins. Atrial stretch and atrial fibrosis shorten the atrial effective refractory period and disrupt the electrical interconnections between the muscle bundles, causing local conduction heterogeneity. This allows ectopic activity originating from the

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

258

Chapter 10.  Atrial Fibrillation  259

Table 10.1  Factors predisposing to atrial fibrillation. • Systemic arterial hypertension • Coronary artery disease • Heart failure • Any acute or chronic structural heart disease • Obesity and sleep apneaa • Atrial inflammation: pericarditis, myocarditis • Metabolic disorders: alcohol, hyperthyroidism, hypokalemia • Pulmonary diseases: COPD, pulmonary embolism • Postoperative state (cardiac, pulmonary, or esophageal surgeries)  Sleep apnea is seen in 18% of patients with AF. CPAP therapy reduces the progression of AF.

a

pulmonary veins or elsewhere to get conducted and initiate multiple microreentry cycles (atrial wavelets). Those microreentrant cycles ­collide like “tornadoes” and generate new tornadoes that propagate throughout the atria. The autonomic system may contribute to the initiation of AF, i.e., an increase in the sympathetic or parasympathetic drive may trigger ectopy in the pulmonary veins and AF.

II.  Types of AF There are three types of AF: paroxysmal, persistent, and permanent:2,12 • Paroxysmal AF is defined as AF that terminates spontaneously in less than 7 days (often 24–48 hours). AF that is terminated with cardioversion at ≤7 days of onset is also considered paroxysmal AF in the most recent classification. • Persistent AF is AF that persists over 7 days or requires cardioversion at >7 days (or unknown duration). Long‐standing persistent AF is continuous AF that persists greater than 12 months, yet the adoption of a rhythm‐control strategy is still planned. • AF is considered permanent or chronic in cases of failure of cardioversion attempts, early recurrences after cardioversion, or decision not to cardiovert. A decision may be made not to cardiovert a patient who is asymptomatic after rate control and has a high likelihood of recurrence (e.g., longstanding AF of over a year or severe left atrial enlargement >5 cm). Paroxysmal and persistent AF may be recurrent. Over time, patients may alternate between paroxysmal and persistent AF. For example, in a particular patient, most of the AF episodes may be self‐terminating, while some of them may require cardioversion. While a paroxysmal AF may recur as paroxysmal AF for years, AF is generally progressive over time, with a rate of progression to persistent or permanent AF of ~15% within the first year. A newly diagnosed AF or “first‐detected AF” could fall into either one of these categories. While the first‐detected AF is often a symptomatic paroxysmal or recently persistent AF, 21% of patients in whom AF is newly diagnosed are asymptomatic, and AF is diagnosed by routine pulse exam during an office visit.13 In the latter patients, AF is likely several weeks, months, or years old. Thus, a newly diagnosed AF does not imply a new AF. The term “valvular AF” is used to describe AF associated with mitral stenosis, prosthetic heart valve (mechanical or bioprosthetic valve), or mitral valve repair, and portends a higher stroke risk than non‐valvular AF.

III.  General therapy of AF There are three main consequences of AF: (i) thrombus formation in the left atrial appendage (LAA) followed by thrombus embolization, (ii) fast and irregular heart rate leading to compromised ventricular filling, and (iii) loss of the atrial kick that contributes to up to 40% of the cardiac output in stable HF patients. Also, a rapid ventricular response of 120 beats per minute or more that persists for over 2 weeks can cause tachycardia‐mediated cardiomyopathy and HF.14 A. Anticoagulation Administer an anticoagulant regardless of whether AF is paroxysmal or permanent. AF often recurs, and asymptomatic recurrences are 12 times more common than symptomatic recurrences.15 In the AFFIRM study, the risk of ischemic stroke was strongly related to absent or suboptimal anticoagulation even in the rhythm‐control strategy.16 Drug therapy makes AF recurrences shorter and slower, hence less symptomatic; the stroke risk, however, is unchanged. B.  Rate control Three classes of drugs may be used: β‐blockers, non‐dihydropyridine‐type calcium channel blockers (CCBs), i.e., diltiazem or verapamil, and digoxin. A β‐blocker or a CCB is used as a first‐line agent. β‐blockers are the most effective rate‐controlling agents chronically, are effective as monotherapy in up to 70% of patients with AF,17 and are first‐line therapy in compensated systolic HF. They also have an antiarrhythmic effect and may convert adrenergically mediated AF into sinus rhythm. Digoxin is less effective as monotherapy and is poorly effective for rate control during exertion. Digoxin is only used as monotherapy in decompensated systolic HF, when the acute initiation of β‐blockers is not possible. Digoxin is effective in combination therapy: the combinations digoxin–β‐blocker and digoxin–CCB are at least as effective and safe as the combination β‐blocker–CCB.18 If the rate is inadequately controlled with the maximum tolerated dose of a β‐blocker, digoxin or diltiazem is added as a second‐line agent; diltiazem is not an appropriate option in systolic HF. The combination of β‐blocker and verapamil has a strong negative inotropic effect and should be avoided in all patients. Triple combination is required in ~15–20% of the cases, but increases the risk of excessive pauses. Pharmacological therapy can achieve rate control in >80% of patients.17 The remaining patients cannot be rate‐controlled with

260  Part 5. Arrhythmias and Electrophysiology

drugs and require rhythm control, provided that long‐term success can be expected, or failing that, atrioventricular nodal ablation with ventricular pacing. Patients with AF, including AF with fast ventricular rates, may also have periods of sinus bradycardia or AF‐related pauses that limit the use of rate‐controlling agents: these patients may require rhythm control or pacemaker placement. In symptomatic patients, the goal of therapy is to reduce the heart rate to 150 ms). RBBB, per se, is associated with a higher risk of mortality than LBBB in HF registries and in the CARE‐HF study,

336  Part 5.  Arrhythmias and Electrophysiology

partly because the prognosis cannot be improved with CRT.25,27 CRT is still reasonable in non‐LBBB with QRS >150 ms and functional class III/IV in light of the pathophysiology described above and some clinical evidence (class IIa recommendation).28 CRT is less reasonable for non‐LBBB pattern with QRS 130–150 ms (class IIb recommendation). Echocardiographic assessment of left‐sided activation delays and dyssynchrony may help fine‐tune the CRT indication in these patients. (c)  Atrial fibrillation i.  CRT for HF purposes. CRT is recommended in AF patients with HF, a low EF, and a wide QRS, similarly to patients in sinus rhythm (class IIa), as long as the rate is controlled enough to allow 100% ventricular pacing. ii.  CRT for AF purposes. If AV nodal ablation and pacing are performed to control the AF rate in a patient with EF ≤35%, CRT is preferred to RV pacing as it prevents pacing‐induced dyssynchrony and is given a class IIa recommendation, regardless of the functional class. One may, however, choose RV pacing early on, followed by CRT at a later time if EF does not simply improve with AV nodal ablation. (d)  Paced ventricular rhythm Similarly to LBBB, RV pacing induces inter‐ and intraventricular dyssynchrony, which may worsen LVEF and increase LV volume. CRT prevents this deleterious negative remodeling and is associated with better symptom control in patients with normal or low EF, as has been shown in patients with permanent AF requiring AV nodal ablation.29,30 Therefore, CRT is recommended in patients with EF ≤35% requiring ventricular pacing >40% of the time for AV block, regardless of the functional class (class IIa recommendation); this also applies to AF patients requiring AV nodal ablation. While the guidelines use a 35% EF cutoff, one randomized study (BLOCK HF) addressed patients with EF ≤50% and HF functional class I–III requiring ventricular pacing for AV block, and showed that CRT reduces HF hospitalization and LV remodeling in comparison to RV pacing.31 In fact, even in patients with normal EF, RV pacing is associated with a ~7% reduction in EF vs. CRT; ~9% of patients with normal EF have EF reduction to 50% of the myocardium are unlikely to benefit).39,41 e.  LV lead positioning outside the area of latest activation on echocardiography.39 The echocardiographic assessment of the site of latest activation before CRT implantation may allow targeted lead placement and significant improvement of LV response and clinical outcomes.42 f.  LV lead positioned in the anterior or apical position rather than the lateral position. Lead position should be analyzed in a short‐axis plane (anterior vs. posterolateral) and in a longitudinal plane (basal vs. apical). In most patients, the posterolateral basal wall is the site of latest activation; however, lateral LV lead position should be avoided in patients with a lateral scar. In the longitudinal plane, the basal wall is the site of latest activation (vs. the apex) (Figure 14.17). While one study suggests that the anterior wall is the site of latest activation in only ~10–25% of patients,43 another study shows that an anterior basal position is acceptable, the apical LV position being the one to avoid.44 This is particularly the case because the patient is also simultaneously paced from the RV apex, further making the LV base a late site of activation. Unfortunately, patients with ischemic cardiomyopathy are less likely to have a left marginal vein for lateral LV lead implantation. Besides, lead placement is limited by constraints of left phrenic nerve pacing, lead stability, and pacing threshold. In the absence of randomized data, if an optimal lateral vein is not accessible for LV pacing or if the lead is not stable in this position, it would be acceptable to implant the LV lead at a suboptimal site. If the patient does not respond adequately, a surgical approach may be performed in a subsequent procedure.43 A lateral CXR displays the location of the LV lead. In general, in responders, an immediate hemodynamic improvement is seen with CRT: improvement of LV filling, reduction of LA pressure, and improvement of LV dP/dt, MR, and cardiac output. Reverse remodeling, LVEF improvement, and further MR reduction are progressively seen over 3–12 months.

Chapter 14.  Permanent Pacemaker and ICD  337

Conversely, up to 25% of patients are super‐responders, i.e., experience 15–20% improvement of LVEF (EF almost normalizes) in 6–12 months. A very wide LBBB, non‐ischemic cardiomyopathy, female sex, and LA volume 150 ms is CARE‐HF,25 in which patients with QRS 140 ms: this is the delay between the onset of QRS and the onset of aortic flow (on the three‐ or five‐ chamber view) • Interventricular delay of >40 ms: this is the difference between the left and right pre‐ejection delay • Septal‐to‐posterior wall motion delay >130 ms (on M‐mode of parasternal views) In addition, myocardial tissue Doppler or tissue speckle‐tracking may be used in the short‐axis and apical views to see the site of latest activation, and to see the difference in peak tissue velocity between the septal and lateral walls. While the PROSPECT trial showed a low predictive yield of individual dyssynchrony parameters (in patients with QRS mostly >140 ms), one study suggested that dyssynchrony parameters are, in fact, useful in predicting which patients with QRS of 130–150 ms benefit from CRT.47 F.  Importance of the change of QRS width after CRT Several studies have shown that a reduction in QRS width after CRT implantation is associated with a positive response to CRT. On average, QRS shortens by 20–40 ms with CRT. This QRS shortening is mostly seen in patients with a baseline QRS >150 ms, in whom the QRS reduction is largest. Typically, non‐responders do not exhibit any reduction of QRS or experience QRS widening.48,49

A

E

A

E

A

E

Diastolic MR Systole with systolic MR

Systole with systolic MR

P

P Long PR with E-A fusion, short filling time in diastole, and overly reduced E wave

P QRS

QRS

Short PR with A truncation, and overly increased E wave

Figure 14.18  CRT: echocardiographic AV synchronization

QRS Appropriate AV delay with clear separation of E and A waves. A wave ends 40 ms after QRS onset (~ at peak of R). E/A reversal should typically be seen

338  Part 5.  Arrhythmias and Electrophysiology

G.  Arrhythmic death in patients with ICD While ICD reduces arrhythmic death, patients with advanced HF eventually die of pump failure or recurrent MI, explaining how ICD may not affect the overall mortality in the early post‐MI setting or in class IV HF (reduction of arrhythmic death with a relative increase in non‐ arrhythmic death). Moreover, while ICD drastically reduces arrhythmic death, it does not fully eliminate it for the following reasons (in order of frequency): (1) in patients with severe or decompensated HF, the sudden death may be pulseless electrical activity (PEA) rather than VF; also, VF may evolve into PEA after defibrillation, this being the most common cause of sudden death in patients with ICD; (2) failure to terminate VF with multiple shocks (ICD delivers a shock for a certain number of times, usually 6–8, then times out); (3) incessantly recurrent VT/VF, i.e., VT/VF that recurs immediately after successful therapy, over and over; (4) the ICD may undersense the VF fibrillatory waves, because of a low sensitivity setting or because of lead dysfunction.50 Reasons (2) and (4) may justify defibrillation testing at the time of ICD implant, during which VF is induced, appropriate sensing ensured, and successful internal defibrillation achieved (with up to 35 J). An ineffective ICD shock may justify changing the lead position to create a different, more effective, shock vector; or changing the shock vector between the can and the coils. However, this defibrillation testing has not been shown to improve outcomes in SAFE-ICD study, and thus may not be necessary in the primary prevention setting, when experienced operators appropriately place ICD leads.

QUESTIONS AND ANSWERS: Cases of PM troubleshooting On a pacemaker ECG, always assess the type of pacemaker by looking at A and V spontaneous activity, A and V pacing, and the A–V relationship; then assess for capture and sensing of the A and V chambers (Figures 14.19–14.34). Occasionally, the ECG or telemetry software places a pacer spike whenever it senses a high‐frequency signal, such as artifact, AF wave, or QRS notching, even in the absence of pacing, which creates a false impression of PM malfunction.

P

V

P

V

P

VP

V

P V

PV

P

V

P

V

P

V

Figure 14.19  Regular V pacing without any spontaneous ventricular activity. Regular P waves are seen but are dissociated from the paced QRS complexes and not tracked by the PM. Thus, there is complete AV block but the PM is functioning in a VVI mode, in which it just senses and paces the ventricle and ignores P waves. Assess capture and sensing. V capture is appropriate. V undersensing is assessed by the reaction of the PM to a spontaneous complex. Since there is no spontaneous QRS complex, it is not possible to comment on ventricular undersensing. There is no ventricular oversensing (which would lead to underpacing). If the PM is programmed in a DDD mode but is behaving as VVI, the differential diagnosis would include: phantom reprogramming; end‐of‐life changes with mode conversion to VVI; atrial oversensing, making the PM “think” there is a fast atrial arrhythmia and switch to VVI mode; or atrial undersensing and subsequent lack of atrial tracking (lead problem). However, in case of atrial undersensing, atrial overpacing should be seen, which is not the case here.

Figure 14.20  DDD pacemaker with atrial pacing and AV sequential pacing. Intermittently, the ventricle is paced at a short interval (fast). As this is AV sequential pacing, there must be a premature P hidden in this short interval that gets tracked by the pacemaker, rather than inappropriate fast pacing. Atrial bigeminy is, in fact, present and evidenced by the alternation of two different T morphologies (P hidden in T) (arrows indicate the premature P waves in leads V1, V2, V4, V5). The PAC falls on the T wave after PVARP ends, and so gets appropriately tracked by the ventricular channel at an interval close to the upper rate limit. PVARP is an interval after QRS during which P wave is not tracked. Is this RV or BiV PM? QRS is positive in V1; however, QRS is also positive in lead I with no Q wave. Thus, this is RV pacing. In ~10% of RV pacing, QRS may be positive in lead V1; however, QRS should always become negative by lead V3. Also, moving the V1 electrode one intercostal space lower should make QRS negative. Summary: Atrial bigeminy, normally functioning AV sequential pacemaker.

Chapter 14.  Permanent Pacemaker and ICD  339

A spike

V spike within QRS

Intrinsic QRSs occurring after atrial spike, at an interval shorter than AV delay

Intrinsic QRSs occuring before atrial pacing, at intervals shorter than AEI

Figure 14.21  Atrial and ventricular pacing spikes are seen. The underlying rhythm is AF and is undersensed by the atrial lead, leading to inappropriate atrial pacing (the pacemaker should mode switch to VVI). The PM paces the ventricle at an AV delay that is appropriately timed to the atrial spike. Intrinsic QRS complexes are seen. They occur after an atrial spike at an interval shorter than the pacing AV delay; or before atrial pacing occurs, at an interval shorter than the atrial escape interval. In the latter case, the atria do not get paced because the intrinsic QRS resets the atrial escape interval (AEI). One pseudofusion complex is seen, wherein a V spike falls within the intrinsic QRS. In this case, the intrinsic QRS falls too close to the atrial spike, in the ventricular safety period, which makes the pacemaker immediately deliver a V spike at an interval shorter than the regular AV delay. Final diagnosis: AF with atrial undersensing, normal AV sequential pacing (V pacing normally follows the abnormal atrial spike), pseudofusion complex with ventricular safety pacing.

1

2

3

Figure 14.22  Ventricular pacing occurs at irregular intervals and one atrial pacing spike is seen (arrow). This is most likely a DDD pacemaker with AV sequential pacing. The pacemaker is tracking an underlying irregular atrial rate. • The baseline rhythm appears to be AF. The pacemaker should sense the very fast atrial activity and mode‐switch to a non‐tracking mode (VVI) and pace at a regular rate. In this case, it seems that there is atrial undersensing, so that the pacemaker senses many of the atrial waves and tracks them irregularly at a fast rate (close to the upper rate interval of the pacemaker); however, it does not sense enough of these waves to mode‐switch. The non‐paced QRS complexes (sequence 3) are QRS complexes that are spontaneously conducted at the fast AF rate, inhibiting any V pacing. • On one occasion, AF is not sensed for a longer time, which triggers an atrial pacing spike (arrows) at the atrial escape interval. However, the atrium is not captured because of AF (this is non‐capture related to undersensing). • Is it BiV or RV pacing? Three different QRS morphologies are seen. The morphology of beats 4–7 (2) fits with RV pacing. The first 3 beats (1) are not preceded by any spike, but may very well represent BiV pacing (QRS positive in V1). Beats 8–10 (3) are different, fast, and may represent the native QRS complexes (LBBB morphology). • The alternation between RV and BiV pacing morphologies means that LV capture is intermittently lost. Summary: AV sequential BiV pacemaker with underlying AF rhythm. Atrial undersensing and lack of mode switch, with pacemaker tracking AF activity. Intermittent LV non‐capture.

340  Part 5.  Arrhythmias and Electrophysiology

1

2

Figure 14.23  Ventricular pacing spikes are seen. They track sinus P waves at a short PR interval. At times, small atrial spikes are seen in lead II. This is a dual‐chamber PM, likely DDD mode. Three issues are seen: 1. There is a long (1) and a short (2) pause (AV block) during which the ventricle is not paced, implying ventricular oversensing. P waves are not tracked during these pauses. Ventricular oversensing explains the lack of tracking of sinus P waves, rather than atrial undersensing; atrial undersensing affects AV synchrony but does not lead to ventricular pauses. 2. Ventricular undersensing is also present at times, as the A and V are paced too soon after an intrinsic QRS, implying that the intrinsic QRS is not sensed (arrowheads point to A pacing after the intrinsic QRS). 3. The paced QRS morphology is variable. The baseline paced morphology is positive in V1–V2, and negative (Q) in lead I, which means that the baseline pacing is BiV pacing. The very short PR interval supports this. One QRS is wider and is more positive in V1–V3 than the BiV‐paced QRS, implying LV pacing and thus an intermittent loss of RV capture (arrow). Conclusion: V oversensing and undersensing, intermittent loss of RV capture. The patient may have fracture of the RV lead, or loose connector set screws.

Sinus P

Retrograde P

PVC Atrial EGM Ventricular EGM VT Marker channel Figure 14.24  Intracardiac electrograms (EGMs) of VT. The atrial and ventricular EGMs are intracardiac ECGs capturing intracardiac activity; the atrial EGM captures the atrial activity A, while the ventricular EGM captures the ventricular activity V. The marker channel indicates how the PM interprets or misinterprets these activities. The tachycardia starts with a PVC falling over the sinus P wave, and is characterized by a number of V deflections = number of A deflections. The V activity drives the A activity; in fact, the tachycardia starts with a V, then A keeps tracking V. Whenever there is a change in the tachycardia interval, the V–V interval changes first, the A–A interval changes afterward (arrows). This indicates that the tachycardia is VT with 1:1 VA conduction.

During pacemaker interrogation of arrhythmias, two types of tracing are available: (1) intracardiac electrograms (EGMs), which record the actual signals from each cardiac chamber (A and V), and (2) the marker representation, which indicates how the pacemaker sees and interprets these signals; AS and VS mean sensed intrinsic atrial and ventricular activities, while AP and VP mean paced atrial and ventricular activities. The pacemaker may interpret a signal as VS on the marker channel, while it is in fact T‐wave oversensing, false signal, or far‐field sensing of an atrial spike. It calls a pacing attempt VP even if the pacemaker does not eventually capture the ventricle. Looking at the EGMs allows one to understand what the issue is, while looking at the marker channel allows one to see how the pacemaker is interpreting or misinterpreting signals.

Chapter 14.  Permanent Pacemaker and ICD  341

Surface ECG and marker channel Atrial EGM Ventricular EGM Premature A starts the tachycardia

Tachycardia

PAC

Figure 14.25  Electrograms of a tachycardia that starts with a premature A wave and ends with a PAC. • SVT vs. VT: a tachycardia that starts with a PAC is often SVT, but a PAC may initiate VT as well. The tachycardia breaks with a PAC that does not conduct to the ventricles, implying SVT. The morphology of the V electrogram does not change after the onset of the tachycardia, also indicating SVT. • Type of SVT: this is a short run of AVNRT, AVRT, or reentrant AT that breaks with a PAC. In contrast, automatic AT does not break with a PAC and is usually initiated by a PAC that has a morphology similar to subsequent A waves (not the case here). The surface ECG may be a true surface ECG obtained with surface electrodes during PM interrogation; in patients with ICD, the vector between the SVC and RV coils may be used as an continuous internal ECG lead.

Conducted sinus Ps

PVCs with retrograde Ps

Atrial EGM Ventricular EGM

Marker channel Figure 14.26  Tachycardia with number of V waves = number of A waves→ could be SVT or VT. It is unclear whether A drives V or V drives A, but since the tachycardia starts with a PVC it is more likely VT (it could also be AVRT, or less likely AVNRT or reentrant AT). Moreover, the morphology of the ventricular activity is different from the sinus‐originating ventricular activity on the ventricular EGM, and similar to the second PVC, which suggests VT.

A A A A A AA A A Atrial EGM Ventricular EGM V

V

V

V

V

Marker channel

Figure 14.27  The analysis of the atrial and ventricular EGMs reveals more atrial waves than ventricular waves, implying SVT. Furthermore, A activity is irregular, which implies AF. The PM senses that the ventricular rate is in the VT zone (>150 bpm), and the marker channel calls the ventricular activity “VT” rather than “VS.” Typically, to avoid unnecessary shocks, a higher rate is used for VT zone (>180–200 bpm), and SVT–VT algorithm is used.

Atrial EGM Ventricular EGM

Marker channel Figure 14.28  The patient presents with multiple shocks. The marker channel shows that the PM calls the ventricular activity “FS” (VF zone). On analysis of the ventricular EGM, the ventricular activity is of large amplitude (which is different from VF) and “noisy,” with a V–V interval that is non‐physiologic (some V–V intervals are 100 ms) or a drop of V wave with fast atrial pacing indicates infra‐Hisian block. Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

346

R T

P S V A

H

Figure 15.1  Normal His recording.

P

ECG

P

QRS

QRS AH

A

HV

RA

His

A

H V

RV A CS

V

Figure 15.2  Example of a typical A, V, His, and CS recording. AH and HV intervals are shown. When looking at an intracardiac tracing, always start by identifying the V wave, which corresponds to the electrocardiographic QRS. The remaining intracardiac waves are mainly A waves. H wave is a small wave that is only seen on the His recording and may be overlooked. The CS recording mainly shows A waves (LA A waves), but low‐amplitude, far‐field V waves may also be seen.

R T

P S V A

A

H

H

No V Infra-Hisian block (Mobitz 2) PM indicated

V A

H

A

No H or V AV nodal block (Mobitz 1) no immediate indication for PM Figure 15.3  Types of AV block.

348  Part 5.  Arrhythmias and Electrophysiology

Extrastimulus technique. Progressively more premature atrial extrastimuli are inserted until A fails to conduct to His. The earliest A–A interval at which A stops leading to H complex is the AV nodal effective refractory period. On the other hand, the earliest interval at which the premature extrastimulus does not lead to A complex is the atrial effective refractory period. Beside having slower conduction than the atrial and ventricular tissues, the AV node normally has a longer refractory period. An AV node effective refractory period >425 ms is abnormal.

III.  Sinus node assessment During fast overdrive atrial pacing (~30 seconds), and similarly to atrial fibrillation, the sinus node activity is inhibited. Upon cessation of atrial pacing, the sinus node needs time to recover its electrical activity. The duration of the pause between the last paced A complex and the recovery A complex is called the sinus node recovery time (SNRT). A diseased sinus node has a prolonged SNRT. The corrected SNRT is equal to SNRT minus basic cycle length, basic cycle length being the A–A interval prior to atrial pacing (e.g., SNRT 1100 ms, basic cycle length 700 ms, corrected SNRT =400 ms). The corrected SNRT is normally 100 ms) is highly specific for a serious conduction disorder and usually mandates pacemaker placement regardless of symptoms.

IV.  Ventricular vs. supraventricular tachycardia AV dissociation is easily characterized on EGM. Identify V deflections, which line up with QRS complexes on the ECG; then identify the other deflections, seen on the atrial and His channels, which correspond to the A deflections. VT is diagnosed if V deflections are more numerous than A deflections. SVT is diagnosed if A deflections are more numerous than V deflections. If A deflections are equal in number to V deflections, the tachycardia could be SVT or VT with 1:1 VA conduction. Assess the onset of the tachycardia (V or A) and which interval changes first (A–A or V–V). In VT, the tachycardia starts with a V deflection and the A–A interval’s length tracks the V–V interval’s length, meaning a change in A–A interval follows, rather than precedes, a similar change in V–V interval. In VT, V deflections are typically more numerous than A deflections and are dissociated from them. However, V and A could be associated in a 1:1 fashion (1:1 VA conduction), or a 2:1 or 3:1 fashion (2:1 or 3:1 VA conduction). In VT with AV dissociation, His spikes are typically absent. In VT with AV association, His spikes may result from retrograde VA conduction.

V.  Dual AV nodal pathways Normally, after a premature atrial extrastimulus, the AV nodal conduction slows and AH interval increases (relative refractory period). With progressively more premature atrial extrastimuli, AH interval progressively increases, and at some point H and V may drop. If, however, with a small decrement of A–A interval (e.g., 340 ms to 330 ms), AH interval disproportionately increases, by >50 ms (as opposed to a slight increase or a block), it is implied that the AV node has a fast and a slow pathway. While the fast pathway conducts the normal, sinus‐initiated beats and the atrial extrastimuli, a very early extrastimulus falls in the absolute refractory period of the fast pathway and fails to conduct through it. Subsequently, this extrastimulus conducts over the slow pathway, leading to an AH jump (Figure 15.4). The slow pathway has a slower conduction but a shorter refractory period, hence the slow pathway conducts when the fast pathway is blocked. This may initiate AVNRT, if the fast pathway recovers quickly enough to allow retrograde conduction (slow–fast reentry).

ECG His

S1 A

V

S2 A

V

V

S1–S2 = 330 msec

AH = 170 msec

ECG His

S1 A

V

S2 A

V

S1–S2 = 320 msec

AH = 250 msec

Figure 15.4  Arrows point to QRS complexes on the ECG, which are the starting point in intracardiac electrogram interpretation. S1 is a baseline pacing train, S2 is a premature pacing stimulus. A slightly earlier pacing stimulus (10 ms earlier) leads to a large jump in AH conduction interval >50 ms, indicative of the presence of dual AV nodal pathways. The latter conduction occurs over the slower pathway. This phenomenon is called AH jump after progressively premature atrial extrastimuli.

Chapter 15.  Basic Electrophysiologic Study  349

VI. AVNRT During AVNRT, A conducts down the AV node’s slow pathway, which then conducts to V and A quickly and almost simultaneously (Figures 15.5, 15.6). The conduction to A occurs retrogradely through the fast pathway. A tachycardia with almost simultaneous V and A deflections is usually AVNRT.

VII.  Accessory pathway, orthodromic AVRT, antidromic AVRT An accessory pathway connects the A and the V. The accessory pathway may conduct from the atrium all the way to the ventricle at baseline (manifest pathway = WPW pattern), or may only partially conduct and not reach the ventricle (concealed pathway). The accessory pathway has a faster conduction than the AV node but a longer refractory period. Thus, a PAC is more likely to conduct through the AV node than the accessory pathway. By the time the electrical activity reaches the ventricle, the accessory pathway may have recovered, and thus fast retrograde conduction may occur and lead to orthodromic AVRT (= AVRT with retrograde conduction through the accessory pathway). In this case, A conducts to V through His, then V rapidly conducts to A retrogradely through the fast‐conducting accessory pathway (Figure 15.7). In contrast to AVNRT, A and V activities are not as close. Antidromic AVRT is a reentrant AV tachycardia which conducts antegradely over the accessory pathway. It is unusual for a PAC to initiate antidromic AVRT, as it blocks through the accessory pathway before it blocks through the AV node (the accessory pathway has a longer refractory period than the AV node). Antidromic AVRT may occur in rare cases where the accessory pathway has a shorter refractory period than the AV node. In this case, A conducts to V through the accessory pathway, then V conducts back to A through His (Figure 15.7). A CS catheter helps further differentiate AVNRT from AVRT and localizes the site of the accessory pathway (Figure 15.8). Analyze the His, CS, and RA channels and see the site of earliest A activity during the tachycardia: in AVNRT the earliest A activity is in His, followed by the proximal part of the CS catheter, whereas in AVRT the earliest A activity is in the distal CS catheter (left‐sided pathway), proximal CS catheter (posteroseptal pathway), or the RA (right‐sided pathway). The site of earliest A activity in the CS (proximal, mid, or distal) allows the localization of the accessory pathway site.

Fast

A

AV node

Slow

V

Slow AV nodal pathway

VA

VA

VA

His recording

Figure 15.5  AVNRT. V and A almost coincide, with a VA interval 10 beats as a positive study. The use of polymorphic VT or

Chapter 15.  Basic Electrophysiologic Study  353

His A 10 9 8 7 Halo 6 5 4 3 2 1

CS

V

A

10

A

A

V

A

A

A

1–2

V

V

ABL

Figure 15.13  Atrial flutter mapping. Note the atrial activation along the halo catheter (10 to 1) with the zigzag shape (solid arrows). Electrodes 1, 2 are the distal tip electrodes, whereas electrodes 9, 10 are the proximal electrodes (see Figure 15.12). Note how the activation spreads in a counterclockwise fashion from 10 to 1, then reaches the coronary sinus and His bundle and reaches back to electrode 10. The RA is constantly activated throughout the recording, with no quiescent isoelectric phase. As always, identify complexes on all channels by correlating with the QRS on ECG. On any channel, V is the complex that aligns with QRS (dashed arrows); the rest are A complexes.

II V1

Halo catheter

A

His 9 8

9 His

1

8 2

7 6

3 5

cs

7 6 5 4 3 2

A

V

A

V

A

A

A

A

A

A

A

A

A

A

A

A A

A A

A

A

A

A A A

A

A A

A

1 Figure 15.14  Another example of atrial flutter mapping across the right atrial halo catheter (electrodes 1–9). The fluoroscopic view is an LAO view of the RA, which looks at the plane of the halo catheter and splays it (as opposed to RAO view, which is aligned with the halo catheter plane, Figure 15.10). Note how the atrial activity spreads from 9 to 1 and His in a counterclockwise fashion. Courtesy of Paul Lelorier, MD.

non‐sustained VT as a positive endpoint lessens the specificity of the study. Only a sustained monomorphic VT 120 ms, as they further impair infranodal conduction; they should be discontinued if QRS prolongs >25% after initiation of therapy. A stress test may be performed a week after therapy initiation to unveil QRS prolongation or arrhythmia with exercise/tachycardia. Note that all class I drugs have a negative inotropic effect. Lidocaine is an intravenous class Ib that is only useful in ventricular arrhythmia, particularly VT secondary to acute ischemia. In the CAST trial, the use of class Ic agents to suppress PVCs in patients with a history of MI and normal or low EF resulted in tripling of cardiac death secondary to arrhythmias and tripling of cardiac death secondary to MI and shock (~8% cardiac death at 10 months). This is related to their proarrhythmic effect (slowing conduction facilitates reentry), which increases sustained arrhythmias at baseline and even more so during MI. They raise defibrillation thresholds and may make VT/VF refractory to shock. The negative inotropic effect also contributes to the increased mortality and shock during MI.

• Class Ia and Ic agents slow the reentrant circuits, thereby reducing the rate of the fibrillatory AF impulses. The non‐conducted atrial impulses partially penetrate the AV node and make it partially refractory to subsequent impulses (concealed conduction); thus, a reduction in the rate of atrial impulses allows more impulses to conduct through the AV node, which paradoxically increases the ventricular rate. Also, class I agents may organize AF into a slow atrial flutter with 1:1 conduction, again increasing the ventricular rate. Class I agents are ineffective in cardioverting atrial flutter and may actually allow it to sustain, as they slow the conduction across the large macroreentry, widening its excitable gap. • Proarrhythmia should be considered whenever a patient on antiarrhythmic drugs presents with a new arrhythmia or even worsening of a pre‐existing arrhythmia.

B.  Class III (amiodarone, dronedarone, sotalol, ibutilide, dofetilide) These drugs are proven efficacious for the treatment of atrial arrhythmias. Amiodarone and sotalol can be used for ventricular arrhythmias as well. Class III drugs prolong QT and are associated with a dose‐dependent risk of TdP (~2% with sotalol or dofetilide, less so with amiodarone). They should be avoided in patients with QTc >460 ms at baseline (or >500 ms when QRS >120 ms), or if QTc increases by >15% or to >500 ms with therapy. The QT prolongation and risk of TdP are dose‐dependent. After initiating therapy with one of these drugs, patients should be hospitalized and monitored for 3 days with twice‐daily ECGs (except amiodarone, where monitoring is often not necessary). Specific examples of these drugs: • Amiodarone mainly has class III and sympatholytic effects, but also class I and vasodilator effects. Acutely, amiodarone mostly causes a sympatholytic and class I effect; class III effect occurs later. Thus, the effect of amiodarone on ventricular repolarization is slow, with QT prolongation appearing at 4–10 days of therapy and peaking several weeks later. Also, in AF, the early effect is rate slowing (the effect on AF conversion being late). Amiodarone reduced total and arrhythmic mortality and progressive HF mortality in patients with ischemic or non‐ischemic HF in the older GESICA trial, most of whom had NSVT. Amiodarone reduced arrhythmic death (but not total death) in the EMIAT trial of post‐MI patients with LV dysfunction. This was not shown in modern trials (SCD‐HeFT), but as opposed to class I agents, amiodarone is a proven

Chapter 16.  Action Potential Features and Propagation  365

safe therapy in HF. Conversely, amiodarone appeared to increase non‐cardiac death in the AFFIRM trial, with a similar trend in the EMIAT and AVID trials. Amiodarone prevents and treats atrial and ventricular arrhythmias in patients with or without underlying heart disease. It is available intravenously and orally. • Dronedarone has a structure similar to amiodarone without the iodine moiety, and thus has reduced extracardiac side effects and a shorter half‐life (1–2 days compared to 2 months). However, it is less effective than amiodarone in preventing AF. • Sotalol has both class III and β‐blocker effects; the β‐blocker effect starts at low doses and is already half‐maximal at 80 mg/d, while the class III effect starts at doses of 160 mg/d. Sotalol prevents AF, less effectively than amiodarone, and is mainly effective in AF associated with CAD (SAFE‐T trial). Sotalol is also effective in preventing VT and shocks in patients with ICD. • Ibutilide is an intravenous drug that acutely cardioverts AF. • Dofetilide is efficacious in AF prevention. It has proven to be safe in HF and CAD (DIAMOND‐CHF and DIAMOND‐MI trials).

VII.  Amiodarone toxicity Thyroid toxicity Amiodarone contains iodine and has the following effects on the thyroid system: 1.  It inhibits the T4‐to‐T3 deiodinase. This leads to increased free T4, reduced T3, and increased TSH early on (first 3–6 months). This is a benign, normal phenomenon. 2.  If the patient has a subclinical hypothyroidism, the excessive iodine delivered by amiodarone inhibits thyroid hormone synthesis. This is the Wolff–Chaikoff effect; normal individuals escape from the Wolff–Chaikoff effect, but not patients with thyroid abnormalities. 3.  If the patient has an autonomous nodule or subclinical Graves disease, the thyroid autoregulation is disturbed and thus the excess of iodine leads to excessive thyroid hormone synthesis. 4.  Amiodarone may lead to an inflammatory thyroiditis, with early hyperthyroidism, followed by normalization of the thyroid function in a few months. Radioiodine uptake study is not very helpful as it shows reduction of iodine uptake in thyroiditis but also in any patient taking amiodarone. It is suggested by elevated inflammatory markers (IL‐6) and by thyroid ultrasound showing hyperemia. If hypothyroidism is present at baseline or develops with therapy, amiodarone may still be used as long as levothyroxine therapy is provided and the thyroid function is closely monitored. If hyperthyroidism develops, amiodarone should often be stopped. Due to the long half‐life of amiodarone, the thyroid function will not improve for a few months. That is why it is acceptable to continue amiodarone for a few more days if necessary (e.g., VT). Hyperthyroidism is treated with β‐blockers and thionamides; radioiodine therapy has no role in iodine overload states, and thyroidectomy may be necessary if thyrotoxicosis cannot be controlled. If thyroiditis is suspected, prednisone therapy is given for 1 month with subsequent taper; amiodarone therapy may be continued in this case. Lung toxicity Interstitial lung disease occurs at a rate of 0.5–1% per year. It may develop acutely in the first few days (rare), subacutely (weeks), or chronically. Acute and subacute presentations are febrile pneumonitis. The risk is likely higher if underlying lung disease, including COPD, is present, and if doses higher than 200 mg/d are used. Amiodarone lung toxicity often simulates pulmonary edema/heart failure progression. Amiodarone toxicity should therefore be sought in any patient receiving amiodarone whose pulmonary function is not improving with diuresis and/or antibiotic therapy. The earliest and most sensitive abnormality is a reduction of diffusion capacity (DLCO). Therefore, it is important to perform a lung function study before initiation of therapy. This study should then be repeated every year. No diagnostic test is specific for amiodarone lung toxicity. Mononuclear cells on bronchoalveolar lavage are consistent with amiodarone therapy and do not necessary imply toxicity. The clinical context, a refractory pulmonary process, and DLCO are most useful for diagnosis. The lung toxicity is reversible only if diagnosed early, and sometimes improves with steroids. Neuropathy, ataxia (dose‐dependent), blue skin discoloration

VIII.  Effect on pacing thresholds and defibrillation thresholds Class I agents and amiodarone increase defibrillation threshold, i.e., increase the energy requirement for defibrillation of VT/VF. Class I agents also increase pacing threshold, which may lead to a loss of capture, particularly in case of toxicity (e.g., propafenone toxicity).

Further reading Chen SA, Chiang CE, Yang CJ, et al. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation 1994; 90: 1262–78. Engelstein ED, Lippman N, Stein KM, Lerman BB. Mechanism‐specific effects of adenosine on atrial tachycardia. Circulation 1994; 89: 2645–54. Roberts‐Thomson KC, Kistler PM, Kalman JM. Atrial tachycardias: mechanisms, diagnosis, and management. Curr Probl Cardiol 2005; 30: 529–73. Fogoros RN. Abnormal heart rhythms; and Treatment of arrhythmias. In: Fogoros RN. Electrophysiologic Testing, 4th edn. Oxford: Blackwell, 2006, pp. 12–22 and 22–34. Markowitz SM, Nemirovsky D, Stein KM, et al. Adenosine‐insensitive focal atrial tachycardia. J Am Coll Cardiol 2007; 49: 1324–33.

Part 6  Pericardial Disorders 17  Pericardial Disorders

1. Acute pericarditis I. Causes of acute pericarditis  368 II. History and physical findings  368 III. ECG findings  368 IV. Echocardiography 368 V. Myopericarditis and perimyocarditis  369 VI. Treatment 369 2. Tamponade I. Definition 370 II. Pathophysiology and hemodynamics  370 III. Diagnosis: tamponade is a clinical diagnosis, not an echocardiographic diagnosis  371 IV. Echocardiographic findings supporting the hemodynamic compromise of tamponade  371 V. Role of hemodynamic evaluation  372 VI. Special circumstances: low‐pressure tamponade, tamponade with absent pulsus paradoxus, regional tamponade  372 VII. Effusive–constrictive pericarditis  373 VIII. Treatment of tamponade  373 3. Pericardial effusion I. Causes of a pericardial effusion with or without tamponade  373 II. Management of asymptomatic effusions and role of pericardiocentesis  374 III. Note on postoperative pericardial effusions (after cardiac surgery)  375 IV. Note on uremic pericardial effusion  376 4. Constrictive pericarditis I. Causes 377 II. Pathophysiology and hemodynamics  377 III. Hemodynamic findings in constrictive pericarditis and differential diagnosis of constrictive pericarditis: restrictive cardiomyopathy, decompensated RV failure, COPD  379 IV. Practical performance of a hemodynamic study when constrictive pericarditis is suspected  381 V. Echocardiographic features of constrictive pericarditis, and differentiation between constrictive pericarditis and restrictive cardiomyopathy 381 VI. Physical exam, ECG findings, BNP, pericardial thickness (CT/MRI)  382 VII. Transient constrictive pericarditis  383 VIII. Treatment 383 Questions and answers  384

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

367

368  Part 6.  Pericardial Disorders

1.  Acute pericarditis I. Causes of acute pericarditis The four most common causes are: 1.  Viral or idiopathic pericarditis is the most common form of acute pericarditis (80–90%). 2.  Metastatic cancer, where a moderate or large effusion is usually seen. 3.  Connective tissue disease (lupus, rheumatoid arthritis, scleroderma). 4.  Infections (HIV, tuberculosis, bacterial, fungal, Lyme disease). In patients with HIV infection, pericarditis may be secondary to HIV itself or to a concomitant infection, particularly tuberculosis. Other common causes of pericarditis, occurring in specific contexts: 1.  Uremia: an effusion is seen in >50% of patients with uremic pericarditis. 2.  Radiation: acute pericarditis, with or without effusion, may develop soon after radiation. 3.  Post‐MI: pericarditis can occur early post‐MI or late (Dressler syndrome). 4.  Post‐cardiac surgery: pericarditis may occur early (in the first few days) or late (between 2 weeks and 2 months, similarly to Dressler syndrome and called post‐pericardiotomy syndrome). 5.  Trauma (blunt or penetrating).

II.  History and physical findings A.  Chest pain • Chest pain is sharp, pleuritic, usually not constricting. It usually has a rapid, sometimes abrupt, onset. It radiates to the trapezius ridge (a typical radiation of pericarditis) and/or the left arm. • Positional feature: pain is relieved by leaning forward and worsens with lying down, swallowing, or moving (including exertion). • Concomitant systemic findings may suggest a neoplastic, tuberculous, or autoimmune disease. B.  Friction rub • The rub is due to the friction of the inflamed visceral and parietal pericardial layers. It is heard during systole, early diastolic filling, and atrial contraction (three components). It is best heard at the left lower sternal border with the patient leaning forward. A sound with a single component is less specific for pericarditis as it may actually represent a murmur. • The rub is dynamic (it comes and goes), and all three components may not be evident all the time, hence the importance of frequent examinations when pericarditis is suspected. • A rub may be heard with pericardial effusion when concomitant inflammatory pericarditis is present.

III. ECG findings (For the differential diagnosis of STEMI vs. pericarditis, see Chapter 31) A. Diffuse concave ST elevation in all leads except aVR and V1 The axis of the subepicardial injury being the axis of the heart (~ + 45°), the ST elevation is most prominent in lead II and in the anterolateral leads, while the ST segment is often depressed in lead aVR, and sometimes V1 (and occasionally V2, III, or aVL, which are close to orthogonal to +45°).1 The ST segment is elevated at some point in >90% of patients, but normalizes in 1–5 days, often within 7 days. Thus, the ECG of pericarditis can look normal within a few days, at the time the patient presents. The return of ST segment to baseline is followed, sometimes, by T‐wave inversion that may last weeks or months. T wave may become biphasic before ST normalization, mimicking ischemia. B.  PR depression The PR segment is depressed in 82% of patients, and this may be the earliest change. It is seen in all leads except lead aVR, where reciprocal PR elevation is always seen. While it commonly coexists with ST elevation, it can be an isolated change in ~25% of patients. ST elevation and PR depression are mainly seen in idiopathic pericarditis, post‐cardiac surgery pericarditis, and traumatic and hemorrhagic pericarditis.2 They are rarely seen in uremic, malignant, or tuberculous pericarditis, probably because of associated processes masking the pericarditis pattern. C. Low QRS voltage and QRS alternans If an effusion is present, the ECG may show low QRS voltage and sometimes QRS electrical alternans (which means an every‐other‐beat alternation of two different QRS morphologies). P‐ and T‐wave alternans, in which two different P‐ and T‐wave morphologies alternate, increases the likelihood of a pericardial effusion. Sinus tachycardia associated with a low QRS voltage or QRS alternans suggests tamponade.

IV. Echocardiography • Echocardiography is usually normal, and most often no effusion is appreciated (“dry” pericarditis). A small effusion is seen in 40% of pericarditis cases. • Moderate or large effusions are uncommon, seen in 5% of acute pericarditis cases. Idiopathic pericarditis is a less likely diagnosis in a patient with a moderate/large effusion but remains the most likely diagnosis; 25–50% of moderate or large pericardial effusions are idiopathic, whereas 80–90% of pericarditis cases with no or small effusions are idiopathic. An effusion increases the likelihood of a ­specific cause, such as malignancy, infection, or connective tissue disorder. • LV dysfunction, sometimes segmental, suggests an associated severe myocarditis.

Chapter 17.  Pericardial Disorders  369

The diagnosis of pericarditis requires two of the following four features:3 (1) chest pain; (2) rub; (3) typical ECG findings (widespread ST‐segment elevation and/or PR depression); (4) pericardial effusion • Pericardial effusion is not necessary but confirms the diagnosis when present. • CRP is a confirmatory finding. CRP is required by some authors for the diagnosis of pericarditis and is a useful monitoring marker. • ESR may be used but is less specific and rises and falls later than CRP. Conversely, a severely elevated ESR has a valuable diagnostic value and suggests tuberculosis or autoimmune disease. • A low‐titer ANA is very common in idiopathic pericarditis (~40%) and often does not have any clinical significance. ANA testing may be useful in high‐risk pericarditis (see below).

V.  Myopericarditis and perimyocarditis Various degrees of myocardial inflammation are seen in patients with pericarditis. In fact, the ST‐segment elevation implies subepicardial myocardial involvement rather than just pericardial involvement, the pericardium being electrically silent. Therefore, a troponin rise is ­common in pericarditis. Myopericarditis implies mild myocardial involvement, as evidenced by an elevated troponin, with a normal EF and no wall motion abnormalities. Myopericarditis has a good prognosis, with normalization of the ECG within 12 months and persistence of a normal EF.3–5 Troponin may be strikingly elevated (median 7 ng/ml, interquartile range 0.5–35 in one study).5 Unlike in ACS, this elevated troponin does not portend an increase in long‐term complications. However, a reduction of the NSAID dose is considered (e.g., aspirin 500 mg TID), exercise is restricted for 4–6 weeks, and return to athletic activity is considered only after 6 months and after normalization of ECG and LV, and in the absence of arrhythmias on Holter and stress test. When the process predominantly involves the myocardium, it is termed perimyocarditis or pure myocarditis and manifests as clinical HF or significant LV dysfunction, sometimes segmental. This predominant myocarditis may have ST changes of pericarditis or, more ­commonly, focal ST changes or Q waves mimicking STEMI. Coronary angiography is done to rule out ACS. Perimyocarditis with mild LV dysfunction (EF 40–50%) is associated with a good long‐term prognosis and persistence of LV dysfunction in only 15% of patients.5 Perimyocarditis with severe LV dysfunction portends an altered long‐term prognosis with persistent LV dysfunction in up to 60% of patients.

VI. Treatment Pericarditis is a self‐limiting disease with no complication or recurrence in >70% of patients. A. Initial therapy 1.  A full anti‐inflammatory dose of NSAID or aspirin is administered for 1–2 weeks. One dose is usually associated with a dramatic symptomatic effect. Some authors suggest the continuation of therapy until CRP normalizes. One regimen consists of the administration of a full‐dose NSAID for a week (e.g., ibuprofen 600 mg TID, aspirin 750–1000 mg TID), followed by gradual tapering over 3 weeks, rather than abrupt cessation (e.g., taper ibuprofen by 200–400 mg per dose every week).3–6 2.  The systematic use of colchicine (for 3 months) as an adjunct to NSAID during the first episode of pericarditis strikingly reduces the recurrence of pericarditis by 70% (COPE trial).6 Colchicine therapy may thus be considered systematically and is given a class I in ESC guidelines (1 mg BID the first day, followed by 0.5 mg BID; a lower dose of 0.5 mg BID the first day followed by 0.5 mg once daily is given to patients weighing 38 °C e. Clinical suspicion of a specific etiology The specific etiologic workup consists of: HIV testing, PPD, ANA/rheumatoid factor, screening for specific cancers. Also, myocarditis warrants hospitalization. B. Recurrent pericarditis Between 15% and 30% of patients with idiopathic or autoimmune pericarditis develop recurrent pericarditis within 20 months after the initial episode, and pericarditis may keep relapsing for several years.8 It is due to an autoimmune process initiated by the initial viral ­infection, although persistent or recurrent infection is possible. A recurrence within 6 weeks of the initial episode is usually considered a persistence of the initial pericarditis and is called “incessant” rather than recurrent pericarditis. In the absence of high‐risk features, recurrent pericarditis is usually idiopathic and does not warrant specific workup.3 Moreover, recurrent idiopathic pericarditis is usually milder than the initial pericarditis and is not associated with pericardial constriction; in fact, the risk of constrictive pericarditis is lower after a recurrence than after the initial episode of pericarditis.9 One‐third of patients have pleuropericardial involvement during these recurrences.

370  Part 6.  Pericardial Disorders

For each recurrence, repeat the course of NSAID for a longer duration (2–4 weeks) with slow tapering over an additional 3–4 weeks, and give a course of colchicine for ≥6 months.10 Avoid glucocorticoids, except for refractory pericarditis. C. If an effusion is present, look for a specific etiology (see Section 3, Pericardial effusion, below) and perform serial echocardiographic exams. Echo is repeated during the hospital stay to ensure stability of the effusion, then serial outpatient echo exams are performed to ensure resolution of the effusion within a few months. D. The occurrence of constrictive pericarditis after acute idiopathic pericarditis is uncommon (10 mmHg

25 A

V X

A V X

No Y Figure 17.1  Simultaneous pericardial and RA pressures are recorded in tamponade, before pericardiocentesis. The RA and pericardial pressures are elevated and equalized (~20 mmHg); this defines tamponade. The two tracings are actually superimposed, particularly in expiration; the pericardial pressure falls a bit more than the RA pressure in inspiration. Furthermore, X descent is seen, but Y descent is flat (mnemonic: Flat Y Tamponade = FYT).

Chapter 17.  Pericardial Disorders  371

Figure 17.2  Pulsus paradoxus. Note the drop of systolic and pulse pressure during normal inspiration (arrows). The arterial waveform also becomes narrower.

with normal inspiration. In addition, the arterial waveform is narrow and the pulse pressure is reduced (arterial tracing is “short” and ­narrow) (Figure 17.2).

III. Diagnosis: tamponade is a clinical diagnosis, not an echocardiographic diagnosis Tamponade is diagnosed when a large pericardial effusion is associated with hemodynamic compromise, i.e., any one of the following clinical findings: 1.  Elevated JVP. 2.  Pulsus paradoxus, which is a decrease of SBP of >10 mmHg during normal, quiet inspiration. Example: when using the BP cuff, the Korotkoff sounds are heard intermittently at a systolic pressure of 150 mmHg and consistently (with each cardiac cycle) at a pressure of 120; therefore, the pulsus paradoxus is 30 mmHg. Avoid deep breathing during this measurement, as deep breathing is normally associated with an inspiratory drop of aortic pressure. The blood pressure is normal or elevated early on. Ultimately, the blood pressure declines. An increase in systolic pressure up to 150– 210 mmHg and diastolic blood pressure up to 100–130 mmHg is frequent in tamponade and occurred in up to one‐third of tamponade cases in one report, particularly in patients with a history of hypertension who are sensitive to the catecholamine surge.15 Hypertension does not imply preserved cardiac output; in fact, cardiac output is as low as in cases of normal arterial pressure, but increased peripheral vascular resistance preserves arterial pressure (pressure = flow × resistance). Patients with tamponade and hypertension have a reduction in blood pressure, reduction in systemic vascular resistance, and increase in cardiac output following pericardiocentesis.15 3.  Sinus tachycardia that attempts to compensate for the low stroke volume. Tachycardia may be absent in hypothyroidism and sometimes uremia (sinus node disease). 4.  Dyspnea/tachypnea/orthopnea with clear lungs. PCWP is increased up to 30 mmHg but the intracardiac and pulmonary venous volume is low, hence the lack of pulmonary edema and lack of significant hypoxemia despite severe dyspnea. A decrease in heart sounds is characteristic of a large effusion but not necessarily tamponade. Even when an effusion is large, a friction rub may still be heard with inflammatory etiologies.

IV. Echocardiographic findings supporting the hemodynamic compromise of tamponade (See also Chapter 32, Section VI) 1.  RV collapse in diastole. This is the most specific echo finding in tamponade. Sometimes, just an early diastolic indentation of the RVOT is seen on the parasternal long‐axis M mode. 2.  RA collapse in ventricular systole. RA collapse lasting over one‐third of systole is specific for tamponade. RA collapse is generally more sensitive but less specific for tamponade than RV collapse. 3.  Inspiratory changes of transmitral and transtricuspid flow. An inspiratory decrease of left‐sided transmitral flow by >25%, or an inspiratory increase of right‐sided transtricuspid flow, during normal breathing, suggests tamponade (this is equivalent to the pulsus ­paradoxus). This is the earliest echo sign of tamponade. 4.  IVC dilatation with poor inspiratory collapse. IVC abnormality has a sensitivity of 97% and a specificity of 40% for tamponade. IVC is rarely normal in tamponade (the so‐called low‐pressure tamponade). Findings on hepatic venous Doppler: the flat Y descent on the RA tracing corresponds to a flat D wave on the hepatic venous Doppler. This contrasts with constriction, where both S and D are prominent. Inspiratory rise of these waves may be seen in both conditions. 5.  Other findings • A rapid change in the effusion size suggests a threatened tamponade. • An abnormal septal motion may be seen as a result of ventricular interdependence. • A swinging heart, i.e., a heart that changes position in a phasic manner, may be seen with a large effusion and corresponds to the electrical alternans seen on ECG. It does not necessarily imply tamponade. • Strands in the pericardial fluid imply inflammation or bleeding and can be seen with most effusions, except transudative effusions. TEE, CT, or MRI may be performed when a loculated effusion with a regional tamponade is suspected.

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V. Role of hemodynamic evaluation The diagnosis of tamponade is established on clinical and echo grounds, and right heart catheterization is not usually necessary. However, if a Swan catheter is in place (e.g., post cardiac surgery), the following findings suggest tamponade: (i) an elevated CVP that approximates PCWP and PA diastolic pressure; (ii) a flat Y descent on RA tracing. Also, right heart catheterization may be performed before and particularly after pericardiocentesis to document the hemodynamic improvement. Pericardial pressure is measured before drainage, in which case it is elevated (>0 mmHg) and equal to the RA pressure. Normalization of the pericardial pressure (to ≤0 mmHg) and the RA pressure must be documented after drainage. In fact, the normal ­pericardial pressure is ≤0 mmHg. The lack of full hemodynamic improvement suggests effusive–constrictive pericarditis.

VI. Special circumstances: low‐pressure tamponade, tamponade with absent pulsus paradoxus, regional tamponade A. Low‐pressure tamponade In patients who are hypovolemic, compression of intracardiac chambers (i.e., tamponade), particularly right‐sided chambers, may occur at a lower intrapericardial pressure of 6–12 mmHg. In this case, there will be equalization of intrapericardial pressure and RA pressure at 6–12 mmHg. Thus, tamponade with pulsus paradoxus or hypotension occurs with a high‐normal or mildly increased right‐sided filling ­pressure and jugular venous pressure.14 Were it not for hypovolemia and the low right‐sided filling pressure, this pericardial effusion would not yet be hemodynamically significant. Fluid administration may correct the pulsus paradoxus; however, excessive fluid administration may sometimes increase the right‐sided volume, which further stretches the already distended pericardium and elevates its pressure, leading to a full‐blown tamponade picture.16,17 That is why fluids are helpful in hypovolemic patients with tamponade but may harm euvolemic or hypervolemic patients. In order to maintain a proper transmural pressure of the cardiac chambers, it is important to maintain a higher level of intracardiac pressure without excessive volume resuscitation (transmural pressure = intracavitary pressure minus pericardial pressure). Ultimately, patients with a low‐pressure tamponade require pericardiocentesis since even at 6–12 mmHg, the intrapericardial pressure is at a steep portion of the pressure–volume relationship and is liable to rise with any change in pericardial volume (Figure 17.3). B.  Underlying RV or LV failure and causes of absent pulsus paradoxus While it is easy to induce tamponade in case of hypovolemia, it is difficult to induce tamponade physiology in patients with severely increased right‐sided or left‐sided diastolic pressure.14 In fact, it is harder for the pericardial pressure to compress both ventricles, and tamponade develops when pericardial pressure equilibrates with the lower‐pressure ventricle. Moreover, the respiratory variation in venous return does not significantly change the cardiac output and the systolic pressure of the failing ventricle (flat portion of the Frank–Starling curve). The latter two conditions, that is, the lack of biventricular compression (and therefore lack of interdependence) and the lack of respiratory variation in ventricular output explain the lack of pulsus paradoxus. This situation may be seen in patients with cor pulmonale and in patients with end‐stage renal disease and underlying left heart failure. In addition, pulsus paradoxus may not be seen in: (1) ASD, where the increase in right‐sided flow during inspiration is ­balanced by an increase in right‐to‐left shunt or reduction in left‐to‐right shunt, leading to less ventricular interdependence; (2) local t­amponade (e.g., localized compression of one ventricle or atrium by a clot after cardiac surgery, leading to a localized increase in pressure); (3) AI, where the diastolic regurgitant flow damps down respiratory fluctuations of flow. In addition, pulsus paradoxus is difficult to detect in case of an irregular rhythm such as atrial fibrillation. C. Regional tamponade This occurs when only one cardiac chamber, a pulmonary vein, or the SVC or IVC is compressed by a loculated effusion (e.g., anterior loculation compressing the RV or RA, posterior loculation compressing the LV or LA). Since there is no uniform compression of the four chambers, there is no equalization of diastolic pressures and no ventricular interdependence/pulsus paradoxus. There is increased pressure of the compressed chamber, e.g., increased RA pressure or PCWP, and hypotension, which in the right context suggest tamponade (e.g., after cardiac surgery). However, loculation can also produce classic tamponade, presumably by tightening the uninvolved pericardium. TEE or cardiac CT or MRI should be performed when a regional tamponade is suspected. Pericardial pressure +20

+10

+20

+10 +20

5–10 mmHg +6

+20

Pericardial volume (a)

(b)

(c)

Figure 17.3  The normal pericardial pressure is negative and reaches 0 mmHg at end‐expiration (–10 to 0 mmHg). (a) Tamponade occurs when the pericardial pressure exceeds the pressure of a cardiac chamber (e.g., RV), thus compressing it and making it equalize with it. Typically, both ventricles get constrained by the pericardial shell, such that their pressure rises and equalizes with the pericardial pressure. They expand at the expense of each other (arrows). (b) Even before the RV gets compressed by the pericardial pressure, the transmural pressure of the RV and the RV expansion are affected (RV diastolic pressure = 10, pericardial pressure = 6 → the RV transmural, expansile pressure is reduced to +4). (c) Compliance curve of the pericardium, showing how the pericardial pressure rises quickly beyond a certain pressure point, even before tamponade occurs (threatened tamponade). This curve is more leftward in sudden acute effusions, wherein the pericardium is not compliant.

Chapter 17.  Pericardial Disorders  373

D.  COPD and other causes of pulsus paradoxus and RV–LV respiratory discordance Because of large intrathoracic pressure swings, COPD, asthma, morbid obesity, or positive‐pressure ventilation may lead to discordance in RV and LV filling and pulsus paradoxus.

VII. Effusive–constrictive pericarditis Some patients have a pericardial effusion with the hemodynamics of tamponade, i.e., pulsus paradoxus with elevated and equalized right‐ and left‐sided filling pressures. However, upon drainage of the pericardial fluid, the hemodynamic compromise does not fully resolve. RV and LV diastolic pressures remain equalized, RA pressure remains elevated (RA pressure declines by 1 week postoperatively, secondarily to a post‐pericardiotomy syndrome; it usually resolves within weeks. 2.  Post‐MI. The effusion may occur early (resolves slowly over months) or late (along with Dressler syndrome). An early small effusion is often not worrisome, per se, and may accompany post‐MI pericarditis or HF. Conversely, an early moderate or large effusion suggests a threatening free wall rupture. 3.  Radiation therapy. An early effusion (1 year) is part of an effusive–constrictive pericarditis. 4.  HF or volume overload states (nephrotic syndrome, cirrhosis). Pericardial effusion is usually small or moderate in size, transudative, and only develops when right heart failure is present, as the pericardial veins drain in the coronary sinus. Isolated left heart failure does not lead to a pericardial effusion. A large pericardial effusion is rare but possible.21 5.  Hemorrhagic pericardial effusion, from a penetrating or blunt trauma, free wall rupture post‐MI, complication of PCI (coronary perforation) or complication of device implantation (RA or RV rupture). Outside these traumatic/rupture contexts, a bloody effusion may be seen with a broad range of etiologies, such as malignant, viral, or infectious, with a prognosis that depends on the underlying etiology. 6.  Drugs (mainly minoxidil and drug‐induced lupus: hydralazine, izoniazide).

374  Part 6.  Pericardial Disorders

A large idiopathic pericardial effusion has a relatively low risk of progression to tamponade. Conversely, neoplastic, bacterial/ tuberculous/HIV, and postoperative large effusions have a high risk of progression to tamponade. Hemorrhagic effusions have an imminent risk of tamponade.

II.  Management of asymptomatic effusions and role of pericardiocentesis A.  General approach to a large asymptomatic effusion (Figure 17.4) Two main concerns dictate the management of asymptomatic effusions: (i) etiology and (ii) risk of progression to tamponade. Up to 60% of patients with moderate/large pericardial effusions have a known medical condition, such as cancer, uremia, previous cardiac surgery, or connective tissue disease, which points toward a specific diagnosis.20 The following strategy is suggested: 1.  In the absence of a known medical condition that could cause a pericardial effusion, screen for some cancers, HIV/tuberculosis, and metabolic disorders using clinical findings and: CXR, mammography, chest CT; PPD, HIV; TSH, renal function, rheumatoid factor, ANA. 2.  Check markers of inflammation (CRP, ESR), which, if elevated without any cancer/infection/autoimmune disease, suggest a pericarditic process (viral/idiopathic).1 3.  If a malignant or bacterial (including tuberculous) etiology is suspected, pericardiocentesis is indicated both for its diagnostic and staging value and because of the high risk of progression to tamponade (“threatened tamponade”).3 Only 50% of effusions in cancer patients are due to malignant metastasis, the remaining being induced by inflammation, obstruction of lymphatic drainage, or radiation; hence the additional diagnostic importance of pericardiocentesis in these patients.25 If a hemorrhagic pericardial effusion is suspected (traumatic, iatrogenic), pericardiocentesis is indicated because of the imminent risk of tamponade. If an effusion is increasing in size, pericardiocentesis is warranted because of the risk of tamponade. 4.  Ensure the patient is truly asymptomatic. Even when the intrapericardial pressure is lower than the right‐sided pressures, the RV or RA transmural pressure (RV pressure minus intrapericardial pressure) is reduced, which impairs RV outward expansion and filling. For example, if the pericardial pressure is 6 mmHg and the RV diastolic pressure is 10 mmHg, the RV does not collapse towards the LV, but it cannot appropriately expand and the cardiac output is already reduced. Also, at this point, pericardial pressure is at a steep slope and there is at least a threatened tamponade (Figure 17.3).26 In fact, one study has shown that almost all patients with a large asymptomatic effusion who underwent pericardiocentesis had a high intrapericardial pressure and a reduced RA transmural pressure.21,25 Thus, vague symptoms of fatigue or dyspnea on exertion often represent early hemodynamic compromise and warrant pericardiocentesis. The same applies to the echo signs of pre‐tamponade. 5.  If all of the above is ruled out, the asymptomatic effusion is likely isolated, i.e., idiopathic. If the inflammatory markers are increased or if inflammatory signs are present (characteristic chest pain, friction rub, fever, or typical ECG changes), a pericarditic process is suspected and may be treated with NSAID and colchicine (class I indication).3,4,25 Echo follow‐up is warranted to detect improvement of the effusion (or lack thereof), on a weekly basis initially.25 An autoimmune process is managed similarly. 6.  A chronic, large idiopathic effusion that persists for >3 months has a significant risk of progression to tamponade of 33%.3,4,21 Tamponade may develop unexpectedly and suddenly in patients who have had a chronic stable effusion for several years.21 The remaining patients remain stable; the effusion may regress at least partially, and a specific cause does not usually emerge with time.21 Thus, close echo surveillance is warranted. Alternatively, pericardial drainage may be considered for effusions persisting >3 months because of the 33% risk of tamponade.3,25 A pericardiocentesis has a therapeutic but also a diagnostic value. The overall diagnostic yield of a pericardiocentesis is ~30%,27 but it is higher in neoplastic or bacterial effusions. The yield in neoplastic effusions is >50% (50%28 to 80%21,23). The pericardial fluid should be sent for cytology, cell count, bacterial and mycobacterial culture, and polymerase chain reaction of Mycobacterium tuberculosis (the latter is highly sensitive for tuberculous pericarditis). Beside idiopathic, rule out: 1-Malignant 2-Infectious 3-Immune 4-Metabolic 5-Radiation 6-Post-op 7-Traumatic

Drainage Yes Clinical setting + General screen + ESR/CRP

Malignant Infectious bacterial Traumatic No

Exertional limitation or dyspnea

Pericardial pressure is ↑ Effusion is not truly asymptomatic

Drainage

ESR/CRP ↑ with no specific context

Idiopathic pericarditis with effusion

NSAID colchicine

Effusion> 3 months Figure 17.4  General approach to a large, asymptomatic pericardial effusion.

Drainage

Chapter 17.  Pericardial Disorders  375

B.  Pericardiocentesis and open pericardiotomy (pericardial window) Pericardiocentesis alone is often a definitive treatment of idiopathic pericardial effusion; in one series, recurrences only occurred in 8% of patients over long‐term follow‐up.3,29 However, another series suggested that recurrences are common and occur in 65% of patients with idiopathic large effusions.21 The duration of catheter drainage may explain the discrepancy. This recurrence rate is higher in malignant e­ ffusions, although pericardiocentesis may still be tried as a first‐line therapy or as a temporizing measure in the unstable patient. Since fluid reaccumulation most commonly occurs in the first 48 hours after drainage, pericardiocentesis with prolonged catheter drainage is associated with an acceptable risk of recurrence of malignant effusions ( mean PCWP. In fact, RVEDP is higher than LVEDP in inspiration, whereas in constriction RVEDP increases only to become equal to LVEDP during inspiration. In RV failure, the severely impaired RA/RV compliance leads to an inspiratory rise in diastolic pressure with the rise in preload, overcoming the direct negative respiratory pressure. b  In constriction, the LV diastolic pressure varies minimally with respiration whereas the PCWP varies markedly, which explains the significant respiratory change of the early diastolic PCWP–LV gradient (lowest during inspiration). In other disease states, the LV diastolic pressure changes as much as the PCWP with respiration, hence the lack of significant change of the PCWP–LV early diastolic gradient. a

380  Part 6.  Pericardial Disorders

In RV failure, the ventricular interdependence is not markedly affected by respiration, as the RV is already markedly distended and may not further distend with inspiration. In addition, the RV is at a flat portion of the Frank–Starling curve, and cannot significantly increase its flow with the inspiratory rise in preload. Thus, the systolic discordance of RV and LV pressures is not as often or as markedly seen.

Expiration 120

Expiration

Inspiration

120 Inspiration

80

80

40

40

A

B

Figure 17.9  Simultaneous RV and LV pressure tracings in two different patients. Analyze three elements on the RV–LV simultaneous tracing: (1) in diastole, dip–plateau pattern of the LV and the RV; (2) in diastole, elevation and equalization of RV and LV end‐diastolic pressures; (3) in systole, concordance vs. discordance of RV–LV systolic peaks. Both patients A and B have the dip–plateau pattern and the elevation and equalization of RV and LV end‐diastolic pressures (in inspiration, blue arrows). Patient A has constrictive pericarditis: note the discordance of the systolic peaks of RV and LV with respiration. Also, the LV and RV areas change discordantly (light and dark shaded areas, respectively). Patient B has a restrictive myocardial disease: note the concordance of the LV and RV systolic peaks.   Concordance pattern is analyzed by choosing the peak inspiratory beat, which is the beat preceded by the lowest diastolic dip, and the peak expiratory beat, which is the beat preceded by the highest diastolic dip. Thus diastole helps determine which beats are selected for systolic analysis. Reproduced with permission from Elsevier from Talreja et al. (2008).39

Only the discordance between LV and RV systolic pressures is highly sensitive and highly specific (>90%) for the diagnosis of constrictive pericarditis (Figure  17.9).39 The second most specific feature is the respiratory change in the early diastolic gradient between PCWP and LV. The other features are useful but have low sensitivity, specificity, and predictive values in the range of 50–70% for constrictive pericarditis. The discordance and the respiratory changes are best evaluated during deep respiration. This contrasts with the clinical evaluation of discordance by pulsus paradoxus, and the Doppler evaluation of discordance by transmitral analysis, performed during normal respiration. Some of the abnormalities of constrictive pericarditis are made more evident by hypovolemia, while others are made more evident with volume loading (500–1000 ml over 10 minutes in the cath lab): • The dip–plateau pattern and the deep and rapid X and Y descents, which are signs of severely reduced compliance, are better shown with volume loading and are masked with hypovolemia. In fact, RA pressure may be normal and may have a normal pulse morphology in hypovolemia (occult constrictive pericarditis).43 • The equalization of diastolic pressures is better shown with volume loading. • The discordant respiratory changes of LV and RV systolic pressures are better seen in hypovolemia (similar to the accentuation of pulsus paradoxus with hypovolemia). While a volume load creates more ventricular interdependence, the respiratory changes of ventricular interdependence become attenuated.44 C.  COPD and other causes of RV–LV respiratory discordance While RV failure may lead to four‐chamber diastolic pressure equalization and abnormal RV and RA pressure tracings mimicking constriction, COPD may mimic another aspect of constriction. Because of large intrathoracic pressure swings, COPD or asthma may lead to discordant RV and LV filling and pulsus paradoxus. This may also be seen in patients receiving mechanical ventilation and in sedated patients breathing deeply, as in many routine cardiac catheterization procedures. With the deep negative intrathoracic pressure, right‐sided filling increases because a large volume is driven from outside the thorax to inside the thorax, which does not happen on the left side. RV and LV will have opposite phasic changes in volume and discordant systolic pressures. These discordant changes in RV–LV filling that lead to pulsus paradoxus may also be seen in normal subjects who are hypovolemic, i.e., are on the steep portion of the cardiac output–preload curve (Frank–Starling curve), and breathing deeply; they are often absent in hypervolemic patients (non‐preload‐dependent). That is why ­discordant RV–LV filling is unusual in restrictive cardiomyopathy and severe heart failure. The phasic changes in RV and LV filling are also present in normal subjects breathing quietly, but are very subtle. In normal subjects, right‐sided flow increases during inspiration but RV and LV systolic pressures both concordantly and mildly decrease during inspiration, due predominantly to the direct effect of the negative intrathoracic pressure on the measured cardiac or vascular pressures, the effect of RV–LV filling discordance being minimal. The same concordance phenomenon is seen in non‐constriction and non‐COPD disease states, such as restriction and RV failure. The filling discordance overwhelms the direct negative inspiratory pressure effect in cases of constrictive ­pericarditis, COPD, or large respiratory swings in hypovolemic patients.

Chapter 17.  Pericardial Disorders  381

In COPD, as opposed to constriction: 1.  The end‐diastolic pressures of the four cardiac chambers are not equalized (RA pressure and RVEDP  RVEDP at one point (vs. RVEDP > LVEDP, which would suggest RV failure) 3. Analyze systole during deep breathing to assess discordance vs. concordance of LV and RV systolic pressure peaks • LV and PCWP simultaneous recording: in constrictive pericarditis, the gradient between PCWP and early diastolic LV dip changes with respiration When constriction is suspected clinically and the mean RA pressure is  1.5) 2.  The right and left ventricular systolic function is preserved, ventricular size is normal, and the atria are enlarged. However, in restrictive cardiomyopathy, there is no ventricular interdependence and the intrathoracic pressures are transmitted to the cardiac chambers. This explains the lack of significant respiratory variation of the transmitral and the transtricuspid flows and the lack of significant respiratory variation of the hepatic and the pulmonary venous flows (in contrast to constrictive pericarditis, where E velocity ­varies by >25% Table 17.3  Echocardiographic differentiation between constrictive pericarditis and restrictive cardiomyopathy.

Similarities E/A E deceleration time Ventricular size/systolic function Atria IVC Differences Respiratory E variation (during normal respiration) Medial annular E’ velocity Hepatic venous pattern Hepatic venous flow respiratory variation Pulmonary venous flow respiratory variation Color M‐mode mitral valve velocity of propagation (Vp) Septal motion on M‐mode and 2D echo Posterior wall motion in diastole on M mode Pulmonary hypertension TR and MR

Constrictive pericarditis

Restrictive cardiomyopathy

>1.5 Reduced 1.5 Reduced 25% >10 cm/s S > D ↑ S and D with inspiration ↓ S and D with partial reversal of flow in expiration ↑ S and D with expiration Normal (>55 cm/s) (implies normal diastolic recoil, like medial E’)

55, and especially radiation etiology are predictors of poorer long‐term outcomes. Post‐radiation pericarditis is often associated with myocardial, valvular, and coronary disease and mediastinal scarring that partially explain the mortality, the residual symptomatology, and the inability to completely resect the pericardium. Symptomatic improvement is seen in ~80% of survivors. B.  Persistent diastolic dysfunction Echocardiographic normalization of diastolic filling pattern occurs slowly over several months and is seen in ~40% of patients at 3 months and 60% at 6 months.50 One‐third of patients are left with a residual restrictive pattern while 10% have a residual constrictive pattern. The diastolic filling pattern normalizes in only ~25% of radiation pericarditis. Patients with a longer duration of symptoms are more likely to have residual diastolic dysfunction and symptoms at later follow‐up. This is presumably due to: a.  Extension of the fibrotic process to the myocardium in longstanding constriction. In fact, a residual restrictive rather than constrictive process is responsible for the residual postoperative symptoms in most patients and may slowly improve with time. b.  Inability to fully resect the pericardium in patients with extensive scarring (residual constriction). C. Systolic function As a result of longstanding underfilling, LV myocardial atrophy occurs in patients with longstanding constrictive pericarditis. The sudden “flooding” of the LV that occurs postoperatively may lead to a transient LV systolic dysfunction with pulmonary edema and a low output syndrome, responsible for some of the early fatalities. In survivors, LV systolic function improves with time. Summary Constrictive pericarditis clinically manifests as HF, particularly right HF, with elevated right‐ and left‐sided filling pressures on echo, biatrial enlargement, yet normal right and left ventricular systolic function and size and normal LV wall thickness, simulating diastolic HF. Keys to diagnosis: On echo → Respiratory variations of mitral/tricuspid inflow and pulmonary/hepatic venous flow. On invasive hemodynamics → respiratory discordance of RV–LV systolic peaks. BNP is typically normal.

384  Part 6.  Pericardial Disorders

Questions and answers Question 1. A 58‐year‐old woman presents with atypical non‐exertional and non‐positional chest pain. She has no significant functional limitation. She is a smoker and hypertensive. Echo shows large circumferential pericardial effusion (2.5 cm sum diastolic diameter). JVP is normal, pulse is 80 bpm, and there is no pulsus paradoxus. All of the following are appropriate, except for which one? A. Screen for breast cancer (mammogram) and lung cancer (chest CT) B. Perform PPD, TSH, creatinine, and HIV testing, and assess joints and skin for rheumatologic disorders C. Perform ESR and CRP D. Drain the effusion for diagnostic purpose and to prevent tamponade E. If CRP is elevated without a suspected malignant or immune process, treat with NSAID and colchicine Question 2.  A 65‐year‐old man, smoker, presents with severe dyspnea, progressive over several days. BP is 145/105 mmHg, pulse is 110 bpm, JVP is 14 cm H2O, peripheral O2 saturation 95%. Chest X‐ray shows clear lungs but cardiomegaly. Echo shows a large pericardial effusion. Which one of the following additional findings is likely to be true? A. On catheterization, RA pressure shows a deep Y descent and a flat X B. RA pressure and RVEDP exceed PCWP and LVEDP C. Tamponade is unlikely as the patient is hypertensive. D. Tamponade is unlikely as the patient has normal O2 saturation E. Pulsus paradoxus is likely to be present on exam F. Pulsus alternans is likely to be present on exam, and electrical alternans may be present on ECG Question 3. The patient in Question 2 undergoes pericardiocentesis. 1200 ml of blood‐tinged fluid is removed. Which of the following is incorrect? A. The likelihood of malignant effusion is ~30% B. A subxiphoid approach targets the posterior aspect of the pericardial space, while an apical acess targets the lateral pericardial space C. Pericardiocentesis followed by 3 days of drainage is often a definitive treatment of idiopathic effusions D. Pericardiocentesis followed by 3 days of drainage is associated with a low effusion recurrence rate, even if the effusion is malignant ( C ~ D > B. In a study of 453 patients with acute pericarditis, 83% of cases were idiopathic, 5% were neoplastic, 7% were autoimmune, 3.5% were due to tuberculosis, and 0.7% were purulent.7 Pericardial effusion: A > B = C > D. In a study of 204 patients with pericardial effusion, 48% of cases were labeled as idiopathic, 16% were infectious, 15% were malignant, and 8% were due to collagen vascular disease (lupus, rheumatoid arthritis, and scleroderma).22 Answer 13.  C. Colchicine is recommended along with NSAID as initial combination therapy for pericarditis (class I, ESC guidelines). Colchicine is used for 3 months. The significant effusion dictates initial inpatient monitoring.

References Acute pericarditis 1. Surawicz B, Lassiter KC. Electrocardiogram in pericarditis. Am J Cardiol 1970; 26: 471–4. 2. Bailey GL, Hampers CL, Hager EB, et al. Uremic pericarditis: clinical features and management. Circulation 1968; 38: 582–91. 3. Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of pericardial diseases. Circulation 2010; 121: 916–28. 4. Adler Y, Charron P, Imazio M, et al. 2015 ESC guidelines for the diagnosis and management of pericardial diseases. Eur Heart J 2015; 36: 2921–64. 5. Imazio M, Brucato A, Barbieri A, et al. Good prognosis for pericarditis with and without myocardial involvement: results from a multicenter, prospective cohort study. Circulation 2013; 128: 42–9. 6. Imazio M, Bobbio M, Cecchi E, et al. Colchicine in addition to conventional therapy for acute pericarditis. Circulation 2005; 112: 2012–16. 7. Imazio M, Cecchi E, Demichelis B, et al. Indicators of poor prognosis of acute pericarditis. Circulation 2007; 115: 2739–44. 8. Imazio M, Trinchero R, Shabetai R. Pathogenesis, management, and prevention of recurrent pericarditis. J Cardiovasc Med 2007; 8: 404–10. 9. Imazio M, Brucato A, Adler Y, et al. Prognosis of idiopathic recurrent pericarditis as determined from previously published reports. Am J Cardiol 2007; 100: 1026–8. 10. Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP–2): a multicentre, double‐ blind, placebo‐controlled, randomised trial. Lancet 2014; 383: 2232–7. 11. Sagrista‐Sauleda J, Permanyer‐Miralda G, Candell‐Riera J, et al. Transient cardiac constriction. an unrecognized pattern of evolution in effusive acute ­idiopathic pericarditis. Am J Cardiol 1987; 59: 961–6.

Tamponade 12. LeWinter MM. Pericardial diseases. In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald’s Heart Disease, 8th edn. Philadelphia, PA: Saunders Elsevier, 2008, pp. 1829–54. 13. Robb JF, Laham RJ. Profiles in pericardial disease. In: Baim DS, ed. Grossman’s Cardiac Catheterization, Angiography, and Intervention, 7th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2006, pp. 725–43. 14. Hanna EB. Tamponade. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012. 15. Brown J, MacKinnon D, King A, Vanderbush E. Elevated arterial blood pressure in cardiac tamponade. N Engl J Med 1992; 327: 463–6. 16. Spodick DH. Threshold of pericardial constraint: the pericardial reserve volume and auxiliary pericardial functions. J Am Coll Cardiol 1985; 6: 296–7. 17. Hashim R, Frankel H, Tandon M, Rabinovici R. Fluid resuscitation‐induced cardiac tamponade. Trauma 2002; 53: 1183–4. 18. Sagrista‐Sauleda J, Angel J, Sanchez A, et al. Effusive–constrictive pericarditis. N Engl J Med 2004; 350: 469–75. 19. Cameron J, Oesterle SN, Baldwin JC, Hancock EW. The etiologic spectrum of constrictive pericarditis. Am Heart J 1987; 113: 354–60.

Pericardial effusion 20. Sagrista‐Sauleda J, Merce J, Permanyer‐Miralda G, Soler‐Soler J. Clinical clues to the causes of large pericardial effusions. Am J Med 2000; 109: 95–101. 21. Sagrista‐Sauleda J, Angel J, Permanyer‐Miralda G, Soler‐Soler J. Long‐term follow‐up of idiopathic chronic pericardial effusion. N Engl J Med 1999; 341: 2054–9. 22. Levy PY, Corey R, Berger P, et al. Etiologic diagnosis of 204 pericardial effusions. Medicine (Baltimore) 2003; 82: 385–91.

Chapter 17.  Pericardial Disorders  387

23. Corey GR, Campbell PT, Van Trigt P, et al. Etiology of large pericardial effusions. Am J Med 1993; 95: 209–13. 24. Heindenrish PA, Eisenberg MJ, Kee LL. Pericardial effusion in AIDS. Circulation 1995; 92: 3229–34. 25. Sagrista‐Sauleda J, Merce AS, Soler‐Soler J. Diagnosis and management of pericardial effusion. World J Cardiol 2011; 3: 135–43. 26. Spodick DH. Acute cardiac tamponade. N Engl J Med 2003; 349: 684–90. 27. Permanyer‐Miralda G, Sagristá‐Sauleda J, Soler‐Soler J. Primary acute pericardial disease: a prospective series of 231 consecutive patients. Am J Cardiol 1985; 56: 623–30. 28. Tsang TS, Seward JB, Barnes ME, et al. Outcomes of primary and secondary treatment of pericardial effusion in patients with malignancy. Mayo Clin Proc 2000; 75: 248–53. 29. Tsang TS, Barnes ME, Gersh BJ, et al. Outcomes of clinically significant idiopathic pericardial effusion requiring intervention. Am J Cardiol 2003; 91: 704–7. 30. Pepi M, Muratori M, Barbier P, et al. Pericardial effusion after cardiac surgery: incidence, site, size and haemodynamic consequences. Br Heart J 1994; 72: 327–31. 31. Meurin P, Tabet JY, Thabut G, et al. NSAID treatment for postoperative pericardial effusion. A multicenter randomized double‐blind trial. Ann Intern Med 2010; 152: 137–43. POPE trial. 32. Meurin P, Wever H, Renaud N, et al. Evolution of the postoperative pericardial effusion after day 15: the problem of the late tamponade. Chest 2004; 125: 2182–7. 33. Ashikhmina EA, Schaff HV, Sinak LJ, et al. Pericardial effusion after cardiac surgery: risk factors, patient profiles, and contemporary management. Ann Thorac Surg 2010; 89: 112–18.

Constrictive pericarditis 34. Haley JH, Tajik AJ, Danielson GK, et al. Transient constrictive pericarditis: causes and natural history. J Am Coll Cardiol 2004; 43: 271–5. 35. Ling LH, Oh JK, Schaff HV, et al. Constrictive pericarditis in the modern era. Evolving clinical spectrum and impact on outcome after pericardiectomy. Circulation 1999; 100: 1380–6. 36. Bertog SC, Thambidorai SK, Parakh K, et al. Constrictive pericarditis: etiology and cause‐specific survival after pericardiectomy. J Am Coll Cardiol 2004; 43: 1445–52. 37. Hanna EB. Constrictive pericarditis. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012. 38. Hurrell DG, Nishimura RA, Higano ST, et al. Value of respiratory changes in left and right ventricular pressures for the diagnosis of constrictive pericarditis. Circulation 1996; 93: 2007–13. 39. Talreja DR, Nishimura RA, Oh JK, Holmes DR. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol 2008; 51: 315–19. 40. Tabata T, Kabbani SS, Murray DR, et al. Difference in the respiratory variations between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation. J Am Coll Cardiol 2001; 37; 1936–42. 41. Patel AR, Dubrey SW, Mendes LA, et al. Right ventricular dilation in primary amyloidosis: an independent predictor of survival. Am J Cardiol 1997; 80: 486–92. 42. Jaber WA, Sorajja P, Borlaug BA, Nishimura RA. Differentiation of tricuspid regurgitation from constrictive pericarditis: novel criteria for diagnosis in the cardiac catheterization laboratory. Heart 2009; 95: 1449–54. 43. Bush CA, Stang JM, Wooley CF, Kilman JW. Occult constrictive pericardial disease diagnosis by rapid volume expansion and correction by pericardiectomy. Circulation 1977; 56: 924–30. 44. Oh JK, Tajik AJ, Appleton CP, et  al. Preload reduction to unmask the characteristic Doppler features of constrictive pericarditis: a new observation. Circulation 1997; 95: 796–9. 45. Boonyaratavej S, Oh JK, Tajik AJ, et al. Comparison of mitral inflow and superior vena cava Doppler velocities in chronic obstructive pulmonary disease and constrictive pericarditis. J Am Coll Cardiol 1998; 32: 2043–8. 46. Klein AL, Cohen GI, Pietrolungo GF, et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler echocardiographic measurements of respiratory variations in pulmonary venous flows. J Am Coll Cardiol 1993; 22: 1935–43. 47. Tabata T, Kabbani SS, Murray DR, et al. Difference in the respiratory variations between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation. J Am Coll Cardiol 2001; 37; 1936–42. 48. Talreja DR, Edwards WD, Danielson GK, et al. Constrictive pericarditis in 26 patients with histologically normal pericardial thickness. Circulation 2003; 108: 1852–7. 49. Feng D, Glockner J, Kim K, et al. Cardiac magnetic resonance imaging pericardial late gadolinium enhancement and elevated inflammatory markers can predict the reversibility of constrictive pericarditis after antiinflammatory medical therapy. Circulation 2011; 124: 1830–7. 50. Senni M, Redfield MM, Ling LH, et al. Left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis. J Am Coll Cardiol 1999; 33: 1182–8.

Further reading Atar S, Chiu J, Forrester JS, et al. Bloody pericardial effusion in patients with cardiac tamponade: is the cause cancerous, tuberculous, or iatrogenic in the 1990s? Chest 1999; 116: 564–9.

Part 7  Congenital Heart Disease 18  Congenital Heart Disease

1. Acyanotic congenital heart disease I. Atrial septal defect (ASD)  389 II. Patent foramen ovale (PFO)  393 III. Ventricular septal defect (VSD)  394 IV. Patent ductus arteriosus (PDA)  396 V. Coarctation of the aorta  397 VI. Other anomalies  397 2. Cyanotic congenital heart disease I. Pulmonary hypertension secondary to shunt  398 II. Tetralogy of Fallot  399 III. Ebstein anomaly  401 3. More complex cyanotic congenital heart disease and shunt procedures I. Functionally single ventricle and Fontan procedure  401 II. Transposition of great arteries (TGA)  403 III. Other anomalies  404 Questions and answers  404

1 .   A c ya n o t i c c o n g e n i ta l h e a rt d i s e a s e I.  Atrial septal defect (ASD) A. Embryology (see Figure 18.1) The interatrial septum has two parts: • A lower part connected to the endocardial cushions at the valvular level and called septum primum. The septum primum is thin and membranous. • An upper part called septum secundum. The septum secundum is thick and muscular. These two septa meet and overlap. The overlap area is called fossa ovalis.1,2 In the fetus, the overlap area is not sealed, leaving a tunnel that allows blood to flow from right to left. This tunnel is called foramen ovale. In the fetus, oxygenated blood flowing from the IVC is directed towards the left heart through the septum secundum and foramen ovale, and is ejected into the ascending aorta, the brain, and upper body. Deoxygenated blood flowing from the SVC continues into the RV  and is ejected into the high‐resistance pulmonary circulation, then the descending aorta through the ductus arteriosus. Overall, the RV provides ~55% of the systemic cardiac output (lower body), while the LV provides ~45% of the systemic output (upper body). The pulmonary vascular resistance is elevated in the fetus, as a reaction to the poorly oxygenated lung, and the pulmonary arterial pressure is higher than the systemic pressure; at birth, the pulmonary resistance and pressure dramatically drop.

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Septum secundum = upper septum (right-sided flap) Fossa ovalis with foramen ovale Septum primum = lower septum (left-sided flap)

LA

LV RA RV

IVC flow Figure 18.1  Interatrial septum. Embryologically, blood coming from the IVC is directed into the LA by the right‐sided, septum secundum flap. The septum primum acts like a one‐way door that opens when the RA pressure rises, and closes when the LA pressure supersedes the RA pressure, closing the foramen ovale. The prominent, septum secundum boundary of the fossa ovalis is called limbus (on the side of the RA). The septum primum was initially localized at the upper portion of the RA. It grew down and touched the endocardial cushions, then developed a defect in its middle and top portions (ostium secundum) to allow blood shunting. This defect got covered by a growing muscular septum secundum, which eventually met the septum primum. V Septum primum 2

IVC Septum secundum

EV

SVC RA Figure 18.2  Bicaval TEE view showing a PFO between the septum primum (thin, at bottom) and the septum secundum (thick, on top). EV, Eustachian valve.

B.  Pathology (see Figures 18.2, 18.3, 18.4) 1.  At birth, the PA pressure significantly drops and the pulmonary arterial and venous flow significantly increase. As a result, the LA ­pressure rises and pushes the septum primum to seal the overlap area.1 If it does not seal, a patent foramen ovale (PFO) persists. PFO is a persistent tunnel or flap; this is different from the gap of an ASD.2 2.  If the two septa do not meet and overlap, a wide, open gap will exist between the two septa in the middle of the interatrial septum: this is called ostium secundum ASD (70% of ASDs). 3.  If the septum primum does not connect with the endocardial cushions, a gap will be present at the lower level of the interatrial septum: this is ostium primum ASD (15–20% of ASDs). No atrial septal tissue is seen above the base of the atrioventricular valves. Ostium primum ASD may be continuous with a defect of the membranous ventricular septum, in which case the defect is called complete atrioventricular (AV) canal defect, or endocardial cushion defect. The endocardial cushions are central embryonic structures that develop into the AV valves and the membranous ventricular septum. In complete AV canal defect, no tissue separates the AV valves; the AV valves are actually one valve at one horizontal plane, with an atrial and ventricular septal defect in the middle. An ostium primum ASD without VSD is called partial AV canal defect. In the partial AV defect, the ventricular septum is closed by the endocardial cushions or by the septal tricuspid leaflet early in life, so that only a primum ASD is present. In another form called transitional AV canal defect, most of the ventricular defect is closed by the septal leaflets of the AV valve, so that only a small residual inlet VSD is seen and two AV valves are present. Thirty‐five percent of patients with AV canal defect have Down syndrome, especially those with complete AV canal defects. Whereas normally the tricuspid valve is a bit lower (more apical) than the mitral valve, the tricuspid and mitral valves are at the same level in AV canal defect, as the mitral valve plane is pulled down. The down‐pulling of the mitral valve elongates the LVOT, creating a “goose neck” narrowing of the LVOT with potential LVOT obstruction (Figure 18.5). Mitral valve defects (cleft valve) are frequently seen and result in eccentric MR; tricuspid defects may also be seen. 4.  Sinus venosus defect is a gap at the upper posterior part of the septum at the SVC–RA connection. It is almost always associated with some degree of anomalous pulmonary venous return, in which the right upper pulmonary vein, and sometimes a right middle or inferior pulmonary vein, drain into the RA.

Chapter 18.  Congenital Heart Disease  391

RV 1 RA

Primum ASD without VSD

1

Secundum ASD

2

2

RA

LA

RV SVC RA

1 Secundum ASD

Sinus venosus ASD with anomalous pulmonary venous return

Pulmonary vein

Primum ASD with inlet VSD

RA

2

= Complete AV septal defect

Figure 18.3  Types of ASD. Secundum ASD results from excessive involution of the top portion of the septum primum (→ does not meet the septum secundum). Primum ASD results from failure of the septum primum to reach the endocardial cushions. Thus, beside primum ASD, secundum ASD is also a defect of the septum primum. Septum primum is the thinner septum, marked by 1; septum secundum is marked by 2.

ASD Septum secundum

Septum primum

PFO

Septum secundum

Septum primum

PFO with multifenestrated ASD

Figure 18.4  En face view of the interatrial septum. Occasionally, both a PFO and a small ASD may be present: ASD in one plane where the septum primum has excessively involuted, PFO in the other planes where the two septa continue to overlap. Alternatively, PFO may be present with multiple small ASD holes.

Aorta

Aorta LVOT LV

Mitral

Normal mitro-aortic continuation

Mitral

Mitral valve plane pulled down in primum ASD, creating a narrowing of the LVOT (goose neck deformity)

Figure 18.5  Goose‐neck deformity of the LVOT in primum ASD.

Partial anomalous pulmonary venous return may also be seen with secundum ASD. A right upper pulmonary vein draining into the RA or SVC is the most common anomaly, accounting for >90% of the anomalous venous return; a left pulmonary vein draining into the innominate vein may also be seen. If only one pulmonary vein is involved, the amount of shunting induced by the anomalous vein is, per se, mild. However, in conjunction with an ASD, the anomalous vein may significantly add to the shunt burden. C. Consequences 1.  A significant ASD is an ASD with a prominent left‐to‐right shunt leading to a pulmonary flow (Qp) 1.5 times larger than the systemic flow (Qs): Qp/Qs ≥1.5/1.0. A large ASD is characterized by a Qp/Qs ≥2.

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2.  A significant ASD causes RA/RV volume overload, dilatation, and failure. This may, rarely, occur in childhood if the ASD is large. Most patients are minimally symptomatic in the first three decades; exercise intolerance and hemodynamic compromise occur later in adulthood (30s to 40s), and most patients are symptomatic by the age of 50. AF and right heart failure develop by the age of 40 in ~10% of patients, then become more prevalent with age. In fact, for the same ASD size, left‐to‐right shunting may become more severe with age, as LV diastolic dysfunction occurs and LA pressure rises. Also, LA enlargement that occurs with age stretches and widens the ASD. ASD does not, by itself, lead to LA enlargement unless AF occurs. A complete AV canal defect, on the other hand, leads to a severe shunt and Eisenmenger syndrome early in infancy if not corrected. Paradoxical embolism may be seen. 3.  Pulmonary hypertension (PH) may occur but is rarely severe, because the RV usually fails before severe PH develops. In a way, the failing RV constitutes a barrier that protects the pulmonary arteries from volume overload. If PH is severe, a second causative diagnosis should be considered, especially if ASD5 Wood units.3 Cyanosis and reversal of the shunt to a right‐to‐left shunt often result from RV failure and the consequent rise of RA pressure, even without any PH. D. Diagnosis 1.  Exam: • Fixed split S2 • Scratchy systolic ejectional murmur at the pulmonic area (left upper sternal border) due to the increased right‐sided flow. Systolic TR murmur may also be heard. • RV heave • Increased JVP with a large V wave indicative of RV failure ± TR RV heave is more prominent in RV volume‐overload states, such as ASD, than in pressure‐overload states (cor pulmonale, pulmonic stenosis). 2.  ECG: • Ostium secundum ASD: RBBB (usually incomplete), right axis deviation, R‐wave notching in the inferior leads (crochetage), right atrial enlargement • Ostium primum ASD: RBBB + left axis deviation ± prolonged PR interval (primum ASD damages the infra‐Hisian conduction system) • Sinus venosus ASD: ectopic atrial rhythm (non‐sinus P waves) • AF or atrial flutter may be present 3.  CXR features: enlarged RV, enlarged central PA knob, and pulmonary plethora from increased flow. 4.  Echo: • TTE often establishes the diagnosis by visualizing the defect and the Doppler flow across it. The defect is usually >8 mm, as smaller defects usually close spontaneously in infancy and do not usually cause hemodynamic compromise. TTE can calculate Qp/Qs ratio (pulmonary to systemic flow ratio), which is equal to: (velocity [VTI] × diameter) at the RVOT, divided by (velocity [VTI] × diameter) at the LVOT TTE also shows RA and RV enlargement, consequences of any significant ASD. • The subcostal view is orthogonal to the interatrial septum and is the best diagnostic view for ASD. Over 90% of secundum ASDs are seen in this view, which is also the best view for the sinus venosus defect and for assessment of shunt direction by spectral Doppler. However, the sinus venosus defect, or, rarely, other defects, may be missed by TTE. SVC view (right parasternal view) or superior angulation in a subcostal view may allow the diagnosis of sinus venosus defect. TEE permits better visualization if the diagnosis is suspected but not clearly established in a patient with RA/RV enlargement. Also, intravenous bubble injection may suggest the diagnosis of ASD in these patients. In PFO or secundum ASD, the bubbles fill the RA then the LA; in sinus venosus ASD, the bubbles simultaneously fill both the RA and LA. RA and RV enlargement without any obvious cause (such as left HF) in an otherwise healthy adult should prompt a search for an overlooked ASD, especially sinus venosus ASD. 5.  Right heart catheterization: catheterization permits the hemodynamic diagnosis of ASD (O2 saturation step‐up ≥8% between SVC and RA), and permits Qp/Qs quantification. E. Treatment 1.  Up to 62% of secundum ASDs may spontaneously close in the first year of life, especially ASD 40 years of age does not prevent AF or stroke. 5.  Secundum ASD does not require endocarditis prophylaxis. After correction and in the absence of a residual shunt, patients require endocarditis prophylaxis for 6 months only (i.e., until the surgical site endothelializes). If a residual defect persists, endocarditis prophylaxis is indicated lifelong.

II.  Patent foramen ovale (PFO) A cryptogenic stroke is a stroke that is unexplained by carotid disease, cardiac disease such as AF or LV thrombus, or prothrombotic coagulopathies (mainly antiphospholipid syndrome). Moreover, to make the diagnosis of a cryptogenic stroke, a lacunar stroke must be excluded (lacunar stroke being a small, deep white‐matter stroke 50). There is an association between PFO and cryptogenic stroke, patients with cryptogenic stroke having a higher prevalence of PFO than the normal population (~40–50% prevalence). This association is particularly established in patients 10–30 microbubbles or PFO tunnel width ≥2–4 mm, meaning that the separation between secundum septum and primum septum is ≥2–4 mm. An atrial septal aneurysm, defined as hypermobility of the thin septum primum >1 cm from midline, is less clearly associated with an increased stroke risk when isolated,7 although one meta‐analysis suggests it is.6 The combination of the following three patient characteristics increases the probability that the stroke is PFO‐related: age 3–5 cycles for the bubbles to appear on the left side, the shunt is at the pulmonary level (e.g., AV malformation). Normally, during quiet breathing, the LA pressure is larger than the RA pressure, thereby closing the septum primum towards the septum secundum and preventing any significant shunting, except very briefly. A physiologic right‐to‐left shunt occurs when the RA volume suddenly and largely increases at a time when the LA volume does not, which reverses the LA–RA pressure differential; this is seen during deep inspiration or during the release phase of the Valsalva maneuver. Conversely, the strain phase of Valsalva may reduce right venous return and right‐to‐left shunting. Treatment of a cryptogenic stroke presumably due to PFO • Aspirin or warfarin. The PICSS trial, a large trial that compared aspirin to warfarin in patients with cryptogenic stroke, did not find any difference in stroke recurrence between the two therapies in patients with PFO.5

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• In patients who had one or more prior strokes/TIAs, PFO closure has not shown superiority to medical therapy in reducing stroke recurrence, according to three randomized trials (in one trial, 37% of patients had more than one prior TIA/stroke). In fact, the risk of stroke recurrence after a cryptogenic stroke is relatively low, ~4–5% at 4 years under antiplatelet therapy (as seen in all three PFO trials), with a potentially higher risk in combined PFO and atrial septal aneurysm.7–10 While low, this risk is cumulative over time and may be particularly consequential in young patients over the long term. PFO closure showed a trend toward stroke reduction, which may become more significant upon long‐term follow‐up. PFO closure may be considered in young patients with cortical stroke and no smoking, diabetes, or HTN.

A PFO can lead to mild and insignificant degree of left‐to‐right (L–R) or right‐to‐left (R–L) shunting, depending on instantaneous RA–LA pressure differential and breathing cycle. PFO, per se, does not lead to a hemodynamically significant shunting or cavitary dilatation. Conversely, severe RA dilatation/pressure elevation may lead to a significant shunting across the PFO. In fact, R–L shunting through a PFO in patients with RV failure is a compensatory, secondary process that relieves RV failure, and PFO is an innocent bystander rather than a primary shunt process. For example, in severe primary pulmonary hypertension, R–L shunt may be seen through a PFO or a small ASD. This shunt is secondary to pulmonary hypertension rather than a cause of pulmonary hypertension, and is associated with improved survival in primary pulmonary hypertension. Rarely, significant R–L shunting occurs across a PFO despite a normal RA/RV; this shunt occurs in the upright position (platypnea–orthodeoxia syndrome) or during exertion. The diagnosis is made by documenting orthostatic or exertional O2 desaturation that is otherwise unexplained. While the higher LA pressure serves to appose the septum primum over the septum secundum and close the PFO tunnel, preventing any shunt, a severely increased LA pressure may lead to a L–R shunt.11,12

III.  Ventricular septal defect (VSD) A. Types (see Figure 18.7) The interventricular septum has a small membranous portion and a large muscular portion. The muscular portion is divided into three zones (inlet between the atrioventricular valves, outlet beneath the great arteries, and trabecular). A VSD is either perimembranous or muscular:13 1.  Perimembranous VSD is the most common VSD (70–80% of VSDs). It involves the membranous septum and extends a bit into one of the three muscular regions (inlet, trabecular, or outlet). An entirely membranous VSD is rare, as the membranous septum is a small fibrous center. 2.  Muscular trabecular VSD is the next most common VSD. 3.  Inlet VSD. The inlet septum separates the septal cusps of the mitral and tricuspid valves. Inlet VSD is mainly a defect of the muscular inlet septum, but the membranous septum is frequently involved. A gross deficiency of the inlet septum is associated with AV canal defect. Conversely, a small inlet VSD is not usually associated with AV canal defect.13 4.  Outlet VSD (subarterial or infundibular VSD). Outlet VSD is mainly a defect of the muscular outlet septum, but the membranous septum is frequently involved. When outlet VSD is very high and abuts both arterial valves, it is called supracristal VSD or doubly committed VSD (the crista supraterminalis being a muscular ridge in the RV outflow). B.  Consequences and associations • A large VSD leads to a left‐to‐right shunt, with progressive pulmonary hypertension and progressively large volume circulating back to the LV and leading to LV failure from volume overload. As pulmonary hypertension becomes more severe, Eisenmenger syndrome and cyanosis occur. A hemodynamically significant VSD leads to LV and LA dilatation and LV failure from volume overload. Since the LV‐to‐RV shunt is systolic, the RV does not get overloaded in diastole and therefore RV failure does not occur. Even when pulmonary hypertension develops, right‐sided enlargement and tricuspid regurgitation are very unusual because the VSD allows decompression of the RV. This is in contrast to ASD, which leads to RV diastolic volume overload, RV dilatation and failure, and tricuspid regurgitation; in ASD, the LV is protected by the unloading that occurs at the LA level.14

• A VSD, especially an outlet VSD, may be associated with aortic insufficiency. This results from high‐velocity jet lesions, similarly to what occurs with subaortic membranous stenosis; also, the outlet defect diminishes the cuspal support and may lead to aortic cusp(s) prolapse. Outlet VSD may be associated with subpulmonic or subaortic stenosis; the subpulmonic stenosis may lead to a right‐to‐left shunt but protects from Eisenmenger syndrome. Any VSD may also be associated with a bicuspid aortic valve and coarctation of the aorta. • The membranous septum has an interventricular portion but also a more proximal (posterior) portion that separates the LV from the RA. A Gerbode defect is a perimembranous VSD extending more proximal to the tricuspid insertion, leading to a high‐velocity LV‐to‐RA shunt and RV failure, in addition to the LV‐to‐RV shunt (Figure 18.8). C. Exam and natural history With the exception of bicuspid aortic valve, VSD is the most common congenital defect in children. A small VSD leads to a loud, harsh pansystolic murmur at the left lower sternal border, sometimes with a thrill, whereas a large VSD has a softer murmur. Thus, a loud murmur implies a more benign VSD than a soft murmur. Small VSDs are called restrictive because they allow only limited shunting.

Chapter 18.  Congenital Heart Disease  395

PV

PV

Membranous septum

Muscular outlet septum

AoV

Outlet muscular septum

AoV Membranous septum Inlet muscular septum

Longitudinal view

TV MV Muscular inlet septum

Muscular trabecular septum

Axial view

Trabecular VSD

RV

Inlet VSD in 4-ch Perimembranous VSD in 5-ch RA

LA

Four chamber view RV

Ao LV

Trabecular VSD

Tricuspid valve

LA

Either perimembranous or outlet VSD

Long-axis view

RV

Perimembranous VSD

RA

Outlet VSD

RVOT RC

NC

Pulmonic valve

LC

LA

Short-axis view at the aortic valve level

Figure 18.7  Anatomic and echocardiographic localization of VSD. The membranous septum is bordered by the septal tricuspid leaflet on the right and the subaortic area on the left; it is superior to the mitral valve. Perimembranous VSD is actually a superior/anterior form of VSD, and therefore it is seen on the long‐axis echo view. Inlet VSD is bordered by the tricuspid valve on the right and the mitral valve on the left and is the one that continues with an atrial septal defect to form the AV canal defect. Note that the pulmonic valve (PV) is higher and more anterior than the aortic valve (AoV), and the outlet septum is larger on the right than the left side. An outlet VSD that extends all the way to the PV is called supracristal VSD.

RV

LV

RA Figure 18.8  Gerbode defect on an apical five‐chamber view. Perimembranous VSD extends more proximal to the tricuspid valve and leads to LV–RA shunt, in addition to the LV–RV shunt. Being a perimembranous defect, it may not be seen on the four‐chamber view. The defect may have an inlet extension.

396  Part 7.  Congenital Heart Disease

Small perimembranous or trabecular VSDs have a high closure rate (50–80%) by 2–10 years of age. A perimembranous VSD may close by the apposition of the septal tricuspid leaflet, which sometimes forms a pouch at the level of the sealed defect.15 A small VSD is hemodynamically insignificant, but is associated with a risk of endocarditis. Large VSDs (non‐restrictive, Qp/Qs >2) have a low spontaneous closure rate and lead to left HF, then Eisenmenger syndrome in infancy or childhood. They are typically corrected early on, before 1 year of age. Moderately large VSDs (Qp/Qs 1.4–2) may be tolerated for years before leading to hemodynamic compromise later on, in adulthood. Adults presenting with VSD usually have a small VSD that did not close spontaneously and is not leading to any hemodynamic compromise. Other possibilities are: VSD that persisted after surgical repair; moderate VSD that is leading to hemodynamic compromise in adulthood (unusual); or large, non‐corrected VSD that led to Eisenmenger syndrome long before adulthood. D.  Diagnosis, location, and shunt fraction Qp/Qs are established by TTE TTE allows estimation of the VSD size: a small VSD has a diameter smaller than 1/3 of the aortic root diameter, a large VSD is a VSD larger than the aortic root. A large VSD typically has a large Qp/Qs ratio (>2), a small velocity, and a small pressure gradient across it because of the high RV systolic pressure (non‐restrictive VSD). TTE may miss a small trabecular VSD but very rarely misses other types of VSD. E. Treatment Surgical closure (direct closure or patch closure) is indicated as soon as possible for: • Significant VSD (moderately restrictive or large non‐restrictive) with a Qp/Qs ≥1.5. • Pulmonary hypertension that is not severe or, if severe, is responsive to vasodilator challenge. The improvement of pulmonary hypertension with vasodilator challenge means it is reversible, as opposed to Eisenmenger syndrome’s pulmonary hypertension. • Large VSD with LV or LA dilatation or LV dysfunction. • Outlet VSD, regardless of its size, because of the risk of progressive AI. Perform the surgery soon in infancy if needed (at the age of 3–6 months). Postoperative patch leaks may be seen but rarely require reoperation. Occasionally, if VSD closure cannot be immediately performed, PA banding is performed to reduce the pulmonary flow and the risk of Eisenmenger syndrome before definitive surgery.

IV.  Patent ductus arteriosus (PDA) A.  Definition and consequences PDA is a persistent communication between the left pulmonary artery and the descending aorta just distal (~1 cm) to the left subclavian artery. It leads to left‐to‐right shunt and massive LV volume overload from the shunt volume that circulates back to the LV. LV failure, which is initially a high‐output failure, subsequently ensues (left HF being the most common complication). It can also lead to progressive pulmonary hypertension and Eisenmenger syndrome with shunt reversal to a right‐to‐left shunt. In this case, a differential rather than a generalized cyanosis is seen (cyanosis of the feet only). The right‐to‐left shunt occurs distal to the innominate artery, so that the O2 saturation in the upper extremities is preserved whereas the O2 saturation in the lower extremities is low, explaining the differential cyanosis and clubbing, i.e., cyanosis that is much more prominent in the lower extremities. The origin of the left subclavian artery may be close enough to the ductus to receive unoxygenated blood, and therefore cyanosis and clubbing of the left hand may be seen. The right hand remains normal until a severely reduced cardiac output leads to generalized cyanosis. Infectious endarteritis at the shunt level may also be seen. B. Severity and presentation Spontaneous closure of a PDA is unlikely in term infants older than 3 months or pre‐term infants older than 12 months. A large shunt (Qp/ Qs >2) is symptomatic in infancy and leads to Eisenmenger syndrome early on, as early as 8 months, if untreated. A moderate shunt (Qp/Qs 1.5–2) may lead to hemodynamic compromise at a later age (childhood or adulthood, up to the third ­decade). A small shunt (Qp/Qs 20 mmHg between the upper and lower extremities with a radial‐to‐femoral pulse delay. The blood pressure discrepancy may attenuate and become unnoticeable as more collaterals develop with age. The murmur is mid‐systolic, heard best over the left upper sternal border, radiates to the back and spine, and may become continuous if the stenosis is severe enough to produce a diastolic pressure gradient. CXR shows rib notching and a figure of 3, which is a double bubble of the descending aorta (pre‐ and post‐stenotic dilatation). 2.  Hemodynamic: a 20 mmHg peak‐to‐peak gradient defines significant aortic coarctation. In patients with collaterals, the aortic gradient may be reduced to 10–20 mmHg; acquired aortic ectasia, significant collateral flow, or left ventricular hypertrophy would define significant coarctation in this case. The diastolic gradient is usually mild; in fact, collateral flow prevents a drop in distal aortic pressure during diastole but is not enough to prevent the systolic drop in pressure. 3.  Echo (suprasternal view), and CT or MRI are useful imaging modalities. B. Treatment The coarctation may be treated surgically: excision followed by end‐to‐end anastomosis with or without patch repair, or excision with placement of an interposition graft. This treatment may be performed in infancy in very severe cases, or in the first 5 years of life in less severe cases. The aorta reaches 50% of its eventual size at 3–5 years of age, such that, when surgery is performed at this age, a lack of growth of the surgical site does not translate into severe stenosis. A younger age at the time of initial repair translates into better long‐term outcomes (less irreversible damage of the aortic wall and less LV hypertrophy). The best survivorship was observed in patients operated at 9 years of age or less.17 Coarctation may be treated percutaneously with angioplasty in patients older than 1 year. At less than 1 year of age, there is a high risk of recurrence and aneurysm formation after angioplasty. Stenting is the percutaneous treatment of choice in patients >30 kg, while angioplasty is the treatment of choice for patients >1 year and 6 Wood units or >2/3 the SVR • Left‐to‐right shunt that has become bidirectional with significant right‐to‐left shunting and hypoxemia A significant response is characterized by a reduction of the mean PA pressure by >10 mmHg to 20% to 1.5. In the absence of a significant response, the pulmonary arterial remodeling is at an advanced and irreversible stage and the shunt should not be closed. If the shunt is closed at this stage, the right‐sided volume overload and the pulmonary hypertension worsen postoperatively. In case of a significant response, the patient is treated with pulmonary vasodilators until the PA pressure declines to an operable range, then the shunt is closed.20 Eisenmenger syndrome is usually due to VSD (most common cause), PDA, or, less commonly, ASD. More specifically in ASD, shunt reversal and cyanosis may be seen without pulmonary hypertension. RV volume overload leads to RV failure, which leads to an increase in RA pressure, at times exceeding LA pressure. In ASD, the right‐to‐left shunt is often determined by RV failure rather than PA pressure, and hypoxemia may be seen without severe pulmonary hypertension.20 In cases of ASD with elevated PVR and/or bidirectional shunting, balloon occlusion testing may be performed. Temporary balloon occlusion of the ASD is performed, and RA pressure, PA pressure, and PCWP are measured through a Swan catheter. A significant increase in right‐sided pressures or a drop in CO indicates a significant risk of right‐sided failure associated with ASD closure. On the other hand, a significant increase in LA pressure measured through the balloon occlusion catheter indicates that the patient has significant LV dysfunction (e.g., LVH with diastolic failure) and was getting relieved by the left‐to‐right shunting, i.e., the preload reduction. LV may not be able to cope with the acute increase in preload following ASD closure, which may lead to acute pulmonary edema. This is mainly seen when ASD is closed in an older population. ASD closure should be postponed and the patient appropriately treated with antihypertensive agents and diuretics before attempting closure.21 B.  Clinical presentation of Eisenmenger syndrome Eisenmenger syndrome that is secondary to VSD or PDA typically develops before the age of 2 years. Eisenmenger patients have a good functional capacity up until their 20s, then develop a progressive functional decline, cyanosis, atrial and ventricular arrhythmias (common), and hemoptysis. Hemoptysis results from the systemic arterial collaterals to the lung; it may be severe and is the cause of death in ~15% of patients. Right heart failure develops later. Stroke and brain abscess from paradoxical emboli may occur; polycythemia is also a factor.

Similarly to pulmonic stenosis, the RV does not fail and TR does not occur until late in the course of disease (age 40s). On the one hand, the congenital RV tolerates pressure overload more than the adult RV, and on the other hand, the right‐to‐left shunt allows RV or PA decompression, therefore delaying failure. This explains why Eisenmenger is much better tolerated than idiopathic pulmonary hypertension. RV heave is present but the RV is not dilated; on JVP exam, A wave is large but V wave and mean JVP are normal. On exam, Eisenmenger is characteristically a silent cyanotic heart disease, i.e., no murmur is heard. The equalization of pressures across chambers makes the right‐to‐left shunt a low‐gradient, silent shunt. In fact, the presence of a VSD or a PDA murmur makes the diagnosis of irreversible pulmonary hypertension unlikely.

Chapter 18.  Congenital Heart Disease  399

CXR is characterized by an enlarged central PA with rapid tapering and lung oligemia. The PA is sometimes calcified, which is not the case in idiopathic pulmonary arterial hypertension, where pulmonary hypertension is not as longstanding. C. Treatment The causal shunt should not be closed at this point, as the right‐to‐left shunt relieves the severity of pulmonary hypertension and prevents RV failure. Treatment consists of avoiding exacerbating factors, such as dehydration, systemic vasodilators (which increase right‐to‐left shunt), and excessive physical activity. Pulmonary vasodilators may be used (bosentan, sildenafil, IV prostacyclin) and have been shown to improve symptoms. Beware that pulmonary vasodilators may increase pulmonary flow and lead to pulmonary edema, in which case diuretics may be required. They may also have an untoward systemic vasodilatory effect. In advanced cases, lung transplant with repair of the cardiac defect may be performed.

In all cases of right‐to‐left shunt, hot conditions, systemic vasodilators, and sedation/anesthesia are risky and should be avoided as much as possible. They reduce SVR and thus increase the right‐to‐left shunt and may lead to hemodynamic collapse. Dehydration may also reduce the marginal right‐sided flow and lead to hemodynamic collapse. If a patient presents with a hyperviscosity syndrome (neurological symptoms accompanying polycythemia, usually hematocrit>65%), first rule out dehydration as a cause of polycythemia. If symptoms persist, phlebotomy with adequate fluid replacement may be considered. Also, search for microcytosis and iron deficiency even in patients with polycythemia, as iron‐ deficient red blood cells are less deformable and more prone to sludging. Polycythemic patients are prone to both thrombosis and bleeding.

II. Tetralogy of Fallot A.  Pathology and consequences Tetralogy of Fallot has four components (Figure 18.9): a.  Outlet VSD with right‐to‐left shunt and cyanosis b.  RV outflow obstruction: the major site of obstruction is usually at the subvalvular, infundibular level. In addition, there is often a stenotic, bicuspid pulmonic valve with supravalvular hypoplasia. There may also be a distal pulmonary arterial stenosis, i.e., pulmonary stenosis may be present at multiple levels. Occasionally, there is an outflow tract atresia (this is a more complex form of tetralogy). c.  Overriding of the aorta over the interventricular septum (Aortic knob *Lung plethora

LAA

RA

RV

*PA “sucked in” *Lung oligemia

LV

LV

RV Normal

Apex points up

ASD

Tetralogy: boot-shaped heart

Aortic prestenotic dilatation

3 Aortic poststenotic dilatation

*PA prominent *Lung oligemia

*PA very prominent, bulging *Normal lung circulation

+rib notching

LV

Apex not up

Eisenmenger LV may be enlarged if VSD or PDA

Coarctation of the aorta

LV

Apex not up

Pulmonic stenosis

Figure 18.10  Radiographic cardiac and mediastinal silhouettes in various congenital heart diseases. In congenital heart disease, assess the following four features: (1) shape of the heart and apex; (2) proximal PA; (3) lung circulation; (4) normal vs. right‐sided aortic arch.

Aorta

Tetralogy with left-sided aortic arch Figure 18.11  CXR in tetralogy with and without right‐sided aortic arch

Aorta

Tetralogy with right-sided aortic arch

Chapter 18.  Congenital Heart Disease  401

2.  Surgical correction. The VSD is closed with a patch. The infundibular muscular stenosis is resected and the RV outflow tract enlarged and patched all the way up to the pulmonic valve. Pulmonic valvotomy is performed in the case of pulmonic stenosis. This can be performed at any age, including the first few months of life. Freedom from late reintervention and normal exercise tolerance are expected in up to 90% of patients.22 3.  Patients may present in adulthood with the following complications: • Severe pulmonary regurgitation is very common and leads to progressive RV enlargement 10–20 years postoperatively. In fact, during surgical repair of tetralogy, the RV outflow is enlarged and patched all the way up to the pulmonic valve, which dilates the valvular annulus and disrupts the valve, making it incompetent; occasionally, the valve is even removed during surgical repair. Pulmonic valve replacement is required whenever severe RV dilatation, RV systolic dysfunction, or exercise limitation occurs. • Persistent RVOT obstruction. • Residual VSD with significant left-to-right shunt (this and the preceding two complications require surgical repair). • Persistent RV dysfunction. • Dilated aortic root, progressive AI secondary to VSD • VT, SVT, and sudden cardiac death, especially in the case of a persistent RV dysfunction or a very wide QRS >180 ms. One‐third of late deaths are sudden. ICD is indicated in case of syncope or sustained VT. The late occurrence of arrhythmia or QRS widening warrants a search for pulmonary regurgitation or other complications.

RV outflow obstruction protects from pulmonary hypertension, and thus patients with tetralogy do not usually develop this complication over the long term. Pulmonary hypertension in a patient with tetralogy may imply peripheral pulmonic stenosis, a mild RV outflow obstruction (before correction) that allowed for a left‐to‐right shunt, or a Blalock–Taussig shunt that produced pulmonary hypertension.

III. Ebstein anomaly The insertion of one or two of the tricuspid valve leaflets (the septal ± posterior leaflets) is displaced toward the apex, which puts part of the RV in the atrium (“atrialization” of the RV and reduction of the “functional RV” mass, which reduces RV output). While the tricuspid valve is normally more apical than the mitral valve, in Ebstein, the distance between the septal tricuspid leaflet and the mitral annulus is excessive, i.e., >8 mm/m2 of BSA. The anterior tricuspid leaflet is never displaced but is elongated and tries to catch the low septal leaflet. Because of the tricuspid abnormality, patients with severe Ebstein anomaly may have severe TR. This is often the biggest issue, as TR leads to progressive RA enlargement, RV failure, and RV volume overload, worsened by the loss of parts of the functional RV. These patients end up with severe right heart failure. They typically present in young adulthood. Fifty percent of patients have an associated ASD, with right‐to‐left shunting and cyanosis at some point. This shunt occurs when the RV fails and RA pressure increases, and early on it may only be exertional. Twenty‐five percent of patients have accessory pathways and SVT. A. Natural history and exam The natural history varies widely and depends on three factors: degree of atrialization of the RV, degree of TR, and presence of right‐to‐left ASD shunt. Some patients develop symptoms as newborns or infants, while some occasionally remain asymptomatic until their 50s or 60s. Patients present with reduced exercise tolerance (reduced cardiac output), right heart failure, and sometimes right‐to‐left shunt with cyanosis, which may only be exertional early on. Exam findings: TR murmur that increases with inspiration, loud and split S1 secondary to the loud closure of the tricuspid valve, and split S2 secondary to ASD. Pectus excavatum may be associated with this anomaly. B. ECG and CXR ECG is characterized by a Himalayan P wave, which is a gigantic, peaked P wave in lead II, as large as the QRS. RBBB may be present and is characteristically splintered, with RSR’S’ pattern. PR may be short, consistent with WPW. CXR shows an enlarged cardiac silhouette (gigantic RA). The lung vasculature is normal or reduced. C. Treatment Ebstein anomaly may be mild. It does not require surgery when the tricuspid displacement and the TR are mild. Surgical intervention, which mainly consists of tricuspid valve repair (rather than replacement) to correct the harmful severe TR, is indicated in cases of deteriorating functional capacity, progressive RV dilatation or RV systolic dysfunction, even if asymptomatic, or any cyanosis (class I indication). Cyanosis is associated with an increased risk of paradoxical embolization.

3 .   M o r e c o mp l e x c ya n o t i c c o n g e n i ta l h e a rt d i s e a s e a n d   s h u n t procedures I.  Functionally single ventricle and Fontan procedure A.  Fontan procedure The Fontan procedure is a palliative surgery that redirects the systemic venous return directly to the pulmonary artery without passing through the RV (= atriopulmonary connection) (Figure 18.12). It is performed in patients who have a “functionally single ventricle,” usually associated with cyanosis. This procedure relieves the chronic volume load on the systemic ventricle that is pumping to both the pulmonary

402  Part 7.  Congenital Heart Disease

SVC

PA

RA

PA

RA

LA

Right PA

LA

Left PA

LA

RA

Aorta

Aorta

RV

LV

LV

IVC

Glenn bidirectional shunt

Fontan RA-PA connection

Tricuspid atresia:

LV

RV is hypoplastic and disconnected from RA (closed tricuspid valve) SVC Right PA

Left PA

LA Caval tunnel

Aorta

LV

IVC

Fontan total cavo-pulmonary connection

Aorta PDA SVC

SVC

PA

RA

Right PA

LA RA

LA

Hypoplastic left heart syndrome: There is no significant LV and the ascending aorta is hypoplastic (aorta fed through PDA)

Caval tunnel

IVC RV

Norwood shunt

Glenn bidirectional shunt after Norwood (RV-aorta communication)

Left PA

LA

Aorta

No LV

RV

Right PA

Left PA

Aorta IVC

RV

Fontan total cavo-pulmonary connection

Figure 18.12  Tricuspid atresia and Fontan procedure (top 2 rows). Hypoplastic left heart syndrome and Fontan procedure (bottom row). Note: a Glenn bidirectional shunt is half of a total cavopulmonary connection: the SVC is disconnected from the RA, then connected to the right PA, while the common PA is tied up; the IVC continues to flow into the RA then the single ventricle (all of the IVC flow is right‐to‐left shunted). Later on, an IVC‐to‐PA tunnel is created, which converts Glenn into a Fontan procedure. When Fontan is done for tricuspid atresia, the pre‐existing ASD is typically closed.

Chapter 18.  Congenital Heart Disease  403

and systemic circulations. What is interesting is that blood flows passively to the PA without an interposed RV, as long as the PA pressure is not increased. In a way, humans who have a normal PA pressure may live without RV for many years or decades; the RV may be forgone for a passive conduit in patients with a normal PA pressure. The venous pressure must be high enough, higher than the pulmonary pressure, to let blood flow towards the pulmonary artery. The systemic venous pressure is, therefore, elevated chronically and allows forward flow. The RA is chronically and severely enlarged. The procedure cannot be performed in patients with pulmonary hypertension.23,24 B. Indications for Fontan The Fontan procedure is indicated for: • Tricuspid atresia: RV is hypoplastic and not connected to the RA (tricuspid valve is closed). Blood flows from the RA to the LA through an ASD, then the LV pumps to the PA through a VSD and to the aorta (Figure 18.12). Initially, these patients temporarily receive a Blalock– Taussig shunt to increase PA flow, then a bidirectional Glenn procedure, then Fontan. • Hypoplastic left heart syndrome: the left heart and the proximal aorta are underdeveloped. The RV pumps to the PA and then the aorta through a PDA. • Double‐inlet single ventricle: double atria and AV valves drain into a single ventricle. In all those complex anomalies, both right‐to‐left and left‐to‐right shunts are present. C.  Variations of Fontan: the three surgeries required in single‐ventricle syndromes One variation of Fontan consists of connecting the SVC to the right PA, and creating a tunnel that connects the IVC to the right PA; this variation reduces blood turbulence and the ensuing waste of blood‐flow energy. Another variation consists of creating fenestrations of the conduit into the RA (and leaving a small ASD), which allows decompression of the venous circulation in case of pulmonary hypertension, so that blood still flows to the left heart and prevents collapse; this allows the performance of the Fontan procedure in patients with pulmonary hypertension. Note that the Fontan procedure is not performed upfront in newborns and infants. Patients 1.5 C. Qp/Qs is 1.5. The patient qualifies for ASD closure D. Regardless of Qp/Qs, the presence of right‐sided enlargement indicates a need for ASD closure Question 3. A 20‐year‐old man presents with dyspnea on exertion. He has a fixed split S2, a systolic murmur, and RV heave. JVP is elevated. He is not hypoxic or cyanotic. Echo shows enlarged RV, secundum ASD of 1 cm with left‐to‐right shunting. Qp/Qs is calculated at 1.3. What is the next step? A. Patient does not qualify for closure as Qp/Qs 3 mm in depth) suggests osteomyelitis Perform X‐ray, which shows bone destruction in osteomyelitis (late finding, occurring several weeks later) ± Perform MRI (sensitive and specific, useful if the diagnosis is not established clinically) Osteomyelitis dictates bone debridement or limited amputation, along with longer antibiotic therapy

2.  Carotid disease Asymptomatic carotid stenosis >70% is associated with a 1.5–2% yearly risk of ipsilateral stroke, much lower than the common perception.40,41 Moreover, this risk is only slightly higher for asymptomatic carotid stenosis >90% (~2.5% yearly stroke risk) and for progressive disease.42 In fact, a recent analysis has shown that even the progression to complete occlusion is usually asymptomatic and is associated with a rather low stroke risk of 50% is associated with ~30% risk of stroke at 2 years, most of which occurs in the first 3 months (~15% at 30 days, 20–30% at 3 months) (NASCET, ECST trials).44–46 The risk decreases with time from the event. The risk is higher, 35% per year, for symptomatic carotid stenosis >90%.47

I. Assessment of carotid stenosis In old trials, invasive angiography has provided the gold‐standard assessment of carotid stenosis. Two angiographic methods have been used to calculate stenosis severity, the NASCET and ECST methods (Figure 19.5). NASCET provides a more conservative estimate of the stenosis; it is the most widely used method and is adopted by the ACC guidelines to define treatment cutoffs.

Chapter 19. Peripheral Arterial Disease  419

NASCET

ECST

B A

Figure 19.5  In the ECST method, the stenosis is measured in reference to the original carotid bulb diameter (A). In the NASCET method, the stenosis is measured in reference to the distal internal carotid diameter (B). A 50% stenosis by NASCET corresponds to ~65% stenosis by ECST.

Doppler ultrasound indirectly estimates the severity of a carotid stenosis by measuring the rise in velocity across the stenosis (severe stenosis >70% is suggested by systolic velocity across the bulb or internal carotid artery >230 cm/s). It may overestimate the severity of a stenosis and therefore, when the stenosis range is equivocal (70–80% range), confirmation with another modality, CTA or MRA, is recommended. In general, after Doppler ultrasound suggests a severe stenosis, CTA or MRA is performed to confirm the finding, define the exact location of the disease, and look for intracranial disease in preparation for CEA. MRA may be performed without gadolinium contrast, although the latter improves arterial delineation. Unlike CTA, MRA is not affected by calcifications and is a better imaging modality in patients with heavy carotid calcifications. Invasive angiography is not usually needed, unless non‐invasive studies yield discordant results or the plan is to perform carotid stenting. CEA may be performed based solely on the result of non‐invasive studies.

II. Medical therapy of carotid stenosis Medical therapy of carotid stenosis consists of: • Aspirin or clopidogrel monotherapy. • Aggressive treatment of HTN; statin therapy. • In patients with prior stroke: ○○ The combination aspirin–dipyridamole (Aggrenox) may be used, but did not prove superior to clopidogrel monotherapy.48 The MATCH trial did not show any advantage of long‐term aspirin–clopidogrel combination vs. clopidogrel monotherapy in patients with a recent stroke (60%, with a reduction of the yearly stroke risk from 2% to 0.5%, at the expense of an early periprocedural stroke hazard of 2%.40,41 However, the benefit of CEA is not dramatic in asymptomatic patients, whose risk of stroke is relatively low despite a severe stenosis. Furthermore, medical therapy has improved since these trials (statin therapy, better HTN control), such that the benefit of CEA over contemporary medical therapy is unclear. CEA is assigned a class IIa recommendation in patients with asymptomatic carotid stenosis >70% if the surgical risk of death or stroke is 70% by non‐invasive studies, or >50% by angiography to qualify for revascularization. Invasive angiography may be needed in symptomatic patients with carotid stenosis of 50–70% on non‐invasive imaging to prove the severity of the stenosis, as non‐invasive imaging frequently overestimates the true severity of a stenosis in this range.

V. Main risks of CEA and carotid stenting Risk of perioperative stroke after CEA or carotid stenting: • 1–2% when performed for asymptomatic carotid stenosis • 3–4% when performed for symptomatic carotid stenosis The risk of minor stroke is slightly higher with carotid stenting than with CEA. The perioperative stroke risk is followed by a 0.5%–1% stroke risk per year (0.5% for asymptomatic and 1% for symptomatic carotid stenosis). There is also a restenosis risk of 5–10%, mainly in the first 18 months (neointimal hyperplasia early on, recurrent atherosclerosis later on). To assess for restenosis, carotid Doppler is performed at 1 month and 6 months, then annually.

VI.  CEA versus carotid stenting The SAPPHIRE trial has shown that in high‐surgical‐risk patients with symptomatic or asymptomatic carotid stenosis, carotid stenting provides a non‐inferior alternative to CEA.54 The CREST trial enrolled average‐risk surgical patients with symptomatic or asymptomatic carotid stenosis (stenosis was symptomatic in ~50% of patients). There was no difference between CEA and stenting for the combined risk of death/MI/stroke up to 4 years (~7%). CEA was associated with a higher risk of periprocedural MI, while carotid stenting was associated with a higher risk of minor strokes, mainly in patients older than 70 years. CEA was associated with ~5% risk of cranial nerve palsy.58 When carotid stenting is performed, the use of embolic protection is mandatory. The procedure should be aborted if difficult anatomy precludes the use of embolic protection. Decisions to perform CEA vs. carotid stenting may be individualized based on the patient’s age, difficult angiographic anatomy (favors CEA), cardiopulmonary or neck comorbidities (favor stenting), and patient’s preference, keeping in mind the higher risk of minor stroke with stenting and the higher risk of MI with CEA (Table 19.7).53 The combination of aspirin and clopidogrel is mandatory for 1 month after stenting, followed by aspirin monotherapy. A 2‐week duration of dual antiplatelet therapy may be acceptable if necessary (SAPPHIRE trial).54

VII.  Carotid disease in a patient undergoing CABG Observational studies have consistently reported that the risk of stroke associated with CABG is ~2% in patients with no significant carotid stenosis and 3% in patients with asymptomatic severe carotid stenosis.59–61 These figures, however, increase to ≥ 5% in those with bilateral carotid stenoses or a history of stroke or TIA. No clear evidence supports prophylactic CEA in CABG patients with unilateral (>80%) asymptomatic carotid stenosis. Most postoperative strokes occur in patients without any carotid disease (76%) or in patients with carotid disease receiving synchronous CEA–CABG.61 In addition, primary carotid disease alone is responsible for less than 40% of postoperative strokes, the rest being due to aortic atheroembolization, postoperative hypercoagulable state, and atrial fibrillation.59 However, there is agreement that prophylactic carotid intervention is still justified in CABG patients with a carotid stenosis >80% and a history of stroke or TIA in the last 6 months (class IIa),53 and probably in patients with asymptomatic severe (>80%) bilateral carotid stenoses. The timing of CABG and CEA is controversial. A systematic review has shown that death is highest for synchronous CEA–CABG, stroke is highest for staged CABG first–CEA second, and MI is highest for staged CEA first–CABG second.59 A registry analysis suggests that the risk of stroke is higher in patients undergoing synchronous CEA–CABG as opposed to staged CEA first–CABG second.61 Concomitant CEA–CABG seems to be the least favored revascularization approach. CABG alone is reasonable for patients with asymptomatic carotid stenosis and critical left main disease, refractory acute coronary syndrome, or other indications for urgent CABG. In contrast, patients with recent (80% should be considered for urgent CEA if CABG can be safely deferred for several days. Carotid stenting followed by CABG 3 weeks later is another alternative (clopidogrel is provided for 2 weeks after carotid stenting, then is interrupted for 5–7 days before CABG). Stenting pre‐CABG, as opposed to CEA pre‐CABG, is associated with lower periprocedural MI and complications in those patients with advanced CAD.62–64

VIII. Subtotal and total carotid occlusions While the yearly risk of ipsilateral stroke is ~10% in patients with symptomatic carotid stenosis of 70–89%, the risk increases to 35% in those with a stenosis 90–95%, but is actually lower, at 10% (or 2% in ECST trial), in those with symptomatic subtotal carotid occlusion, Table 19.7  High‐risk features for CEA and carotid stenting. Features increasing CEA risk (carotid stenting may be preferred [SAPPHIRE criteria])

Features increasing the risk of carotid stenting (CEA is preferred)

High surgical risk from comorbidities: • Major cardiac or pulmonary disease High surgical risk for anatomical reasons: • Prior neck surgery, prior neck radiation • Postsurgical restenosis •  ± Contralateral occlusion • High lesions above C2 or low lesions below the clavicle

• Age >70, much more if >80 Technical reasons: • Circumferential, heavy carotid calcifications • Tortuosity • Type 3 aortic arch • Heavy aortic arch atherosclerosis • Visible thrombus

Chapter 19. Peripheral Arterial Disease  421

where the carotid artery fills antegradely but faintly and is reduced in size (string sign).47,65 A similar, reduced yearly risk of ipsilateral stroke of 2–10% is found in patients with symptomatic total carotid occlusion.66 The reduced antegrade flow in subtotal and total occlusions lessens arterial emboli. However, recurrent ipsilateral stroke may still occur and is related to reduced perfusion, depending on the robustness of collaterals; the risk is highest, ~8%, within 30 days of an ischemic event.66 Note that the stroke risk is very low with asymptomatic carotid occlusion. The NASCET trial included patients with subtotal carotid occlusion and found that the benefit of CEA in those patients was similar to that in patients with lesser stenosis.47 Carotid stenting is risky in those patients, as the string sign often implies a large thrombus burden, which is a strong negative predictor of outcomes with carotid stenting, making CEA the preferred approach. Total carotid occlusion, on the other hand, while associated with a risk of stroke that approximates that of subtotal occlusion, is technically challenging for both CEA and percutaneous recanalization.67 Medical therapy is therefore the standard therapy for total carotid occlusion.

3 .  R e n a l a rt e ry s t e n o s i s I.  Forms of renal artery stenosis There are two major forms of renal artery stenosis (RAS): a.  Atherosclerotic RAS, which typically involves the ostia of renal arteries. It is frequently accompanied by parenchymal renal disease, often secondary to hypertension or diabetes rather than RAS, which attenuates any potential benefit from renal artery revascularization. In a subgroup of patients with RAS, renal failure is secondary to renal ischemia and may be improved with revascularization (even CKD stages 4 and 5). According to old data, atherosclerotic RAS is progressive, with 50% of significant lesions progressing over 2–3 years, and 5–10% progressing to a total occlusion. Occlusion leads to renal atrophy and irreversible loss of renal function.68 Aggressive control of blood pressure and risk factors reduces this risk. b.  Fibromuscular dysplasia (FMD) is characterized by intimal or medial constriction without any intimal thickening on IVUS. The intima is thin but is rigid and constricted, a form of negative remodeling (fibroplasia). This may lead to serial areas of constriction (string of beads) or to one focally constricted area. The process often involves the mid‐ to distal parts of the renal artery. It typically occurs in women 15–50 years old (female/male ratio = 8:1) and tends to progress. Progressive renal failure and renal atrophy are, however, unusual.68 Because of vasoconstriction, RAS‐induced hypertension usually affects both the systolic and diastolic components of blood pressure and is not usually an isolated systolic hypertension.

II. Screening and indications to revascularize renal artery stenosis A. Screen with renal arterial Doppler and consider renal revascularization for the following three groups: • Recurrent, unexplained flash pulmonary edema/acute HF • Refractory HTN (on ≥ 3–4 drugs at optimal dose, including a diuretic) • Progressive azotemia, seen with bilateral RAS or unilateral RAS of a solitary kidney B. Once RAS is diagnosed in one of the three scenarios above, assess non‐invasively and invasively for:69,70 1.  Lack of renal parenchymal disease 2.  Functional significance of a stenosis (a lesion >50–70% is not necessarily significant hemodynamically) Patients most likely to benefit are those with no intrinsic parenchymal renal disease and a functionally significant stenosis, rather than just an anatomically significant stenosis (Table 19.8, Figure 19.6). This combination proves that HTN and the decline in GFR result from reduced perfusion rather than severe intrinsic nephron damage (from diabetes, hypertension, or glomerulopathy). Only after assessment of these two features non‐invasively, then invasively if needed, is stenting appropriate. Invasively, a lack of cortical blush and a lack of cortical vascularity

Table 19.8  Signs of advanced renal parenchymal disease and signs of functional significance of a renal artery stenosis. Signs suggestive of advanced parenchymal disease • Proteinuria >1 g/24 h • Renal atrophy (renal size 0.8, which indicates a high intrarenal microvascular resistance • On renal angiography: poor cortical blood flow, cortical vascular pruning (no cortical ramifications) Signs suggestive of functional significance of renal artery stenosis • Renal asymmetry >1.5 cm without atrophy (conversely, atrophy implies advanced intrinsic damage) • Creatinine rise >20% with ACE inhibitors, along with bilateral RAS • Invasively: Translesional systolic pressure gradient under maximal hyperemia (papaverine) >21 mmHga FFR 5% per year Question 3. A 58‐year‐old man, active, former smoker, complains of bilateral calf pain (right > left) after walking one block. This is impeding his daily walks. ABI is 0.6 on the right, 0.7 on the left. He tried a daily walking routine to improve his symptoms, without success. Angiography shows a totally occluded right SFA, ~15–20 cm in length, calcified, with reconstitution at the popliteal level. What is the next step? A. Add cilostazol, recommend daily walking program, for 3 months B. Percutaneous revascularization is not acceptable, as this is a TASC D lesion C. Percutaneous revascularization is acceptable, as this is a TASC C lesion. The 1‐year patency is ≤ 60% D. Percutaneous revascularization is acceptable, as this is a TASC C lesion. The 1‐year patency is >60% Question 4. A patient presents with left great toe ulcer and dorsum of the foot ulcer. He has non‐compressible left tibial vessels with ABI >1.5. His left distal pulses are not palpable. Which statement is incorrect? A. The elevated ABI does not rule out significant PAD but rules out critical PAD B. The elevated ABI has at least the same negative cardiovascular implication as a low ABI, especially in symptomatic patients C. A toe–brachial index or arterial Doppler may be used to confirm the severity of PAD D. Abdominal aortic angiography with bilateral femoropopliteal runoff is warranted Question 5. The patient in Question 4 is found to have a severely diseased left external iliac, a heavily calcified, totally occluded left SFA, and severely diseased but patent AT, with a patent, non‐obstructed PT. AT feeds the ulcerated area. What is the next step? A. Perform stenting of the left iliac. If the ulcer does not heal, bring back for angioplasty/stenting of the SFA B. Perform percutaneous therapy of both the iliac and the SFA C. Perform percutaneous therapy of the iliac, SFA, and AT D. Perform iliac stenting and femoropopliteal bypass Question 6. A patient has severe left lower extremity claudication (Rutherford category 3). He has severe disease of the left external iliac, a totally occluded SFA, and infrapopliteal disease across the AT. What is the next step? A. Perform stenting of the left iliac. If severe claudication persists, bring back for angioplasty/stenting of the SFA B. Perform percutaneous therapy of both the iliac and the SFA C. Perform percutaneous therapy of the iliac, SFA and AT D. Perform iliac stenting and femoropopliteal bypass Question 7. Which statement is incorrect? A. Surgical bypass has higher patency than percutaneous therapy for all lower extremity segments (aortofemoral graft, femoropopliteal graft, femorotibial graft) except when a synthetic graft is used for below‐knee femoropopliteal grafting or femorotibial grafting B. For initial revascularization, percutaneous therapy is generally preferred to surgical bypass because of the lower perioperative morbidity, mortality, and convalescence period C. For infrapopliteal disease, femorotibial grafting is preferred to percutaneous therapy, as it allows better ulcer healing D. For common femoral disease, femoral endarterectomy is the preferred therapy and is a relatively low‐risk vascular surgery Question 8. A patient has lifestyle‐limiting claudication while walking one block, mostly involving the thighs. Distal pulses are palpable and femoral pulses are normal. Which statement is correct? A. The patient likely has pseudo‐claudication from hip osteoarthritis or spinal stenosis B. Arterial claudication is possible. The patient may have moderate iliac or distal aortic disease, with normal flow and pulses at rest but insufficient flow and reduced pulses with exercise. C. Perform ABI D. Perform ABI at rest and with exercise E. B + D F. B + C Question 9. A patient presents with severe right foot pain, persistent for the last 2 days. His foot is mottled blue. What is the most important immediate step? A. Emergent angiography and revascularization B. Doppler the distal pulses and perform sensory and motor exam of the right lower extremity C. CTA

424  Part 8. Peripheral Arterial Disease

Question 10. A 72‐year‐old man, heavy smoker, presents with pain, mottling, and cyanosis of his right great toe, which has been progressive over the last week. He has purple patches on his calf. The femoral pulse is mildly reduced (1+). The PT and DP are not palpable but have a good Doppler signal. The right ABI is 0.75; on Doppler, the flow is monophasic throughout the right lower extremity. CTA shows a heavy atherosclerotic aorta and iliac arteries, with 80% right iliac stenosis. The femoral, popliteal, and infrapopliteal arteries are patent. Creatinine is 1.7 mg/dl. What is the next step? A. Heparin and urgent stenting of the right iliac B. Conservative management Question 11. A 71‐year‐old smoker with a history of CAD has a right carotid bruit. He has no history of stroke or TIA. A carotid Doppler reveals a 260 cm/s velocity across the right internal carotid. Which statement is incorrect? A. The yearly risk of stroke is 2% B. CT or MRA may be needed to confirm the severity of the stenosis before an intervention C. CEA is recommended but only has a marginal benefit in an asymptomatic patient D. Revascularization with either CEA or stenting is recommended; stenting has the same level of recommendation as CEA E. Invasive angiography is not necessary before CEA F. Before deciding whether stenting is an acceptable alternative, the carotid anatomy needs to be defined by invasive angiography Question 12. A 64‐year‐old man, smoker, diabetic, has uncontrolled HTN (BP 160/80, on optimal doses of chlorthalidone, amlodipine, and lisinopril). Creatinine is 1.6 mg/dl (GFR 45). Renal Doppler suggests severe right renal artery stenosis. The renal resistive index is 0.85. Invasive angiography shows 80% right renal artery stenosis. What is the next step? A. Renal artery stenting is unlikely to improve BP control or renal function B. Renal stenting is warranted for refractory HTN Answer 1. C. The patient has acute rather than critical limb ischemia, as evidenced by the absent pulses on Doppler, the constant (rather than intermittent) rest pain, and the degree of cyanosis. In this context, the distal sensory loss implies an emergent need for revascularization. This acute limb ischemia is, in fact, subacute and suggestive of in‐situ thrombosis (on top of severe atherosclerosis), rather than an abrupt embolic event. Answer 2. E. The patient has claudication, without CLI (Rutherford 1–3). The risk of symptom progression over the next 5 years is 20% and the risk of progression to CLI is 4%, particularly if he quits smoking. Revascularization, at this point, can only improve symptoms, not the risk of limb loss. Since his symptoms are not severe, revascularization is not indicated. In contrast to the benign limb outcomes, the patient has a high risk of MI, stroke, and cardiac death. Answer 3. C. The occlusion is a TASC C occlusion, as it is >15 cm (> TASC B), but does not extend to the popliteal or common femoral artery (which would make it TASC D). Percutaneous revascularization is an acceptable strategy for TASC C occlusions, albeit at a high risk of restenosis. Surgical bypass should be considered for restenosis. A is a wrong answer as the patient has already tried the conservative strategy of daily walking. Answer 4. A. An elevated ABI with claudication or ulcer often corresponds to significant, obstructive PAD, sometimes critical (37% of symptomatic patients with elevated ABI have CLI). Also, a “pulseless” elevated ABI often implies obstructive PAD. Answer 5. C. In case of critical limb ischemia, one unobstructed straight line of flow should be achieved. All diseased segments should be treated. At the infrapopliteal level, at least one artery should be unobstructed, preferably the artery supplying the ulcer if its recanalization is technically feasible (angiosome concept). In this case, the AT supplies the ulcer and should be treated. Answer 6. A. In case of claudication, the goal is symptom control. When disease involves multiple segments, the inflow disease (iliac) may be treated first. Percutaneous therapy of the SFA may be performed in the same session but is not necessary. The patient may be brought back if symptoms persist. As opposed to CLI, in claudication, infrapopliteal disease does not need to be treated unless it is the only diseased segment. Answer 7. C. The long‐term patency of femorotibial graft, even venous graft, is not much higher than contemporary tibial percutaneous angioplasty/DES. Moreover, percutaneous therapy is good enough over the short and intermediate term to allow ulcer healing. Restenosis usually occurs after the ulcer has healed; much less flow is required to prevent an ulcer than to heal an ulcer. Restenosis does not usually result in recurrent CLI. Answer 8. E. Pulses may be palpable and only mildly reduced in patients with true arterial claudication that is related to moderate aortoiliac disease. The lesion allows normal flow at rest, but cannot accommodate the dramatic increase in flow required from the iliac artery with exertion. During exercise, the required increase in flow across the iliac is far larger than that across the SFA, as the iliac supplies a much larger territory. ABI and pulses may be normal or mildly reduced at rest but drastically drop with exercise. Answer 9. B. The patient’s persistent foot pain and severe cyanosis are suggestive of acute limb ischemia. He typically requires emergent revascularization. However, a thorough exam is required to classify the stage of ALI. Pulses are typically absent on Doppler exam. In the absence of motor loss, percutaneous recanalization with local, prolonged r‐tPA infusion is appropriate. If motor loss is present, surgical revascularization with fasciotomy is often more appropriate. Profound paralysis or acute tissue gangrene dictates amputation. CTA is a useful test later on (looks for aortic or popliteal aneurysm, as a source of emboli).

Chapter 19. Peripheral Arterial Disease  425

Answer 10. B. The patient has atheroembolization from the aortoiliac segments. This is evidenced by the discrepancy between the severity of foot ischemia and the rather mild impairment of pulses (good pulse signals) and the mild ABI reduction. In fact, the patient has foot ischemia with much less ankle ischemia, implying very distal atheroemboli. Stenting the right iliac may lead to more atheroembolization and may aggravate the foot ischemia. Conservative management and foot care is warranted; foot ischemia improves in most of these cases. Answer 11. D. The yearly risk of stroke with asymptomatic stenosis is low. CEA is a class IIa recommendation (based on ACAS and ACST trials), while stenting is class IIb (based on the carotid stenting trials, such as CREST, which included asymptomatic patients). In addition, before finalizing the decision to stent, the patient must have appropriate anatomical features (heavy calcium, tortuosity, type 3 arch). Answer 12. A. The patient has unilateral RAS yet significant CKD, implying that CKD is related to intrinsic renal disease (from diabetes, HTN) rather than renal ischemia. The high renal resistive index implies intrarenal microvascular disease, i.e., intrinsic renal disease. Renal disease is likely the mechanism of severe HTN. Renal artery stenting is unlikely to improve outcomes in this patient.

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32. Rastan A, Krankenberg H, Baumgartner I, et al. Stent placement versus balloon angioplasty for the treatment of obstructive lesions of the popliteal artery: a prospective, multicenter, randomized trial. Circulation 2013; 127: 2535–41. 33. Bosiers M. DESTINY trial: 12 months clinical and angiographic findings. Presented at the Leipzig Interventional Course. Leipzig, Germany, 19 January 2011. 34. Scheinert D, Ulrich M, Scheinert S, et  al. Comparison of sirolimus‐eluting vs. bare‐metal stents for the treatment of infrapopliteal obstructions. EuroIntervention 2006; 2: 169–74. 35. Ballotta E, Gruppo M, Mazzalai F, Da Giau G. Common femoral artery endarterectomy for occlusive disease: an 8‐year single‐center prospective study. Surgery 2010; 147: 268–74. 36. Bonvini RF. Rastan A, Sixt S. Endovascular treatment of common femoral artery disease: medium‐term outcomes of 360 consecutive procedures. J Am Coll Cardiol 2011; 58: 792–8. 37. Ouriel K, Veith FJ, Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or peripheral arterial surgery (TOPAS) investigators. N Engl J Med 1998; 338: 1105–11. 38. Browse DJ, Torrie EP, Galland RB. Low‐dose intra‐arterial thrombolysis in the treatment of occluded vascular grafts. Br J Surg 1992; 79: 86–8. 39. Gardiner GA, Harrington DP, Koltum W, et al. Salvage of occluded arterial bypass grafts by means of thrombolysis. J Vasc Surg 1989; 9: 426–31.

Carotid disease 40. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. JAMA 1995; 273: 1421–8. ACAS trial. 41. Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004; 363: 1491–502. ACST trial. 42. Nicolaides AN, Kakkos SK, Griffin M, et al. Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from ACSRS. Eur J Vasc Endovasc Surg 2005; 30: 275–84. 43. Yang C, Bogiatzi C, Spence D. Risk of stroke at the time of carotid occlusion. JAMA Neurol 2015; 72: 1261–7. 44. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high‐grade carotid stenosis. N Engl J Med 1991; 325: 445–53. NASCET trial. 45. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351: 1379–87. 46. White CJ. Carotid artery stent placement. J Am Coll Cardiol 2010; 3: 467–74. 47. Morgenstern LB, Fox AJ, Sharpe BL, et al, for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. The risks and benefits of carotid endarterectomy in patients with near occlusion of the carotid artery. Neurology 1997; 48: 911–15. 48. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high‐risk patients (MATCH): randomised, double‐blind, placebo‐controlled trial. Lancet 2004; 364: 331–7. 49. Sacco RL, Diener HC, Yusuf S, et  al. Aspirin and extended‐release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008; 359: 1238–51. 50. Wang Y, Wang Y, Zhao X, et al. CHANCE Investigators. 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Renal artery stenosis 68. Main J. Atherosclerotic renal artery stenosis, ACE inhibitors, and avoiding cardiovascular death. Heart 2005; 91: 548–52. 69. Safian RD, Madder RD. Refining the approach to renal artery revascularization. JACC Cardiovasc Interv 2009; 2: 161–74. 70. Leesar MA, Varma J, Shapira A, et al. Prediction of hypertension improvement after stenting of renal artery stenosis: comparative accuracy of translesional pressure gradients, intravascular ultrasound, and angiography. J Am Coll Cardiol 2009; 53: 2363–71. 71. ASTRAL Investigators, Wheatley K, Ives N, et al. Revascularization versus medical therapy for renal artery stenosis. N Engl J Med 2009; 361: 1953–62. 72. Cooper CJ, Murphy TP, Cutlip DE, et al; CORAL Investigators. Stenting and medical therapy for atherosclerotic renal‐artery stenosis. N Engl J Med 2014; 370: 13–22. 73. Mitchell JA, Subramanian R, White CJ, et al. Predicting blood pressure improvement in hypertensive patients after renal artery stent placement. Catheter Cardiovasc Interv 2007; 69: 685–9. 74. Kalra PA, Chrysochou C, Green D, et al. The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease. Cath Cardiovasc Interv 2010; 75: 1–10. 75. Van de Ven PJ, Beutler JJ, Kaatee R, et al. Angiotensin converting enzyme inhibitor‐induced renal dysfunction in atherosclerotic renovascular disease. Kidney Int 1998; 53: 986–93.

20  Aortic Diseases

I. Aortic dissection  428 II. Thoracic aortic aneurysm  432 III. Abdominal aortic aneurysm  436

I.  Aortic dissection A.  Two types of aortic dissection • Type A dissection involves the ascending aorta, with or without any other part of the aorta. Type A dissection is the most common type of aortic dissection (>65% of aortic dissections), and generally requires emergent surgical correction. • Type B dissection involves the descending aorta and/or the aortic arch, without extension to the ascending aorta. Involvement of the aortic arch without the ascending aorta is labeled as type B dissection (ACC guidelines). Non‐surgical treatment is generally recommended, with surgery reserved for vital branch compromise. Aortic dissection, whether type A or B, can be acute (onset within the last 2 weeks) or chronic. B. Causes The media of the ascending aorta is rich in elastic fibers. Medial degeneration consists of a loss of elastic fibers and predisposes to ascending aortic aneurysm and dissection. Medial degeneration may be seen with repetitive injury (HTN) and aging; in fact, the combination of age and HTN is responsible for aortic dissection in most patients. More severe medial degeneration, called cystic medial necrosis, may occur in the contexts of bicuspid aortic valve, Marfan syndrome, or coarctation of the aorta. The aortic wall stress drastically increases with aortic size. Thus, the risk of aortic dissection and progressive aortic dilatation is drastically increased in patients whose aorta is already dilated. The yearly risk of aortic dissection or rupture is 2% if the aortic diameter is 4–5 cm, and ≥7% if the aortic diameter is >5.5–6 cm. However, since a normal‐size aorta is much more common than a dilated aorta, only 40% of aortic dissections occur in patients with an aortic diameter of 5.5 cm or more, while 10–20% occur in patients with an aortic diameter of 4 cm or less.1 C.  Mechanisms of acute and chronic aortic dissection The typical aortic dissection consists of an intimal tear that allows blood to penetrate a diseased medial layer and cleave this media longitudinally. The blood‐filled space within the media is the false lumen. Distention of the false lumen with blood may cause the intimal flap to bow into the true lumen and obstruct the lumen or the branches causing ischemia (e.g., carotid, mesenteric, or renal artery). The false lumen may also extend into the branches and cause ischemia. Most intimal tears occur in the ascending aorta, within a few centimeters of the aortic valve, or in the descending aorta just distal to the left subclavian artery. In chronic aortic dissection, one or more spontaneous fenestrations occur in the intimal flap, which allows the false lumen to decompress and allows blood to flow through it. The false lumen becomes a functional lumen. Flow to vital branches supplied by the false lumen is improved, and organ ischemia improves (Figure 20.1). In fact, one of the endovascular therapies of aortic dissection consists of creating fenestrations in the intimal layer. D.  Other acute aortic syndromes: intramural hematoma and penetrating atherosclerotic ulcer Intramural hematoma is characterized by bleeding within the media from rupture of vasa vasorum vessels without any obvious intimal tear, and thus without communication with the true lumen. This can usually be distinguished by CT: the intramural hematoma does not enhance with contrast. Invasive angiography misses intramural hematoma, owing to the lack of communication between the true and false lumens. However, the management is identical to the classical type A or B aortic dissection (intramural hematoma is more often distal, i.e., type B, than A). The prognosis and complications are similar to aortic dissection, and intramural hematoma often progresses to dissection, aneurysm, or rupture.2,3 Penetrating atherosclerotic ulcer is an ulceration of an atherosclerotic lesion of the aorta, usually the descending aorta, that penetrates into the media and results in a localized hematoma. There is a focal aortic outpouching rather than a false lumen. However, this ulcer may progress to a typical aortic dissection or aortic perforation, and, over time, it often leads to the late formation of aortic aneurysm or contained aortic perforation, i.e., pseudoaneurysm. Atherosclerotic ulcer is often seen in elderly patients with a heavily atherosclerotic and

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Chapter 20.  Aortic Diseases  429

F

F

Cross-sectional view of the left renal artery, with the false lumen extending into it and compressing the true lumen

T Acute dissection

Chronic dissection

Figure 20.1  In acute aortic dissection, the false lumen (F) is tense with sluggish flow and becomes larger than the true lumen (dashed arrow). In chronic dissection, multiple tears occur in the intimal flap and allow the false lumen to decompress and blood to flow through it (arrows). In this illustration, the dissection extends into the left renal artery rather than around it. Thus, the left renal artery is now practically supplied by the false lumen. There is no flow through the renal artery acutely, but once the false lumen decompresses, some flow is re‐established through the false lumen of the renal artery, which becomes a functional lumen.

ulcerated descending aorta, many of whom already have a descending or abdominal aortic aneurysm. CT can distinguish it from a typical dissection. A penetrating ulcer is generally treated conservatively with surveillance. The treatment is surgical in case of persistent or recurrent pain, transmural extension with pseudoaneurysm, or progressive aneurysmal dilatation. E.  Clinical suspicion Three clinical features suggest the possibility of aortic dissection:4 • Predisposing condition (aortic valve disease, known aortic aneurysm, Marfan, or family history of dissection). • Suggestive symptoms: chest, back, or abdominal pain that is very abrupt (within seconds), severe, or tearing. Contrary to common belief, the pain of aortic dissection is commonly sharp rather than tearing. • Suggestive exam findings: AI murmur (in 25–45%), pulse deficit or blood pressure differential between both arms (~20%), neurologic deficit concomitant to chest pain (5%). The presence of two or three features makes aortic dissection highly probable. In the presence of one feature, the probability is intermediate and aortic imaging is warranted if the patient’s symptoms are not clearly explained on chest X‐ray or ECG. Up to 5% of aortic dissections have none of these features, but may be suspected by a widened mediastinum on chest X‐ray.4 Aortic dissection should be suspected in any patient with chest pain and concomitant stroke, mental status changes, or peripheral ischemia.

F. Diagnosis Chest X‐ray shows widening of the aorta and mediastinal silhouette and widening of the aortic knob in 80–90% of patients (Figures 20.2, 20.3). The “calcium sign” may be seen (outer displacement of the aortic knob calcium by more than 1 cm). Perform any of the following three gold‐standard studies to establish the diagnosis and define the type of dissection: • CT angiogram. • MR angiogram. • TEE. This has the additional potential of assessing acute AI and the coronary ostia. It is also advantageous if the patient is unstable, because TEE can be performed at the bedside. • Invasive aortography used to be the gold standard. It is still useful if the ECG shows acute STEMI but the clinical picture suggests aortic dissection. In the latter case, aortography may be performed, followed by coronary angiography once dissection is ruled out. Typically, the false lumen is larger than the true lumen because of its slower emptying (or lack of emptying). On a TEE short‐axis cut: (i) the true lumen is compressed and crescentic, while the false lumen is oval; (ii) the false lumen has “smoke” and no flow, or less flow, on Doppler imaging (Figure 20.4).

430  Part 8.  Peripheral Arterial Disease

Ascending aorta

Aortic knob Widening of aortic knob

Figure 20.2  Chest X‐ray in aortic dissection or dilatation.

(a)

(b)

Figure 20.3  (a) Widening of aortic knob (arrow) indicative of descending aortic dissection or aneurysm. (b) Widening of the ascending aortic shadow (right arrow) and the descending aortic knob (left arrow). This patient has ascending and descending aortic dilatation and dissection.

T

F

Figure 20.4  Axial cut across aortic dissection. True lumen (T) and false lumen (F) are shown.

Tubular aorta Sinotubular junction Sinuses of Valsalva Aortic and sinotubular dilatation

Loose sinotubular junction with cusp prolapse

Dissection flap prolapse

Figure 20.5  Mechanisms of aortic insufficiency (AI) with aortic dissection: (i) dissection dilates the sinotubular junction, preventing leaflet coaptation; (ii) dissection extends into the sinotubular junction, where the sinuses of Valsalva insert, resulting in leaflet prolapse and eccentric AI; (iii) dissection flap prolapses through the aortic orifice and prevents leaflet coaptation. AI may also be pre‐existent, secondary to a bicuspid aortic valve. Note that the valvular leaflets (cusps) are attached to the sinuses of Valsalva.

G. Complications • Aortic regurgitation (Figure 20.5). • Aortic rupture into the pericardium, leading to tamponade. • Stroke is seen in 6% of type A aortic dissections. It is due to carotid obstruction by an aortic flap or extension of the dissection into a carotid artery.

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• STEMI is seen in 4% of type A aortic dissections. It is easier for the dissection to extend on the outer curve of the aorta into the RCA, explaining why two‐thirds of MIs are inferior MIs (IRAD registry).2 MI may be due to the false lumen compressing the coronary ostium or extending into it. In addition, ST depression or T inversion occurs in up to 50% of patients with type A aortic dissection, as a result of demand/supply mismatch or catecholamine‐induced ST–T abnormalities.5 Those ST–T abnormalities may mimic ACS and delay the diagnosis of aortic dissection. • Hemorrhagic, large pleural effusion may be seen with descending aortic dissection. It results from aortic leakage into the mediastinal pleural space. • Peripheral and mesenteric ischemia. H. Treatment 1.  Administer IV β‐blockers to decrease the aortic wall stress dP/dt • Aggressively control blood pressure with β‐blockers ± vasodilators. IV labetalol or the combination of IV esmolol + IV nitroprusside may be used. β‐Blockers reduce the stroke volume and thus reduce the pulse pressure (dP), the slope of aortic pressure rise in systole (dP/dt), and the frequency of aortic exposure to the pulse pressure. The aortic pressure rises gradually rather than sharply (↓ dP/dt). Diltiazem IV may be used if β‐blockers are contraindicated. Morphine may be used for pain control. • Goal: Mean BP 60–70 mm Hg, SBP 2 weeks prior) Whether it is type A or B, chronic medical therapy without surgical intervention is the initial treatment of choice at this point. Medical therapy consists of aggressive BP control (SBP  4–4.5 cm, it may need to be replaced to allow a good proximal seal of the stent graft. The ascending aorta is replaced first, with hypothermic arrest for the distal anastomosis and cardiopulmonary bypass for the proximal anastomosis. If the ascending aorta does not need replacement, cardiopulmonary bypass may not be needed.

graft may be positioned in an open antegrade fashion to cover the arch (and the descending aorta if needed), after debranching the brachiocephalic arteries and attaching them to the ascending aorta (hybrid procedure) (ACC guidelines) (Figure  20.11).6 This is done without hypothermic arrest, and sometimes without a need for cardiopulmonary bypass, using a partial aortic clamp. Aortic arch procedures are associated with a high mortality that approaches 10% and a stroke risk of ~8–10%. When aortic arch aneurysm is associated with ascending aortic aneurysm, the ascending aorta is replaced, the brachiocephalic vessels are then debranched and attached to the ascending aortic graft, and a stent graft is antegradely placed to cover the arch. In patients with aneurysm involving the ascending aorta, arch, and descending aorta, a complex surgery called elephant trunk may be performed (replacement of the ascending aorta and arch, with part of the graft protruding into the descending aorta; this is followed by placement of an endograft in the descending aorta, attached to the protruded graft). Alternatively, an ascending aortic graft is placed, followed by debranching of the brachiocephalic vessels then endograft placement over the arch and descending aorta. D.  Traumatic transection of the aorta Deceleration trauma leads to aortic transection, most commonly at the level of the isthmus, immediately past the left subclavian artery. Most of these individuals die immediately. The remaining patients form a pseudoaneurysm and may be treated surgically or with an endograft (class I indication). Stable patients may not need to be treated urgently. Some undiagnosed patients go on to develop a chronic aortic pseudoaneurysm, which, as opposed to an aneurysm, is usually eccentric and saccular rather than fusiform. A pseudoaneurysm may also be postoperative or spontaneous (penetrating aortic ulcer). Since it implies a contained aortic rupture, it is appropriately treated with an endograft, regardless of size. E.  Medical therapy of TAA β‐Blocker therapy reduces stroke volume and thus reduces pulse pressure and ejectional wall stress (dP/dt or sharpness of pressure rise). However, only one small randomized trial supports its specific use in Marfan TAA.16 Some evidence suggests that ARB reduces the progression of aortic dilatation in Marfan.17 Overall, in patients with TAA from any cause and no surgical indication, β‐blocker therapy and aggressive blood pressure reduction with a β‐blocker and an ARB are recommended (ACC guidelines recommend blood pressure reduction to the lowest point tolerated).

III.  Abdominal aortic aneurysm An arterial aneurysm is defined as a focal arterial dilatation over 1.5 times the normal baseline diameter or the expected normal diameter. Abdominal aortic aneurysm (AAA) is generally defined as an abdominal aorta >3 cm. AAA is often infrarenal, but may extend above the renal arteries and may be thoracoabdominal. Similarly to descending TAA, AAA is related to atherosclerotic weakening of the aortic wall, smoking being the primary risk factor for AAA. Genetics contribute to the occurrence of AAA, and AAA occurs in up to 30% of siblings of patients with AAA.18 Approximately 10% of patients with AAA have popliteal aneurysms, usually bilateral aneurysms, which should always be sought. On the other hand, ~40% of patients with popliteal aneurysms have AAA. The main risks of popliteal aneurysms are thrombosis, embolization, and limb ischemia rather than rupture.

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Table 20.1  Types of endoleaks. Type 1 Type 2 Type 3 a

Poor sealing at the proximal or distal end of the graft. Retrograde endoleak from collateral flow. Leak from lumbar, inferior mesenteric, internal iliac or middle sacral artery that are covered by the endograft but receive retrograde flow through collateralsa Fabric tear or stent frame fracture or separation

 Type 2 endoleak may be followed with serial CT scans and treated selectively if the aneurysmal sac grows.

A. Diagnosis Ultrasound is the best screening tool, but CT generally provides more accurate sizing and better defines the extent of AAA and its relation with branch vessels (e.g., renal arteries). CT is a better modality in patients whose AAA is close to surgical cutoffs (>4 cm). MRI may alternatively be used. The wall of AAA being usually laminated with thrombus, invasive angiography underestimates the true size of AAA. AAA usually grows by 0.4 cm/year (faster than TAA, as the aortic pressure further amplifies distally).13 B.  Surgical treatment of AAA, iliac aneurysm, popliteal aneurysm In men, the yearly risk of rupture is 1.5% for AAA 6.5 cm, EVAR is associated with a high risk of late complications, because of inappropriate seal and inability to fully exclude AAA. Types 1 and 3 endoleaks have, however, been recently reduced with the newer generation of devices. In patients unsuitable for open repair, EVAR is performed, but in those high‐risk patients even EVAR has a high early mortality (8%) and most patients die from comorbidities within 5 years, without a clear benefit of EVAR in terms of overall survival (EVAR‐2 trial).24 The technical requirements for EVAR are: at least 1.5 cm of normal aorta (diameter 7 cm: 40%. The hinge point for the sharp rise of rupture/dissection is 6 cm for ascending aorta, 7 cm for descending aorta. 12. Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA 2011; 306: 1104–12. 13. Isselbacher E. Thoracic and abdominal aortic aneurysms. Circulation. 2005; 111: 816–28. 14. Ellozy SH, Carroccio A, Minor M, et al. Challenges of endovascular tube graft repair of thoracic aortic aneurysm: midterm follow‐up and lessons learned. J Vasc Surg 2003; 38: 676–83. 15. Flye MW, Choi ET, Sanchez LA, et al. Retrograde visceral vessel revascularization followed by endovascular aneurysm exclusion as an alternative to open surgical repair of thoracoabdominal aortic aneurysm. J Vasc Surg 2004; 39: 454–8. 16. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long‐term β‐adrenergic blockade in Marfan’s syndrome. N Engl J Med 1994; 330: 1335–41. 17. Groenink M, Alexander W. den Hartog, Franken R, et al. Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. Eur Heart J 2013; 34: 3491–500. 18. Frydman G, Walker PJ, Summers K, et al. The value of screening in siblings of patients with abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2003; 26: 396–400. 19. Lederle FA, Wilson SE, Johnson GR, et al. Aneurysm Detection And Management Veterans Affairs Cooperative Study Group. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002; 346: 1437–44. 20. UK Small Aneurysm Trial Participants. Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet 1998; 352: 1649–55. 21. Lederle FA, Johnson JR, Wilson SE, et al. Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. JAMA 2002; 287: 2968–72. 22. United Kingdom EVAR Trial Investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med 2010; 362: 1863–71. 23. De Bruin J, Baas A, Buth J. Long‐term outcome of open or endovascular repair of abdominal aortic aneurysm. N Engl J Med 2010; 362: 1881–9. DREAM trial. 24. United Kingdom EVAR Trial Investigators. Endovascular repair of aortic aneurysm in patients physically ineligible for open repair. N Engl J Med 2010; 362: 1872–80. In comparison to no repair, EVAR reduces aneurysm‐related mortality but has a high early procedural mortality and late need for reintervention. Overall, no effect on late mortality in those high risk patients. 25. Diehm M, Baumgartner I. ACE inhibitors and abdominal aortic aneurysms. Lancet 2006; 368: 659–65.

Part 9  Other Cardiovascular Disease States 21  Pulmonary Embolism and Deep Vein Thrombosis

1. Pulmonary embolism I. Presentation of pulmonary embolism (PE) and risk factors  439 II. Probability of PE  440 III. Initial workup  440 IV. Specific PE workup  440 V. Submassive PE, pulmonary hypertension, and thrombolysis  442 VI. PE and chronic pulmonary hypertension  443 VII. Acute treatment of PE  443 VIII. Duration of anticoagulation  444 IX. Thrombophilias 445 X. PE prognosis  445 2. Deep vein thrombosis I. Types 445 II. Diagnosis 445 III. Treatment 446 3. Immune heparin‐induced thrombocytopenia I. Incidence 446 II. Diagnosis 446 III. Treatment 446 Questions and answers  447

1 .   P u l m o n a ry e m b o l i s m I.  Presentation of pulmonary embolism (PE) and risk factors A. Signs and symptoms • Dyspnea and tachypnea are the most common findings; however, they may not be seen at rest and may be purely exertional. • Tachycardia is common and is occasionally an isolated finding. Frequently, however, tachycardia is either transient or relative (80–90 bpm). • Chest pain is usually a pleuritic pain in patients with distal emboli; angina‐like pain may be seen in patients with large central emboli and secondary RV ischemia. Hemoptysis is seen with pulmonary infarction, often resulting from small distal emboli. • Hypotension, syncope, and RV failure with increased JVP/RV heave/right‐sided S3 are seen with large PE and imply reduced hemodynamic reserve. • Lower extremity edema or tenderness on palpation is seen in 50% of DVTs.

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440  Part 9.  Other Cardiovascular Disease States

B. Risk factors (see Table 21.1) Table 21.1  Risk factors for PE/DVT. • Active cancer within the last 6 months, or active therapy for cancer • Transient major risk factors within the last 4 weeks: acute medical illness with hospitalization, surgery, trauma • Transient minor risk factors: pregnancy, oral contraceptive therapy, travel >8 hours • History of PE/DVT • Hypercoagulability ○○ Genetic: factor V Leiden, prothrombin gene mutation, protein C or S deficiency, antithrombin III deficiency ○○ Acquired: antiphospholipid syndrome, active cancer, myeloproliferative disorders, nephrotic syndrome • Idiopathic: ~10% of patients with idiopathic PE/DVT will end up being diagnosed with cancer within the next year • Other risk factors: age, smoking, obesity

II.  Probability of PE The clinical probability of PE is assessed using the Wells criteria, which essentially give weight to three features:1 • No alternative diagnosis for the patient’s presentation, whether it is dyspnea, hypoxia 10 mmHg at ambient air, >50 mmHg on high‐dose O2). O2 saturation and A–a gradient are, however, normal in up to 20% of the patients.5 An abnormal A–a gradient is non‐specific and is seen in most pulmonary illnesses as a result of ventilation/perfusion mismatch. Hypercapnia is rare and frequently suggests a different diagnosis or an associated illness (e.g., COPD). Only a massive PE with massive increase in dead space can cause hypercapnia, per se. C.  Chest X‐ray Chest X‐ray is grossly normal. It often shows some subtle abnormalities (linear atelectasis, pleural effusion, pulmonary artery cutoff sign). D. D‐dimer D‐dimer is a fibrin degradation product that results from the intrinsic, albeit ineffective, lysis of a clot. If the PE pre‐test probability is low and D‐dimer is negative, PE can be ruled out. A positive D‐dimer, on the other hand, is non‐specific and may be seen with any inflammation, pregnancy, or active clotting for any reason, e.g., cancer, bleed, trauma, medical procedure, or even venipuncture. D‐dimer should not be used in the high pre‐test probability population, especially the cancer population (in whom falsely negative and positive results may be seen).

IV. Specific PE workup A diagnostic strategy is provided in Figure 21.1 (ESC).1,5 If PE is highly probable and the bleeding risk is low, start IV unfractionated heparin (UFH) therapy, then establish a definitive diagnosis: • Spiral CT PE protocol is very sensitive but may miss subsegmental, small PEs (Figure 21.2). Meta‐analyses of long‐term follow‐ups of CT results have shown that CT is almost as accurate as pulmonary angiogram for ruling out PE. The negative predictive value is 95–99%, and in patients with a negative study the rate of PE diagnosis or mortality on 3‐month follow‐up is very low (30 mm on long‐axis view, or RV >LV on four‐chamber view); (ii) systolic PA pressure >35 mmHg; or (iii) D‐shaped septum in systole (pressure overload). Systolic PA pressure >50 mmHg cannot be generated by an acutely failing RV, and thus PA pressure over 50 mmHg suggests some degree of chronicity. Rarely, a thrombus in transit is seen in the right‐sided chambers (~4%); this is associated with a high mortality.

442  Part 9.  Other Cardiovascular Disease States

In a patient with shock and suspected PE, these echo features can make a presumptive diagnosis of PE and may be enough to justify thrombolytic therapy in this unstable context, even without further definitive diagnostic studies.11,12 In those unstable patients, emergent TTE may also help rule out other causes of shock, such as MI or tamponade. TEE may show a saddle embolus in the proximal PA branches but is rarely needed. The McConnell sign signifies hypokinesis of the RV free wall with normal RV apical motion. In hospitalized patients with RV dysfunction of any cause, this sign is highly specific for PE (>94%) but not very sensitive (20–77%); i.e., it is frequently absent in PE‐induced RV dysfunction.13,14 BNP and troponin I as prognostic markers. Troponin increases in 50% of patients with moderate‐to‐large PE associated with RV strain. Also, BNP often increases in large PE (the degree of increase in PE is less marked than in HF).

V. Submassive PE, pulmonary hypertension, and thrombolysis Acute pulmonary hypertension occurs when emboli obstruct >30% of the pulmonary vascular bed, or less so in a patient with prior cardiopulmonary disease. The thin RV is poorly tolerant of the acute rise in afterload and, as a result, fails and dilates; the dilatation further increases RV afterload and leads to a vicious circle of RV failure. RV dilatation compresses the LV and further reduces cardiac output. Hypotension may ensue and worsen RV ischemia, as the RV is more dependent on systolic blood pressure than the LV. Peripheral vasoconstriction and tachycardia acutely preserve the systemic pressure. Thrombolytics achieve quick lysis of the PE (a few hours) and a quick, almost immediate improvement in pulmonary pressure and RV function in 92% of patients.5,15 However, intrinsic thrombolysis is also potent and often dissolves a large part of the thrombus burden in patients receiving anticoagulation only, in a way that the hemodynamic superiority of thrombolysis over anticoagulation may be limited to a few days only. In addition, while acute pulmonary hypertension mainly results from the embolic obstruction per se, pulmonary vasoconstriction is a secondary contributor that improves over the course of therapy (vasoconstriction results from hypoxemia and from platelet‐released serotonin and thromboxane).16 Several studies suggest that 1 week after therapy, the degree of vascular obstruction on perfusion imaging and the degree of RV dysfunction are similar between thrombolysis‐treated and anticoagulation‐treated patients. PA pressure dramatically improves within a week of therapy, and heparin‐treated patients often catch up with thrombolysis‐treated patients.11,17–20 Thus, thrombolysis is mostly useful in patients who are in shock, since those patients are unlikely to survive the first few days and catch up with thrombolysis‐ treated patients.

Massive PE is defined as shock, i.e., sustained hypotension (SBP 40 mmHg, often implying severe pulmonary hypertension since the RV cannot generate pressures >50 mmHg acutely). • RV dysfunction by imaging, with either hypokinetic or dilated RV (RV/LV diameter >0.9 on echo or CT four‐chamber view). • Biochemical evidence of RV necrosis (elevated troponin beyond the “gray zone,” e.g., >0.1–0.4 ng/ml) or RV dysfunction (BNP >90). • Hypoxemia with O2 saturation 1 (the first three clinical features are components of the “PE shock index”). ESC guidelines use the term intermediate–high‐risk PE to characterize these patients, and mandate the presence of RV involvement both by imaging (RV dilatation or pulmonary hypertension) and biomarker assessment (troponin, BNP).5 Massive and submassive PE are clinical terms that correlate with the size of PE but also with the patient’s underlying cardiopulmonary reserve. Whereas most stable, anticoagulated patients catch up with thrombolysis‐treated patients, data suggest that a subgroup of patients with submassive PE are at risk of persistent pulmonary hypertension, RV failure, and long‐term persistence of symptoms (25–50% of patients).11,21,22 This subgroup is also at risk of acute clinical deterioration. In two studies, thrombolysis of stable patients with evidence of RV dysfunction or pulmonary hypertension dramatically and more effectively reduced PA pressure than standard anticoagulation, not only acutely but over the long term.21,22 Thrombolysis also reduces the rate of acute clinical deterioration in submassive PE.23 In a trial of systematic thrombolysis vs. anticoagulation with selective thrombolysis for submassive PE (defined by a combination of both RV imaging features and troponin >0.06 ng/ml), systematic thrombolysis reduced acute deterioration but did not affect the overall acute mortality and was associated with increased bleeding events, including a 2% rate of intracranial bleeding, mostly occurring in patients older than 75.24 Thus, the widespread use of thrombolysis in submassive PE was not clearly superior to its selective use. As such, standalone anticoagulation is an appropriate initial strategy, as many patients improve their PA and RV parameters quickly; thrombolysis may be reserved for patients who do not improve their PA pressure within 1–2 days, those who deteriorate clinically, or those with pre‐shock findings (persistent tachycardia, borderline BP, persistent severe hypoxia) (class IIa in ESC guidelines)5. While mostly useful in the first few days after the onset of PE symptoms, thrombolysis remains useful in patients who have had symptoms for 6–14 days, with 70% of the latter patients demonstrating improvement with thrombolysis on lung scan.25 In practice, it is often difficult to define the onset of PE, especially in patients who have subacute symptoms of several weeks and who may have multiple emboli of various ages, some of which are acute;25 thrombolysis may be attempted in patients with recent symptoms and persistent

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pulmonary hypertension. The benefit of thrombolysis is less time‐dependent in PE than in MI or stroke for the following reasons: (i) thrombolysis is more effective in lysing a PA clot than a coronary or cerebral clot; 100% of the cardiac output goes through the pulmonary circulation, while only 5% and 15% of the cardiac output goes to the coronary and cerebral circulations, respectively; (ii) as opposed to a coronary occlusion, which quickly leads to MI and makes late thrombolysis futile, pulmonary arterial occlusion rarely leads to a large pulmonary infarction, as the pulmonary parenchyma receives most of its supply from the bronchial arterial circulation. Only small infarctions may be seen with distal emboli. Catheter‐directed therapy of the main and lobar PA branches may be performed in patients who have a high bleeding risk with a full thrombolytic dose. Typically, catheter therapy consists of thrombus fragmentation and aspiration, often followed by a low‐dose direct catheter infusion of alteplase over 12–24 hours. This relatively low dose of alteplase is assumed to be safer.5 Considering the high mortality of patients with submassive PE and free‐floating right heart thrombus seen on echo (>20%), those patients are best treated with systemic thrombolysis or surgical thromboembolectomy in an experienced center. Catheter thrombectomy is risky in those patients, as it may dislodge emboli into the right circulation, but also the left circulation if PFO is present.

VI.  PE and chronic pulmonary hypertension A first episode of PE leads to a significant risk of symptomatic chronic thromboembolic pulmonary hypertension (CTPH) of about 4% at 2 years, even without recurrence of PE.26 This risk is higher in patients whose initial presentation is submassive PE, where up to 25–50% of patients have persistent pulmonary hypertension and where acute therapy with thrombolysis reduces this risk.21,22 Think of CTPH in any case of chronic pulmonary hypertension. CTPH is treatable with surgical pulmonary thromboendarterectomy when the pulmonary obstruction is central (~70% of the cases), but not when it is distal and microvascular.

VII. Acute treatment of PE A.  Initial anticoagulation One of the following three regimens is recommended: • IV UFH, 80 units/kg bolus then 18 units/kg IV drip, with PTT monitoring Q6h. The PTT goal is 1.5–2.5 times normal. • LMWH (enoxaparin), 1 mg/kg SQ Q12h or 1.5 mg/kg SQ Q24h. Reduce the dose to 1 mg/kg Q24h if GFR 4). Give warfarin for at least 3 months (the duration of warfarin therapy depends on the underlying cause of DVT, as detailed above in Section 1, Pulmonary embolism). Even in the absence of thrombosis or HITTS, HIT itself mandates the use of a DTI to prevent the associated high incidence of thrombosis. DTI is initiated as soon as possible, whenever there is a moderate/high suspicion of HIT, without awaiting the result of HIT antibody testing.

Chapter 21.  Pulmonary Embolism and Deep Vein Thrombosis  447

DTI is continued until the platelet count returns to baseline, at which time warfarin is initiated and continued for ~30 days. In HIT, low platelets are not a contraindication to DTI, unless the patient is actively bleeding. Platelet transfusions should be avoided unless there is active bleeding. Note: Anticoagulant therapies in a patient with a prior history of HIT • DVT prophylaxis in a patient with a history of HIT: fondaparinux (anti‐Xa) 2.5 mg SQ QD. • Coronary intervention in a patient with a history of HIT: bivalirudin IV or argatroban IV. • A patient with a history of HIT over 90 days ago can be anticoagulated with heparin for short durations, 90%. Troponin I is 1 ng/ml. Echo shows severe RV hypokinesis and a worm‐like structure in the RA, intermittingly flopping into the RV. What is the next step? A. IV heparin B. IV heparin + IV thrombolysis C. IV heparin + surgical thrombectomy D. IV heparin + catheter thrombectomy E. B or C Question 3. A 60‐year‐old woman had a PE with no identifiable trigger and no cancer on chest X‐ray and mammography. She was given apixaban therapy for 3 months, uneventfully. She is asking about the need to continue therapy beyond 3 months. All the following statements are true, except which one? A. Anticoagulation should be continued for at least 6 months, which is the highest‐risk period for recurrence B. The risk of recurrence after discontinuation of anticoagulation is steady, whether anticoagulation is discontinued at 3 months or 6 months C. Three months is the mandatory duration of therapy. But anticoagulation is preferably continued >3 months in all patients with low bleeding risk D. Beyond 3 months, thrombophilia testing, D‐dimer testing (3 weeks after stopping anticoagulation), and lower extremity venous study help decide which patients are more likely to benefit from long‐term therapy E. After 3 months, the yearly risk of recurrence is 3% in the absence of any abnormality on thrombophilia or D‐dimer testing, vs. 6–10% risk in the presence of any abnormality F. She has a 10% probability of cancer diagnosis within the next year Answer 1. C. With heparin therapy, this patient will likely catch up with thrombolytic‐treated patients. However, data suggest that thrombolysis may be beneficial in patients with both radiological and biomarker evidence of RV dysfunction (submassive PE), a significant proportion of whom do not catch up with thrombolytic‐treated patients. Thrombolysis reduces acute deterioration and the long‐term risk of pulmonary hypertension. Yet, considering its risk, thrombolysis is mainly indicated if cardiopulmonary deterioration occurs (class IIa ESC guidelines). Answer 2. E. While the patients of Questions 1 and 2 both have submassive PE, the current patient is clearly a higher‐risk patient within the large spectrum of submassive PE. SBP is lower, tachycardia is persistent with heart rate/SBP ratio >1 (shock index >1), and hypoxemia is more severe, suggesting that she is less stable and less likely to improve with heparin only. Moreover, the thrombus in transit is a very high‐risk finding that advocates for more aggressive therapy (sudden death may occur if it moves into the PA). Catheter thrombectomy may dislodge the clot and may lead to right‐ and left‐sided emboli (if PFO is present). Answer 3. A.

References 1. Piazza G, Goldhaber SZ. Acute pulmonary embolism. Part I: epidemiology and diagnosis. Circulation 2006; 114: 28–32. 2. Ferrari E, Imbert AI, Chevalier T, et al. The ECG in pulmonary embolism, predictive value of negative T waves in precordial leads: 80 case reports. Chest 1997; 111: 537–43. 3. Sreeram N, Cheriex EC, Smeets JL, et al. Value of the 12‐lead electrocardiogram at hospital admission in the diagnosis of pulmonary embolism. Am J Cardiol 1994; 73: 298–303. 4. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, and roentgenographic findings in patients with acute pulmonary embolism and no pre‐existing cardiac or pulmonary disease. Chest 1991; 100: 598–603. 5. Konstantinides SV, Torbicki A, Agnelli G, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35: 3033–80.

448  Part 9.  Other Cardiovascular Disease States

6. Moores LK, Jackson WL, Shorr AF, Jackson JL. Meta‐analysis: outcomes in patients with suspected pulmonary embolism managed with CT pulmonary angiography. Ann Intern Med 2004; 141: 866–74. 7. Quiroz R, Kuchner N, Zou KH, et al. Clinical validity of a negative CT scan in patients with suspected pulmonary embolism: a systematic review. JAMA 2005; 293: 2012–17. 8. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354: 2317–27. PIOPED II: sensitivity 83% (in comparison to a combination of V/Q, Doppler ± angiography), specificity 96%, sensitivity increased to 90% with venous CT. 9. Nijkeuter M, Hovens MMC, Davidson BL, et al. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 2006; 129: 192–7. 10. Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher. Arch Intern Med 2005; 165: 1777–81. 11. Jaff MR, McMurtry S, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123: 1788–830. 12. Rudoni RR, Jackson RE, Godfrey GW, et al. Use of two‐dimensional echocardiography for the diagnosis of pulmonary embolus. J Emerg Med 1998; 16: 5–8. 13. McConnell MV, Solomon SD, Rayan ME, et al. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol 1996; 78: 469–73. 14. Kurzyna M, Torbicki A, Pruszczyk P, et al. Disturbed right ventricular ejection pattern as a new Doppler echocardiographic sign of acute pulmonary embolism. Am J Cardiol 2002; 90: 507–51. 15. Goldhaber SZ, Come PC, Lee RT, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right‐ventricular function and pulmonary perfusion. Lancet 1993; 341: 507–11. 16. Lualdi JC, Goldhaber SZ. Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications. Am Heart J 1995; 130: 1276–82. 17. The urokinase pulmonary embolism trial. A national cooperative study. Circulation 1973; 47 (2 Suppl): II1–108. 18. Dalla‐Volta S, Palla A, Santolicandro A, et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol 1992; 20: 520–6. 19. Konstantinides S, Tiede N, Geibel A, et al. Comparison of alteplase versus heparin for resolution of major pulmonary embolism. Am J Cardiol 1998; 82: 966–70. 20. Ribeiro A, Lindmarker P, Johnsson H, et  al. Pulmonary embolism: one‐year follow‐up with echocardiography doppler and five‐year survival analysis. Circulation 1999; 99: 1325–30. 21. Kline JA, Steuerwald MT, Marchick MR, et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009; 136: 1202–10. 22. Sharifi M, Bay C, Skrocki L, et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol 2013; 111: 273–7. 23. Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase versus heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347: 1143–50. MAPPET 3 trial. 24. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate‐risk pulmonary embolism. N Engl J Med 2014; 370: 1402–11. PEITHO trial. 25. Daniels LB, Parker JA, Patel SR, Grodstein F, Goldhaber SZ. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol 1997; 80: 184–8. 26. Pengo V, Lensing AWA, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350: 2257–64. 27. Matisse investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.N Engl J Med 2003; 349: 1695–702. 28. Low‐molecular‐weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators. N Engl J Med 1997; 337: 657–62. 29. Kovacs MJ, Rodger M, Anderson DR, et al. Comparison of 10‐mg and 5‐mg warfarin initiation nomograms together with low‐molecular‐weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double‐blind, controlled trial. Ann Intern Med 2003; 1389: 714–19. 30. Guyalt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th edition. American College of Chest Physicians Evidence‐Based Clinical Practice‐Based Guidelines. Chest 2012; 141: 7S–47S. 31. Prepic study group. Eight‐year follow‐up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC randomized study. Circulation 2005; 112: 416–22. 32. Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population‐based cohort study. Arch Intern Med 2000; 160: 761–8. 33. Agnelli G, Prandoni P, Becattini C, et al.; Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003; 139: 19–25. 34. Boutitie F, Pinede L, Schulman S, et al. Influence of preceding duration of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping therapy: analysis of individual participants’ data from seven trials. BMJ 2011; 342: d3036 35. Palareti G, Cosmi B, Legnani C, et al. D‐dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355: 1780–9. 36. Prandoni P, Lensing AW, Prins MH, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002; 137: 955–60. A meta‐analysis of 11 RCTs found that the amount of residual thrombus after anticoagulant therapy correlated strongly with the risk of recurrent VTE. It is unknown whether this is a causal relationship, with residual thrombus creating a physical nidus for the development of new thrombus, or whether the presence of residual thrombus is simply a marker for a separate biological process that leads to recurrent VTE. 37. Lee AY, Levine MN, Baker RI, et al Randomized Comparison of Low‐Molecular‐Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low‐molecular‐weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146–53. 38. Brighton TA, Eikelboom JW, Mann K, et al. Low‐dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367: 1979–87. 39. Heit JA. Thrombophilia: common questions in laboratory assessment and management. Hematology Am Soc Hematol Educ 2007: 127–35. 40. Gerhardt A, Scharf RE, Beckmann MW,et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342: 374–80. 41. Kahn SR, Ginsberg JS. Relationship between deep venous thrombosis and the post thrombotic syndrome. Arch Intern Med 2004; 164: 17–26. 42. Engelberger RP, Kucher N. Management of deep vein thrombosis of the upper extremity. Circulation 2012; 126: 768–73.

22  Shock and Fluid Responsiveness

1. Shock I. Shock definition and mechanisms  449 II. Goals of shock treatment  450 III. Immediate management of any shock  450 2. Fluid responsiveness Appendix. Hemodynamic equations, transfusion, and miscellaneous concepts  454

1. Shock See Chapter 2 for the specific management of cardiogenic shock. See Chapter 38 for ventricular support devices.

I.  Shock definition and mechanisms Shock is defined as sustained hypotension along with evidence of low tissue perfusion (oliguria 12.5% with passive leg raising, but also an IVC diameter 12% between inspiration and expiration or IVC collapsibility >12% predicts volume responsiveness in mechanically ventilated patients.9,21,22 Patients who are mechanically ventilated tend to have a larger IVC diameter and reduced IVC collapsibility because of the positive intrathoracic pressure that impedes venous return; that’s why 12% collapsibility, as opposed to 50% in spontaneously breathing patients, is considered a sign of volume responsiveness.21 In any patient, whether spontaneously breathing or mechanically ventilated, a hyperdynamic LV with systolic cavity collapse or a hyperdynamic LV with intracavitary LV pressure gradient and SAM of the mitral valve implies severe hypovolemia, particularly hypovolemia associated with excessive use of inotropes. However, a small LV cavity may also be seen in overloaded patients with restrictive cardiomyopathy. In mechanically ventilated patients who do not have an arterial line, the pulse oximetry tracing may be used to predict volume responsiveness. The plethysmographic waveform of pulse oximeters is a qualitative indicator of blood volume changes at the fingertip. One study suggested a correlation between pulse waveform variation provided by pulse oximetry and systolic pressure variation; thus, pulse waveform variation predicts volume responsiveness in mechanically ventilated patients.23 However, the pulse oximetry tracing is not useful in hypotensive patients whose finger perfusion is reduced.

454  Part 9.  Other Cardiovascular Disease States

Appendix. Hemodynamic equations, transfusion, and miscellaneous concepts A.  Hemodynamic variables and equations • O2 arterial content (ml O2/dl) = SaO2 × Hb × capacity of 1 g Hb to carry O2 (=1.36 ml of O2 per g of Hb) • O2 venous content (ml O2/dl) = SvO2 × Hb × 1.36 • O2 delivery (ml O2/min) = O2 arterial content × CO × 10 • O2 consumption (ml O2/min) = (O2 arterial content – O2 venous content) × CO × 10. This is the Fick equation. • CVP = RA pressure: normal 70%. D.  Colloid fluids (Dextran, Hetastarch) In sepsis, colloid fluids have not been shown to be superior to crystalloid fluids (such as normal saline). In fact, colloid fluids may lead to more renal failure, coagulopathy, and mortality than crystalloids.24 E.  Intensive insulin therapy Intensive insulin therapy given to achieve a glycemic control of 80–110 mg/dl has been shown to decrease mortality in surgical ICU patients. However, in medical ICU patients and in patients with sepsis, aggressive insulin therapy to achieve a glucose level of 65) or patients with CAD, a J curve is seen for DBP and SBP: a high DBP (>90 mmHg) increases cardiovascular risk, but a low DBP (10 ng/dl, primary hyperaldosteronism is suggested.a ACE inhibitors and β‐blockers affect this testing, but not enough to warrant drug interruption (the former ↑ PRA, the latter ↓PRA).7 Aldosterone antagonists should, however, be stopped C. Serum‐free metanephrines and normetanephrines, and 24‐hour urinary metanephrines and normetanephrines (these two tests have the best yield for the diagnosis of pheochromocytoma) D. TSH E. Consider sleep study in the appropriate context  A primary elevation in aldosterone level leads to a feedback decrease in PRA. Aldosterone is expressed in ng/dl while PRA is expressed in ng/ml/h.

a

458  Part 9.  Other Cardiovascular Disease States

III. Treatment of HTN: goals of therapy A.  Goal ≤140/90 mmHg, including in patients with diabetes, CKD or CAD11,12 Possible goal ≤120–130 mmHg in select high‐risk patients (e.g., CAD) who can tolerate lower pressure In the HOT trial, which randomized patients to multiple DBP goals (7). Flushing improves with time and is reduced by slow titration, premedication with aspirin, and the use of an extended‐release niacin form (Niaspan). Dosage: Niaspan 500 mg QHS. The dosage is doubled every month up to a maximum of 2000 mg QHS. D. Fibrates Adverse effects: gallstones (gemfibrozil), hepatitis, myositis. Gemfibrozil interacts with warfarin (↑ INR). Gemfibrozil is contraindicated in conjunction with statin. Fenofibrate is contraindicated if GFR 70, or if the patient cannot tolerate statin, add PCSK9 inhibitor

Chapter 24.  Dyslipidemia  477

Question 2. A 45‐year‐old woman is obese and has prediabetes and controlled HTN. She has premature CAD in first‐degree relatives at the age of 50. LDL is 118 mg/dl, HDL is 45 mg/dl. Her 10‐year ACC cardiovascular risk score is 2% if she is a non‐smoker and 6% if she is a smoker. Which of the following indicates statin therapy in this patient, according to ACC guidelines? A. The cardiovascular risk of 5–7.5% (in case of smoking) B. The family history of premature CAD C. Metabolic syndrome D. Prediabetes E. A or B Question 3. A patient had a recent ACS and AF and was placed on atorvastatin 80 mg. He is also on diltiazem, amiodarone, aspirin, and clopidogrel. On his follow‐up clinic visit, he notes significant proximal myalgias. Which of the following is incorrect? A. Diltiazem and amiodarone are inhibitors of cytochrome P450 3A4, and increase the level and toxicity of atorvastatin B. Simvastatin can be used, as it is not a substrate of cytochrome P450 3A4 C. Pravastatin is not metabolized by any cytochrome, while rosuvastatin and fluvastatin are metabolized by different cytochromes (2C9 rather than 3A4). The latter two can be used with diltiazem or amiodarone. D. PCSK9 inhibitors can be used, and are associated with a low discontinuation rate in patients intolerant to statins Answer 1. D. Frequently, muscular symptoms are not solely related to statin, and may be related to low vitamin D, thyroid disorder, or drug interaction. The patient may tolerate statin, especially a different statin, upon reinitiation. Two objectives should be achieved: (1) provide statin therapy and (2) reduce LDL 15 mmHg). • Diastolic PA pressure is passively increased and is equal to PCWP or is up to 7 mmHg higher than PCWP. • Pulmonary vascular resistance (PVR) is 3 Wood units.5,6 In fact, a precapillary component accompanies PH in 20–35% of patients with advanced left HF,6–8 and may accompany PH of mitral stenosis and diastolic HF. In addition, this situation may be seen in patients with mixed disorders, such as left HF and COPD. The active, precapillary PH component resolves after treatment of HF, but may take weeks or months to fully resolve.3 Resting PCWP may be normal despite LV failure, especially in patients appropriately treated with diuretics. The improvement of pulmonary pressure lags behind the improvement of PCWP, and these patients may have a normal PCWP with elevated PA pressure, simulating precapillary PH, except for a PVR that is only mildly increased. Exercise testing, volume loading, or pulmonary vasodilator challenge are appropriate strategies that increase PCWP in occult LV dysfunction and thus unveil the diagnosis of postcapillary PH. Patients who are suspected of having left heart disease‐associated PH or mixed postcapillary PH and precapillary PH are approached as in Figure 25.1. Up to 70% of patients with systolic LV dysfunction or isolated LV diastolic dysfunction may develop PH, and the presence of PH is associated with a poor prognosis in these patient populations.2,9,10 One study documented a high prevalence of PH in patients with heart failure and preserved EF; 83% of patients in this study had PH, the median PA systolic pressure being 48 mmHg.10 Interestingly, PA pressure was out of proportion to what would be expected from the rise in PCWP. For the same PCWP, patients with heart failure had a much higher PA pressure than patients with hypertension and no heart failure. Thus, in addition to the postcapillary PH, a precapillary pulmonary hypertension frequently coexists or develops during the course of heart failure with preserved EF.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

479

480  Part 9.  Other Cardiovascular Disease States

Table 25.1  Classification of severity of pulmonary hypertension.

Mild PH Moderate PH Severe PH

Systolic PA pressure

Mean PA pressure

35–50 mmHg 50–70 mmHg >70 mmHg

25–35 mmHg 35–45 mmHg >45 mmHg or PVR >6–7 Wood units

WHO classification- WHO group 1 is PAH; WHO group 2 is left heart disease-related PH; WHO group 3 is PH secondary to lung disease or hypoxemia; WHO group 4 is chronic thromboembolic PH.

PH + normal LV EF

PCWP >15 PVR 15 PVR ≥3*

Are there DHF risk factors*

DHF

Yes

No

Exercise or volume loading PCWP >20–25

DHF

Precapillary PH

PCWP ≤20–25

Precapillary PH

Post-capillary PH (DHF) with reactive precapillary PH OR mixed post-capillary PH (DHF) + precapillary PH (idiopathic or other) OR Precapillary PH with RV dilatation and secondary increase in LVEDP and PCWP (ventricular interdependence) Vasodilator challenge with nitroprusside** PCWP ≤15 PVR 15 PVR ≥3 DHF+ precapillary PH ? Value of PH vasodilator therapy

Figure 25.1  Diagnostic approach to distinguish between precapillary PH (pulmonary arterial hypertension) and PH related to diastolic heart failure (DHF). PVR 15. With exercise, PCWP may normally rise up to 20–25 mmHg. Exertional PCWP is abnormal if it exceeds 20–25 mmHg. **Adenosine or epoprostenol may further increase LV preload and PCWP in left heart failure, and may be used to show that DHF is the primary driver of PH. Otherwise, when addressing vasoreactivity in patients with an established HF diagnosis, nitroprusside as a pulmonary vasodilator is preferred as it reduces afterload and may actually reduce PCWP. Modified with permission of Elsevier from Hoeper et al. (2009).3

B.  Precapillary PH Precapillary PH is characterized by PCWP and LVEDP ≤15 mmHg, PVR ≥3 Wood units, and a transpulmonary gradient >12 mmHg.1,2,11 In cases of precapillary PH associated with severe RV failure, pericardial distension and functional pericardial constriction may occur, leading to ventricular interdependence and equalization of RV and LV end‐diastolic pressures, with a subsequent rise in LV end‐diastolic pressure and PCWP to 15–20 mmHg.12 As opposed to left heart disease, the increase in PCWP is, in this case, the result of PH rather than the cause of PH. Yet, in such an instance, PH may be erroneously labeled as left heart disease‐associated PH. The presence of signs of LV diastolic dysfunction on echocardiography supports the diagnosis of left heart disease‐associated PH, while severe RV dilatation and severe elevation of PVR >7 Wood units support the diagnosis of precapillary PH. There are three major categories of precapillary PH: 1.  Pulmonary arterial hypertension (PAH), which is related to a pulmonary vascular disease affecting the pulmonary arterioles. PAH may be idiopathic, familial, or related to connective tissue disease, toxins (amphetamines, anorexigen), cirrhosis (portopulmonary hypertension), HIV, or Eisenmenger syndrome. Idiopathic PAH may be seen at any age or sex but is more common in female patients (female/ male ratio 3:1; age 36 ± 15 years). In congenital heart disease with a large left‐to‐right shunt (e.g., VSD, PDA, or less often ASD), PA pressure initially increases as a result of the increase in right‐sided flow, PVR remaining initially low (pressure = flow × resistance; an increase in flow leads to an increase in pressure). This “dynamic” PH resolves with shunt closure. Over time, the increased pulmonary flow induces progressive pulmonary vascular disease and severe increase in PVR to a point that PVR approaches SVR, PA pressure approaches systemic pressure, and the shunt reverses and becomes directed right‐to‐left or bidirectional. This is Eisenmenger syndrome and, except in ASD, is usually established in infancy or childhood. It is unusual for VSD or PDA to be diagnosed as a cause of PH in an adult.

Chapter 25.  Pulmonary Hypertension  481

Pulmonary veno‐occlusive disease is characterized by primary venular abnormalities similar to the arteriolar abnormalities seen in idiopathic PAH and may be idiopathic or associated with scleroderma. Similar to PAH, true pulmonary arterial wedging is difficult during catheterization, but, if successful, it still creates a column of stagnant blood between the catheter and the LA; thus, the truly wedged PCWP approximates the LA pressure, albeit damped through the venular obstruction, and is normal in value. The wedged PA pressure, i.e., LA pressure, is normal, but the pulmonary capillary pressure is increased and pulmonary edema may be seen. 2.  PH secondary to thromboembolic disease. Approximately 4% of patients who develop acute PE do not fully resolve their thrombus burden and go on to develop chronic PH. This often occurs after single PE episodes. Most often, the thrombus involves the main lobar pulmonary artery or the proximal arteries (80%), with small‐vessel arteriopathy and thrombosis that subsequently occur and contribute to disease progression. In a smaller category of cases, the thromboembolic process is purely distal, involving the small distal pulmonary arteries (the distal type is less likely to benefit from surgical thromboendarterectomy). 3.  PH secondary to hypoxic lung disease. Mild PH is common in patients with COPD, but severe PH is very unusual. In fact, moderate and severe PH are only seen in 5–10% and 2% of severe COPD cases, respectively.13,14 Also, sleep apnea does not usually lead to more than mild PH. Conversely, severe PH may be seen with advanced‐stage fibrotic lung disease that obliterates the pulmonary capillaries, sarcoidosis, or obesity–hypoventilation syndrome.

III.  Two tips in the evaluation of PH The following two ideas are essential to the evaluation of PH: 1.  In chronic severe PH, the PA pressure number may start declining into the mild range as the RV develops severe failure and becomes unable to generate high PA pressure. PVR, on the other hand, remains severely elevated. 2.  In acute PH (e.g., pulmonary embolism), the RV is not able to generate a systolic PA pressure higher than 45–50 mmHg. Therefore, in a case of acute pulmonary embolism, a systolic PA pressure higher than 40 mmHg implies severe pulmonary hypertension.11 A systolic PA pressure higher than 50 mmHg suggests a subacute or chronic process. In both cases, the PA pressure number underestimates the true severity of the pulmonary vascular abnormality. The presence of severe RV dysfunction, a severely elevated RA pressure, or a severely elevated PVR >6–7 Wood units is diagnostic of severe PH. In fact, in patients with severe PH that is evidenced by elevated PVR and RV failure, a high systolic PA pressure predicts recovery of RV function with therapy and better outcomes than a low systolic PA pressure. A higher systolic PA pressure corresponds to a better RV function.15,16

IV.  Hypoxemia in patients with PH Hypoxemia may be related to the cause of PH, such as pulmonary edema (left heart disease), lung disease, hypoventilation syndrome, or Eisenmenger syndrome and right‐to‐left shunting. On the other hand, PAH may, by itself, lead to hypoxemia, mainly in patients with patent foramen ovale. In those patients, the increased RA pressure “opens” the PFO, leading to a secondary right‐to‐left shunt (this shunt is the result rather than the cause of PAH). Also, a degree of arteriovenous shunting may occur at the pulmonary level, as a diversion from the “plugged” pulmonary microvascular flow. While hypoxemia may be seen in any PH, cyanosis at rest or with exercise characterizes Eisenmenger syndrome more than other causes of PH. Exercise‐induced cyanosis or marked drop in O2 desaturation is characteristic of an intracardiac shunt, wherein further right‐to‐left shunting occurs during exercise, as venous return increases.

V.  Diagnosis: echocardiography; right and left heart catheterization A. Echocardiography PH is often initially suggested by echocardiography. Echocardiography estimates PA pressure, and: 1.  Suggests a left‐sided etiology. In addition to valvular function and LV systolic function, echocardiography assesses LA pressure, LV diastolic function, and left atrial size. 2.  Looks for signs of severity of PH: RV and RA dilatation, severe TR, RV systolic dysfunction, and abnormal interventricular septal motion (the high, right‐sided pressure or volume makes the septum bow to the left). Frequently, PA pressure cannot be directly measured by echo; those signs indirectly suggest PH. B. Catheterization Catheterization is needed to confirm the diagnosis and the etiology of PH, particularly in cases of moderate‐to‐severe PH without a clear cause. Patients with a clear clinical and echo diagnosis of left HF do not require cardiac catheterization for PH assessment. Also, patients with an acute PE diagnosis do not require cardiac catheterization (this may, however, be required for chronic thromboembolic PH). The goals of catheterization are: 1.  Confirm the diagnosis of PH by measuring PA pressure and calculating PVR (PVR = [mean PA – PCWP]/cardiac output). The spectral Doppler profile of TR is too weak or insufficient to measure the PA pressure in approximately 25–55% of patients referred for PA pressure evaluation; TR may not be present even when PH is severe.17 The echocardiographic diagnosis of PH is falsely positive in up to 50% of patients, and, overall, the PA pressure value differs from the catheterization value by >10 mmHg in 50% of patients. Echocardiography may under‐ or overestimate PA pressure in various PH etiologies.17,18 2.  Assess PCWP to determine if PH is secondary to left HF. The assessment of PCWP may be difficult in patients with severe PH:19–21 (i) segmental PA branches are dilated, which makes them difficult to wedge; thus, a hybrid PCWP–PA pressure tracing may be obtained and lead to overestimation of the true PCWP; (ii) on the other hand, the true PCWP waveform may be flattened without distinct waves, as the retrograde transmission of LA pressure through the constricted pulmonary vasculature is damped. Moreover, wedging a PA catheter in a patient with PH is associated with an increased risk of PA rupture.

482  Part 9.  Other Cardiovascular Disease States

In the absence of an appropriate PCWP tracing, LVEDP needs to be measured. A case can be made to perform left heart catheterization and measure LVEDP in all patients with PH. Not only can PCWP overestimate LVEDP, but according to a large analysis of 4000 heart catheterizations in patients with PH, PCWP underestimates LVEDP in over 50% of patients and misclassifies postcapillary PH as precapillary PH. This is related to wedging issues, damping of the pressure transmission from LA to the wedged PA, but also to the fact that LVEDP is larger than PCWP in patients with compensated LV dysfunction.22 Patients with normal LVEDP and PCWP may still have occult HF. If suspected clinically, give a volume load or perform exercise testing or vasodilator challenge and see if PCWP or LVEDP increases, unveiling left HF as the cause of PH. 3.  Assess for a left‐to‐right shunt (oximetry screen of SVC, IVC, and PA). Right‐to‐left shunt, on the other hand, is suspected when hypoxemia is present at rest and does not quickly improve with deep breathing or O2 therapy. 4.  Perform acute vasoreactivity testing if PAH is suspected. Vasodilator challenge should not be performed in overt left HF with marked PCWP elevation, as it may increase pulmonary blood flow and thus PCWP, which leads to pulmonary edema. It should not be performed in case of PH secondary to severe lung disease, as vasodilators worsen V/Q mismatch and hypoxemia. It may, however, be performed when severe PH is concomitant with lung disease, as severe PH often implies a primary pulmonary vascular disease independent of lung disease. Only 10% of patients with PAH have a positive response to vasodilator challenge. Since non‐responders still respond well to the chronic administration of potent pulmonary vasodilators (prostacyclin, bosentan, sildenafil), one may wonder what the rationale for vasodilator challenge is. The rationale for vasodilator challenge is threefold: (1) positive responders to vasodilator challenge may respond to chronic calcium channel blocker therapy; (2) positive responders have a better long‐term prognosis; (3) the hemodynamic tolerance to vasodilator therapy is assessed. One should ensure that PCWP does not increase and cardiac output and systemic pressure do not decrease with vasodilators. In fact, a vasodilator challenge may be used as a form of left heart stress testing, unveiling occult left HF. An acute response to vasodilator testing is defined by the ACC and pulmonary societies as a drop of mean PA pressure by >10 mmHg to 2/3 SVR or >6 Wood units need to have vasoreactivity testing before shunt correction to ensure that PH is reversible; otherwise shunt closure may precipitate right heart failure. Patients with advanced left HF who are considered for cardiac transplantation and who have PH with high PVR require vasoreactivity testing to assess the reversibility of PH and their operability. In this case, however, the use of prostanoids may increase PCWP and is poorly tolerated. Nitroprusside and milrinone are the vasodilators of choice, as they reduce PVR in reactive PH but also reduce LV afterload, which prevents the increase in PCWP. C.  Other tests Depending on the context, these tests are performed before or after confirmation of PH: 1.  Chest CTA or V/Q scan for the diagnosis of thromboembolic PH. These studies do not usually miss the proximal form of thromboembolic PH, which is the most common form and the treatable form of thromboembolic PH. To definitely rule out PE and diagnose multiple distal PEs missed by the above, a pulmonary angiogram may need to be performed if the clinical suspicion is high. 2.  Chest X‐ray, arterial blood gases, pulmonary function testing with diffusion capacity, ± high‐resolution CT scan of the chest for the diagnosis of lung diseases. Remember, however, that lung diseases do not usually lead to severe PH. On chest X‐ray, look for pulmonary edema or parenchymal lung disease. Pulmonary hypertension, per se, leads to enlarged central pulmonary arteries, i.e., enlarged hila, with marked tapering of the peripheral arteries and oligemia of the lung fields. This is opposed to the diffuse vascular engorgement seen with pulmonary edema. 3.  Sleep study in most patients. 4.  HIV, liver function testing, antinuclear antibodies, TSH, BNP.

VI. Treatment A.  PH secondary to left heart failure, pulmonary thromboembolic disease, or lung disease: treat the underlying cause 1.  Treat LV failure, aggressively treat hypertension, and perform valvular surgery in case of severe valvular disease. PH is expected to be reversible, but the process may be slow, and temporary support with vasodilators may be needed perioperatively. 2.  Pulmonary thromboendarterectomy in thromboembolic PH with proximal thromboembolic disease. 3.  Bronchodilators and O2 in the case of lung disease. 4.  Pulmonary vasodilators are not recommended and may be harmful. They may worsen V/Q mismatch by vasodilating the hypoventilated areas of the lungs, which worsens hypoxemia. They may increase pulmonary blood flow and lead to pulmonary edema in the case of LV dysfunction.

Chapter 25.  Pulmonary Hypertension  483

B.  Pulmonary arterial hypertension Without specific therapy, idiopathic PAH has a poor prognosis with a median survival of 2.8 years. PAH related to Eisenmenger syndrome has a better prognosis, as the right‐to‐left shunt relieves the RV overload. Conversely, PAH associated with connective tissue disease (scleroderma) or HIV has a worse prognosis.23 Several high‐risk features imply a poor prognosis: • NYHA class IV; syncope (implies a severe reduction of the cardiac output reserve) • 6‐minute walking distance 14 mmHg, low cardiac index 180 pg/ml • The severity of PA pressure rise, per se, is not an indicator of poor prognosis. In fact, a declining PA pressure in the face of a severely increased PVR is a marker of reduced cardiac output and RV failure (poor prognosis). Pulmonary vasodilator therapy improves symptoms and survival very significantly (meta‐analysis).24 It is targeted to patients with pulmonary arterial hypertension and NYHA classes II–IV (Figure 25.2). Calcium channel blockers (CCBs) are associated with a dramatic improvement in survival of the few patients who acutely respond to vasodilator testing and achieve a sustained clinical response; thus, those select patients (5%) are initially treated with CCBs.21,25 Non‐responders to vasodilator testing are treated with one of the four categories of selective pulmonary vasodilators:26 (i) prostacyclin (IV, SQ, inhaled, and more recently oral), (ii) endothelin‐receptor antagonists (ERA) (bosentan, ambrisentan, macitentan), (iii) phosphodiesterase‐5 inhibitors (sildenafil and tadalafil), which reduce the degradation of the vasodilator cGMP, (iv) stimulator of guanylate cyclase (riociguat), which enhances cGMP production. The latter two categories of drugs are related, as they both act on the cGMP system, i.e., the downstream nitric oxide system. In fact, nitric oxide binds to the intracellular guanylate cyclase and activates it, generating cGMP. Riociguat should not be combined with phosphodiesterase inhibitors, as they both act on the cGMP system (risk of hypotension without much benefit). Nitrates increase cGMP in the systemic but not pulmonary arteries and are not effective in PAH.

Acute vasodilator response No

Yes (10%) Class I-III symptoms Class II Oral high-dose CCBs (nifedipine 180 mg/day diltiazem 720 mg/day) Response = Sustained improvement to class I-II and near-normalization of hemodynamics on repeated cath (3 months) No Yes (5%) Continue CCB with careful monitoring

Class III

ERA PDE-5 inh Riociguat

Class IV or other high-risk features

ERA PDE-5 inh Riociguat IV prostacyclin pump (Epoprostenol) Inhaled prostacyclin (Iloprost) SQ Prostacyclin (Treprostinil)

*1st choice: † IV prostacyclin pump (Epoprostenol) *2nd choice Inhaled prostacyclin (Iloprost) SQ Prostacyclin (Treprostinil) *3rd choice: ERA PDE-5 inh

+ Consider initial combination therapy Clinical response (=sustained class l–II) No consider combined therapies (2 of the following: ERA, PDE-5 inh, prostanoids) Still no response + severe RV failure: Atrial septostomy and/or lung transplantation

Figure 25.2  Treatment algorithm for patients with PAH, which is mainly validated for idiopathic PAH, familial PAH, and scleroderma PAH. This algorithm is cautiously extrapolated to other forms of PAH, Eisenmenger syndrome, and thromboembolic PAH that cannot be treated surgically or that persists after surgical therapy. This algorithm is adapted from recommendations from references 1 and 25. †In class IV, intravenous epoprostenol is preferred because it is the therapy that has shown a mortality reduction in a randomized fashion, and is the therapy most widely studied in class IV.28 CCB, calcium channel blocker; ERA, endothelin‐receptor antagonist; PDE‐5 inh, phosphodiesterase‐5 inhibitors.

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Even in the absence of a positive vasodilator response upon testing, these potent pulmonary vasodilators reduce PVR over the long term, and, more importantly, prevent arterial remodeling, scarring, and the further increase in PA pressure. Therapy needs to be started as soon as possible, as it dramatically reduces mortality over the short‐term follow‐up (14 weeks in a meta‐ analysis).24 Clinical non‐responders to pulmonary‐specific vasodilators, i.e., those who do not improve to a functional class I or II, may be treated with combined therapies. A recent study has suggested that initial combination therapy with tadalafil and ambrisentan, vs. initial therapy with either one of them, is associated with a 50% reduction in clinical events and twice the increase in walking distance. Note that, except for the rare dramatic responder to CCB, PAH therapies only mildly reduce PA pressure (by ~10%), and thus PA pressure is not used as a therapeutic endpoint. PAH therapies improve PVR, RV function and size on echo, RA pressure, and cardiac output without much of an effect on PA pressure.1,27,28 Along with the reduction in PVR, cardiac output increases, which may mask any PA pressure improvement (PA pressure ~ PVR × cardiac output). Thus, therapy targets clinical improvement (sustained class I–II, improved 6‐minute walking distance), and improvement of echo parameters and BNP. Invasive reassessment, after several months of therapy, is done in high‐risk patients or those who do not improve clinically. Chronic anticoagulation (warfarin) is associated with improved survival. This is based on retrospective analyses that included patients with idiopathic or familial PAH.24,26 This therapy has been extrapolated to other patients with PAH.1 Anticoagulation prevents the progressive, thrombotic pulmonary arteriopathy that occurs with PAH. Supportive measures are frequently used: O2 for severe hypoxemia and diuretics for RV volume overload. Diuretics are useful for symptom relief and are usually well tolerated, as the dilated RV is not preload‐dependent. In case of florid edema, gently diurese by 1000 ml/day.

Q u e s ti o n s a n d   a n s w e r s Question 1. Among elderly patients referred for the evaluation of pulmonary hypertension, what is the most commonly missed diagnosis? A. Sleep apnea B. Chronic lung disease C. HFpEF D. PE Question 2. A 57‐year‐old obese woman has dyspnea on exertion, NYHA III. She has a history of hypertension. Her BP is currently 136/85 mmHg. No clinical signs of HF are present. Her echo shows a systolic PA pressure of 75 mmHg with RV pressure overload pattern, mild concentric LV remodeling, and mild LA enlargement with normal LA pressure. What is the next step? A. Prescribe a diuretic and reassess PA pressure B. Sleep study C. Right and left heart catheterization with vasoreactivity and exercise testing D. Prescribe sildenafil Question 3. The patient in Question 2 underwent cardiac catheterization that confirmed severe PAH: PA pressure 75/35, mean 45 mmHg; PCWP and LVEDP 13 mmHg at rest and 19 mmHg with exercise; no significant drop of PA pressure with adenosine testing. A chest X‐ray and a lung perfusion scan are normal. She is placed on bosentan therapy. Three months later, her functional capacity and dyspnea have improved significantly (NYHA II). No signs of right HF are present on exam. An echo is performed and still shows severe PH, PA pressure 75 mmHg. What is the next step? A. Switch to sildenafil B. Switch to prostacyclin products C. Add sildenafil D. Continue the same therapy Question 4. Vasodilator therapy is initiated in a patient with severe PAH, elevated RA pressure, and severe RV dilatation on echo. All of the following parameters are endpoints of therapy, except for which one? A. Improving functional class to NYHA I–II B. Reducing RA pressure to 380–440 m (or more in young patients) D. Reducing PA pressure by 20% E. Reducing RV dilation to normal or near‐normal F. Increasing cardiac index to >2.5–3 l/min/m2 G. Normal BNP Question 5. A 55‐year‐old woman presents with class III dyspnea. She is diagnosed with PAH. Based on recent data, which therapy is the best first‐line therapy? A. Sildenafil B. Ambrisentan C. IV epoprostenol D. Combination tadalafil–ambrisentan Question 6. A 49‐year‐old man has a history of thromboembolic PH with RV failure. A year ago, his cardiac catheterization demonstrated RA pressure 25 mmHg, PA pressure 95/55 mmHg, PCWP 20–22 mmHg, and PVR 11 Wood units. He is placed on bosentan and sildenafil. More recently, due to progressive symptoms, subcutaneous treprostinil is added. However, his symptoms continue to worsen. A right heart

Chapter 25.  Pulmonary Hypertension  485

100

0

PA

50

PCWP

PCWP deflated into PA

Figure 25.3 

catheterization is repeated, revealing the PA and PCWP shown in Figure 25.3. His RA pressure is 14 mmHg and his cardiac output is 8 l/min by thermodilution. What is the next step? A. The patient’s PH is refractory. Up‐titrate the dose of treprostinil B. Continue the current regimen. RA pressure, CO, and PVR have improved C. Reduce the dose of vasodilator therapy and consider adding furosemide Question 7. A 35‐year‐old woman presents with class III dyspnea. She is found to have severe PAH with PA pressure 100 mmHg and PVR 9 Wood units. Echo shows ASD of 1 cm with right‐to‐left shunt across it. The RV is mildly dilated, and it mostly displays signs of pressure overload. What is the diagnosis and next management? A. Eisenmenger syndrome. ASD closure is contraindicated at this point B. Idiopathic PAH. ASD is an incidental finding and should not be closed C. PAH secondary to ASD, but not a definite Eisenmenger. Attempt vasodilator testing: if PVR declines and the shunt converts from right‐ to‐left to left‐to‐right with testing, ASD may be closed. Question 8. Of the following PAH medications, select the one which has the most liver toxicity (10%), the one which has most been associated with peripheral edema, the one which has most interactions with cytochrome P450 3A4 and 2C9, and the one which reduces the blood levels of oral contraceptives: A. Sildenafil B. Bosentan C. Ambrisentan D. Macitentan Answer 1. C. Answer 2. C. The patient’s PH may be precapillary (PAH) or may be related to left heart diastolic dysfunction. In the absence of overt hypervolemia or HTN, and without proof that PCWP is elevated, adding a diuretic is not appropriate. A diuretic would be an appropriate first step in a patient with florid left HF/pulmonary edema. Sildenafil is not prescribed before a right heart catheterization confirms the diagnosis of PH and the precapillary origin of PH. Right and left heart catheterization is the next step: resting pressures are obtained, then, if PCWP and LVEDP are normal or borderline at rest, exercise testing is performed to unveil LV diastolic dysfunction, especially in a patient with LA enlargement and concentric LV remodeling. Vasoreactivity testing is also a left heart stressor that may increase PCWP/LVEDP and unveil LV diastolic dysfunction. A sleep study needs to be performed and sleep apnea treated; however, this is not the most important next step, especially because sleep apnea does not usually explain severe PH. In fact, sleep apnea may aggravate LV diastolic failure.

486  Part 9.  Other Cardiovascular Disease States

Answer 3. D. Except for a rare dramatic response seen in patients who have a positive response to vasoreactivity testing, PAH therapies only mildly reduce PA pressure (by ~10%), if at all, and thus PA pressure is not used as a therapeutic endpoint. The improvement in functional class to I–II and the improvement of RV failure and RA pressure are endpoints of therapy. Vasodilators reduce PVR and increase cardiac output, both of which are desirable effects that correlate with clinical improvement. However, PA pressure, which is ~ PVR × cardiac output, remains unchanged. The 75 mmHg value that follows therapy is different from the initial 75 mmHg value, as the underlying components (CO × PVR) have favorably changed. Combination therapy may be considered simply because it is a superior initial strategy, not because of the persistent PA pressure elevation. Answer 4. D. Answer 5. D. Initial combination therapy was superior to initial monotherapy in the AMBITION trial. Prostanoids are first‐line therapy in patients with NYHA class IV or other high‐risk, RV failure features (Section VI.B), not this patient. Answer 6. C. Initially (a year ago), the patient had severe pulmonary arterial (precapillary) hypertension, with RV failure and severely elevated RA pressure. PCWP was mildly elevated as a result of RV failure and the inherent equalization of left and right diastolic pressures (with RA pressure remaining slightly higher than PCWP). The elevation of PCWP did not match the severity of PVR elevation. On the current study, note the very wide PA pulse pressure and the near‐ventricularization of the PA pressure waveform. This may imply either (i) severe pulmonic valve insufficiency or (ii) high‐cardiac‐output state. The high cardiac output obtained by thermodilution suggests the latter. In pulmonary insufficiency, the thermodilution injectate keeps recirculating away from the PA sensor and a low cardiac output is obtained, or sometimes no CO can be obtained. PCWP is very elevated (mean ~35 mmHg) with a very large V wave that approximates 50 mmHg. This implies severe LV failure. In fact, PCWP > >RA pressure, definitely implying that LV failure is the primary process at this point. Moreover, PVR is calculated at ~2.5 Wood units (PVR = [mean PA – PCWP]/CO). Thus, at this point, the severe pulmonary hypertension is secondary to both LV failure and the high‐output state, rather than elevated PVR (PA pressure being proportional to CO × PVR, a high cardiac output may lead to a high PA pressure, even if PVR is reduced). LV failure, by itself, is secondary to the excessive vasodilator therapy that floods the left heart with a high pulmonary and systemic flow. Answer 7. B. When a small defect is found in an adult with severe PH and severe PVR elevation (usually VSD male) and, contrary to a common misconception, may occur in the elderly as well.7 Usually, it is not only preceded but followed by nausea, malaise, fatigue, or diaphoresis;4,5,8 the patient’s full revival may be slow. When the syncope is prolonged >30–60 seconds, clonic movements and loss of bladder control are common.9 Mechanism. Vasovagal syncope is initiated by anything that leads to strong myocardial contractions on an “empty” heart. Emotional stress, reduced venous return (from dehydration or prolonged standing), or vasodilatation (hot environment) stimulates the sympathetic system and reduces the LV cavity size, which leads to strong hyperdynamic contractions in a relatively empty heart. This hyperdynamic cavity obliteration activates the myocardial mechanoreceptors, initiating a paradoxical vagal reflex with vasodilatation and relative bradycardia.10 Vasodilatation is usually the predominant mechanism (vasodepressor response), particularly in older patients, but severe bradycardia is also possible (cardioinhibitory response), particularly in younger patients.7 Diuretic and vasodilator therapies increase the predisposition to vasovagal syncope, particularly in the elderly. On tilt table testing, vasovagal syncope is characterized by hypotension and a relative bradycardia, sometimes severe.10 B.  Situational syncope This syncope is caused by a reflex triggered in specific circumstances such as micturition, defecation, coughing, weightlifting, laughing, or deglutition. The reflex may be initiated by a receptor on the visceral wall (e.g., bladder wall) or by the strain that reduces venous return.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

488

Chapter 26.  Syncope  489

C.  Carotid sinus hypersensitivity Carotid sinus hypersensitivity (CSH) is an abnormal response to carotid massage that is predominantly found in patients over 50 years of age. Spontaneous carotid sinus syndrome is a form of CSH where syncope clearly occurs in a situation that stimulates the carotid sinus (head rotation, head extension, shaving, tight collar); this is a rare cause of syncope (~1% of syncope cases). Conversely, induced carotid sinus syndrome is much more common and represents CSH in a patient with unexplained syncope and without obvious triggers; the abnormal response is induced during carotid massage rather than spontaneously. In induced carotid sinus syndrome, carotid sinus hypersensitivity is a marker of a diseased sinus node or AV node that cannot withstand any inhibition; this diseased node is the true cause of syncope rather than CSH per se, and carotid massage is a “stress test” that unveils conduction disease. Thus, carotid sinus massage is indicated in unexplained syncope regardless of circumstantial triggers. It consists of applying firm pressure over each carotid bifurcation (just below the angle of the jaw) consecutively for 10 seconds. It is performed at the bedside, and may be performed in both supine and erect positions during tilt table testing; erect positioning increases the sensitivity of carotid massage. An abnormal response to carotid sinus massage is defined as any of the following: 11–13 i.  Vasodepressor response: systolic blood pressure (SBP) decreases by ≥50 mmHg ii.  Cardioinhibitory response: pause ≥3 seconds (sinus pause or AV block) iii.  Mixed vasodepressor and cardioinhibitory response Overall, a cardioinhibitory component is present in ~2/3 of CSH cases. CSH is found in 25–50% of patients over 50 years of age with unexplained syncope or fall, and is almost equally seen in men and women.11 One study correlated CSH with the later occurrence of asystolic syncope during prolonged internal loop monitoring; subsequent pacemaker therapy reduced the burden of syncope. 12 Another study, in patients >50 years old with unexplained falls, found that 16% of them had cardioinhibitory CSH; pacemaker placement reduced falls and syncope by 70% compared with no pacemaker therapy in these patients.13 On the other hand, CSH is seen in 39% of elderly patients who do not have a history of syncope or fall, and thus it is important to rule out other causes of ­syncope before attributing it to CSH. D.  Post‐exertional syncope While exertional syncope is alarming for a malignant cardiac or arrhythmic cause, post‐exertional syncope is usually a form of vasovagal syncope. Upon exercise cessation, venous blood stops getting pumped back to the heart through the peripheral muscular contraction, yet the heart is still exposed to the catecholamine surge and hypercontracts on an empty cavity. This triggers a vagal reflex. Post‐exertional syncope may also be seen in hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS), where the small left ventricular cavity is less likely to tolerate the reduced preload after exercise and is more likely to obliterate.

II.  Orthostatic hypotension Orthostatic hypotension accounts for ~10% of cases of syncope.1–3 Normally, after the first few minutes of standing, ~25–30% of blood pools in the veins of the pelvis and the lower extremities, strikingly reducing venous return and stroke volume. Upon prolonged standing, additional blood volume extravasates in the extravascular space, further reducing venous return. This normally leads to a reflex increase of sympathetic tone, peripheral and splanchnic vasoconstriction, and an increase in heart rate of 10–15 bpm. Overall, cardiac output (CO) is reduced while blood pressure (BP) is maintained (BP = CO × vascular resistance: vascular resistance ↑, CO ↓). Orthostatic hypotension is characterized by autonomic failure, with a lack of compensatory increase in vascular resistance or heart rate upon orthostasis; or by significant hypovolemia that cannot be overcome by sympathetic mechanisms. It is defined as a drop of SBP ≥20 mmHg or DBP ≥10 mmHg after 30 seconds to 5 minutes of orthostasis. BP is checked immediately upon standing and at 3 and 5 minutes of orthostasis; this may be done at the bedside or during tilt table testing. 2,4 Some patients may have an immediate BP drop of >40 mmHg upon standing, with a quick return to normal within 30 seconds. This “initial orthostatic hypotension” may be common in elderly patients receiving antihypertensive drugs and may elude detection upon standard BP measurement.2 Other patients with milder orthostatic hypotension may develop a more delayed hypotension 10–15 minutes later, as more blood pools in the periphery.14 Along with the BP drop, a failure to increase heart rate identifies autonomic dysfunction. On the other hand, an excessive increase in heart rate >20–30 bpm may signify a hypovolemic state even if BP is maintained, the lack of BP drop being related to the excessive heart rate increase. Orthostatic hypotension is the most common cause of syncope in the elderly and may be due to: (i) autonomic dysfunction (age, diabetes, uremia, Parkinson’s disease), (ii) volume depletion, (iii) drugs that block autonomic effects or cause hypovolemia (vasodilators, β‐blockers, diuretics, neuropsychiatric medications, alcohol). Since digestion leads to peripheral vasodilatation and splanchnic blood pooling, syncope that occurs within 1 hour postprandially has a similar mechanism to orthostatic syncope. Supine HTN with orthostatic hypotension. Some patients with severe autonomic dysfunction or severely non‐compliant arteries are unable to regulate vascular tone. They display severe HTN when supine and significant hypotension when upright. Postural orthostatic tachycardia syndrome (POTS) is another form of orthostatic failure that occurs most frequently in young women (30 bpm within the first 10 minutes of orthostasis, or an absolute heart rate >120 bpm. Unlike in orthostatic hypotension, BP and cardiac output are maintained through this increase in heart rate, yet the patient still develops symptoms of severe fatigue or near‐syncope, possibly because of flow maldistribution and reduced cerebral flow.2 While POTS, per se, does not induce syncope,2 it may be associated with a vasovagal form of syncope that occurs beyond the first 10 minutes of orthostasis in up to 38% of these patients.15 In a less common, hyperadrenergic form of POTS, there is no autonomic failure but the sympathetic system gets overly activated, with orthostasis leading to this excessive tachycardia.10,16

490  Part 9.  Other Cardiovascular Disease States

III.  Cardiac syncope Accounting for ~10‐20% of cases of syncope, a cardiac etiology is the main concern in patients presenting with syncope, and the main predictor of mortality and sudden death.1,2,8,17,18 Syncope often occurs suddenly without any warning signs (sudden syncope is also called malignant syncope). As opposed to neurally mediated syncope, the post‐recovery period is not usually marked by lingering malaise. There are three forms of cardiac syncope: 1.  Structural heart disease with cardiac obstruction: AS, HOCM, severe pulmonary arterial hypertension. Peripheral vasodilatation occurs during exercise, but CO cannot increase because of the fixed or dynamic obstruction to the ventricular outflow. Since BP = CO × peripheral vascular resistance, BP drops with the reduction in vascular resistance. Exertional ventricular arrhythmias may also occur in these patients. Syncope may also occur after exercise. 2.  Ventricular tachycardia (VT) secondary to: i.  Underlying structural heart disease, with or without reduced LVEF, such as coronary arterial disease, hypertrophic cardiomyopathy, hypertensive cardiomyopathy, or valvular disease. ii.  Primary electrical disease (long QT syndrome, Wolff–Parkinson–White syndrome, Brugada syndrome, arrhythmogenic right ventricular dysplasia, sarcoidosis). Occasionally, fast supraventricular tachycardia causes syncope at its onset, before vascular compensation develops. This occurs in patients with underlying heart disease.2,10,11 3.  Bradyarrhythmias, with or without underlying structural heart disease. Bradyarrhythmias are most often related to degeneration of the conduction system or to medications, rather than cardiomyopathies. MI/ischemia causes syncope only when complicated by arrhythmias or by a shock.

When a patient with a history of heart failure presents with syncope, VT and bradyarrhythmias are top considerations. Nevertheless, about half of cases of syncope in patients with cardiac disease have a non‐cardiac cause,17 including the hypotensive or bradycardic side effect of drugs.

IV.  Other causes of syncope Acute medical or cardiovascular illnesses may cause syncope and are sought in the appropriate clinical context: (1) severe hypovolemia or gastrointestinal bleed; (2) large pulmonary embolus with hemodynamic compromise; (3) tamponade; (4) aortic dissection; (5) hypoglycemia. Bilateral critical carotid disease or severe vertebrobasilar disease very rarely causes syncope, and, when it does, it is associated with focal neurologic deficits.2 Vertebrobasilar disease may cause “drop attacks,” i.e., a loss of muscular tone with fall but without loss of consciousness.19 Severe proximal subclavian disease leads to reversal of the flow in the ipsilateral vertebral artery as blood is shunted toward the upper extremity. It manifests as dizziness and syncope during the ipsilateral upper extremity activity, usually with focal neurological signs (subclavian steal syndrome).2 Psychogenic pseudosyncope is characterized by a high frequency of attacks that typically last longer than a true syncope and occur multiple times per day or week, sometimes with a loss of motor tone. 2 It occurs in patients with anxiety or somatization disorders. Note Reflex syncope is the most frequent etiology of syncope. However, long asystolic pauses due to sinus or AV nodal block are the most frequent mechanism of unexplained syncope and are seen in >50% of syncope cases on prolonged rhythm monitoring.1,20 These pauses may be related to intrinsic sinus or AV nodal disease or, more commonly, to extrinsic effects, such as the vasovagal mechanism. Some experts favor classifying and treating syncope based on the mechanism rather than the etiology, but this is not universally accepted.1,21

V.  Syncope mimic: seizure (see Table 26.1) Table 26.1  Features that suggest seizure rather than syncope. • Unconsciousness often lasts longer than 5 minutes • Postictal confusion or paralysis • Prolonged tonic–clonic movements. Clonic movements may be seen with any prolonged syncope (>30 sec), in a more limited and brief form (5 seconds → reflex syncope • No or 4 years8

VII.  Diagnostic evaluation of syncope (Figure 26.1) Underlying structural heart disease is the most important predictor of ventricular arrhythmias and death.18,22–24 Thus, the primary goal of syncope evaluation is to rule out structural heart disease by history, examination, ECG, and echocardiography. A.  Basic initial strategy The etiology of syncope is determined by history and physical examination alone in up to 50% of cases, mainly vasovagal syncope, orthostatic syncope, or seizure.2,3,17 Always check blood pressure both lying and standing and in both arms, and obtain an ECG. Perform carotid massage in all patients older than 50 years if syncope is not clearly vasovagal or orthostatic and if cardiac syncope is not likely. Carotid massage is contraindicated if the patient has a carotid bruit or any history of stroke. ECG establishes or suggests a diagnosis in 10% of patients (Table 26.3).2,8,17,25 A normal ECG, or mild non‐specific ST–T abnormality, suggests a low likelihood of cardiac syncope and is associated with an excellent prognosis. Abnormal ECG findings are seen in 90% of cases of cardiac syncope and only 6% of cases of neurally mediated syncope.26 In one study of syncope patients with a normal ECG and a negative cardiac history, none had an abnormal echocardiogram.27 B.  If the heart is normal clinically and by ECG If the history suggests neurally mediated syncope or orthostatic hypotension, and the history, examination, and ECG are not suggestive of CAD or any other cardiac disease, the workup is stopped. C.  If the patient has signs or symptoms of heart disease If the patient has signs or symptoms of heart disease (angina, dyspnea, clinical signs of HF, murmur), a history of heart disease, or exertional, supine, or malignant features, heart disease should be sought and the following performed: • Echocardiography to assess LV function, severe valvular disease, and LV hypertrophy. • Stress test (possibly) in case of exertional syncope or associated angina. However, the overall yield of stress testing in syncope is low (35% LVH ECG conduction abnormalities ↓ EP study ↓ • If VT ICD • If bradyarrhythmia PM • If normal Tilt test or event monitor/loop recorder†

• Cardiac disease (–) • Consider syncope vasovagal or orthostatic and stop here • Carotid massage if age >50 3. If malignant (no warning), recurrent or severe (injury) ↓ Carotid massage Tilt test ↓ + Event monitor or loop recorder if above (–) ± EP study if recurrent malignant syncope (low yield if no heart disease)

Figure 26.1  Management of syncope. *Also, consider severe hypovolemia, bleeding, pulmonary embolism, and tamponade and rule them out clinically. Carotid Doppler and head CT scan are not indicated, especially given that carotid stenoses, per se, very rarely lead to syncope. † EP study may have missed bradyarrhythmias and some forms of VT. CAD, coronary arterial disease; EF, ejection fraction; EP, electrophysiological; LVH, left ventricular hypertrophy; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter defibrillator; PM, pacemaker. Table 26.3  ECG or Holter findings suggestive of cardiac syncope. 1. Bradyarrhythmia‐related syncope is established with any of the following: • Sinus bradycardia 3 s while awake • Mobitz II, high‐grade, or complete AV block • Alternating LBBB or RBBB (on the same ECG or on ECGs obtained on separate occasions) 2. Bradyarrythmia‐related syncope is suggested with: • Isolated RBBB or LBBB (VT also possible, depending on the underlying cardiac disease) • Mobitz I AV block 3. Tachyarrhthmia‐related syncope is established with: • Sustained VT or fast SVT (>160 bpm) 4. Underlying heart disease and VT is suggested with: • Q waves • AF • LBBB, RBBB, QRS >0.11 s • LVH, RVH, large R wave in V1 5. Primary electrical disorders are suggested with: • Long QTc, pre‐excitation, RBBB with Brugada pattern, or T‐wave inversion in V1–V3 or epsilon waves (ARVD) 6. Acute ST–T abnormalities

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• Carotid sinus massage in patients >50 years old, if not already performed. Up to 50% of these patients with unexplained syncope have CSH.11 • 24‐hour Holter monitoring. A significant arrhythmia is rarely detected; on the other hand, syncope or dizziness may occur without any arrhythmia, ruling out arrhythmia as a cause of the symptoms.30 The diagnostic yield of Holter monitoring is low (1–2%) in patients with infrequent symptoms,1,2 and is not improved with 72‐hour monitoring.30 The yield is higher in patients with very frequent, daily symptoms, many of whom have psychogenic pseudosyncope.2 • Tilt table testing to diagnose vasovagal syncope. It is positive for a vasovagal response in up to 66% of patients with unexplained syncope.1,17 Patients with heart disease taking vasodilators or β‐blockers may have abnormal baroreflexes; therefore, a positive tilt test is not necessarily indicative of vasovagal syncope in patients with heart disease (tilt testing is less specific in these patients). • If the etiology remains unclear or there are some concerns about arrhythmia, an event monitor (4 weeks of external rhythm monitoring) or an implantable loop recorder (implanted subcutaneously in the prepectoral area for 1–2 years) is placed. Those monitors record the rhythm when the rate is lower or higher than predefined cutoffs or when the rhythm is irregular, regardless of symptoms. The patient or an observer may also activate the event monitor during or after an event, which freezes the recording of the 2–5 minutes preceding the activation and the 1 minute following it. In a patient who has had syncope, a pacemaker is indicated for episodes of high‐grade AV block, pauses >3 seconds, or bradycardia 3 seconds or bradycardia 30 bpm or an absolute rate >120 bpm). Significant hypotension does not occur (blood pressure is normal or low normal) 5. Cerebral syncope: no significant hemodynamic change, but intense cerebral vasoconstriction on transcranial Doppler 6. Psychogenic syncope: syncope without hemodynamic or transcranial Doppler change To be considered positive for vasovagal syncope, hypotension (with or without bradycardia) needs to occur along with reproduction of syncope or near‐syncope. A hemodynamic effect without symptoms is not considered an abnormal tilt test result.

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X.  Treatment of neurally mediated syncope A.  Treatment of vasovagal syncope Vasovagal therapy consists of the following: • Maintain euvolemia and good fluid intake at all times. Patients with premonitory symptoms should sit or lie down at the onset of symptoms. Crossing the legs or isometric handgrip at the onset of symptoms often abort the episode. • Compression stockings (30 mmHg). Since venous blood pools in the pelvic veins, these stockings should be waist‐high. • Tilt training. Tilt training consists of two 30‐minute sessions of upright standing against a vertical wall every day. Also, head‐up, semi‐recumbent tilt sleeping may help. • Non‐pharmacological measures are the key therapy. If syncope recurs despite these interventions, consider: ○○ Midodrine (α‐agonist) or fludrocortisone (mineralocorticoid). ○○ While β‐blockers have been used, one randomized trial has shown that β‐blocker therapy is not more effective than placebo.43 ○○ Intracerebral serotonin appears to facilitate the sympathetic withdrawal that eventually leads to vasovagal syncope. Selective serotonin reuptake inhibitors have reduced the occurrence of vasovagal syncope in several studies (one randomized trial with paroxetine).44 • Role of pacing. In the ISSUE‐3 trial, patients with vasovagal syncope and ≥3 recurrences underwent loop recorder implantation. About one‐third of these patients had a recurrence of syncope during recording, with asystole (≥3 seconds) in half of them. In this subgroup with cardioinhibitory recurrence, pacemaker therapy reduced the 2‐year recurrence from 57% to 25%.21 This study supports the paradigm of treating syncope based on the mechanism rather than the etiology (according to these investigators, asystole secondary to a vasovagal mechanism is treated similarly to asystole secondary to sinus node disease). Other studies have shown that pacemaker therapy is highly effective when asystole is documented at the time of syncope, regardless of the etiology.20 Thus, pacing may be considered in recurrent vasovagal syncope with asystolic mechanism. B.  Carotid sinus hypersensitivity Carotid sinus syndrome, which is a syncope clearly occurring in a circumstance wherein the carotid sinus is manipulated, along with a cardioinhibitory response to carotid sinus massage, is an indication for dual‐chamber pacing. Unexplained syncope with a cardioinhibitory carotid sinus hypersensitivity is a class IIa indication for dual‐chamber pacing. C.  Orthostatic hypotension and POTS Therapy consists of the following: • Treat hypovolemia and maintain good fluid and salt intake. Treat hypokalemia. Rule out adrenal insufficiency. • Arise slowly in stages, avoid activities after eating. • May need to withhold diuretics and other antihypertensives. In elderly patients with orthostatic hypotension and supine HTN, antihypertensive drugs are initiated slowly, diuretics are avoided, and some degree of supine HTN may be accepted (e.g., 150 mmHg). Sleeping in an upright position may attenuate nocturnal HTN (as BP drops in the upright position) and decrease renal perfusion, thereby activating the renin–angiotensin system and increasing the extracellular volume. • Waist‐high compression stockings may help. • If the above fails, fludrocortisone is the medication of first choice, but it may worsen supine HTN or promote HF and edema. Other options: midodrine (may worsen supine HTN), cholinesterase inhibitor (pyridostigmine). D.  Syncope and driving In survivors of VT/VF, the highest risk of arrhythmic events and syncope recurrence is in the first 6–12 months.45 Thus, patients with cardiac syncope or possible cardiac syncope should refrain from driving for at least 6 months, even if ICD is implanted. In general, the risk of recurrence after a vasovagal syncope is ~10–30%, being highest in patients with multiple prior recurrences.6 A study showed that the most common cause of syncope while driving is vasovagal syncope. In all patients, the risk of another syncope was relatively higher in the first 6 months after the event, with a 12% recurrence rate during this period. However, ~50% of all recurrences occurred >6 months later, with a 12% recurrence rate between 6 months and 4–5 years.6 Despite this recurrence risk that persists for several years, the recurrence during driving was unusual in appropriately diagnosed and treated patients (up to 7% per 8 years), and, importantly, patients who had syncope while driving and no underlying structural heart disease had the same long‐term survival as the general population. Long drives increase the risk of recurrence by increasing the peripheral venous pooling; also, recurrence of syncope is more likely and more dangerous for commercial drivers who spend a significant proportion of their time driving. In general, patients with syncope should be prohibited from driving for at least a period of time (e.g., 6 months), during which the risk of recurrence is highest and serious cardiac disease or arrhythmia, if present, would emerge. The above study shows that it is relatively safe to resume driving beyond 6 months, particularly short drives with proper hydration, after appropriate evaluation for cardiac disease. Commercial driving may need to be permanently prohibited.

Q u e stions a nd   a ns w e r s Question 1. A 62‐year‐old man presents with syncope while working in his yard (standing position). He did not have any prodrome and sustained a head bruise. He does not report any recent chest discomfort or dyspnea. He has a history of myocardial infarction 5 years previously, and he takes aspirin, metoprolol, lisinopril, thiazide diuretic, and atorvastatin. His electrocardiogram shows inferior Q waves, but no ischemic ST–T abnormalities and no conduction abnormality. His echocardiogram shows inferior hypokinesis with an overall LVEF of 45%. His troponin I level is normal. What is the next best step? A. Coronary angiography B. Admit for telemetry monitoring then discharge home next day if no arrhythmia is seen, with a diagnosis of vasovagal syncope

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C. Place a 30‐day event monitor D. Place an implantable loop recorder E. Tilt table testing F. Admit for telemetry monitoring and perform an electrophysiologic (EP) study Question 2. A 66‐year‐old man presents with syncope. It occurred while he was walking his dog. He has a facial laceration and does not recall any premonitory symptom. A similar episode occurred 8 months previously. He has no known cardiac history and takes a thiazide diuretic for hypertension. His exam is overall unremarkable and shows a blood pressure of 135/80 without any orthostatic hypotension. An ECG shows non‐specific low T‐wave voltage and an echocardiogram is normal. Telemetry monitoring for 24 hours did not reveal any significant arrhythmia. What is the next management step? A. Reassurance, no further workup B. Tilt table testing C. Carotid sinus massage followed, if negative, by tilt table testing D. 30‐day event monitor E. Stress testing F. Electrophysiologic study Question 3. A 30‐year‐old man who grew up in Mexico, and who has no prior medical problems, presents with syncope while playing basketball. He had very brief premonitory dizziness. He is admitted to the hospital. Telemetry monitoring does not show any arrhythmia. ECG and echo are normal. What is the next step? A. Reassurance B. Exercise stress test C. Event monitoring D. Tilt table testing Question 4. The patient in Question 3 undergoes stress testing, which shows monomorphic VT at peak exercise, along with dyspnea and no syncope. This VT appears to be originating from the LV inferolateral wall. Coronary angiography shows normal coronary arteries. What is the next step? A. Ablation for idiopathic LV VT B. Cardiac MRI Question 5. A 66‐year‐old woman has a history of permanent AF that is rate‐controlled without any AV nodal blocking agent. She has a history of obesity and mild LVH. Her medications consist of warfarin and amlodipine. She had syncope upon standing up after eating a large meal. Another episode of near‐syncope occurred while driving for 10 minutes, 3 months later. ECG shows AF, rate 55 bpm, LAFB, and incomplete RBBB. Telemetry monitoring shows AF pauses of up to 2.6 seconds during sleep. Echo shows normal LVEF with LVH. What is the next step? A. Reassurance (vasovagal syncope) B. Tilt table testing C. Pacemaker placement D. Carotid sinus massage, followed by EP study, followed by tilt table testing then implantable loop recording Answer 1. F. An acute coronary event is not likely in the absence of cardiac complaints surrounding the syncope and in the absence of acute electrocardiographic or troponin abnormalities. Coronary angiography has a low yield in this context. While vasovagal syncope is possible (syncope in a hot environment, vasodilatory and diuretic medications), the first diagnosis to eliminate is cardiac syncope secondary to ventricular tachycardia from a myocardial scar, especially when the syncope is sudden and has an exertional trigger. An EP study is the next step in a patient with structural heart disease and EF >35%. If EP study does not induce a tachyarrhythmia or does not detect a conduction abnormality, it is reasonable to proceed with either tilt table testing (vasovagal syncope) or implantable loop recorder (arrhythmia undetected by EP study). Answer 2. C. In light of the benign ECG and echocardiogram, it is unlikely that this patient has a cardiac or arrhythmic syncope. However, in light of the syncope recurrence, the abruptness (no premonitory symptom), and the physical injury, further workup is necessary to establish a definite cause and treat it. Carotid sinus massage is necessary in any unexplained syncope over the age of 50. If carotid massage is negative, and in the absence of structural heart disease, tilt table testing is an appropriate next step. Vasovagal syncope of the elderly is a likely diagnosis. An alternative strategy would be implanting a loop recorder for long‐term rhythm monitoring. The yield of EP study is low when the ECG and echocardiogram are normal. The yield of a 30‐day event monitor is low in patients with infrequent syncope recurrences. In the absence of angina, the yield of stress testing is low. Answer 3. B. The syncope occurrence during exercise is suggestive of arrhythmia or heart disease. Even if ECG and echo are normal, stress testing is warranted. Answer 4. B. The normal ECG and echo suggest that VT may be idiopathic, but the occurrence of syncope and the inferolateral origin make idiopathic VT less likely. In this case, cardiac MRI is performed. It shows a large inferolateral scar. In addition, the patient develops a complete RBBB on his ECG few months later. Cardiac sarcoidosis or Chagas disease is most likely in this patient. Answer 5. D. The patient’s syncope, especially the first episode, may be suggestive of vasovagal syncope. However, the conduction abnormality present on the ECG (AF with slow conduction), is suggestive of AV nodal disease. Also, LAFB and incomplete RBBB suggest the

Chapter 26.  Syncope  497

possibility of AV block. In this context, syncope is likely due to AV block, manifesting as a long AF pause. However, a pacemaker is not indicated as none of the findings, per se, is diagnostic of AV block and syncope could still be vasovagal. EP study should be performed, seeking a long HV interval or an infra‐His block, or VT in a patient with underlying cardiac abnormality. This is followed by implanting a loop recorder, then a pacemaker if a long pause (>3 seconds) is documented during wakefulness. Tilt table testing may also be performed, even in a patient with structural heart disease, as long as EF is >35% and EP study has not suggested any arrhythmia (case where the likelihood of vasovagal syncope is not low).

References 1. Brignole M, Hamdan MH. New concepts in the assessment of syncope. J Am Coll Cardiol 2012; 50: 1583–91. 2. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30: 2631–71. 3. Kapoor W. Syncope. N Engl J Med 2000; 343: 1856–62. 4. Graham LA, Kenny RA. Clinical characteristics of patients with vasovagal syncope presenting as unexplained syncope. Europace 2001; 3: 141–6. 5. Calkins H, Shyr Y, Frumin H, et al. The value of clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block and neurocardiogenic syncope. Am J Med 1995; 38: 365–73. 6. Sorajja D, Nesbitt GC, Hodge DO, et al. Syncope while driving: clinical characteristics, causes, and prognosis. Circulation 2009; 120: 928–34. 7. Kochiadakis GE, Papadimitriou EA, Marketou ME, et al. Autonomous nervous system changes in vasovagal syncope. Is there a difference between young and older patients Pacing Clin Electrophysiol 2004; 10: 1371–7. 8. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope with and without heart disease. J Am Coll Cardiol 2001; 37: 1921–8. 9. Brignole M, Alboni D, Benditt D, et al. Task force on syncope, European Society of Cardiology. Part 1. The initial evaluation of patients with syncope. Europace 2001; 3: 253–60. 10. Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance. Circulation 2005; 111: 2997–3006. 11. Brignole M, Menozzi C, Gianfranchi L, et al. Carotid sinus massage, eyeball compression, and head‐up tilt test in patients with syncope of uncertain origin and in healthy control subjects. Am Heart J 1991; 122: 1644–51. 12. Maggi R, Menozzi C, Brignole M, et al. Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous neurally mediated syncope. Europace 2007; 9: 563–7. 13. Kenny RM, Richardson DA, Steen N, et al. Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol 2001; 38: 1491–5. 14. Gibbons CH, Freeman R. Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance. Neurology 2006; 67: 28–32. 15. Ojha A, McNeeley K, Heller E, et al. Orthostatic syndromes differ in syncope frequency. Am J Med 2010; 123: 245–9. 16. Kanjwal Y, Kosinski D, Grubb BP. The postural tachycardia syndrome: definitions, diagnosis and management. Pacing Clin Electrophysiol 2003; 26: 1747–57. 17. Brignole M, Alboni P, Benditt DG, et al.; European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22: 1256–306. 18. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347: 878–85. 19. Kubak MJ, Millikan CH. Diagnosis, pathogenesis, and treatment of “drop attacks”. Arch Neurol 1964; 11: 107–13. 20. Brignole M, Menozzi C, Bartoletti A, et al. Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope. Eur Heart J 2006; 27: 1085–92. 21. Brignole M, Menozzi C, Moya A, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE‐3): a randomized trial. Circulation 2012; 125: 2566–71. 22. Quinn J, McDermott D, Stiell I, Kohn M, Wells G. Prospective validation of the San Francisco Syncope Rule to predict patients with serious outcomes. Ann Emerg Med 2006; 47: 448–54. 23. Colivicchi F, Ammirati F, Melina D, et al.; OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) Study Investigators. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J 2003; 24: 811–19. 24. Kapoor WN, Hanusa BH. Is syncope a risk factor for poor outcomes? Comparison of patients with and without syncope. Am J Med 1996; 100: 646–55. 25. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ACCF scientific statement on the evaluation of syncope. J Am Coll Cardiol 2006; 47: 473–84. 26. Sarasin FP, Louis‐Simonet M, Carballo D, et al. Prospective evaluation of patients with syncope. Am J Med 2001; 111: 177–84 27. Sarasin FP, Junod AF, Carballo D, et al. Role of echocardiography in the evaluation of syncope: a prospective study. Heart 2002; 88: 363–7. 28. AlJaroudi WA, Alraies MC, Wazni O, Cerqueira MD, Jaber WA. Yield and diagnostic value of stress myocardial perfusion imaging in patients without known coronary artery disease presenting with syncope. Circ Cardiovasc Imaging 2013; 6: 384–91. 29. Ungar A, Del Rosso A, Giada F, et al. Early and late outcome of treated patients referred for syncope to emergency department. The EGSYS 2 follow‐up study. Eur Heart J 31 2010: 2021–6. 30. Linzer M, Yang EH, Estes NA III, et al. Diagnosing syncope. 2. Unexplained syncope: Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997; 127: 76–86. 31. Fujimara O, Yee R, Klein GJ, et al. The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. N Engl J Med 1989; 62: 1703–7. 32. Linzer M, Pritchett EL, Pontinen M, et al. Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope. Am J Cardiol 1990; 66: 214–19. 33. Edvardsson N, Frykman V, van Mechelen R. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace 2011; 13: 262–9. 34. Brignole M, Sutton R, Menozzi C, et al. Early application of an implantable loop recorder allows a mechanism‐based effective therapy in patients with recurrent suspected neurally mediated syncope. Eur Heart J 2006; 27: 1085–92. 35. Brugada J, Aguinaga L, Mont L, et al. Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome. J Am Coll Cardiol 2001; 37: 529–33.

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36. Moya A, Garcia‐Civera R, Croci F, et al. Diagnosis, management, and outcomes of patients with syncope and bundle branch block. Eur Heart J 2011; 32: 1535–41. 37. Brignole M, Menozzi C, Moya A, et al. Mechanism of syncope in patients with bundle branch block and negative electrophysiological test. Circulation 2001; 104: 2045–53. 38. Brignole M, Menozzi C, Del Rosso A, et al. New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the presyncopal phase of the tilt test without and with nitroglycerin challenge. Europace 2000; 2: 66–76. 39. Grubb BP, Kosinski D. Tilt table testing: concepts and limitations. Pacing Clin Electrophysiol 1997; 20: 781–7. 40. Brignole M, Chen WK. Syncope management from emergency department to hospital. J Am Coll Cardiol 2008; 51: 284–7. 41. Daccarett M, Jetter TL, Wasmund SL, Brignole M, Hamdan MH. Syncope in emergency department: comparison of standardized admission criteria with clinical practice. Europace 2011; 13: 1632–8. 42. Costantino G, Perego F, Dipaola F, et al.; STePS Investigators. Short‐ and long‐term prognosis of syncope, risk factors, and role of hospital admission results from the STePS (Short‐Term Prognosis of Syncope) study. J Am Coll Cardiol 2008; 51: 276–83. 43. Sheldon R, Connolly S, Rose S, et al. Prevention of Syncope Trial (POST). A randomized, placebo‐controlled study of metoprolol in the prevention of vasovagal syncope. Circulation 2006; 116: 1164–70. 44. Di Gerolamo E, Di Iorio C, Sabatini O, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double‐blind, placebo‐controlled study. J Am Coll Cardiol 1999; 33: 1227–30. 45. Larsen GC, Stupey MR, Walance CG, et al. Recurrent cardiac events in survivors of ventricular fibrillation or tachycardia: implications for driving restrictions. JAMA 1994; 271: 1335–9.

27  Chest Pain, Dyspnea, Palpitations

1. Chest pain  I. Causes 499 II. Features 500 III. Management of chronic chest pain  501 IV. Management of acute chest pain  501 2. Acute dyspnea  I. Causes 502 II. Notes 503 III. Management 503 3. Palpitations  I. Causes 504 II. Diagnosis 504

1 .   C h e s t pa i n I.  Causes (see Table 27.1) Table 27.1  Causes of chest pain. A. Cardiac 1. CAD: stable angina, ACS 2. Aortic dissection 3. Acute pericarditis 4. Secondary ischemia from cardiac causes: acute HF,a acute HTN, AS, HOCM 5. Secondary ischemia from non‐cardiac causes: tachyarrhythmia, anemia B. Pulmonary 1. Pneumothorax 2. Pneumonia 3. Exudative pleural effusion 4. Pulmonary embolism 5. Pulmonary hypertension (→ chest pain + dyspnea + syncope on exertion) C. Gastrointestinal 1. Esophageal spasm or reflux 2. Esophageal ulceration after vomiting (Mallory–Weiss syndrome) 3. Peptic ulcer disease 4. Acute pancreatitis, cholecystitis, biliary colic D. Chest wall 1. Strain of muscles or ligaments 2. Costochondritis (“Tietze’s syndrome” is a costochondritis with swollen red costochondral joints) 3. Shoulder or cervical joint problem (pain is exacerbated by a particular movement of neck/shoulder rather than exertion) E. Psychogenic  The increase in LVEDP reduces the pressure gradient between aortic diastolic pressure and LVEDP, and thus reduces coronary flow even in the absence of CAD. Also, elevated LVEDP increases microvascular resistance.

a

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

499

500  Part 9.  Other Cardiovascular Disease States

Only 25% of patients presenting to the ED with chest pain have true unstable angina/ACS. However, ACS should be the first consideration and should always be ruled out. Approximately 5% of patients discharged home with a presumed non‐cardiac chest pain are eventually diagnosed with MI or unstable angina.1 Also, consider other emergencies like aortic dissection, PE, pericarditis, and gastrointestinal urgencies (pancreatitis, complicated peptic ulcer), and rule them out at least clinically and by chest X‐ray and ECG.

II. Features A.  Angina and acute coronary syndrome • Typical angina occurs with exertion and is relieved with rest. It is precipitated by walking uphill, in the cold, or after a meal. Chest pain that occurs at rest and is not reproduced with exertion is unlikely to be angina, the exception being vasospastic angina. Postprandial angina is often a marker of severe, sometimes multivessel CAD; as opposed to biliary colic or peptic ulcer disease, angina occurs immediately after the meal and is exacerbated by postprandial physical activity. Nocturnal angina may imply severe CAD or vasospasm on top of fixed CAD; the increased venous return in the recumbent position increases O2 demands and triggers ischemia in patients with critical, sometimes multivessel, CAD. • The duration of angina is typically a few minutes. If chest pain lasts over 20–30 minutes, the cardiac markers should be positive; otherwise, angina is an unlikely diagnosis. If chest pain lasts  50 mmHg on high‐dose O2). O2 saturation and A–a gradient are, however, normal in up to 20% of patients. A–a gradient increases in most pulmonary pathologies as a result of V/Q mismatch, and thus is not specific for PE. Hypercapnia is rare, and only a massive PE with a massive increase in dead space can cause hypercapnia, per se. • Chest X‐ray is grossly normal. • ECG shows sinus tachycardia or relative tachycardia (80–100 bpm). In large PE, it shows more pronounced tachycardia and signs of RV strain in up to 85% of patients: T inversion in the anterior leads V1–V3, RVH/right axis deviation/RBBB, S1Q3T3, and P pulmonale. Atrial arrhythmias may also be seen. Look at the admission ECG, as tachycardia may be transient. D.  Acute pericarditis Pericarditis is characterized by pleuritic chest pain that increases with recumbency and movements, and improves with leaning forward. It typically radiates to the trapezius. It has a rapid onset. • On exam, a pericardial friction rub with a systolic and a diastolic component is heard. • ECG shows diffuse ST elevation and/or PR depression in 90% of patients. These changes may resolve after one to several days. • CRP is highly sensitive for the diagnosis of acute pericarditis. • The diagnosis of pericarditis requires two of the following four features: (1) chest pain; (2) rub; (3) typical ECG findings (widespread ST‐segment elevation and/or PR depression); (4) pericardial effusion (which is only present in 40% of pericarditis cases and usually small). CRP is a confirmatory finding. E.  Pneumonia, pleural effusion, pneumothorax Pleural and pulmonary illnesses are characterized by dyspnea, cough, and pleuritic chest pain, i.e., sharp pain that increases with deep inspiration, cough, or movement.

III.  Management of chronic chest pain See Chapter 3, Section II and Figures 3.1 and 3.2.

IV.  Management of acute chest pain A. ECG If the ECG shows ST elevation consistent with STEMI, perform emergent reperfusion with primary PCI or fibrinolysis. If the ECG shows ST depression or deep T inversion consistent with ischemia, especially if dynamic, consider the diagnosis of non‐ST elevation ACS, but keep in mind the possibility of aortic dissection, PE, or pericarditis if clinically plausible. B.  CXR, cardiac biomarkers, ± bedside echo during active pain In ACS, a bedside echo performed during active chest pain should reveal a wall motion abnormality. In fact, a normal echo during active chest pain strikingly reduces the likelihood of ACS. Echo is not sensitive if performed after pain resolution. Conversely, echo is not very specific for ongoing ischemia, as a wall motion abnormality may correspond to an old infarct. C. If any clinical, X‐ray, or ECG feature suggests aortic dissection, PE, pericarditis, or a pulmonary cause of chest pain, proceed to the appropriate workup and therapy. Avoid anticoagulation if the clinical or radiographic likelihood of aortic dissection is more than low. Before starting anticoagulation, verify the lack of mediastinal enlargement on CXR. If aortic dissection is suggested, perform aortic CT or emergent TEE and start aggressive BP control and intravenous β‐blockers. If PE is suggested, perform chest CT angiography, PE protocol. The same CT and contrast injection are usually appropriate for the diagnosis of aortic dissection as well (but not vice versa). V/Q scan may be performed instead of CT in renal failure and in the absence of severe CXR abnormalities; CXR abnormalities decrease the specificity and the diagnostic yield of the V/Q scan. Anticoagulation is started early on, before the workup, if PE is probable and the bleeding risk is low.

502  Part 9.  Other Cardiovascular Disease States

If pericarditis is suggested, the diagnosis will be established by clinical, ECG, and CRP features. If a pulmonary cause is suggested, the diagnosis will be established by CXR and chest CT if needed. If cholecystitis or acute pancreatitis is suggested, the diagnosis will be established by a liver function panel, amylase/lipase, and abdominal ultrasound. D. In the absence of aortic dissection, PE, pericarditis, or pulmonary features, consider the diagnosis of ACS regardless of the initial ECG and cardiac biomarkers, and obtain serial ECGs and cardiac biomarkers. Repeat the ECG during each recurrence of pain. Proceed to full ACS therapy and early coronary angiography within 24–72 hours of presentation, with revascularization if appropriate (CABG or PCI), in high‐risk ACS, i.e., ACS with any of following features: • Ischemic ST depression, transient ST elevation (< 20 minutes), or deeply inverted or biphasic T waves. • Elevated troponin. Any troponin elevation (e.g., 0.05 ng/ml) in a patient with chest pain and no other obvious cardiac or systemic insult (HF, critical illness) implies a high‐risk ACS. • Recurrent true rest angina. • Prior PCI in the last 6–12 months, or CABG. • Hemodynamic or electrical instability. • LV dysfunction, LV wall motion abnormalities. PCI becomes emergent in the following cases: refractory true angina, ST elevation, hemodynamic instability or electrical instability (recurrent VT). In the absence of high‐risk features, perform stress testing or coronary CT angiography at 6–12 hours after a brief clinical, ECG, and troponin monitoring in a chest pain unit (troponin must be negative 3–6 hours after chest pain onset). Alternatively, low‐risk or low‐probability patients may be discharged home with plans for outpatient stress testing within 72 hours, as they have a low risk of coronary events in the short term.4

2 .  Ac u t e d y s p n e a I.  Causes (see Table 27.2) Table 27.2  Causes of acute dyspnea. A. Cardiac 1.  Acute pulmonary edema due to acutely decompensated HF, or to acute new‐onset HF (acute MI, acute hypertension, acute valvular insufficiency, arrhythmia) Diagnosis: history (orthopnea, paroxysmal nocturnal dyspnea, recent quick weight gain, and past cardiac history), exam (↑ JVP, S3, ± S4, crackles, peripheral edema), elevated BNP, chest X‐ray 2.  Tamponade (↑ JVP, pulsus paradoxus) 3.  Always remember that dyspnea could be an angina equivalent B. Pulmonary embolism Diagnosed by the following three features: (i) PE/DVT risk factors; (ii) DVT signs; and (iii) absence of other causes of dyspnea (no gross abnormalities on chest X‐ray) C. Pulmonary 1.  Pneumonia 2.  Asthma attack or COPD exacerbation: asthma may occasionally lead to cough and/or dyspnea in the absence of wheezes on examination (variant or atypical asthma). Wheezing may be uncovered with maximal forced expiration. Also, severe asthma exacerbation may not produce wheezes (airways are so narrow that there is total interruption of airflow and decrease in breath sounds) 3.  Pneumothorax or large pleural effusion 4.  ARDS in the context of pneumonia, aspiration, septic shock, or trauma D. Laryngeal causes (laryngospasm, laryngeal edema [anaphylaxis]) lead to an inspiratory stridor ± urticaria E. Metabolic causes Metabolic acidosis (such as diabetic ketoacidosis), hypocalcemia, dyskalemia, severe acute anemia, hyperthyroid storm. + Shock of any cause leads to hyperventilation and tachypnea

Beside HF, there are two additional causes of nocturnal dyspnea:5 • Patients with COPD may have mucus hypersecretion, so that, after a few hours of sleep, secretions accumulate and produce dyspnea and wheezing, which are relieved by cough and sputum expectoration. • Patients with asthma may have their most severe bronchospasm between 2 a.m. and 4 a.m. and wake up with severe dyspnea and wheezing. Inhaled bronchodilators usually improve symptoms quickly. In HF, paroxysmal nocturnal dyspnea (PND) usually develops 2–4 hours after sleep and improves after 15–30 minutes of sitting upright or walking. Dyspnea is often accompanied by cough (dry or productive of frothy sputum), wheezing, and diaphoresis. Orthopnea is mainly seen in HF but may also be seen with pericardial diseases, advanced asthma/COPD with diaphragmatic flattening and weakness, bilateral diaphragmatic paralysis, severe obesity and severe ascites, all cases where the diaphragm tends be pushed up in a supine position.

Chapter 27.  Chest Pain, Dyspnea, Palpitations  503

Platypnea is dyspnea that worsens in the upright position. Platypnea is seen with pulmonary right‐to‐left shunts such as pulmonary AV fistulas (including hepatopulmonary syndrome), or the rare case of PFO that allows right‐to‐left shunting in the upright position. Trepopnea is orthopnea that mainly occurs in one lateral decubitus position. Patients with HF are typically more comfortable in the right lateral decubitus position, as this position raises the level of the heart (especially the left ventricle), which slows venous return. This position may partly explain the predominance of right pleural effusion in HF.6 Note that nocturnal or exertional cough, rather than dyspnea, may be the primary complaint of patients with HF.

II. Notes A.  Differential diagnosis of shock + respiratory distress • Cardiogenic shock with pulmonary edema • Septic shock due to pneumonia or septic shock with ARDS • Tamponade • Massive PE • Anaphylactic shock with bronchospasm, laryngeal edema + Any shock leads to tachypnea (the patient hyperventilates in order to improve O2 supply) B. Wheezing Wheezing may indicate COPD/asthma but may also indicate pulmonary edema (“cardiac asthma”), PE, or pneumonia. In cardiac asthma, cyanosis and diaphoresis occur more often than in bronchial asthma, and adventitious breath sounds are more common (crackles, rhonchi). True asthma has more musical, pure wheezes.5 C.  Pulmonary shunt and pulmonary shunt effect Most of the disorders listed in Table 27.2, A–C, lead to a pulmonary shunt effect in which pulmonary blood is not oxygenated because of obstruction of the airways, or to a true pulmonary shunt in which the alveoli, per se, are obstructed and filled with fluid. A pulmonary shunt or shunt effect initially leads to hypocapnia, hypoxemia, or normoxemia (pO2 may be normal early on), and elevated A–a gradient. A–a gradient increases in most pulmonary pathologies; it implies V/Q mismatch but does not identify it (could be PE, pulmonary edema, COPD exacerbation, pneumonia, ARDS). The more severe the process, the higher the A–a gradient rises. A–a gradient = alveolar PO2 – arterial PO2 = (FiO2 × [atmospheric pressure – 47] – PaCO2 /0.8) – PaO2 = (~150 mmHg on ambient air, sea level – PaCO2 /0.8) – PaO2 Normal  5 g/dl. There are two forms of cyanosis: (i) central cyanosis related to severe hypoxemia (respiratory issue or cardiac right‐to‐left shunt); (ii) peripheral cyanosis related to a shock state where arterial O2 saturation is normal but peripheral tissue hypoxia occurs. There is tongue cyanosis in the former, not the latter. Cyanosis manifests less easily in anemic patients.

Respiratory distress without gross abnormalities on CXR: • PE • Bronchospasm, COPD exacerbation • Severe sepsis, shock states, or metabolic acidosis • Acutely decompensated chronic HF, where CXR findings are frequently subtle (exam and BNP findings help with the diagnosis) • Also, myocardial ischemia or systolic or diastolic LV dysfunction can increase the pulmonary capillary pressure and the pulmonary engorgement on exertion without leading to frank pulmonary edema.

III. Management The hemodynamics and the volume status are quickly assessed clinically. The following is obtained: ECG (seeking ischemia and arrhythmias), CXR, arterial blood gas, basic lab tests including cardiac markers and BNP. BNP helps differentiate a cardiac from a pulmonary origin of dyspnea in the acute setting (BNP  35/min, not improving quickly with furosemide, O2, and nebulizer therapy regardless of O2 saturation (the patient is getting more tired, breathing is getting more shallow with accessory muscle use and paradoxical respiration). 2.  Hypoxemia not responding to maximal O2 therapy (O2 saturation 10 mm or >15 mm is associated with a 60% or 83% risk of embolization, respectively.11 Therefore: • Surgery seems reasonable (class IIa) in patients who already had an embolization, have a persistently large vegetation >1 cm, and are in the early phase of IE treatment (first 2 weeks). • Surgery may be performed in patients with vegetation >10 or 15 mm without prior embolization, particularly when the regurgitation is severe (class IIa). If surgery is considered for this indication, it should be done urgently, at the time the risk of embolization is highest. This indication is supported by one randomized trial.12 • Since most patients with severe valvular regurgitation eventually need surgery sooner or later, the early performance of surgery appears to be the preferred strategy if a large vegetation is associated with severe valvular regurgitation.12 Seventy‐six patients with a vegetation >1 cm in diameter and severe valvular disease were randomized to early surgery (within 48 hours of randomization) or conventional treatment with surgery as needed, later on (77% eventually underwent surgery, mostly during hospitalization). Patients with classic indications for early surgery (HF, abscess) and patients without severe valvular disease were excluded. Patients with major stroke were also excluded. Patients with smaller strokes, TIA, or renal/splenic embolism were included, and ~45% of randomized patients had a prior embolism (~28% cerebral). Early surgery dramatically reduced the risk of symptomatic recurrent events (eight cases [21% vs. 0%], seven of which occurred between 2 and 9 days, especially at 2–5 days, after randomization, and included five major strokes, one anterior MI, one limb ischemia). Surgery in patients with a large vegetation and without severe valvular disease is more controversial. The clearest indication is the patient with a large vegetation, severe valvular disease, and peripheral embolism or cerebral embolism not associated with a major stroke. The problem is, however, that when patients have already had a cerebral embolization, early surgery within the first 2 weeks after a stroke is associated with a high risk of neurologic deterioration. Neurologic deterioration may result from hemorrhagic transformation during cardiopulmonary bypass/anticoagulation, or exacerbation or expansion of ischemia from perioperative hypotension. These factors make a recent embolic stroke a relative contraindication to valvular surgery in infective endocarditis (STS guidelines).13 In fact, after an ischemic stroke, the risk of deterioration with surgery is 20% in the first 3 days, 20–50% between 4 and 14 days, 6–10% between 15 and 28 days, and 2.2 big boxes) • R in I ≥ 15 mm (3 boxes); R in I + S in III > 25 mm • S in V1 + R in V5 or V6 ≥ 35 mm; R in V5 > 26 mm

B.  Look for RVH (Figure 31.21) RVH is characterized by: 1.  Right‐axis deviation (net QRS [–] in lead I, [+] in lead aVF) and 2.  Big R wave in the right lead V1 (≥7 mm), or big S wave in the left leads V5–V6 (≥7 mm) Or big R > S in V1, big S > R in V6, or small S in V1 ≤ 2 mm Or R in V1 + S in V6 > 10.5 mm In the absence of RBBB, a monophasic R wave in V1 or a qR pattern in V1 signifies severely increased RV pressure (higher than systemic pressure in the case of qR pattern). RVH differential diagnosis and coexisting patterns

• Posterior MI may lead to a prominent R wave in V1. In posterior MI, R wave is not only high but is also wide > 1 mm (≠ RVH), T wave is positive in V1–V2 (vs. inverted in RVH), the axis is not right, and there are often Q waves in V7–V9 and in the inferior or lateral leads. • An incomplete RBBB pattern with RSR’ may be seen along with RVH. This pattern is often secondary to the slow conduction across the enlarged RV rather than a diseased right bundle. In fact, incomplete RBBB with right axis is frequently secondary to RVH, more specifically a volume overload pattern of RVH. RVH is definitely diagnosed if the axis is right and R’ > 10 mm. As RVH progresses, R’ becomes taller and a monophasic R may develop, particularly with pressure overload patterns. • Lung disease, such as COPD, is characterized by: (1) right‐axis deviation in the frontal plane as the heart is pushed down and made more vertical; (2) deep S wave in all precordial leads, V1 through V6, as the heart rotates posteriorly; (3) reduced overall QRS voltage in all leads, especially limb leads, because of increased chest air; while dominant, S wave is not particularly deep in the precordial leads. This chronic lung disease pattern simulates an old anterolateral MI, wherein R is diminished across all precordial leads and in the lateral leads I and a VL (rS pattern throughout all those leads). The presence of true RVH in conjunction with lung disease is characterized by one of the following: large R or small S in V1 (≤2 mm), RSR’ pattern, or T‐wave inversion in V1–V2. P pulmonale may be seen with lung disease even without RVH. Additional notes • Right‐axis deviation may be less evident in patients with an associated LVH or LAFB. • Higher voltage and more strain pattern is seen with pressure overload (pulmonary hypertension) than with volume overload (ASD). ASD is often only characterized by rSR’ pattern, and rarely leads to tall monophasic R waves. • Left atrial enlargement supports the diagnosis of LVH, and right atrial enlargement supports the diagnosis of RVH in cases of borderline voltage criteria. LVH with right atrial enlargement or RVH with left atrial enlargement suggests biventricular hypertrophy, unless MS is present (MS may lead to left atrial enlargement + RVH).

548  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

C.  Biventricular enlargement Biventricular enlargement is characterized by any one of the following: 1.  Voltage criteria for both LVH and RVH. This usually implies tall R waves in V5–V6 (LVH) with a small S wave in V1, or R > S in V1 (R is not usually large in V1, but is larger than S). 2.  LVH with right‐axis deviation. 3.  LVH with right atrial or biatrial enlargement. 4.  LVH with T inversion in V1–V2 (T going in the same direction as QRS). This T inversion can be secondary to RV strain or anterior ischemia. 5.  Tall R wave and tall S wave in the mid‐precordial leads V3–V4 (Katz–Wachtel sign).

Figure 31.21  QRS is (–) in lead I and (+) in lead aVF, implying a right‐axis deviation. The smallest net QRS is in leads I and aVR. QRS axis is thus between perpendicular to I (+90°) and aVR (+120°). Axis is ~ +105°. RVH is diagnosed by the fact that axis is right and R > S in V1. In fact, there is a qR pattern in V1 (S = 0) (arrow), signifying severely increased RV pressure. P pulmonale and secondary T inversion are also seen.

VII.  Width of QRS. Conduction abnormalities: bundle brunch blocks The normal QRS duration is r In some patients, r may be isoelectric RBBB has QR morphology

r

V1,III,aVF

V5–6, I, aVL R

R’

r

LV

septum

R q

S

q is septum, R is LV S is RV

S

QS

-r is RV -Sharp S is septum followed by LV -If RV depolarization is late, r may be lost and rS becomes QS

No q wave as septum depolarizes from right to left

Figure 31.22  In RBBB, the vector of depolarization spreads from the left septum to the right and left ventricles. RSR’ is seen in V1, R being septal depolarization, S being LV depolarization, and R’ being the late RV depolarization. RS is seen in V6, R being LV depolarization, and the wide S being the slow RV depolarization.   In LBBB, the vector of depolarization spreads from the right septum to the left septum and the left ventricle. The vector looks toward V6 and away from V1. Thus, in LBBB, QRS is positive in V5–V6 and widely negative in V1. The septal q wave that is normally seen in the left lateral leads is lost, as the septum depolarizes from the right to the left. The presence of any q wave in leads V5–V6 or lead I is not typical of LBBB and suggests an old MI. Only rarely, a q wave may be seen in lead aVL.

Chapter 31.  Electrocardiography  549

A. RBBB In RBBB, QRS has a slurred positivity in the right leads. Beside QRS ≥ 120 ms, both the following two criteria are required to make the diagnosis of RBBB: • rSR’, rsR’, or rsr’ pattern in the right leads V1 and/or V2. R’ is usually wider and taller than the initial R wave. A qR pattern may replace rSR’ in lead V1 when the initial r wave is isoelectric. A single wide R wave, often notched, may be seen instead of rSR’. • A wide S wave in the left leads I and V6. S wave must be wider than R wave or wider than 40 ms. In addition, T‐wave inversion in V1–V2 is common but not mandatory (T directed in an opposite direction to QRS).

I

aVR

V1

V4

R’

r S

II

aVL

V2

V5

III

aVF

V3

V6

R’

R

r s

q

Figure 31.23  RBBB. rSR’ is seen in V1, notched R wave is seen in V2, and rsR’ and qR patterns are shown on the right (rsR’ means small R, small S, big R’). Any of those patterns is consistent with RBBB in V1–V2. S wave is wide and slurred in leads I, aVL, and V5–V6.

Figure 31.24  Sinus tachycardia with RBBB (rSR’ in V1–V2, wide and slurred S in V5–V6 and I–aVL, arrows). Right‐axis deviation (QRS [–] in lead I, [+] in lead aVF) signifies an associated RVH (most commonly) or LPFB. T‐wave inversion in V1–V3 and II/III/aVF is secondary to RBBB and RVH. The patient is diagnosed with PE. Reproduced with permission of Scrub Hill Press from Hanna et al. (2009).1

B. LBBB In LBBB, QRS has a slurred positivity in the left leads. The first four criteria are required to make the diagnosis of LBBB: 1.  Wide notched R wave in leads I, aVL, and V5–V6 (M‐shaped or slurred, plateaued R wave). 2.  QRS is negative in leads V1, V2, V3 with an rS or QS pattern. QS pattern may also occur in leads III and aVF, simulating an inferior MI, but not in lead II. QR pattern does not occur with LBBB and always implies an associated MI.

550  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

3.  The septal q wave should be absent in the left leads I and V5–V6. A narrow q wave may be seen in aVL. 4.  The ST segment and T wave should be directed opposite to QRS. Unlike LVH, RBBB, and RVH, secondary ST–T changes are mandatory in LBBB. 5.  Two less usual features may be seen in LBBB and do not preclude the diagnosis of LBBB: • q wave in aVL. • RS pattern (rather than a plateaued R pattern) in leads V5–V6. This occurs in patients with delayed QRS transition, such as patients with enlarged LV or LV depolarization that spreads from apex to base; the frontal QRS axis is leftward in both of these cases. An incomplete RBBB or LBBB, also called bundle branch delay, is characterized by a QRS of 110–119 ms with QRS features of the respective bundle branch block in V1, V6, and I. Similarly to a complete block, an incomplete block is accompanied by the secondary repolarization abnormalities.

I

II

III

aVR

V1

V4

aVL

V2

V5

aVF

V3

V6

Figure 31.25  LBBB. In the lateral leads, there may be an “M‐shaped” R wave (as seen here in I and V5) or a broad slurred R wave (as seen in V6). When the LV is enlarged or the depolarization is turned further leftward, the transition zone and the wide R wave may not be reached in lead V6, and an RS pattern is seen in leads V5–V6. The wide, M‐shaped R wave will still be seen in leads I‐aVL and will also be seen more laterally in leads V7–V9. Reproduced with permission of Scrub Hill Press from Hanna et al. (2009).1

Figure 31.26  LBBB (slurred R wave in the left leads: V5–V6 and I–aVL) (arrows). ST depression in V5–V6, I, and aVL, and ST elevation in V1–V3, directed opposite to QRS, are secondary to LBBB (circles).

Chapter 31.  Electrocardiography  551

• rSR’ or rSr’ patterns in V1–V2 may be normal variants if QRS is 180–200 ms) should always suggest hyperkalemia or WPW pattern.

Figure 31.27  WPW with short PR segment and slurred R wave. The upslope of R wave is slow (≠ LBBB).

VIII.  Conduction abnormalities: fascicular blocks The left bundle divides into the left anterior and the left posterior fascicles. In fascicular blocks, unlike bundle branch blocks, QRS must not be very wide and must be  120 ms with rSR’ in V1 and a wide S in V5–V6 = RBBB. • The net QRS is (–) in lead aVF and equiphasic in lead I, implying a left axis of ~ –90°. In the absence of LBBB, this is diagnostic of LAFB. Also, a q wave is seen in lead aVL, which is often necessary to define LAFB. Reproduced with permission of Scrub Hill Press from Hanna et al. (2009).1

A combination of RBBB and left‐axis deviation suggests the presence of LAFB in addition to the RBBB (= bifascicular block). This is a common conduction abnormality. B. LPFB • LPFB is uncommon and typically occurs in conjunction with RBBB. • LPFB is defined as “an unexplained right‐axis deviation” (more than +90°) = right‐axis deviation without RVH, COPD, or lateral MI (R wave in V1 and S wave in V6 are not large). A qR pattern is seen in the inferior leads III/aVF. LPFB does not lead to ST–T abnormalities. C.  Bifascicular and trifascicular blocks A bifascicular block is a block in two of the three conduction fascicles (right bundle, left anterior fascicle, and left posterior fascicle). It can take one of the following forms: (i) LBBB; (ii) RBBB + LAFB = RBBB with left‐axis deviation; (iii) RBBB + LPFB = RBBB with right‐axis deviation (which could also be RBBB + RVH).

Chapter 31.  Electrocardiography  553

Figure 31.30  RBBB + LPFB. Since QRS is wide > 120 ms, look in V1 and in V6 to determine if the morphology fits more with LBBB or RBBB. In this case, QR morphology is seen in V1 (box), with a wide slurred S wave in V5–V6 and I, aVL (circles): this is RBBB. The axis is right (net QRS is negative in I and positive in aVF). Exact axis: QRS is closest to equiphasic in lead II → axis perpendicular to +60° → +150°. The cause of right axis could be RVH or LPFB. Because there are no RVH criteria (R’  10 mm in V1, or S > R in V6. R’ > S or R’ > 10 mm more strongly suggests RVH in incomplete RBBB than in complete RBBB. Answer 12. No. A wide S wave, wider than R wave or wider than 40 ms, is also needed in the lateral leads to define RBBB. Answer 13. No. A septal q wave should not be seen in the lateral leads in LBBB (except, occasionally, in lead aVL). Answer 14. Yes (Section VII.B). Answer 15. A. LAFB should have QRS  5 mm is not very sensitive or specific for the diagnosis of STEMI. Relative discordance is more helpful. Answer 26. E (Figures 31.64, 31.65). Answer 27. See Figures 31.66 and 31.67. Hypokalemia leads to T flattening, then ST depression with prominent T‐U wave. Answer 28. Leads II, V5–V6 are the best leads for measurement of QT. Leads V2–V3 have the most prominent phase 4 U waves and may not show a good separation of T and U waves, leading to overestimation of QT interval. Leads II, V5–V6 show distinct T waves with good separation from U waves. Answer 29. QTc corresponds to the patient’s QT interval had the heart rate been 60 bpm. QT decreases by 17.5 ms for every 10‐beat increase in heart rate, and increases 17.5 ms for every 10‐beat decrease in heart rate. If a patient has a QT of 400 ms at a rate of 100 bpm, QTc would be (400 + 17.5 × 4) = 470 ms. Answer 30. Yes. This is a T2 wave, which some may call a repolarization U wave (not phase 4 U wave).This may be seen with hypokalemia or QT‐prolonging drugs. This type of U wave, when prominent in size and fused with T, should be included in the QT measurement as it is a part of repolarization. Answer 31. E. The ECG shows diffuse ST‐segment depression that is most prominent in leads V2–V3. This should point towards true posterior STEMI rather than non‐ST‐elevation ischemia and lead to recording of the leads V7–V9 and emergent cardiac catheterization. T‐wave inversion in the anterior and/or inferior leads, rather than ST‐segment depression, may suggest pulmonary embolism in the right clinical context. Hypokalemia is unlikely as T wave is not flattened, no prominent U wave is seen and QT interval is not prolonged. Answer 32. A. This ECG has a few features suggestive of pericarditis (PR depression and diffuse ST elevation). However, the ECG also shows features suggestive of STEMI. The presence of even one STEMI feature, any of the top four features described in Table 31.2, usually implies STEMI and outweighs other diagnoses. In addition, PR depression may be seen in STEMI (ischemic atrial injury). Diffuse ST elevation without reciprocal ST depression (except possibly in lead aVR) may be seen with occlusion of the mid‐portion of the left anterior descending artery. Answer 33. C and E. In LBBB, discordant ST elevation ≥ 25% of the QRS height (relative discordance) has good sensitivity and specificity for the diagnosis of STEMI, particularly when the size of ST elevation approximates the size of the QRS complex. Convex discordance or absolute discordance > 5 mm is less specific for STEMI. Answer 34. D. There is diffuse ST depression with upright “T”wave. QT is prolonged, and on further inspection a notch on the upslope of the ST segment is seen in V5, suggesting that the prominent wave is actually a U wave and the notch is a flattened T wave. Answer 35. C. Prominent U wave is seen along with ST depression. The ECG may mimic hypokalemia, except that QT is not prolonged and the TU separation is more clear than in hypokalemia.

References 1. Hanna EB. Electrocardiography. In: Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009, pp. 328–54.

ST‐segment depression and T‐wave inversion 2. Hanna EB, Glancy DL. ST‐segment depression and T‐wave inversion: classification, differential diagnosis, and caveats. Clev Clin J Med 2011; 78: 404–14. 3. Rautaharju PM, Surawicz B, Gettes LS, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval. J Am Coll Cardiol 2009; 53: 982–91. 4. Surawicz B, Knilans TK. Non‐Q wave myocardial infarction, unstable angina pectoris, myocardial ischemia. In: Chou’s Electrocardiography in Clinical Practice: Adult and Pediatric, 5th edn. Philadelphia, PA: WB Saunders, 2001, pp. 194–207. 5. O’Gara PT, Kushner FG, Ascheim DD, et  al. 2013 ACCF/AHA guideline for the management of ST‐elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: e78–140. 6. Okin PM, Devereux RB, Nieminen MS, et al. Electrocardiographic strain pattern and prediction of new‐onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. Circulation 2006; 113: 67–73. 7. Huwez FU, Pringle SD, Macfarlane PW. Variable patterns of ST–T abnormalities in patients with left ventricular hypertrophy and normal coronary arteries. Br Heart J 1992; 67: 304–7.

Chapter 31.  Electrocardiography  599

8. Li D, Li CY, Yong AC, et al. Source of electrocardiographic ST changes in subendocardial ischemia. Circ Res 1998; 82: 957–70. 9. Gorgels AP, Vos MA, Mulleneers R, et al. Value of the electrocardiogram in diagnosing the number of severely narrowed coronary arteries in rest angina pectoris. Am J Cardiol 1993; 72: 999–1003. 10. Glancy DL. Electrocardiographic diagnosis of acute myocardial infarction. J La State Med Soc 2002; 154: 66–75. 11. Yamagi H, Iwasaki K, Kusachi S, et al. Prediction of acute left main coronary artery obstruction by 12‐lead electrocardiography: ST‐segment elevation in lead aVR with less ST‐segment elevation in lead V1. J Am Coll Cardiol 2001; 38: 1348–54. 12. de Zwann C, Bar FW, Wellens HJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J 1982; 103: 730–6. 13. de Zwaan C, Bar FW, Janssen JH, et al. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J 1989; 117: 657–65. 14. Lilaonitkul M, Robinson K, Roberts M. Wellens’ syndrome: significance of ECG pattern recognition in the emergency department. Emerg Med J 2009; 26: 750–1. 15. Glancy DL, Khuri B, Cospolich B. Heed the warning: Wellens’ type T‐wave inversion is caused by proximal left anterior descending artery lesion. Proc (Bayl Univ Med Cent) 2000; 13: 416–18. 16. Savonitto S, Ardissino D, Granger CB, et  al. Prognostic value of the admission electrocardiogram in acute coronary syndromes. JAMA 1999; 281: 707–13. 17. Mueller C, Neumann F, Perach W, et al. Prognostic value of the admission electrocardiogram in patients with unstable angina/non–ST segment elevation myocardial infarction treated with very early revascularization. Am J Med 2004; 117: 145–50. 18. Boden WE, Spodick DH. Diagnostic significance of precordial ST‐segment depression. Am J Cardiol 1989; 63: 358–61. 19. Shah A, Wagner GS, Green CL, et al. Electrocardiographic differentiation of the ST‐segment depression of acute myocardial injury due to the left circumflex artery occlusion from that of myocardial ischemia of nonocclusive etiologies. Am J Cardiol 1997; 80: 512–13. 20. Krishnaswamy A, Lincoff AM, Menon V. Magnitude and consequences of missing the acute infarct‐related circumflex artery. Am Heart J 2009; 158: 706–12. 21. Matetzky S, Freimark D, Feinberg MS, et al. Acute myocardial infarction with isolated ST‐segment elevation in posterior chest leads V7–9: “hidden” ST‐segment elevations revealing acute posterior infarction. J Am Coll Cardiol 1999; 34: 748–53. 22. Matetzky S, Freimark D, Chouraqui P, et al. Significance of ST segment elevations in posterior chest leads (V7 to V9) in patients with acute inferior myocardial infarction: application for thrombolytic therapy. J Am Coll Cardiol 1998; 31: 506–11. 23. Huey BL, Beller GA, Kaiser DL, et al. A comprehensive analysis of myocardial infarction due to left circumflex artery occlusion: comparison with infarction due to right coronary artery and left anterior descending artery occlusion. J Am Coll Cardiol 1988; 12: 1156–66. 24. Gibson C, Pride YB, Mohanavelu S, et al. Angiographic and clinical outcomes among patients with acute coronary syndrome presenting with isolated anterior ST‐segment depressions. Circulation 2008; 118: S‐654. Abstract 1999. 25. Ferrari E, Imbert AI, Chevalier T, et al. The ECG in pulmonary embolism, predictive value of negative T waves in precordial leads 80 case reports. Chest 1997; 111: 537–43. 26. Sreeram N, Cheriex EC, Smeets JL, et al. Value of the 12‐lead electrocardiogram at hospital admission in the diagnosis of pulmonary embolism. Am J Cardiol 1994; 73: 298–303. 27. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, and roentgenographic findings in patients with acute pulmonary embolism and no pre‐existing cardiac or pulmonary disease. Chest 1991; 100: 598–603. 28. Surawicz B, Knilans TK. Chou’s Electrocardiography in Clinical Practice: Adult and Pediatric, 5th edn. Philadelphia, PA: WB Saunders, 2001, pp. 122–53. 29. Norell MS, Lyons JP, Gardener JE, et  al. Significance of « reciprocal » ST‐segment depression: left ventriculographic observations during left anterior descending coronary angioplasty. J Am Coll Cardiol 1989; 13: 1270–4. 30. Haraphongse M, Tanomsup S, Jugdutt BI. Inferior ST‐segment depression during acute anterior myocardial infarction: clinical and angiographic correlations. J Am Coll Cardiol 1984; 4: 467–76. 31. Wagner GS, Macfarlane P, Wellens H, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part VI: acute ischemia/infarction. J Am Coll Cardiol 2009; 53: 1003–11. 32. Brady WJ, Perron AD, Syverud SA, et al. Reciprocal ST‐segment depression: impact on the electrocardiographic diagnosis of ST segment elevation acute myocardial infarction. Am J Emerg Med 2002; 20: 35–8. 33. Surawicz B. Electrolytes and the electrocardiogram. Postgrad Med 1974; 55: 123–9. 34. Dierks DB, Shumaik GM, Harrigan RA, et al. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med 2004; 27: 153–60. 35. Glancy DL, Wang WL. Abnormal electrocardiogram in a woman with urinary tract infection. J La State Med Soc 2007; 159: 5–6. 36. Surawicz B, Braun H, Crum B, et al. Quantitative analysis of the electrocardiographic pattern of hypopotassemia. Circulation 1957; 16: 750–63. 37. Rosenbaum MB, Blanco HH, Elizari V, et al. Electronic modulation of the T wave and cardiac memory. Am J Cardiol 1982; 50; 213–22. 38. Paparella N, Ouyang F, Fuca G, et al. Significance of newly acquired negative T waves after interruption of paroxysmal reentrant tachycardia with narrow QRS complex. Am J Cardiol 2000; 85: 261–3. 39. Glancy DL, Rochon BJ, Ilie CC, et al. Global T‐wave inversion in a 77‐year‐old woman. Proc (Baylor Univ Med Cent) 2009; 22: 81–2. 40. Walder LA, Spodick DH. Global T wave inversion. J Am Coll Cardiol 1991; 17: 1479–85. 41. Lui CY. Acute pulmonary ambolism as the cause of global T wave inversion and QT prolongation. J Electrocardiol 1993; 26: 91–5. 42. Walder LA, Spodick DH. Global T wave inversion: long‐term follow‐up. J Am Coll Cardiol 1993; 21: 1652–6. 43. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST segment elevation myocardial infarction. Ann Intern Med 2004; 141: 858–65. 44. Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539–48. 45. Spodick DH. The electrocardiogram in acute pericarditis: distributions of morphologic and axial changes in stages. Am J Cardiol 1974; 33: 470–5. 46. Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation 2006; 113: 876–90. 47. Kaid KA, Maqsood A, Cohen M, Rothfeld E. Further characterization of the “persistent juvenile T‐wave pattern in adults.” J Electrocardiol 2008; 41: 644–5.

600  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

ST‐segment elevation 48. Hanna EB, Glancy DL. ST‐segment elevation: differential diagnosis, caveats. Clev Clin J Med 2015; 82: 373–84. 49. Smith SW, Khalil A, Henry TD, et al. Electrocardiographic differentiation of early repolarization from subtle anterior ST‐segment elevation myocardial infarction. Ann Emerg Med 2012; 60: 45–56. 50. Smith SW. Upwardly concave ST segment morphology is common in acute left anterior descending coronary occlusion. J Emerg Med 2006; 31: 69–77. 51. Kosuge M, Kimura K, Ishikawa T, et al. Value of ST‐segment elevation pattern in predicting infarct size and left ventricular function at discharge in patients with reperfused acute anterior myocardial infarction.Am Heart J 1999; 137: 522–7. 52. Brady WJ, Syverud SA, Beagle C, et al. Electrocardiographic ST‐segment elevation: the diagnosis of acute myocardial infarction by morphologic analysis of the ST segment. Acad Emerg Med 2001; 8: 961–7. 53. Birnbaum Y, Sclarovsky S, Mager A, et al. ST segment depression in a VL: a sensitive marker for acute inferior myocardial infarction. Eur Heart J 1993; 14: 4–7. 54. Engelen DJ, Gorgels AP, Cheriex EC, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction. J Am Coll Cardiol 1999; 34: 389–95. 55. Collins MS, Carter JE, Dougherty JM, et al. Hyperacute T wave criteria using computer ECG analysis.Ann Emerg Med 1990; 19: 114–20. 56. Smith SW. T/QRS ratio best distinguishes ventricular aneurysm from anterior myocardial infarction. Am J Emerg Med 2005; 23: 279–87. 57. Surawicz B, Parikh SR. Prevalence of male and female patterns of early ventricular repolarization in the normal ECG of males and females from childhood to old age. J Am Coll Cardiol 2002; 40: 1870–6. 58. Klatsky AL, Oehm R, Cooper RA, et al. The early repolarization normal variant electrocardiogram: correlates and consequences. Am J Med 2003; 115: 171–7. 59. Mehta M, Jain AC, Mehta A. Early repolarization. Clin Cardiol 1999; 22: 59–65. 60. Mehta MC, Jain AC. Early repolarization on scalar electrocardiogram. Am J Med Sci 1995; 309: 305–11. 61. Rollin A, Maury P, Bongard V, et al. Prevalence, prognosis, and identification of the malignant form of early repolarization pattern in a population‐based study. Am J Cardiol 2012; 110: 1302–8. 62. Tikkanen JT, Anttonnen O, Junttila MJ, et al. Long‐term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009; 361: 2529–37. 63. Tikkanen JT, Junttila MJ, Anttonen O, et al. Early repolarization: electrocardiographic phenotypes associated with favorable long‐term outcome. Circulation 2011; 123: 2666–73. 64. Noseworthy PA, Tikkanen JT, Porthan K, et al. The early repolarization pattern in the general population: clinical correlates and heritability. J Am Coll Cardiol 2011; 57: 2284–9. 65. Kralios FA, Martin L, Burgess MJ, Millar K. Local ventricular repolarization changes due to sympathetic nerve‐branch stimulation. Am J Physiol 1975; 228: 1621–6. 66. Spratt KA, Borans SM, Michelson EL. Early repolarization: normalization of the electrocardiogram with exercise as a clinically useful diagnostic feature. J Invasive Cardiol 1995; 7: 238–42. 67. Wu SA, Lin XX, Cheng YJ, et al. Early repolarization pattern and risk of arrhythmia death: a meta‐analysis. J Am Col Cardiol 2013; 61: 645–50. 68. Surawicz B, Lassiter KC. Electrocardiogram in pericarditis. Am J Cardiol 1970; 26: 471–4. 69. Hull E. The electrocardiogram in pericarditis. Am J Cardiol 1961: 7: 21–6. 70. Spodick DH. Diagnostic electrocardiographic sequences in acute pericarditis. Significance of PR segment and PR vector changes. Circulation 1973; 48: 575–80. 71. Spodick DH. Acute pericarditis: current concepts and practice. JAMA 2003; 289: 1150–3. 72. Charles MA, Besinger TA, Glasser SP. Atrial injury current in pericarditis. Arch Intern Med 1973; 131; 657–62. 73. Noth PH, Barnes HR: Electrocardiographic changes associated with pericarditis. Arch Intern Med 1940; 65: 291–320. 74. Ginzton LE, Laks MM. The differential diagnosis of acute pericarditis from the normal variant: new electrocardiographic criteria. Circulation 1982; 65: 1004–9. 75. Armstrong EJ, Kulkarni AR, Bhave PD, et al. Electrocardiographic criteria for ST‐ elevation myocardial infarction in patients with left ventricular hypertrophy. Am J Cardiol 2012; 110: 977–83. 76. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle‐branch block. N Engl J Med 1996; 334: 481–7. 77. Madias JE, Sinha A, Agarwal H, Ashtiani R. ST‐segment elevation in leads V1–V3 in patients with LBBB. J Electrocardiol 2001; 34: 87–8. 5 mm ST elevation not useful in LBBB. 78. Smith SW, Dodd KW, Henry TD, et al. Diagnosis of ST‐elevation myocardial infarction in the presence of left bundle branch block with the ST‐elevation to S‐wave ratio in a modified Sgarbossa rule. Ann Emerg Med 2012; 60: 766–76. 79. Hanna EB, Lathia V, Ali M, Deschamps EH. New or presumably new left bundle branch block in patients with suspected acute coronary syndrome. J Electrocardiol 2015; 48: 505–11. 80. Sgarbossa EB, Pinski SL, Topol EJ, et al. Acute myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics and outcome in the thrombolytic era. J Am Coll Cardiol 1998; 105–10. 81. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST segment elevation myocardial infarction. Ann Intern Med 2004; 141: 858–65. 82. Glancy DL, Mikdadi GM. Syncope in a 67‐year‐old man. Proc (Bayl Univ Med Cent). 2005; 18: 74–5. 83. Wilde AA, Antzelevitch C, Borggrefe M, et  al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation 2002; 106: 2514–19.

Large or tall T wave 84. de Winter RJ, Verouden NJ, Wellens HJ, Wilde AA. A new ECG sign of proximal LAD occlusion. N Engl J Med 2008; 359: 2071–3.

Q waves and their regression 85. Nagase K, Tamura A, Mikuriya Y, et al. Significance of Q‐wave regression after anterior wall acute myocardial infarction. Eur Heart J 1998: 19: 742–6. 86. Voon WC, Chen YW, Hsu CC, et al. Q‐wave regression after acute myocardial infarction assessed by Tl‐201 myocardial perfusion SPECT. J Nucl Cardiol 2004; 11: 165–70.

Chapter 31.  Electrocardiography  601

87. Coll S, Betriu A, De Flores T, et al. Significance of Q‐wave regression after transmural acute myocardial infarction. Am J Cardiol 1988: 61: 739–42. 88. Delewi R, Ijff G, van de Hoef TP, et al. Pathological Q waves in myocardial infarction in patients treated by primary PCI. JACC Cardiovasc Imaging 2013; 6: 324–31.

Further reading Surawicz B, Childers R, Deal BJ, Gettes LS. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances. Circulation 2009; 119: e235–40. Rautaharju PM, Surawicz B, Gettes LS. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram: Part IV: The ST Segment, T and U Waves, and the QT. J Am Coll Cardiol 2009; 53: 982–91. Hancock EW, Deal BJ, Mirvis DM, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy. Circulation 2009; 119: e251–61.

Poor precordial R‐wave progression Zema MJ, Collins M, Alonso DR, Kligfield P. Electrocardiographic poor R‐wave progression: correlation with postmortem findings. Chest 1981; 79: 195–200.

Anatomical LA enlargement mimicking RA enlargement Chou TC, Helm RA. The pseudo P pulmonale. Circulation 1965; 32: 96–105.

LAFB Jacobson LB, LaFollette L, Cohn K. An appraisal of initial QRS forces in left anterior fascicular block. Am Heart J 1977; 94: 407–13. Q wave may be absent in I and/or aVL. Elizari MV, Acunzo RS, Ferreiro M. Hemiblocks revisited. Circulation 2007; 115: 1154–63.

Long QT Hodges formula Chiladakis J, Kalogeropoulos A, Arvanitis P, et al. Preferred QT correction formula for the assessment of drug‐induced QT interval prolongation. J Cardiovasc Electrophysiol 2010; 21(8): 905–13.

U wave is T2 wave in hypokalemia and LQT Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long‐QT syndrome. Circulation 1998; 98: 1928–36.

Localization of anterior MI Engelen DJ, Gorgels AP, Cheriex EC, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction. J Am Coll Cardiol 1999; 34: 389–95.

Inferior STEMI RCA vs. LCx Nair R, Glancy DL. ECG discrimination between right and left circumflex coronary arterial occlusion in patients with acute myocardial infarction. Chest 2002; 122: 134–9.

32  Echocardiography

1. General echocardiography  I. The five major echocardiographic views and the myocardial wall segments  602 II. Global echo assessment of cardiac function and structure  602 III. Doppler: mainly assesses blood flow direction (→ regurgitation), timing, and velocity  612 IV. Summary of features characterizing severe valvular regurgitation and stenosis  623 V. M‐mode echocardiography is derived from 2D echo  624 VI. Pericardial effusion  624 VII. Echocardiographic determination of LV filling pressure and diastolic function  628 VIII. Additional echocardiographic hemodynamics  630 IX. Prosthetic valves  634 X. Brief note on Doppler physics and echo artifacts  637 2. Transesophageal echocardiography (TEE) views 

1.  General echocardiography I.  The five major echocardiographic views and the myocardial wall segments A.  Parasternal short‐axis view (Figures 32.1–32.5) B.  Parasternal long‐axis view (Figures 32.6, 32.7, 32.8) C.  Apical four‐chamber view (Figure 32.9). Beware of an apical view that does not cut through the true apex, and thus may miss apical akinesis. A true apex is usually thinner than the septal and lateral walls, and, as opposed to the other walls, moves horizontally rather than longitudinally. D.  Apical two‐chamber view (Figure 32.10). E.  Subcostal four‐chamber view. This view is particularly useful in COPD patients and patients receiving ventilator support, in whom the previous views have a poor quality (Figures 32.11, 32.12). Arterial distribution (Figures 32.2, 32.13). Note that LAD supplies the anterior two‐thirds of the septum, while RCA supplies the inferior one‐third of the septum.

II.  Global echo assessment of cardiac function and structure A.  Global assessment of myocardial function A normal wall motion is characterized by an appropriate inward endocardial movement but also appropriate myocardial thickening. A segment can be hypokinetic, akinetic, or dyskinetic. Dyskinesis is outward movement of a myocardial wall during systole, when the remaining walls have an inward movement. Dyskinesis is therefore myocardial outpouching in systole, whereas aneurysm is myocardial outpouching in both systole and diastole (see Chapter 2). Views that are orthogonal to a structure allow better endocardial definition of that structure. 1.  Overall assessment of LV function • EF: ○○ Normal: > 50% ○○ Mildly decreased: 40–50% ○○ Moderately decreased: 30–40% ○○ Severely decreased: < 30% • The loss of the inferior and posterior walls typically leads to an EF of 35–50%, while the loss of the anteroseptal and apical walls typically leads to an EF  1 cm.

Chapter 32.  Echocardiography  605

Sinuses of Valsalva

Sinotubular junction

Annulus

Aortic valve and aorta (a)

(b)

Figure 32.7  (a) Parasternal long‐axis view. Measurements are obtained from top to bottom, between delineated points, at an oblique line crossing the mitral leaflet tips and orthogonal to the axis of the LV (line). (b) Aortic measurements. The annulus is a stable structure that is part of the ventricle/outflow tract and does not usually dilate. The aortic diameter at the level of the sinuses of Valsalva (i.e., the aortic dilatations that suspend the aortic cusps) is normally up to 3.7 cm, while the diameter of the proximal ascending aorta and the sinotubular junction (junction of the ascending aorta with the sinuses of Valsalva) is normally up to 3.2 cm. Aortic dilatation may occur at the level of the ascending aorta and sinotubular junction (e.g., HTN), or may involve the sinuses of Valsalva in addition to the ascending aorta (bicuspid aortic valve, Marfan disease). The normal diameter at the sinuses is affected by age and body surface area and should generally be 3 small papillary muscles. A muscular band where the right bundle is embedded, the moderator band, may sometimes be seen at the RV apex (spanning from the septal to the lateral RV wall, similar to the false tendon on the left). The tricuspid valve is more apical than the mitral valve. When both valves are at the same level, endocardial cushion defect is suspected. Advanced note: The anterior cusp (1) is A2 ± A3, the posterior cusp (2) is P1, the most lateral one; see Figure 32.3 to understand how the cusps are cut and the relation between leaflets and papillary muscles.

Apex

LV

Anterior

Inferior P3

A2 LA

Ao Ao can be opened at this point

(a)

(b)

(c)

Figure 32.10  (a) Diagram and (b) echocardiogram of the apical two‐chamber view; and (c) echocardiogram of the apical three‐chamber view. By opening the aorta with a counterclockwise rotation, the apical two‐chamber view becomes the apical three‐chamber view, where the anterior and inferior walls are replaced by the septal and posterior walls, respectively. The apical three‐chamber view, also called apical long‐axis view, is similar to the parasternal long‐axis view, except for a different heart orientation (the beam is parallel to the aortic flow and the true apex is intercepted). Depending on the cut, three mitral cusps with two orifices may be seen on the two‐chamber view (P3 next to the inferior wall, A2 in the middle, and P1 or A1 next to the anterolateral wall). Use Figure 32.3 for guidance. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Chapter 32.  Echocardiography  607

Liver RV RA LV LA

(a)

(b)

Figure 32.11  (a) Diagram and (b) example of the subcostal view.

IVC

RA

LA

Figure 32.12  Subcostal view with a medial tilt to visualize the IVC. A large IVC (>2.1 cm), as well as its lack of 50% collapse with inspiration or sniff, signals high RA pressure. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

LAD LAD LAD +/– LCx

LAD +/– RCA RCA

RCA

LCx RCA

LCx +/– LAD

LAD

LAD

LV LCx +/– LAD

LCx or RCA

Figure 32.13  Arterial distribution of various echo segments on the short‐axis view, long‐axis view, and apical four‐chamber view. Note that the inferior septum (on the short‐axis view) and the basal septum (on the four‐chamber view) are supplied by the RCA. If the four‐chamber cut is angled a bit posteriorly, some of the visualized mid‐septum may be supplied by the RCA as well.

608  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

2. Assess for LV dilatation and RV dilatation, which are associated with LV and RV systolic dysfunction, respectively. a.  LV dilatation is characterized by LV diameter (obtained from the short‐ or long‐axis view) > 4 cm in systole or > 5.3 cm (women) or > 5.8 cm (men) in diastole. Measurements are obtained at the level of the mitral leaflet tips, at the base of the LV. b.  RV dilatation (Figure 32.14) is characterized by: • RV size larger than LV size on the apical four‐chamber view • RV rounded rather than wedge‐shaped on the parasternal long‐axis view. • RVOT diameter ≥ 3.0 cm on the long‐axis view or the aortic short‐axis view; RV maximal diameter on the four‐chamber view, around the tricuspid annulus, ≥ 2.9 cm (mild dilatation) or ≥ 3.9 cm (severe). However, these measurements vary according to the way the RV is cut, particularly because the RV has a complex pyramidal shape, which limits their accuracy. • RV pressure overload pattern associated with severe pulmonary hypertension: the RV compresses the LV in systole and leads to a compressed D‐shaped septum in systole. • RV volume overload pattern: the RV compresses the LV in diastole and leads to a paradoxical septal motion towards the RV in systole. In mixed RV volume and pressure overload pattern, the septum remains compressed towards the LV in both diastole and systole. • RA is enlarged if it is larger than LA on the four‐chamber view, or if the interatrial septum bows to the left, or if the septal‐lateral diameter is > 2.2 cm/m2 of BSA (4.5 cm). IVC is typically dilated in RA enlargement. c.  A left ventricular segment that is bright and thin ( 115 g/m2 in men, or > 95 g/m2 in women. Increased wall thickness, which often underlies LVH, is characterized by an interventricular septal thickness or a posterior wall thickness ≥ 1.1 cm in men, or ≥ 1 cm in women. The wall thickness is severely increased if it is ≥ 1.7 cm in men, or ≥ 1.6 cm in women. LVH is concentric when the walls are thick but the LV is not dilated. LVH is eccentric when the walls are thick and the LV is dilated. Concentric LV remodeling is characterized by thick walls without overall LVH; i.e., the LV mass is normal LV mass is calculated using the LV wall thickness and the LV diameter on the parasternal long‐axis view. 4. Left atrial size is the “hemoglobin A1c” of the left heart; if LA size is normal, it is unlikely that there are any major systolic, diastolic, or left valvular issues. A quick way of assessing LA size is by comparing it to the aorta on the long‐axis view. LA is enlarged if it is > 1.1× the aortic size. Normal LA end‐systolic diameter is  5 cm. LA volume should be assessed using the planimetered LA areas on both the four‐ and two‐chamber views (disk summation technique). This is the preferred method for LA size assessment: LA ­volume is normally  48 ml/m2. B.  Paradoxical septal motion Normally, the septum moves in towards the LV in systole, and relaxes towards the RV in diastole. Abnormal septal motion is characterized by a septum that moves out towards the RV in systole, or at least at one point of systole, leading to ineffective septal contraction; and moves in towards the LV in diastole, compressing the LV. Five differential diagnoses (Figures 32.15–32.18): 1.  LBBB and RV pacing. The abnormal septal motion of RV pacing is similar to LBBB, except that it involves the distal/apical septum (rather than the entirety of the septum). 2.  RV dilatation with RV volume overload. 3.  Pericardial processes (constrictive pericarditis, tamponade). Large respiratory swings (e.g., COPD) may simulate the abnormal septal motion of pericardial processes. 4.  Abnormal septal motion post‐cardiac surgery. 5.  Septal akinesis in a patient with septal MI. Unlike all the other causes of septal motion abnormality, anterior and apical akinesis is also seen in this case. As opposed to other diagnoses, pericardial processes, whether constriction or tamponade, are characterized by an abnormal septal motion that increases with inspiration and thus varies between beats, i.e., the septal collapse towards the LV in diastole varies with respiration. In other processes, the abnormal septal motion does not vary as much across beats. In addition, characteristic of constrictive pericarditis, a septal bounce may be seen during each diastole, representing an instantaneous change in the RV‐to‐LV push with instantaneous pressure changes. A septal motion abnormality may also be seen in patients breathing deeply, wherein the RV pushes the septum towards the LV in deep inspiration. Like pericardial processes, this septal position varies with respiration, but septal bounce is not seen. In a tachycardic patient, sorting out the respiratory effect may prove difficult. M‐mode imaging is particularly helpful because of its high frame rate. The abnormal postoperative septal motion is related to the fact that, after cardiac surgery, the heart is fixed anteriorly to the thorax (meaning, the RV is fixated). During systole, the whole heart moves toward that fixation site, leading to what looks like septal motion abnormality. In fact, it is an abnormal anterior motion of the whole heart, including the posterolateral wall.

Chapter 32.  Echocardiography  609

RV

LV

Figure 32.14  Example of RV enlargement and RV volume overload on the parasternal short‐axis view and apical four‐chamber view. The interventricular septum is flattened and pushed toward the LV in diastole (lines). The interatrial septum is also bowing towards the LA (cross).

RV free wall

Septum 2 1

3

Posterior LV wall Systole Figure 32.15  During systole, in LBBB: (1) the septum moves in towards the LV; (2) then the septum relaxes while the posterior wall moves in; (3) the septum moves in again at the end, not because it is contracting but because the RV is relaxing and pushing it. Thus, the septum moves in twice (1 and 3), while the posterior wall moves in between (2), when the septum is relaxed. The distance between the peak of (1) and the peak of (2) is the septal‐to‐lateral M‐mode delay, an index of dyssynchrony (>130 ms → significant).

RV

systole

diastole

Septum LV cavity Posterior wall

Figure 32.16  M‐mode imaging shows paradoxical septal motion of RV volume overload (outward in systole, inward in diastole). This paradoxical motion is seen in both inspiration and expiration; it may be a bit more prominent in inspiration, but unlike constrictive pericarditis or tamponade, it is not much more prominent. M‐mode allows a fine analysis of how various structures move during the cardiac cycle. QRS is used to time events.

610  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

RV

D

Septum

exp

D

D

D

insp D

LV cavity Posterior wall

Figure 32.17  Constrictive pericarditis. Three septal abnormalities and one posterior wall abnormality are seen on M‐mode (D corresponds to the septal position in diastole): • Septum collapses towards the LV in diastole rather than expands towards the RV (arrow). • This septal collapse is particularly evident in inspiration (insp) and the septal position varies between inspiration and expiration. • The RV‐to‐LV diastolic push varies with instantaneous pressures (= septal bounce, circle). • The posterior wall is stiff/horizontal in diastole after the initial brisk expansion (= plateau, line). In RV volume overload, the RV pushes the septum towards the LV in all diastolic cycles, only slightly more so in inspiration. Moreover, only one sharp septal motion towards the LV is seen in diastole.

-Septal compression towards the LV in diastole -Variable septal positions in diastole in pericardial processes

Septum

Figure 32.18  Pericardial processes are characterized by septal compression towards the LV in diastole, similar to RV volume overload. However, this RV septal compression varies with respiration, and consequently septal position varies across different cycles.

C.  Valvular structure assessment 1.  Mitral valve (Figures 32.19–32.21) • Degenerative valve: leaflet(s) are thick, elongated, ± prolapsed into the LA. If, in addition to the prolapse of the leaflet body, the free edge is overriding the other leaflet and turned towards the LA rather than the LV, the leaflet is called flail leaflet; this is usually secondary to chordal rupture (a piece of chorda is usually seen flopping in the LA). • Rheumatic valve: thick, calcified valve with a stiff posterior leaflet and a stiff anterior leaflet tip. The anterior leaflet body is, however, mobile. The combination of a stiff anterior leaflet tip and a flexible body gives the anterior leaflet a hockeystick shape on the

Chapter 32.  Echocardiography  611

parasternal long‐axis view. On the short‐axis view, the commissures are fused and the valve only opens in its center (“fish mouth” mitral valve). • Mitral annular calcifications involve the mitral annulus rather than the leaflets (in contrast to a rheumatic process). The annulus is ­calcified, but the leaflets’ tips are free. Calcifications are mainly seen at the posterior aspect of the annulus and increase in incidence with age, high LV pressure (HTN, AS), and renal disease. Only the posterior annulus, which is a muscular structure, calcifies; the anterior annulus is a fibrous structure that only calcifies in radiation heart disease. Calcifications may, however, extend to the base of both the posterior and anterior leaflets on the four‐chamber view (not the leaflet tips, and not the anterior annulus on the long‐axis view). 2.  Aortic valve • Aortic valve thickening (sclerosis) and calcification are precursors of AS. Also, aortic sclerosis and calcification are associated with coronary atherosclerosis • A bicuspid aortic valve is characterized by fusion of two cusps, most commonly the right and left cusps (85%); a raphe is frequently seen between the two fused cusps, and this may create the false impression of a tricuspid valve. Therefore, on the aortic short‐axis view, instead of analyzing how many cusps are seen when the valve is closed, it is best to analyze how the aortic valve opens. An elliptical rather than a triangular opening is a hint to a bicuspid valve (Figure 32.22).

Posterior leaflet Figure 32.19  Posterior mitral leaflet prolapse. In systole, the leaflet prolapses posteriorly to the mitral annular plane (blue line).

(b) (a) Figure 32.20  Rheumatic mitral valve. (a) Long‐axis view in diastole. See the hockeystick shape of the anterior leaflet (arrow), the tip of which looks attached to the stiff posterior leaflet (line), with no diastolic opening. In fact, both leaflets are tied together by the commissural fusion. Note the severe LA enlargement, due to MS in this case. Also, note the aortic valve calcification (white aortic valve leaflet tips [dot]). Make sure the aortic calcification is not a false impression related to a high echo gain; the fact that the aortic walls appear bright may be a hint to the increased echo gain. (b) Short‐axis view. Commissural fusion (arrow) explains the “fish mouth” opening.

612  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

Posterior leaflet

MAC

MAC

Figure 32.21  Posterior mitral annular calcifications (MAC) in the long‐axis and four‐chamber views. These posterior calcifications project at the base of the posterior leaflet on the long‐axis view and the base of both the posterior and anterior leaflets on the four‐chamber view.

RC

NC

Fused RC and LC

LC

NC

Tricuspid aortic valve on TTE

Fused RC and LC on TTE

RA

NC

Bicuspid aortic valve on TTE LA

Bicuspid

Rather than opening all the way to the aortic wall, the bicuspid leaflets have a domed configuration in systole Figure 32.22  Difference in aortic orifice shape between the tricuspid and bicuspid aortic valves (short‐axis view). Note that one cusp is larger than the other in bicuspid aortic valve, and hence the aortic opening/closure becomes eccentric; this is evident on the M‐mode analysis of the aortic valve. The leaflets open in a domed fashion on a longitudinal view (long‐axis view), as they are restricted by the lack of a third commissure. A severely stenotic bicuspid valve may appear to open well on the long‐axis view. The stenosis being eccentric, it is three‐dimensionally more severe than it may appear on a two‐dimensional view. LC, left coronary cusp; NC, non‐coronary cusp; RC, right coronary cusp.

III. Doppler: mainly assesses blood flow direction (→ regurgitation), timing, and velocity A. Types 1.  Color Doppler: color Doppler assigns color to blood flow velocity and direction. The maximal Doppler velocity that can be sampled unambiguously and attributed a blue or red color is called the Nyquist or aliasing limit. Beyond this limit, the color becomes mosaic. 2.  Continuous‐wave (CW) spectral Doppler: CW Doppler traces the highest flow velocity along one line swept by the Doppler probe. Therefore, it captures the velocity across the narrowest point or obstruction. It continuously captures waves and is not dependent on the Nyquist limit. 3.  Pulsed‐wave (PW) spectral Doppler: PW Doppler traces the velocity at one point along the line swept by the cursor, rather than the whole line swept. It samples waves intermittently, at a specified sampling rate. Therefore, the maximal velocity that can be detected across this one point cannot exceed a certain limit, called the Nyquist limit.

Chapter 32.  Echocardiography  613

B.  Routine Doppler interrogations 1.  Color Doppler is performed at the level of each valve to assess regurgitation (see Figures 32.23–32.33) By “eyeballing” the view, regurgitation appears as a color going backward between chambers, opposite to the normal flow (e.g., any flow from LV to LA, RV to RA, or aorta to LV). It is blue (backward) for the mitral and tricuspid valves on TTE. It usually has a higher velocity than the Nyquist limit, which leads to color aliasing (= mixed, mosaic color). Also, when severe, it is usually turbulent, with high variance of velocities (turbulent flow, coded as green color). Reducing the Nyquist limit from 60 cm/s to 30 cm/s increases the area of regurgitant flow by Doppler. Increasing the color gain also increases the area of regurgitant flow. Therefore, an inappropriately low Nyquist limit or a high Doppler gain overestimates the regurgitation severity, while the opposite underestimates the regurgitation severity. Inappropriately low color gain is particularly common in patients with poor windows, wherein the color definition is reduced, similarly to the reduction in echo resolution. Increase the color gain until noise is seen and until color pixels appear within the cardiac tissue, then slightly reduce the gain just until the noise disappears; the latter gain corresponds to the appropriate color gain. For evaluation of regurgitation, the best Nyquist limit is 50–60 cm/s. Also, narrow the Doppler sector to focus on the valve of interest; a large sector reduces the color resolution across the valve of interest.

2.  CW Doppler is performed at the level of each valve to assess forward‐flow velocity, and, consequently, valvular stenosis (see Figures 32.34, 32.35, 32.36) Normally, the forward peak velocity across each valve is 1 m/s. An increase in flow velocity corresponds to valvular stenosis. The peak pressure gradient across a valve can be estimated using this equation (modified Bernoulli equation):

Peak gradient 4 Vvalve2

This is how gradient is estimated across the aortic valve and the severity of a stenosis is assessed. For spectral Doppler assessment, it is important to obtain a view parallel to the flow. 3.  PW Doppler is used to see the velocity at one particular point, such as the mitral inflow (E/A), tricuspid inflow, pulmonary vein inflow (systolic, diastolic, atrial waves), and LVOT flow (Figures 32.37, 32.38) PW has a limited capacity to measure high velocities that exceed twice the Nyquist limit (>2 m/s), particularly at greater depths. Two types of velocities are analyzed on CW or PW Doppler: peak velocity and velocity–time integral (VTI).VTI corresponds to the area enclosed by the CW or PW Doppler velocity profile. It is measured in cm (velocity × time) and corresponds to the distance traveled by blood across the interrogated point during one cardiac cycle. All Doppler modalities are angle‐dependent and best measure the flow that is aligned with the ultrasound beam. For best assessment of stenosis or regurgitation and for velocity measurement, the ultrasound beam should be parallel to the flow (or within a 20° angle).

4.  Tissue Doppler assesses the movement of cardiac structures rather than blood flow (Figures 32.39, 32.40) Tissue Doppler is useful to assess: a.  Mitral annular velocities during diastole (E’ and A’). E’ is the annular recoil toward the base during early diastolic filling; A’ is the annular recoil during atrial systole. Lateral E’ is normally ≥ 10 cm/s, medial E’ is ≥ 7 cm/s. The reduction of E’ indicates diastolic dysfunction or high left‐sided filling pressures. b.  Dyssynchrony of various myocardial segments, manifested as different times from QRS onset to peak systolic velocity (or peak strain) between different walls. The assessment of mechanical dyssynchrony is particularly useful in patients with low EF and QRS 130–150 ms, as it may help identify the responders to biventricular pacing. In patients with HF and QRS  50% inspiratory collapse → RA pressure = 0–5 mmHg ii.  IVC ≤ 2.1 cm but  2.1 cm with > 50% inspiratory collapse → RA pressure = 5–10 mmHg iii.  IVC > 2.1 cm with  40% LA area → severe MR (this also applies for TR: jet area > 30% of RA area → severe TR). This provides a quick idea of the severity of MR, but is not very reliable. Increasing the color gain or lowering the Nyquist limit of the backward flow on the color scale (horizontal arrow) increases the regurgitant/turbulent area and makes the MR look more severe. The best Nyquist limit for regurgitation assessment is 50–60 cm/s. To obtain the best color gain, increase the gain until noise is seen in cardiac tissues, then slightly reduce it just until the noise disappears. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

LA

VC

PISA

LV Figure 32.24  Severe MR on four‐chamber TEE view. Severity criteria of MR: 1. Look at the small spherical portion of the regurgitant jet that is on the side of the ventricle rather than the atrium. As the blood is flowing back from the LV to the LA, it goes through a narrow neck that corresponds to the vena contracta (VC) of the mitral orifice. The flow converging towards the mitral orifice forms hemispheres of increasing velocities, the areas of which are called proximal isovelocity surface areas (PISA). The hemisphere of interest is the one where aliasing occurs (double arrow). Thus, the radius of the PISA corresponds to the distance between the narrowest neck of flow and the outer aliasing line (double arrow). The larger this hemisphere (>0.9–1.0 cm), the more severe the MR. PISA allows calculation of the effective regurgitant orifice (ERO). If the backward aliasing limit is set at 40 cm/s on the regurgitant color bar (arrow), ERO is estimated as: (PISA radius)2/2 If PISA radius is 0.9 cm, ERO is ~0.4 cm2. MR is severe if ERO ≥ 0.4 cm2. ERO can be used to calculate the regurgitant volume (= ERO × VTI of the regurgitant flow) and the regurgitant fraction. Regurgitant volume > 60 ml or regurgitant fraction > 50% signifies severe MR. PISA is affected by eccentricity of the jet, but less than MR jet area; another limitation is that the PISA should be a 180° hemisphere, not less and not a cylinder. 2. The diameter of the MR flow at its vena contracta neck, i.e., the narrowest part (mitral valve level), can be estimated. The larger the diameter, the more severe the MR (≥7 mm → severe MR). 3. A severe regurgitation should lead to enlargement of the backward chamber (LA in MR, RA in TR, LV in AI). In addition, the forward chamber often enlarges because of the volume overload. Except in acute cases, a normal‐size backward chamber rules out severe regurgitation. 4. Other severity criteria of MR: • Increased forward flow and velocity across the mitral valve in diastole: E velocity > 1.2 m/s • Reversal of the systolic S flow of one or more pulmonary vein(s): specific for severe MR, but not sensitive, as LA compliance may prevent this flow reversal (compensated chronic MR). Moreover, if the jet is eccentric, reversal of flow may be seen in some but not all of the veins. Blunting of S flow, rather than reversal, is also consistent with severe MR but is not specific. When MR seems severe but LA is not enlarged, make sure that MR is present throughout systole. What seems like severe MR by color or PISA is moderate if it only encompasses 50% of systole or end‐systole (this may occur with mitral valve prolapse and with functional MR). The duration of MR is evaluated by CW Doppler or by color M‐mode across the mitral valve.

Figure 32.25  MR, long‐axis view. The blue flow between LV and LA is MR (arrow). It is eccentric, posteriorly directed, and at least moderate in severity. When MR is eccentric, consider it more severe than it appears (MR that appears mild is likely moderate). An eccentric jet that turns around the left atrial wall in a circular way is severe MR (Coanda effect). A well‐visualized PISA hemisphere (arrowhead) despite a Nyquist limit of 69 cm/s is concerning for severe MR. A posteriorly directed MR usually implies either anterior leaflet prolapse or posterior leaflet tethering from inferior akinesis.

616  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

D

S

D

S

Figure 32.26  Systolic flow reversal of pulmonary venous flow in a patient with severe MR. Normally, S flow has the same direction as D flow.

Figure 32.27  CW Doppler across the mitral valve on an apical four‐chamber view. The flow is directed backward (arrow) from the LV to the LA, and projects below the baseline on CW Doppler. It is dense (white) but not as white as the forward flow, and thus is probably moderate MR. Acute or decompensated severe MR may lead to a late indentation of the CW signal (would be at the location of the arrowhead), related to a large V wave and decreased LV–LA pressure gradient at end‐systole. This is called the V‐wave cutoff sign, and leads to an early‐peaking, triangular MR shape. On the apical views, because of similarities in direction of AS and MR jets and because of beam width artifact, AS Doppler interrogation may capture MR jet, creating the false impression of severe AS velocity. Unlike AS, MR jet starts immediately at MV closure, immediately after the mitral inflow A wave, at the peak of R wave on the ECG (dashed line). The timing of the two jets and a back‐and‐forth sweeping of the transducer help differentiate the two. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Chapter 32.  Echocardiography  617

Figure 32.28  Severe TR seen from the short‐axis view (aortic valve level) (arrow). The same criteria described under Figure 32.24 can be used for TR to assess severity. To estimate ERO, set the backward flow aliasing limit at 28 cm/s (instead of 40). Also, annular dilatation ≥ 3.5 cm correlates with severe functional TR. Use the same vena contracta and ERO values as in MR, use jet area > 30% RA area, and look for hepatic vein flow reversal and RA enlargement. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Figure 32.29  TR. CW Doppler across the tricuspid valve on a four‐chamber view (see that the line swept is on the right side, arrow). TR looks very dense (white) on CW Doppler, which often means large‐volume moderate or severe regurgitation. Unlike the density of the regurgitation, the peak velocity does not correlate with the severity of the regurgitation. This peak velocity correlates with the pressure gradient between the two chambers (here: RV to RA), and hence PA pressure. Severe pulmonary hypertension may occur with mild, non‐dense TR, yet the velocity would be high (>4 m/s); conversely, severe, dense TR may be seen with a low TR velocity when PA pressure is not elevated (e.g., primary TR).

618  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

(a)

(b)

Figure 32.30  Aortic insufficiency (AI). Long‐axis views (a and b) show blue–backward flow from the aorta to the LV (arrows), i.e., AI. Assess AI severity by looking at: 1. The width of the AI jet just below the aortic valve, on the long‐axis view (between the two dots). If AI jet > 60% of the LVOT diameter (which is the diameter between the two walls at the aortic valve insertion) → severe AI. AI jet is better evaluated on the parasternal views than the apical views, which tend to falsely “widen” the AI jet. 2. Pressure half‐time (on CW Doppler, Figure 32.33) 3. Diastolic reversal of flow in the thoracic aorta (suprasternal view) or abdominal aorta (subcostal view). A holodiastolic flow reversal signals severe AI. This is the most important parameter in AI assessment. In (a), AI is moderate; in (b), AI is mild. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Figure 32.31  AI. The width of the AI jet may also be assessed on the aortic short‐axis view. Here, look for a central blue or mixed‐color “flame” in diastole (arrow), which corresponds to AI jet. AI jet area that is > 60% of the whole aortic circle area implies severe AI. AI jet may look falsely enlarged if the cut is well below the regurgitant orifice, or falsely reduced if AI is eccentric. In order to obtain the accurate AI width, the transducer may be angled up until the AI flow is lost; the AI that is seen just before the flow is lost corresponds to the jet width. The latter maneuver is best performed on the TEE’ aortic short‐axis view. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Chapter 32.  Echocardiography  619

Figure 32.32  AI on three‐chamber apical view. This view is not accurate for measurement of the jet width area and vena contracta. Being parallel to the flow, it is excellent for recording of Doppler flow and measurement of AS gradient or AI pressure half‐time, but it is not accurate for width measurement. When assessing thickness of a structure or flow, it is best to be orthogonal to the structure or flow.

Compensated AI Doppler Gradual PHT

Decompensated AI Doppler Steep PHT

Figure 32.33  AI spectral Doppler assessment on an apical five‐chamber view. The flow between the aorta and the LV is directed upward (along the direction of the arrow). The slope of this regurgitant flow depends on how closely the LV and aortic pressures approximate during diastole, and thus how severe and acute AI is. The steeper the slope, the more severe and quick is the rise of LV diastolic pressure. This is called pressure half‐time (PHT), which is the time needed for the pressure gradient to decrease in half. If PHT  250 ms. PHT correlates more with acuity and decompensation of AI than its severity. PHT of AI is different from PHT of MS, where a steeper slope implies less severe MS. Also, the density of this regurgitant flow correlates with severity (the whiter it is in comparison to the forward flow, the larger the AI volume and the more severe the regurgitation). In this case, note that the patient has AI with PHT  2 m/s signals AS; velocity ≥ 4 m/s implies severe AS, which is the case here. The peak pressure gradient may be calculated from peak velocity using the modified Bernoulli equation (= 4 V2). The mean pressure gradient integrates all the gradients underneath the velocity envelope. Echo may underestimate the pressure gradient if the interrogation angle is not parallel to the flow, or if the jet envelope is incomplete (may need to increase the gain settings). Search for the best envelope and the highest gradient in multiple views (apical five‐chamber, apical three‐chamber, right parasternal, and suprasternal views). Caution: increased CW velocity is not necessarily AS, because CW samples the highest velocity along the whole line swept and not only the aortic valve. It may be LVOT obstruction, where the velocity is increased across the LVOT rather than the aortic valve. In this case, the PW velocity is increased across the LVOT, whereas the localized aortic PW velocity is not increased (PW localizes the site of obstruction, even though it may not be able to record the exact velocity). Also, in LVOT obstruction, the gradient peaks late and the CW velocity has a late‐peaking dagger shape. High velocity across the aortic valve may occur in high‐output states (sepsis, fever, anemia) and in severe AI (increased stroke volume). In these cases, the velocity is increased across the LVOT and the aorta. The way to figure out the presence of AS is to use the dimensionless index (LVOT PW velocity divided by aortic valve CW velocity). Either VTI or peak velocity may be used. The index is normally ~1, and an index  5 mmHg at rest, or 10–15 mmHg with exercise, corresponds to severe MS. Passive leg raising should be performed to assess stress gradient. CW, not PW, should be used to capture the gradient. Also, the downslope of the rapid diastolic filling (E wave, first wave) may be used to estimate MV area: a slow downslope means that LA pressure does not equalize with LV pressure even in late diastole (no diastasis), which corresponds to severe MS. The pressure half‐time is the time it takes the pressure gradient to decrease in half [i.e., time it takes E velocity to decrease by 30%], and is long in severe MS. MV area = 220 divided by pressure half‐time. However, for the same valve area, LA and LV pressures more readily equalize in case of increased LV diastolic pressure (AI, severe LVH), which makes the downslope look steeper → MV area will be seemingly larger and MS will be seemingly less severe. (b) If E wave has a “ski slope” shape, (i.e., initially steep then slow downslope), use the slow downslope portion to calculate the pressure half‐time. An associated MR or high output state increases the early E‐wave velocity and the overall gradient, but the later E slope remains unchanged. In AF, the pressure gradient varies between different beats (↑ with short R–R cycles, as LA emptying decreases), but the shape and slope of the CW envelope remain unchanged. Mean gradient increases as in any tachycardia (or exercise), but pressure half‐time and MV area remain unchanged. PHT = pressure half‐time.

Mitral valve velocity E A E

A

MR

Diastole

Systole

Figure 32.37  PW Doppler at the level of the mitral valve. During diastole, forward flow is recorded across the MV: E is the rapid diastolic filling, A is the filling related to atrial contraction. E occurs after T wave, while A occurs after P wave and almost coincides with QRS. Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

S

D

S A

D A

Figure 32.38  PW Doppler across the pulmonary veins on a four‐chamber view, pulmonary veins being behind the LA (cursor). S and D represent, as it is seen, forward systolic and diastolic flow toward the LA. A wave corresponds to atrial systole, when LA pressure increases and prevents forward blood flow: A is a reversed flow wave. Normally, S is slightly > D or slightly  7 mm (Nyquist limit 50–60 cm/s) 3. PISA radius > 0.9 cm (at a Nyquist limit of 28 cm/s ≠ MR) 4. TR jet dense ± triangular with early peaking (V‐wave cutoff) 5. Hepatic venous S blunting, or, worse, reversal (reversal is specific for severe TR) RA/IVC size is always increased in severe chronic TR Pulmonic regurgitation • As opposed to AI, where the jet width below the neck determines severity, in PR, the jet length and the total jet area in the RV correlate with severity. In severe PR, the color jet goes deep into the RV, beyond the RVOT (use a large Doppler sector to visualize). In mild PR, the jet length is  25% inspiratory increase of tricuspid inflow E velocity. The last two findings are the earliest pre‐tamponade findings. Tamponade is a clinical diagnosis. The echocardiographic signs suggest hemodynamic abnormalities that are the substrate for tamponade, but on their own they do not establish the diagnosis of tamponade. Tamponade may occur as a result of a localized effusion compressing one particular chamber, such as RV, LV, LA, RA, or pulmonary veins, as after cardiac surgery. This is more difficult to diagnose, and only some of the tamponade echocardiographic signs are seen. TEE may be more helpful in showing the localized effusion and cardiac chamber compression (e.g., isolated pulmonary venous compression).

1 2

3

4

1 2 3 E

A F

Systole

4

5

5

Diastole

Figure 32.41  M‐mode across the mitral valve on the parasternal long‐axis view. The first structure intercepted, at the top, is the RVOT wall (white line); the second structure is the RV cavity (dark); the third structure is the septum; the fourth structure is the anterior leaflet of the MV (closes in systole and opens in diastole), and the fifth structure is the posterior mitral leaflet. The anterior mitral leaflet has two waves in diastole: E (rapid filling) and A, similar to the mitral inflow Doppler. Examples of disease states: • In MS, the E‐wave downslope becomes flat horizontal (flat EF slope), and the posterior leaflet is drawn to the anterior leaflet. • In high LVEDP, there will be a small extra wave (B bump) at the end of A wave (at the location of the dot). • In SAM, the anterior leaflet will be drawn to the septum in end‐systole or, worse, all systole (in the direction of the arrow). • In severe AI, one may have early closure of the mitral valve or diastolic mitral fluttering. • In tamponade, early diastolic inward indentation of the RVOT is seen. By moving the interrogation line towards the mid LV, the systolic movement of the septum and the LV posterior wall can be assessed (see Figures 32.15–32.18).

Figure 32.42  M‐mode across the aortic valve on the long‐axis view. The first structures encountered are the RVOT wall and cavity. Then the aortic walls (rather than LV walls) are encountered and, inside them, the aortic valve. The aortic valve opens well here (open box in systole [arrow]). Disease states: • In severe AS, the box becomes flat. In bicuspid aortic valve, the line of closure in diastole is eccentric • In HOCM, there is mid‐systolic notching (partial closure) of the box. • In low cardiac output, there is early gradual closure of the aortic valve (the box becomes a triangle: >). Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

626  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

SAM, with a gap between leaflets Flat EF slope

E

A

E

Ant

F

Post

(a)

(b)

Diastole

Systole

(c)

Figure 32.43  Examples of M‐mode across the mitral valve. (a) Posterior mitral leaflet prolapse. See how the posterior leaflet moves posteriorly in mid‐to‐late systole, creating a “gap” in the mitral closure, and thus MR (arrows). (b) SAM of the anterior leaflet in HOCM, with the anterior leaflet touching the septum in systole, creating a gap away from the posterior leaflet. (c) Flat EF slope in diastole suggests MS (mitral valve is open throughout diastole, with no diastasis). Also, the posterior leaflet is pulled towards the anterior leaflet (commissural fusion) (arrow). Ant, anterior mitral leaflet; Post, posterior mitral leaflet.

Figure 32.44  Diffuse pericardial effusion on long‐axis view, identified as a black band above the RV (upper arrow) and a black band posterior to the LV. In this case, posterior to the LV, there are two black bands separated by the pericardium: pericardial effusion and pleural effusion (lower arrows). Differentiate pleural from pericardial effusion: the pericardial effusion is anterior to the descending aorta (X), whereas the pleural effusion extends behind the aorta. The coronary sinus is in the AV groove, anterior to the pericardium (dot). Reproduced with permission from Hanna EB, Quintal R, Jain N. Cardiology: Handbook for Clinicians. Arlington, VA: Scrub Hill Press, 2009.

Chapter 32.  Echocardiography  627

Short-axis view Anterior aspect

Long-axis view

Subcostal view Inferior aspect B

Posterior aspect Apical 4-chamber view

Posterior aspect Posterior/lateral aspect

Inferior aspect of the effusion, accessible to subcostal approach

Posterior aspect of the effusion, inaccessible to subcostal approach

Figure 32.45  Pericardial effusion on multiple views. In a supine position, a free‐flowing effusion gravitates and predominates over the posterior aspect of the LV. The posterior aspect is the one seen on the long‐axis view (posterolateral aspect) and the four‐chamber view. This has to be distinguished from the effusion at the inferior/diaphragmatic aspect of the LV, which is more anterior and is the one seen on the subcostal view (used for subcostal pericardiocentesis).

Effusion RVOT

D

S D

S

D

Effusion

(a)

(b)

Figure 32.46  (a) Pericardial effusion (stars) and pleural effusion (bar). The latter is behind the level of the descending aorta. RVOT is compressed in diastole, at a time when the mitral valve is open (RVOT diastolic indentation is marked by arrow). (b) RVOT collapse in early diastole on M‐mode. Always time events to the ECG; systole starts at the peak of R wave and occupies the ST–T segment, whereas diastole starts beyond the T wave. Events may also be timed to the mitral opening on M‐mode. After the systolic dip, the RVOT should be expanding outward in diastole (as in the solid line), rather than pushed inward (dashed line). The presence of two dips, a systolic dip and a diastolic dip soon after the RV starts to expand out, is characteristic of tamponade. For the diastolic dip to be diagnostic, the M‐mode has to cut the RVOT in an orthogonal fashion. D, diastole; S, systole.

628  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

VII. Echocardiographic determination of LV filling pressure and diastolic function A.  Main parameters (see Chapter 5, Figure 5.1) Diastolic E flow and E/A ratio-Diastolic E flow is affected by: (1) LA pressure, (2) LV relaxation, which is impaired in both diastolic dysfunction and systolic dysfunction, and (3) heart rate and PR interval. Impaired LV relaxation reduces E velocity; however, severe hypovolemia with low left‐sided filling pressure may reduce E and E/A ratio even in the absence of a relaxation problem. Prolonged PR interval and sinus tachycardia reduce E and E/A ratio and may be associated with E–A fusion without any relaxation problem. On the other hand, high left‐sided filling pressures but also high elastic recoil in normal young patients may elevate E velocity. Two echocardiographic parameters correlate solely with relaxation and are thus reduced in any LV dysfunction, systolic or diastolic, regardless of filling pressure: mitral annular recoil velocity (E’) and the velocity of Doppler propagation from the mitral valve to the apex on four‐chamber color M‐mode (Vp). Therefore:

E/E

LA filling pressure LV relaxation / LV relaxation LA filling pressure

The same applies for E/Vp. E/E’ ratio strongly correlates with LA pressure in both systolic and diastolic dysfunction. E/E’ ratio > 14 establishes the diagnosis of LV failure and high LA pressure. When E/E’ is between 9 and 14, other echocardiographic or BNP features are required to assess left‐sided filling pressures. E/E’, E deceleration time, Vp, and E/Vp are still reliable in case of atrial fibrillation, where measurements should be averaged from three non‐consecutive beats with cycle lengths within 20% of the average heart rate. E/E’ has pitfalls in some contexts (Table 32.3). E’ value may be obtained from the septal or lateral side of the mitral annulus on the four‐chamber view; septal E’ is normally lower than lateral E’. Both values should be used and averaged and usually trend in the same direction. Note that all these parameters correlate with LA pressure. Only one parameter correlates with LVEDP: (pulmonary vein A duration) minus (mitral valve A duration). If prolonged > 30 ms, it corresponds to a prolonged retrograde atrial flow, which correlates with elevated LVEDP even at a stage of normal mean LA pressure (compensated LV dysfunction). This parameter remains useful regardless of EF, mitral valve disease, or HCM. LA enlargement is a landmark of diastolic dysfunction and/or increased LA pressure. However, LA size may be normal in mild or moderate, compensated diastolic dysfunction. Conversely, LA may remain enlarged for some time after normalization of a previously elevated LA pressure, or in case of atrial arrhythmia or mitral disease. B.  Other parameters that correlate with left‐sided filling pressure • S and D on pulmonary venous flow. The more depressed the systolic S wave, the higher the LA pressure. Patients with elevated LA pressure have a large V wave and a deep Y descent; X descent, on the other hand, is flattened and pulled up by the large V. This explains the large D wave (D = Y) and the flat S (S = X). • Isovolumic relaxation time (IVRT). IVRT is prolonged (>110 ms) with stage 1 diastolic dysfunction, and reduced ( 15 (medial) > 13 (lateral)

≤8

Normal LA pressure

High LA pressure 9−14 Usually with LA enlargement

-E/A ≤ 0.8 and E ≤ 0.5 m/s -PA pressure < 35 mmHg -E/A ratio changes with Valsalva 200 ms -PV A –Mitral A < 30 ms - S>D on PV flow with low EF

-E/A ≥ 2 -PA pressure > 35 mmHg -E/A changes with Valsalva > 50% -E/Vp ≥ 2.5 -E flow DT < 160 ms -PV A – Mitral A > 30 ms -S < D on PV flow with low EF -B-bump on M mode of the mitral valve

Normal LA pressure

High LA pressure

Figure 32.48  Assessment of left‐sided filling pressures in patients with normal or abnormal systolic function. *E/A ≤ 0.8 correlates with normal filling pressures in patients with low LVEF and in most patients with normal LV EF; a patient with severely impaired LV relaxation may have a low LA–LV gradient in early diastole, i.e., low E velocity and E/A ratio, despite a high LA pressure. A depressed S wave (= X descent) on pulmonary venous recording corresponds to a high LA pressure, mainly in the case of a depressed EF. LA enlargement correlates with high LA pressure but LA may remain enlarged even after normalization of LA pressure. E/A and pulmonary venous patterns are not helpful in atrial fibrillation or sinus tachycardia > 100 bpm. DT, mitral inflow deceleration time; PV, pulmonary vein.

630  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

D.  Assess the volume status and cardiac output of critically ill patients • The following findings suggest high left‐sided filling pressures: high E/A, high E/E’ with a small E’, low/flat systolic wave on the pulmonary vein flow, high PA pressure. • LV cavity collapse, with or without high LVOT velocity, suggests hypovolemia. However, this may be seen in patients with a stiff, restricted myocardium and volume overload. • IVC plethora or poor inspiratory collapse implies high RA pressure and probable RV volume overload. Note, however, that IVC dilates with positive‐pressure ventilation. Thus, for patients who are mechanically ventilated, IVC dilatation and IVC respiratory variations correlate poorly with RA pressure, yet a small IVC 12%) correlates with volume responsiveness. • Cardiac output can be estimated from the LVOT pulsed‐wave Doppler. Aortic or LVOT flow variation > 12% with respiration (mechanical ventilation), or stroke volume increase > 12% with passive leg raising predicts volume responsiveness.

VIII. Additional echocardiographic hemodynamics Doppler hemodynamics mostly rely on the Bernoulli equation:

Peak instantaneous pressure gradient 4 peak velocity 2across the obstruction – peak velocity 2proximal to this obstruction

The velocity proximal to the obstruction being usually ~1 m/s, the square of this velocity is negligible in patients with a high velocity across the obstruction. Therefore, the simplified Bernoulli equation is:

Peak instantaneous pressure gradient 4 peak velocity 2across the obstruction

A.  Proximal isovelocity surface area (PISA) of MR (Figure 32.49) As blood flows back from the LV to the LA, it converges into multiple sequential hemispheres before reaching the narrow neck of the mitral orifice. This is the convergence flow seen on the LV side, and it is equal to the regurgitant flow seen in the LA. The closer this flow is to the mitral orifice, the higher its velocity, at one point equaling then superseding the aliasing velocity, with all points across one hemispheric line having the same velocity. If the line where aliasing occurs is chosen, the velocity of this line would be equal to the Nyquist limit. The inner boundary of the flow convergence is the vena contracta, and the outer boundary is the aliasing color. The area of this flow, PISA, being a hemisphere rather than a 2D circle, is equal to 2πr2 rather than πr2, and its velocity is equal to the aliasing limit. The aliasing velocity of the regurgitant color (usually blue on TTE, red on TEE) is the one used for calculation.

Regurgitant color=red LA

MR

VC or ERO PISA

LV MR flow at the LA side = MR flow coming from the LV ERO x Peak MR velocity on CW Doppler = PISA area x aliasing velocity of the red color = 2π (PISA radius)2 x aliasing velocity →ERO = 2π (PISA radius)2 x aliasing velocity/ peak MR velocity ~ (PISA radius)2 /2 if aliasing 40 cm/s Regurgitant volume = ERO x MR VTI Regurgitant fraction = Regurgitant volume/ total forward mitral flow = Regurgitant volume/ (Regurgitant volume + Stroke volume) Figure 32.49  Aliasing velocity of the regurgitant color, which is red in this case and equal to 40 cm/s, is used for PISA calculation. It is the one that should be set at 40 cm/s for the simplified equation. The PISA calculation may also be performed for AI: the peak velocity of the AI spectral envelope is used to calculate ERO, and the VTI of the AI envelope is used to calculate the regurgitant volume. ERO, effective regurgitant orifice area; VC, vena contracta.

Chapter 32.  Echocardiography  631

The effective regurgitant orifice area (ERO), which corresponds to the narrow regurgitant orifice (or vena contracta), can be calculated using the continuity equation. An ERO ≥ 0.4 cm2 indicates severe MR. In order to accurately visualize a rounded PISA and measure its radius, the Nyquist limit should be reduced to 40 cm/s; moreover, at this Nyquist limit, the simplified ERO equation applies (ERO ~ PISA radius2/2). The PISA principle may also be used to calculate the aortic ERO in AI in an apical view, but it is more technically challenging to delineate the hemisphere of PISA AI than MR; ERO ≥ 0.3 cm2 indicates severe AI. PISA may also be used to calculate MVA in MS. Peak velocity of MR is used to calculate ERO by the PISA method. Subsequently, VTI velocity of MR is used to calculate the regurgitant volume (Figure 32.49). B.  Other modality of regurgitant volume calculation As an alternative to PISA, the regurgitant volume of MR or AI may be calculated using the continuity equation at the level of the LVOT and the mitral valve (volumetric method): Stroke volume at the LVOT = LVOT VTI × 0.785 × LVOT diameter2 Stroke volume at the mitral valve = transmitral VTI × 0.785 × mitral annular diameter2 Transmitral VTI is obtained by tracing the diastolic PW mitral inflow, E–A, in an apical view; mitral annular diameter is also measured in diastole, in an apical view. The difference between these two stroke volumes is the regurgitant volume of MR or AI. LVOT stroke volume is the larger stroke volume in AI, while mitral stroke volume is the larger stroke volume in MR. This calculation has pitfalls, particularly the measurement of the mitral annular diameter. Moreover, it cannot be used in patients with combined MR and AI, or in patients with MS whose diastolic mitral area is different from the annular area. C.  Pitfalls in MS assessment, pitfalls in mitral valve area calculation using pressure half‐time, and various methods of mitral valve area calculation (Figures 32.50, 32.51) Since it is easy to align the Doppler beam with the mitral inflow on the apical views, the echocardiographic determination of transmitral gradient is usually highly accurate. On continuous‐wave Doppler, the downslope of the mitral inflow E wave can be used to estimate the mitral valve area. The time it takes the pressure gradient to decrease in half, i.e. the time it takes the velocity to decrease by 30%, is the pressure half‐time (PHT); mitral valve area (MVA) is equal to 220/PHT. A slow decay corresponds to severe MS, wherein the LA pressure remains higher than LV pressure throughout diastole (no diastasis). However, for the same valve area, LA and LV pressures more readily equalize in case of poor LV compliance or severe AI that briskly increases LV diastolic pressure, which makes the decay look steeper and leads to overestimation of the mitral valve area (i.e., less severe). This is more commonly the case in elderly or severely hypertensive patients with MS.

Figure 32.50  Simultaneous LV pressure and PCWP recording is shown on the left, with a mean transmitral pressure gradient of 10 mmHg. The transmitral Doppler flow velocity is shown on the right. The peak velocity is > 2 m/s, which suggests MS (may also signify MR or severely restricted LV filling with hypervolemia). The mean pressure gradient obtained by tracing the Doppler envelope is ~11 mmHg at a rate of 70 bpm, suggesting severe MS. The valve area calculation using the pressure half‐time method, i.e., the steepness of deceleration of E velocity (gray line), yields a valve area of 2.6 cm2. In fact, E velocity falls steeply with a pressure half‐ time of 80 ms. However, the valve area is calculated invasively at 1.3 cm2. This discrepancy is expected in light of the patient’s severe systemic hypertension (180/100 mmHg) and increased LVEDP. When LV compliance is impaired, LV diastolic pressure increases steeply and therefore, for the same orifice area, LA–LV diastolic pressure gradient decrements faster. This leads to a faster pressure half‐time for the same orifice area and creates the false impression of a larger orifice area. The pressure half‐time method of orifice area calculation is inaccurate in cases of impaired LV compliance and high LVEDP. A similar limitation of the pressure half‐time is seen when MS is associated with AI.

632  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

PISA

LV

a LA

Figure 32.51  PISA of MS on a long‐axis view. PISA of MS consists of flow acceleration on the LA side of the mitral valve (≠ PISA of MR, which is on the LV side). On the LA side, the mitral leaflets form an acute angle (≠ obtuse angle on the LV side for MR); thus, PISA of MS is not usually a hemisphere but a cone with an angle (a) that corresponds to the angle formed by the mitral leaflets, and angle adjustment is applied during PISA calculation: MVA × peak diastolic velocity across the mitral valve = 2 π (PISA radius)2 × red aliasing velocity × a/180°

In the case of MS associated with concomitant MR or high‐output state, the early LA–LV gradient is increased, creating a steep early E flow decay; however, because of MS, the slope of the E flow decay in mid/late diastole is slow. MVA calculation by the pressure half‐time method remains accurate using this later slope. In atrial fibrillation, the pressure gradient varies between beats but the shape and the slope of the mitral Doppler envelope remain unchanged, and thus MVA calculation remains accurate. There are three other modalities for the calculation of MVA: a.  Continuity equation. The stroke volume across the LVOT is: (LVOT area × LVOT VTI). The stroke volume across the mitral valve is: (MVA × MV VTI). Therefore:

MVA

0.785 LVOT diameter2 LVOT VTI / MV VTI

This equation cannot be used in case of concomitant MR, where the flow across the LVOT is lower than the flow across the mitral valve, or AI, where the flow across the LVOT is higher than the flow across the mitral valve. b.  PISA of the mitral valve. As opposed to PISA of MR, which is seen on the LV side, a hemisphere of flow acceleration is seen on the LA side in MS. An adjusted PISA equation may be used (Figure 32.51). c.  Planimetry. Planimetry consists of tracing the restrictive orifice on the mitral valve short‐axis view (“fish mouth”). However, the image should be frozen at the actual leaflet tips, not more proximally where the valvular area would be overestimated. On the other hand, calcium or a high gain may blur the orifice boundaries and underestimate the valvular area. In summary, echocardiography assesses the transmitral gradient very accurately. However, the estimation of the valvular area using one of the four methods (mitral inflow pressure half‐time, continuity equation, PISA method, and planimetry) may be subject to measurement errors. A high gradient does not necessarily imply severe MS; mild MS with MVA > 1.5 cm2 may have a severe gradient in the presence of tachycardia or high‐output state. Invasive hemodynamics are, thus, valuable for the assessment of MS whenever there is discrepancy between echocardiographic MVA and transmitral gradient; and whenever it is not clear whether the patient’s symptoms or pulmonary hypertension are purely secondary to MS, or rather secondary to mild MS + high output state, MS + LV diastolic dysfunction, or intrinsic pulmonary arterial hypertension D.  Pitfalls in PHT use for AI assessment (Figure 32.52) A compensated or mildly decompensated chronic AI is characterized by a gradual LV diastolic pressure slope and an increase in LVEDP that remains much lower than the aortic pressure, e.g., LVEDP of 20 mmHg with a diastolic aortic pressure of 70 mmHg. On Doppler, this ­corresponds to a gradual drop of the regurgitant flow velocity with a PHT that is > 250 ms, even if AI is severe. Acute AI or decompensated chronic AI with LV failure is characterized by a steeply rising LV diastolic pressure and equilibration of LVEDP and aortic end‐diastolic ­pressure. On Doppler, this corresponds to a steep drop of regurgitant flow velocity with a short pressure half‐time 4 m/s Abnormal 100 ms 1 second), this corresponds to a small window of the cardiac cycle, during which the motion is limited. A dual‐source CT scans an area with only 90° of rotation, thus requiring ~80 ms only. This improves the temporal resolution. With retrospective gating, each slice is acquired multiple times at multiple phases of the cardiac cycle. Multiple gantry rotations (180 ms) and multiple acquisitions are performed over each slice, using the spiral CT technique. The table moves slowly, allowing images of the same area to overlap. The fact that each area is imaged at multiple points of the cardiac cycle allows a retrospective search for the cardiac phase during which the images have less artifacts. This reconstruction is called multiphasic retrospective gating. Sequential prospective gating images each slice at one cardiac phase only, and is more sensitive to rate irregularities between the different gantry rotations. This may be less of a problem with 256‐slice CT covering the whole heart in one rotation and one cycle. D.  CTA Artifacts • Irregular heart rate may cause misalignment of adjacent slices, because adjacent slices are at different phases of the cardiac cycle for the same R–R phase (e.g., 70% of R–R corresponds to a different cardiac phase during a different cardiac cycle). This is called step artifact. Fast heart rate may also cause it by increasing the number of cardiac cycles acquired during the ~10 seconds of imaging, and by increasing the relative importance of slight timing variations. Respiratory motions may also cause these malalignments. • Motion artifacts related to cardiac, coronary, or respiratory motion may occur during each cardiac cycle, leading to streaks and blurring artifacts. These artifacts are less likely to occur in the relatively quiet mid‐ to end‐diastolic phase (~60–80% of R–R interval), and at the end‐systolic phase when the coronaries are relatively stationary (~30% of R–R interval). These artifacts are increased in case of fast rate (less stationary time). Motion and step artifacts may be less pronounced at one R–R phase, hence the need to analyze the coronaries at multiple phases and the value of multiphasic reconstruction in this context. • Increased image noise (grainy appearance) in obese patients. This may be improved by increasing the tube voltage. • Partial volume effect or beam hardening is the artifact caused by an adjacent structure that has a high/bright CT attenuation (PM lead, coronary calcification). A high CT number will be assigned to the whole pixel, which will thus appear bright. This leads to overestimation of the dimension of coronary calcium. • Poor timing of contrast injection leading to inappropriate aortic and coronary filling (the left side appears less dense than the right side of the heart).

Chapter 33.  Stress Testing, Nuclear Imaging, CT Angiography  663

References 1. Bouzas‐Mosquera A, Peteiro J, Alvarez‐Garcia N, et al. Prognostic value of exercise echocardiography in patients with left bundle branch block. JACC Cardiovasc Imaging 2009; 2: 251–9. 29% of patients with LBBB have ischemia, translating into a double mortality, ~5% per year. 2. Christman MP, Bittencourt MS, Hulten E, et al. Yield of downstream tests after exercise treadmill testing. J Am Coll Cardiol 2014; 63: 1264–74. 3. Barlow JB. The “false positive” exercise electrocardiogram: value of time course patterns in assessment of depressed ST segments and inverted T waves. Am Heart J 1985; 110: 1328–36. 4. Lachterman B, Lehmann KG, Abrahamson D, Froelicher VF. ‘Recovery only’ ST‐segment depression and the predictive accuracy of the exercise test. Ann Intern Med 1990; 112: 11–16. 5. Lauer MS, Francis GS, Okin PM, et al. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA 1999; 281: 524–9. 6. Shaw LJ, Peterson ED, Shaw LK, et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation 1998; 98: 1622–30.

Low‐risk DTS/exercise test 7. Hachamovitch R, Berman DS, Kiat H, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification. Circulation 1996; 93: 905–14. 8. Poornima IG, Miller TD, Christian TF, et al. Utility of myocardial perfusion imaging in patients with low‐risk treadmill scores. J Am Coll Cardiol 2004; 43: 194–9. 9. Bouzas‐Mosquera A, Peteiro J, Álvarez‐García N. Prediction of mortality and major cardiac events by exercise echocardiography in patients with normal exercise electrocardiographic testing. J Am Coll Cardiol 2009; 53: 1981–90. 10. Bourque JM, Holland BH, Watson DA, Beller GA. Achieving an exercise workload of ≥10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol 2009; 54: 538–45.

ST changes in women 11. Barolsky SM, Gilbert CA, Faruqui A, et al. Differences in electrocardiographic response to exercise of women and men: a non‐Bayesian factor. Circulation 1979; 60: 1021–7. 12. Gulati M, Pandey DK, Arnsdorf MF, et al. Exercise capacity and the risk of death in women: the St James Women Take Heart Project. Circulation 2003; 108: 1554–9. 13. Mora S, Redberg RF, Cui Y, et al. Ability of exercise testing to predict cardiovascular and all‐cause death in asymptomatic women: a 20‐year follow‐up of the Lipid Research Clinics Prevalence Study. JAMA 2003; 290: 1600–7. 14. Kohli P, Gulati M. Exercise stress testing in women. Circulation 2010; 122: 2570–80.

Strongly positive stress ECG 15. Krishnan R, Lu J, Dae M, et al. Does myocardial perfusion scintigraphy demonstrate clinical usefulness in patients with markedly positive exercise tests? An assessment of the method in a high‐risk subset. Am Heart J 1994; 127: 804–16. 16. Shalet BD, Kegel JG, Heo J, et al. Prognostic implications of normal exercise SPECT imaging in patients with markedly positive exercise electrocardiograms. Am J Cardiol 1993; 72: 1201–3. 17. Kobal SL, Wilkof‐Segev R, Patchett MS, et al. Prognostic value of myocardial ischemic electrocardiographic response in patients with normal stress echocardiographic study. Am J Cardiol 2014; 113: 945–9. 18. Hachamovitch R, Hayes S, Friedman JD, et al. Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans. What is the warranty period of a normal scan? J Am Coll Cardiol 2003; 41:1329–40. 19. Geleijnse ML, Vigna C, Kasprzak JD, et al. Usefulness and limitations of dobutamine–atropine stress echocardiography for the diagnosis of coronary artery disease in patients with left bundle branch block: a multicentre study. Eur Heart J 2000; 21: 1666–73.

Nuclear myocardial perfusion imaging in multivessel disease: 20. Lima RSL, Watson DD, Goode AR, et al. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three vessel coronary artery disease. J Am Coll Cardiol 2003; 42: 64–70. 21. Melikian N, De Bondt P, Tonino O, et al. Fractional flow reserve and myocardial perfusion imaging in patients with angiographic multivessel coronary artery disease. JACC Cardiovasc Interv 2010; 3: 307–14.

TID 22. Mazzanti M, Germano G, Kiat H, et al. Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual‐isotope myocardial perfusion SPECT. J Am Coll Cardiol 1996; 27: 1612–20. 23. Heston TF, Sigg DM. Quantifying transient ischemic dilation using gated SPECT. J Nucl Med 2005; 46: 1990–6. By gated SPECT, TID is best assessed as (EDV + 5 × ESV) stress/(EDV + 5 × ESV) rest.

Fixed defects 24. Liu P, Kiess MC. Okada RD, et al. The persistent defect on exercise thallium imaging and its fate after myocardial revascularization: Does it represent scar or ischemia? Am Heart J 1985; 110: 996–1001. 25. Gibson RS, Watson DD, Craddock GB, et al. Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium‐201 scintigraphy and coronary angiography. Circulation 1983; 68: 321–36. 26. Brown KA. Prognostic value of Thallium 201 myocardial perfusion imaging A diagnostic tool comes of age. Circulation 1991; 83: 363–81. 27. Bodenheimer MM, Wackers FJT, Schwartz RG, et al. Prognostic significance of a fixed thallium defect one to six months after onset of acute myocardial infarction or unstable angina. Multicenter Myocardial Ischemia Research Group. Am J Cardiol 1994; 74: 1196–2000.

Attenuation artifacts 28. Hendel RC, Gibbons RJ, Bateman TM. Use of rotating (cine) planar projection images in the interpretation of a tomographic myocardial perfusion study. J Nucl Cardiol 1999; 6: 234–40.

664  Part 10.  Cardiac Tests: ECG, Echocardiography, Stress Testing

CT 29. Litt HI, Gatsonis C, Snyder B, et al. CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med 2012; 366: 1393–403. 30. Graham M, Cook JA, Hillis GS, et al. 64‐slice computed tomography angiography in the diagnosis and assessment of coronary artery disease : systematic review and meta‐analysis. Heart 2008; 94: 1386–93. 31. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015; 372: 1291–300. PROMISE trial. 32. Henneman MM, Schuijf JD, Pundziute G, et al. Noninvasive evaluation with multislice computed tomography in suspected acute coronary syndrome: plaque morphology on multislice computed tomography versus coronary calcium score. J Am Coll Cardiol 2008; 52: 216–22. 33. Detrano R, Guerci AD, Carr JJ, et  al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008; 358:1336–45.

Further reading Gibbons R, Chatterjee K, Daley J, et al. ACC/AHA/ACP‐ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 1999; 33: 2092–197. Tavel M. Stress test. In: Surawicz B, Knilans T. Chou’s Electrocardiography in Clinical Practice, 5th edn. Philadelphia, PA: Saunders, 2001, pp. 208–38. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with ischemic heart disease. J Am Coll Cardiol 2012; 60: e44–164.

Part 11  CARDIAC TESTS: INVASIVE CORONARY AND CARDIAC PROCEDURES 34  A  ngiographic Views: Coronary Arteries and Grafts, Left Ventricle, Aorta, Coronary Anomalies, Peripheral Arteries, Carotid Arteries

I. Right coronary artery  665 II. Left coronary artery  666 III. Coronary angiography views. Recognize the angle of a view: LAO vs. RAO, cranial vs. caudal  667 IV. Coronary angiography views. General ideas: cranial vs. caudal views  667 V. Coronary angiography views. General ideas: foreshortening and identifying branches  670 VI. Left coronary views  670 VII. Right coronary views  679 VIII. Improve the angiographic view in case of vessel overlap or foreshortening: effects of changing the angulation, effects of respiration, and vertical vs. horizontal heart  681 IX. Saphenous venous graft views  682 X. LIMA‐to‐LAD or LIMA‐to‐diagonal views  684 XI. Left ventriculography  685 XII. Aortography for assessment of aortic insufficiency  688 XIII. Coronary anomalies  688 XIV. Lower extremity angiography  691 XV. Carotid angiography  696 Questions and answers  697

I.  Right coronary artery A. Course The right coronary artery (RCA) courses over the right AV groove, turns around and continues over the posterior AV groove, then reaches the intersection of the AV groove and the posterior interventricular groove (designated the crux), where it gives the PDA and PLB branches. B.  Branches (proximally to distally) (Figure 34.1) 1.  Conus branch (CB) is the first RCA branch. It supplies the RVOT and has a separate ostium in 50% of individuals. 2.  Sinus node branch (SN) originates from the RCA in 60% of individuals and from the LCx in 40%. 3.  Acute marginal branches (AM) supply the RV (1–3 branches). 4.  Posterior descending artery (PDA) runs on the posterior interventricular groove and supplies inferior septal branches to the inferior 25–30% of the septum (known as “inferior wall”). PDA runs parallel to the LAD, which supplies the anterior 70–75% of the septum. 5.  Posterolateral branches (PLBs) originate from the posterior AV groove past the crux and supply the posterior wall. This part of the RCA gives rise to the AV nodal branch. C.  Segments of the RCA • Proximal RCA: RCA before the AM branches. • Mid‐RCA: RCA around the AM branches. • Distal RCA: RCA past the AM branches, including distal RCA at the level of the crux, PDA, and PLBs. Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

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SN CB AM

AM

AV branch

PLB1

Crux

PLB2

PLB3

PDA Figure 34.1  RCA course and branches. The intersection of the AV groove and the inferior septum is the crux.

LM Anterior Diagonal 1

LCx

OM Septals

OM

Diagonal 2

PLB

Lateral

OM

Diagonal 3

Inferior

LAD Apex

Septum

(b)

Crux

Posterior

LM LCx OM LAD

Diagonal

OM RI

Diagonal

(a) Figure 34.2  (a) Left coronary system on LAO cranial view. (b) LV walls on cross‐sectional view of the LV.

II.  Left coronary artery A.  Left main (LM) branches into the left anterior descending and left circumflex arteries B.  Left anterior descending artery (LAD) (see Figure 34.2) 1.  LAD courses over the anterior interventricular groove, then reaches and frequently (80%) wraps around the apex distally. LAD gives: (i) diagonal (Dg) branches, usually 1–3 large diagonal branches which supply the anterior and high lateral walls; and (ii) septal branches which supply the anterior septum, i.e., ~70–75% of the thickness of the septum. The inferior septum is supplied by the PDA, which runs parallel

Chapter 34.  Angiographic Views  667

to the LAD. Some patients have a dual LAD system, in which one trunk (frequently intramyocardial) gives all the septal branches and another trunk gives all the diagonal branches. 2.  Segments • Proximal LAD = LAD proximal to the first septal branch (which is often, but not always, proximal to the first diagonal branch) • Mid LAD = LAD around all the major diagonal branches • Distal LAD = LAD distal to the major diagonal branches C.  Left circumflex coronary artery (LCx) (see Figure 34.2) 1.  LCx courses over the left AV groove (like the RCA on the opposite side). It does not usually reach the crux, unless the left system is dominant. 2.  Branches a. One to several obtuse marginal (OM) branches supply the LV free lateral wall. b. One or more left PLBs arise from the left AV groove before the crux. These left PLBs are adjacent to the right PLBs. c. PDA branch may arise from the distal LCx at the crux level in a dominant or co‐dominant left system. D.  Ramus intermedius (RI) branch Sometimes, the left main (LM) trifurcates into LAD, RI, and LCx (instead of bifurcating into LAD and LCx). RI is, in a way, a very proximal diagonal or a very proximal OM, and supplies the anterolateral wall.

Dominance refers to which artery, RCA or LCx, gives the PDA (inferior wall) and the PLB branches (posterior wall). • RCA dominance (85% of the population): RCA gives both the PDA and the PLBs. LCx gives only the OM branches and may give some, but not all, PLBs. LCx does not reach the crux. • Left dominance (8% of the population): LCx gives both the PDA and the PLBs. In this case, RCA is small and does not reach the crux. • Co‐dominance (7% of the population): RCA gives the PDA while LCx gives all of the PLBs and sometimes a second, parallel PDA. At or near the crux, the dominant artery gives rise to the AV nodal branch. In ~25% of patients with RCA dominance, there are significant anatomic variations in the origin of the PDA: double PDA, early origin of the PDA proximal to the crux, or partial supply of the PDA territory by a low AM branch that wraps around the inferior RV wall and reaches the inferior septum (streaker branch). Also, the inferior wall may be partially supplied by a long wraparound LAD or by OM branches that wrap around the posterior wall.

In ACS, the unstable ruptured lesion is identified as: 1. Eccentric stenosis with irregular, overhanging borders 2. Contrast staining at the lesion site after it clears from the rest of the vessel 3. Round filling defect inside the lumen, with swirling around it The latter two features signify thrombus (Figure  34.3). Unlike angioscopy or OCT, coronary angiography allows thrombus visualization in only 50% of the cases. Lesion haziness may signify (Figure 34.3): 1. Ulcerated plaque, with contrast faintly seeping inside the ruptured intima 2. Eccentric stenosis unseen on the current view (in this case, an orthogonal view may show severe stenosis) 3. Heavy calcification

III.  Coronary angiography views. Recognize the angle of a view: LAO vs. RAO, cranial vs. caudal A.  Differentiate left anterior oblique (LAO) from right anterior oblique (RAO) views Look at the spine or the central catheter in the descending aorta, then see whether the tip of the catheter is at its left (LAO) or right (RAO). For example, in the LAO view, one “grabs” the catheter tip with the left hand while “grabbing” the central aortic catheter (or spine) with the right hand (Figure 34.4). If the catheter tip overlaps with the central catheter or the spine, it is an anteroposterior (AP) view or a shallow‐angled view. B.  Differentiate cranial from caudal views In cranial views, the dome of the diaphragm is seen over the heart shadow (Figure 34.5).

IV.  Coronary angiography views. General ideas: cranial vs. caudal views • Caudal views properly assess the distal LM bifurcation, proximal LAD, and the whole LCx. The mid and distal LAD segments are usually foreshortened and overlapped with the Dg branches. • Cranial views properly assess the mid and distal LAD, diagonal branches, and septal branches. Cranial views are usually good views for the ostial LM, but are often inadequate for the LM bifurcation area (distal LM and proximal LAD and LCx) (Figure 34.6).

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Smooth eccentric

Smooth concentric

Smooth stenoses (broad base, hourglass) Dye stain overhang

Eccentric irregular

Eccentric overhanging edges Thrombus: intraluminal filling defect OR dye stain

Eccentric unstable stenoses (narrow base)

(a)

(b)

(c)

(d)

Hazy lesions Figure 34.3  The top two rows show the difference in morphology between stable stenoses (usually smooth), unstable stenoses, and thrombus. The bottom row shows hazy lesions. A hazy lesion could be an eccentric stenosis with no angiographic view orthogonal to the narrow lumen (a and b, arrows are angiographic angles). The narrow lumen is white and falsely projects as a large lumen at all angles. A hazy lesion could also be (c) a ruptured plaque, or (d) a lesion surrounded by a concentric shell of calcium. It often implies severe or unstable stenosis.

LAD

LCx

Left

Diaphragm

Diaphragm

Figure 34.4  LAO view, cranial. Note the diaphragm overlapping with the heart shadow, and note the catheter tip at the left of the central aortic catheter/spine.

Chapter 34.  Angiographic Views  669

Diaphragm

Figure 34.5  Shallow RAO view, cranial. Note the diaphragm overlapping with the heart shadow and the catheter tip slightly to the right of the central catheter in the descending aorta (the catheter tip is grabbed with the right hand, while the central catheter is grabbed with the left hand). Also, if the ribs are looking down towards the right‐hand side of the operator, the view is RAO.

LCx

OM

LAD

Dg

LCx

Septal LAD

LM

RAO caudal

RAO cranial

Figure 34.6  Illustration of the difference between caudal and cranial views. Caudal views show well the LM bifurcation into the LAD and LCx, as well as the LCx. Cranial views pull the LCx up and do not properly show the LM bifurcation and the proximal LAD–LCx area, but show the areas outside it (mid and distal LAD and ostial LM). The circles indicate the areas that are not well seen in each view.

*Segment is laid out, fully expanded *Lesion is not missed

Projection

View in line with the segment Projection

View orthogonal to the segment

*Segment is collapsed = foreshortened *Lesion is missed

Figure 34.7  View orthogonal to a segment vs. view foreshortening a segment.

• In fact, on the caudal views, LCx is down, LAD is up; LAD and LCx are well separated, and their bifurcation off the LM is well visualized. On the cranial views, LCx moves up, along with the cranial angulation, and overlaps with the proximal LAD ± first diagonals; in addition to the overlap, the distal LM bifurcation and the proximal LAD are foreshortened. Yet, in patients with a vertical heart or a long LM, the caudal views may not open up the LM bifurcation properly; the cranial views may prove better for this purpose, particularly upon deep inspiration, which makes the heart even more vertical.

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V.  Coronary angiography views. General ideas: foreshortening and identifying branches A. Foreshortening A coronary segment is best assessed by a view orthogonal to it, i.e., a view that lays it out and fully expands it. Foreshortening implies looking at a coronary segment in line with its path, which, in two‐dimensional imaging, condenses this segment and hides a stenosis by the contrast filling proximal and distal to it (Figure 34.7). B.  Arteries running on the border of the heart shadow On any standard view, arteries that run on the border of the heart shadow, or are directed towards that border or touch it are usually diagonal or OM branches (depending on the view), not LAD.

VI.  Left coronary views (see Figure 34.8) A.  RAO caudal (25° RAO, 25° caudal) This is the best overall view and the best LCx view (Figures 34.9–34.12). In addition, it allows good assessment of the distal LM and the proximal LAD. The mid LAD is not well seen on this view as it is often foreshortened and overlapped with Dg branches that run above it and underneath it. The very distal apical LAD is usually well seen. If the ostial LCx overlaps with the distal LM, going more caudal will better separate the ostial LCx and the distal LM. The RAO caudal view may be confusing when the LAD is totally occluded, in which case a large diagonal may simulate the LAD; a diagonal aims toward the heart border, whereas the LAD remains within the center of the heart shadow (Figure 34.13). In this instance, the cranial views further define whether the artery in question is LAD or Dg. In patients with a tortuous or sharply angulated LCx, this view may foreshorten the proximal LCx, the proximal tortuosity, and even a proximal stenosis. This is reduced by deep inspiration (elongates the LCx). Also, AP caudal or LAO caudal complements this limitation of RAO caudal by showing the ostial/proximal angulation and tortuosity. The AP caudal view often gives similar information to the RAO caudal view (Figure 34.14). LCx moves in the same direction as the image intensifier, while LAD moves in an opposite direction. When LM and proximal LCx are overlapped on RAO caudal view, going more caudal pulls LCx further down and LAD up, opening up the LM bifurcation. AP cranial

RAO cranial LAO cranial

LCx RCA

LAD RAO caudal LAO caudal LM

Figure 34.8  Heart in an anteroposterior view. Imagine how you look at the coronary arteries from various angles.

Dg

LAD LCx Dg OM

OM

Figure 34.9  RAO caudal view (25°, 25°).

Dg

Bifurcation area well seen

Too much LAD/Dg overlap in this area + LAD foreshortened

LAD foreshortening Dg

Dg

Figure 34.10  RAO caudal view. Distal LM bifurcation area is well seen; if not, the view may be angled more caudally to pull the LCx down. The mid‐LAD is foreshortened and overlapped with diagonal branches. The foreshortened area looks more dense, as it is “squashed.” The proximal LCx has a foreshortened area: this may be improved by imaging in deep inspiration, which straightens tortuosities.

LAD

Overlap of LAD-Dg Overlap of LAD-Dg Foreshortened LAD

Dg

Figure 34.11  RAO caudal view. The ribs are looking down towards the right‐hand side of the operator (RAO view) and the diaphragm is not seen (caudal view). Note how this view is good for the distal LM bifurcation, and how the mid‐LAD overlaps with the diagonals and has some bends looking towards the X‐ray detector (foreshortening).

LAD

Dg Dg Dg LAD

Figure 34.12  RAO caudal view in a patient with a vertical heart. Note that, in this particular case, even the LM bifurcation is not well opened. The distal LM, ostial LCx, and ostial LAD are overlapped (left arrow). This bifurcation may be opened by going more caudal; since the LCx follows the image intensifier, going more caudal pulls the LCx down and the LAD up, which opens up the bifurcation. In addition, the first diagonal is overlapped with the proximal/mid LAD (right arrow), which is expected in RAO caudal view.

672  Part 11.  Cardiac Tests: Invasive Procedures

LCx looping in the AV groove

Septal

Large Dg

(a) LAD occluded

(b) Figure 34.13  (a) RAO caudal with a large diagonal and a totally occluded LAD. The arrow points to a diagonal branch that simulates the LAD. The fact that it goes out towards the heart border implies that it is a diagonal branch rather than LAD, the LAD being totally occluded. (b) LAO cranial of the same patient. LAO cranial shows the Dg going to the side, towards the heart border. No LAD is seen in the center of the heart shadow; the LAD is occluded past the diagonal and septal branches. Of note, the LAD usually runs parallel to the spine on this view (dashed arrow). This view confirms that the LAD is occluded when the RAO caudal view is suspicious. LAD overlapped with Dg and foreshortened Dg

Foreshortened mid-LAD

Ramus

LAD

LCx

Ramus

LAD

Figure 34.14  AP caudal view. Similarly to RAO caudal view, the AP caudal view shows the distal LM and the proximal LAD and LCx. The LM trifurcation is well visualized here. Note the foreshortening of the mid‐LAD, wherein a large mid‐LAD loop is looking towards the detector. The ramus reaches out towards the heart border, while the LAD remains inside the heart shadow.

B.  LAO caudal (40° LAO, 30° caudal) This view allows a good assessment of the LM, proximal LAD, proximal LCx, and proximal branches (Figure 34.15). To obtain a good LAO caudal view, angle the image intensifier so that the tip of the catheter is positioned in the center of the cardiac silhouette. If it is not in the center of the cardiac silhouette, move the image intensifier more caudal or less LAO to obtain a good LAO caudal view, or instruct the patient to hold his breath in end-expiration, which makes the heart more horizontal. This view looks at the heart from below and is best in patients with a horizontal heart, where the image intensifier can be almost perpendicular to the heart. This view may not properly open the LM bifurcation in patients with a vertical heart, and may be suboptimal in obese patients with a lot of soft tissue attenuation (may skip this view in those cases and rather obtain an AP caudal view). On the other hand, in patients with a vertical heart or a long LM, cranial views may allow better delineation of the distal LM and proximal and early mid‐LAD than caudal views (Figures 34.16, 34.17, 34.18).

Chapter 34.  Angiographic Views  673

Dg LAD

Dg

OM LM OM LCx Figure 34.15  LAO caudal view (40°, 30°). Catheter tip is at the center of heart shadow. LM is at the center, LAD is up, and LCx is down. OM and Dg are in the sector between LAD and LCx.

LAD Dg

LCx

Figure 34.16  LAO caudal view of a vertical heart. The catheter tip (star) is not in the center of the heart shadow (delineated by the blue line); hence, the distal LM bifurcation is not properly opened. The view needs to be angled more caudally or less LAO to center the catheter tip, or the view needs to be taken in deep expiration to make the heart horizontal. LAO caudal is difficult to optimize in patients with a vertical heart.

Figure 34.17  LAO caudal view of a horizontal heart. Note that the catheter tip is at the center of the cardiac silhouette, and the delineation of the LM bifurcation is excellent. 1, LAD; 2, LCx; 3, diagonal; 4, OM; x, LCx stenosis.

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AP cranial: is orthogonal to the whole LAD, including proximally LAO cranial: is orthogonal to the whole LAD, including proximally

LAO cranial

LCx

LAD RAO caudal: overlap of LM and proximal segments

LAO caudal: is orthogonal to the distal LM

LAO caudal: is coaxial with LM and proximal segments foreshortening and overlap of proximal segments (a)

Vertical heart

(b)

Horizontal heart

Figure 34.18  (a) Vertical heart. LAO caudal is not orthogonal to the LM bifurcation and does not “see” it well. Cranial views, on the other hand, are orthogonal to the LM bifurcation and may allow good visualization of the distal LM/proximal LAD. (b) Horizontal heart. LAO cranial view is suboptimal with overlap and foreshortening of the proximal and mid LAD/LCx/Dg. LAO caudal view, on the other hand, is optimal and opens the bifurcation well. Deep inspiration makes the heart more vertical and may optimize the LAO cranial view, particularly the LM bifurcation, while imaging at end‐expiration provides a better LAO caudal view.

C.  AP cranial or shallow RAO cranial (5° RAO, 35° cranial) This view allows good assessment of the mid and distal LAD, as well as the diagonal and septal branches that originate from the mid and distal LAD and their points of bifurcation from the LAD. The distal LM, proximal LAD, proximal LCx, and the proximal branches are overlapped together and not well delineated (Figures 34.19, 34.20). Disease in the proximal portion of the LAD, LCx, ramus, or Dg may look like distal LM disease. Away from the LM bifurcation, the ostial LM is often well seen, as in all cranial views. Sometimes, however, in patients with a vertical heart or a long LM, the distal LM bifurcation is well seen, especially with deep inspiration.

LCx LM OM Septal Dg

Continuation of a dominant LCx

LAD

Figure 34.19  Shallow RAO cranial view (5°, 35°).

Chapter 34.  Angiographic Views  675

OM

LCx

Ramus LCx

OM LAD

left PLBs

Figure 34.20  Shallow RAO cranial view. Note the overlap of the distal LM, proximal LAD, proximal LCx, and proximal ramus (circled area). When LCx is dominant, the distal LCx and distal OMs (left PLB branches) may be well seen on cranial views, including this view, but more so on the LAO cranial view.

D.  LAO cranial (40° LAO, 30° cranial) This view allows a good assessment of the mid and distal LAD, as well as the diagonal and septal branches that originate from the mid and distal LAD. The distal LM, proximal LAD, and proximal LCx are overlapped and foreshortened. The LCx is not well seen because of its overlap with the OM branches, but the mid/distal segments of the OM branches may be well seen as they run over the heart border (Figures 34.21–34.24). Similarly to the AP cranial view, the distal LM bifurcation may be well seen without foreshortening in patients with a vertical heart or long LM, particularly with deep inspiration.

LM LCx OM Septal Dg

OM

Dg Continuation of a dominant LCx

Left PDA

LAD Figure 34.21  LAO cranial view (40°, 30°). The LCx and OMs run on the border of the heart shadow in this view, whereas the LAD runs over the center of the heart shadow, parallel to the spine. The diagonal and OM branches are in the sector between the LAD and LCx.

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LCx Cannot rule out distal LM disease or ostial LAD/LCx disease (overlap and foreshortening)

Mid-LCx looping OM

LAD PLBs

Figure 34.22  LAO cranial view. Note the overlap at the level of the distal LM.

Dg or high OM

Dominant LCx

PDA PLBs

Figure 34.23  LAO cranial view showing a dominant LCx. The distal PLBs and PDA are well seen on this view. This view is the best view for the distal, dominant LCx.

LCx

Inspiration LAD

Dg and OMs

Figure 34.24  LAO cranial view. If there is too much overlap in the proximal area (left‐sided images), move the view more cranially, as this will bring the LCx up and the LAD down. Alternatively, one may image in end‐inspiration (right‐sided images), which makes the heart more vertical and relieves the proximal overlap. Cranial views are usually best in patients with a vertical heart.

Chapter 34.  Angiographic Views  677

This is also the best view to determine whether the LCx is a dominant LCx (Figure 34.23). In such a case, the LCx is seen looping all the way down the AV groove until the crux and giving a left PDA which runs parallel to the LAD. Thus, the LAO cranial view allows a good assessment of the distal, dominant LCx as well as the left PDA, the same way it allows a good assessment of the distal RCA and right PDA. This view is also the view that best differentiates a large Dg branch from the LAD in the case of a totally occluded LAD. Two features distinguish the LAD from an enlarged diagonal: 1.  The diagonal loops to the left and reaches toward the border of the heart shadow, whereas the LAD runs parallel to the spine and loops at the apex (Figures 34.25, 34.26). Occasionally, in an enlarged LV, the apex is moved to the left and thus the LAD course may simulate a diagonal course. 2.  The LAD always gives septal branches, straight parallel branches which buckle very little in systole. In contrast, the diagonal does not give any septal branch and buckles in systole. Shallow RAO cranial may also help define a dominant LCx, and may help in the LAD/diagonal differentiation when the LAD is totally occluded.

LAD with Dg?

LCx

Figure 34.25  RAO caudal view. One gets the impression that the LAD is patent and is seen along with large diagonal branches. See Figure 34.26.

Septal (does not torque in systole)

LAD should be here, parallel to the spine. LAD is not seen here because it is occluded

OMs

Diagonal (torques in systole)

OM or Ramus

Figure 34.26  LAO cranial view of the patient from Figure 34.25. What seems like LAD on the RAO caudal view is actually a ramus or a high OM. On Figure 34.25, the outmost branch indicated by the arrow is a diagonal branch (which runs on the heart border of an RAO caudal view), while the other two branches, including the large branch that mimics LAD, are OM branches.

678  Part 11.  Cardiac Tests: Invasive Procedures

E.  RAO cranial (30° RAO, 30° cranial) Similarly to other cranial views, this view allows good assessment of the mid and distal LAD and the diagonal branches originating from the mid and distal LAD, as well as the ostial LM (Figures 34.27, 34.28).

LCx

OM

Dg

Septal

LM

Continuation of a dominant LCx LAD Figure 34.27  RAO cranial view (30°, 30°).

First OM

First diagonal Second diagonal

LAD

LCx and distal OMs

Figure 34.28  RAO cranial view. The circled area is the area where the distal LM, proximal LAD, first diagonal, and first OM overlap.

F.  Other views: 90° left lateral, LAO straight, RAO straight The 90° left lateral view is appropriate for the assessment of the very proximal and the distal LAD. It is usually inadequate for the assessment of the mid‐LAD, because of LAD–diagonal overlap at the mid‐LAD level. It is particularly useful when other views do not adequately display the ostial/proximal LAD and may be the only view that shows the ostial LAD. RAO straight resembles RAO caudal, and LAO straight resembles LAO cranial, with more overlap. Straight views are particularly useful during interventions in obese patients. They reduce the blurriness induced by soft tissue (caudal views) or the diaphragm (cranial views). G.  Views useful for left main assessment In general, both cranial and caudal views are useful to assess the ostial LM. Also, the straight AP or shallow RAO view (5°) and the straight LAO view (30°) are often excellent additional views for ostial LM assessment. Collimation with magnification over the LM is also helpful. The distal LM is best assessed in the caudal views. H.  A minimum of two views is required for left coronary assessment The RAO caudal view and one cranial view may be performed. The former allows the assessment of LM, LCx, and proximal and apical LAD; the latter allows the assessment of the mid and distal LAD and diagonal branches.

Chapter 34.  Angiographic Views  679

VII.  Right coronary views A.  LAO straight This is an en‐face view of the AV groove. It allows good assessment of the proximal and mid RCA. The distal RCA, PDA, and PLBs are all overlapped (Figures 34.29, 34.30). B.  LAO cranial (30° LAO, 15° cranial) This is the best RCA view. It shows the proximal and mid RCA, but also opens up the distal RCA bifurcation (Figures 34.29, 34.30). Cranial views are important for the assessment of the distal RCA bifurcation, and one should obtain at least an LAO ­cranial or AP cranial view. C.  AP cranial (30° cranial) This view allows the best assessment of the distal RCA bifurcation and serves as an adjunctive view when LAO cranial does not open up the bifurcation well. This view foreshortens the mid‐ RCA, and thus is not appropriate for mid‐RCA assessment (Figure 34.31).

On the LAO straight, LAO cranial, and AP cranial views, the true RCA course has two bends (Figure 34.32). The lack of those bends signifies that the artery seen is actually a large AM branch rather than the main RCA continuing into the PDA. In this case, the main RCA is either non‐dominant or occluded and does not provide a PDA. Moreover, in some anatomical variants, one large AM branch loops down to the inferior septum and provides a distal PDA. This AM branch is called the streaker branch; it has no bend, and should not be confused with the true RCA (Figures 34.33, 34.34).

LAO straight: PDA and PL branches are overlapped, especially at their bifurcation points

AM

PDA/PLBs

LAO cranial: opens up the bifurcation points AM PLB2 Mid-RCA a bit foreshortened

PDA

PLB1

PLB3

Figure 34.29  RCA views: LAO straight vs. LAO cranial. LAO cranial opens the distal RCA bifurcation.

LAO straight Figure 34.30  Note how the LAO cranial opens the distal RCA branches (arrows).

LAO cranial

680  Part 11.  Cardiac Tests: Invasive Procedures

Excellent view for distal bifurcation points

Mid RCA significantly foreshortened

PDA

PLB1

PLB2

Figure 34.31  AP cranial view. Note how the distal RCA is well laid out.

Figure 34.32  The true RCA has two distal bends on the LAO and AP cranial views (arrows). This is an AP cranial view.

Atrial branches

True RCA Conus

AMs True RCA AM (a)

(b)

Figure 34.33  (a) LAO cranial view. It may seem that the RCA continues down and gives the PDA. In reality, the RCA finishes early in the AV groove (true RCA being the posterior‐most straight branch). The branch continuing down is actually an AM branch. The lack of any bend is the clue to this interpretation. The patient either has a non‐dominant RCA or an occluded mid‐RCA. RAO view would confirm this interpretation. In this case, the RCA is non‐dominant. (b) RAO straight view from the same patient. The main RCA is posterior, in the AV groove. This view separates the AM branches, which go to the right, from the atrial branches, which go to the left.

Chapter 34.  Angiographic Views  681

AV continuation of RCA True PDA PLBs True PDA Streaker AM branch (a)

(b)

Distal PDA provided by the streaker branch

Figure 34.34  (a) LAO cranial view of the RCA. Try to identify the true RCA, PDA, and PL branches. (b) Same LAO cranial view with annotations. The true RCA makes a bend (double arrow). The branch that does not make a bend is actually a distal AM branch that loops down to the inferior septum and provides a distal PDA; this AM branch is called the streaker branch.

D.  RAO straight (30° RAO) This view looks at the AV groove from the side, and thus directly looks at the mid‐RCA running in the AV groove, allowing excellent assessment of the mid‐RCA. The proximal RCA is foreshortened (“looking toward us”), the distal RCA is foreshortened, and the distal RCA branches (PDA, PL) are overlapped as they run towards the apex (Figure 34.35). This view has two additional uses: (1) if, on the LAO view, there is a question whether the artery seen is the true RCA ending into a PDA vs. a large AM branch in a patient with occluded or non‐dominant RCA, the RAO view will delineate the true RCA in the AV groove. The true RCA will keep looping down towards the crux, as opposed to an AM branch, which will run to the right (Figures 34.33, 34.34); (2) during coronary interventions, this view indicates whether the guide is coaxial with the ostium (“looking toward us”) and facilitates wiring of the true RCA instead of AM branches.

Atrial branches

Proximal RCA foreshortened

RCA AMs RAO

Distal RCA foreshortened, branches are overlapped Figure 34.35  RAO straight (30°) looks at the AV groove from the side rather than en face, and shows the mid‐RCA. It separates the ventricle from the atrium. AM branches go towards the ventricular side, while atrial branches go towards the atrial side.

E.  Routine RCA views In routine cases, image the RCA in two views: LAO cranial and RCA straight. Alternatively, one may obtain LAO straight and AP cranial views. Take at least one cranial view, sometimes two, to define distal bifurcation disease. If the ostial RCA needs to be further assessed, two views are particularly useful: steep LAO view (50–60°) and LAO caudal view. These views are also useful during stent positioning in the ostial RCA.

VIII.  Improve the angiographic view in case of vessel overlap or foreshortening: effects of changing the angulation, effects of respiration, and vertical vs. horizontal heart A.  LCx moves with the image intensifier In case of overlap of branches that need to be set apart, remember that the LCx moves in the same direction as the image intensifier, whereas the LAD, Dg, catheter tip, and sternal wires move in the opposite direction. For example, if the image intensifier moves to a steeper LAO angle, LCx will move to the left and the catheter tip will move to the right.

682  Part 11.  Cardiac Tests: Invasive Procedures

Examples: • On LAO cranial view: ○○ Steeper LAO allows more LAD–LCx separation. ○○ Steeper cranial allows more LAD–LCx and diagonal–LCx separation (similar to deep inspiration, Figure 34.24). • On RAO cranial view: ○○ If the LCx overlaps with the LAD and is a bit above the LAD, move the image intensifier more cranial or take the picture during deep inspiration to lift the LCx further above the LAD; or move leftward to AP cranial view to move the LCx a bit more leftward. ○○ If the LCx (or OM) overlaps with the LAD and is a bit below the LAD, go less cranial. ○○ If the first diagonals overlap with the LAD and are a bit above the LAD, go more cranial. Moving to AP cranial also helps. B.  Effects of respiration Expiration makes the heart horizontal, thus improving the vessel separation on the LAO caudal view but worsening the vessel overlap on the LAO cranial and RAO cranial views, i.e., the overlap of LAD, Dg, and proximal LCx/proximal OMs. Deep inspiration makes the heart more vertical. On a cranial view, if the LCx is overlapped with the LAD or is slightly above it, deep inspiration will push the LCx further up and the diaphragm down, allowing better exposure of the LAD (Figure 34.24). On a caudal view, if the LCx is overlapped with the LAD, deep inspiration will worsen the proximal LAD/LCx overlap. In addition, deep inspiration elongates the heart and thus straightens tortuosities, allowing better visualization of tortuous segments. C.  Vertical vs. horizontal heart In the case of a vertical heart, LAO caudal is not orthogonal to the LM bifurcation and does not “see” it well. Cranial views, on the other hand, are orthogonal to the LAD and LCx planes and may allow good visualization of the distal LM and proximal LAD (Figure 34.18).

IX.  Saphenous venous graft views For the angiographic assessment of SVGs, obtain at least two views: 1.  One straight oblique view, typically the view used to engage the graft (RAO for a left graft and LAO for a right graft). This view is useful to assess the ostium and body of the graft. 2.  One angled view for the assessment of the graft anastomosis and the native vessel. For example (Figures 34.36–34.39): a. RAO caudal or AP caudal view for an OM graft b. RAO cranial, AP cranial, or LAO cranial view for a Dg or LAD graft c. LAO cranial ± AP cranial for an RCA graft (Figure 34.36). If one view does not allow proper assessment of the anastomosis, obtain the second listed view. In addition, similarly to the LIMA‐to‐LAD, a left lateral view may be used to assess the anastomosis of the SVG‐to‐LAD graft. In many cases, it is difficult to define whether the native branch is an OM or a Dg branch, especially when the native branch is a proximal OM or Dg. The LAO cranial (or straight) often proves helpful: in this view, OM branches run on the border of the cardiac ­silhouette, whereas Dg branches run over the heart shadow (Figure  34.37). RAO caudal and LAO caudal may prove useful as well (Figure 34.38). The comparison of the graft angiogram and the native vessel angiogram obtained in the same view also allows the identification of the grafted branch. In addition, there are cases where one needs to identify which OM is grafted or if the grafted OM is the same OM visualized on the native angiogram (as opposed to an OM that is totally occluded and not visualized on the native angiogram). Again, comparing the graft angiogram and native vessel angiogram obtained in the same view and referencing vessels to the sternal wires will prove useful.

Native RCA Diaphragm

SVG-RCA anastomosis Figure 34.36  AP cranial view properly showing the SVG‐to‐RCA anastomosis and the native RCA.

Figure 34.37  On this LAO cranial view, the grafted artery is at the left rather than right heart shadow  → left coronary branch. It is running at the border of the heart, which, on LAO cranial view, implies OM branch rather than Dg.

OMs

Figure 34.38  AP caudal view showing sequential SVG to OM2 and OM3. In this view, diagonal branches would be on top, running on the border of the heart shadow.

Dg directed to the border of the heart Diaphragm Figure 34.39  RAO cranial view (diaphragm is seen over the heart shadow, ribs are looking down towards the right). Is this SVG connected to a Dg, LAD, or OM? The anastomosed artery is not running at the border of the cardiac silhouette and is going to the apex. Thus, SVG is connected to the LAD and retrogradely fills a diagonal.

LAD in the center of the cardiac silhouette

684  Part 11.  Cardiac Tests: Invasive Procedures

In order to identify the original target of a totally occluded SVG, see which view is orthogonal to the ostium/stump. If the LAO view is orthogonal to the ostium, it is a right‐sided graft; if the RAO view is orthogonal to it, it is a left‐sided graft (Figure 34.40). If  multiple SVGs are occluded, confirm that you are engaging different ones by referencing to the sternal wires in a straight view (RAO or LAO). Some grafts connect to two or more distal targets (Figure 34.41). A sequential graft (or jump graft) connects to one branch, e.g., OM1, in a side‐to‐side anastomosis, then continues and connects to another branch, e.g., OM2, in an end‐to‐side anastomosis. A split graft (or Y graft) consists of two grafts, A and B, with a common stem: graft A connects to one branch, e.g. OM1, and graft B comes off graft A and separately connects to another branch, e.g., diagonal. Sequential and jump grafts reduce the number of aortic anastomoses and may, in selective cases, have a lower likelihood of failure as a result of the higher flow across the graft.

(a)

(b)

Figure 34.40  (a) SVG to RCA on LAO view (catheter at the left of the spine). In this case, the surgeon had placed rings around the venous grafts’ origins to allow identification during angiography. (b) SVG to a left coronary branch on RAO view (catheter tip at the right of the spine, ribs are looking down towards the right).

Graft B

Graft

Diagonal A OM1

OM2

Sequential part of the graft

Sequential graft

OM

Split graft (or Y graft)

Figure 34.41  Sequential and split grafts (RAO caudal view). Graft anastomoses are circled.

X.  LIMA‐to‐LAD or LIMA‐to‐diagonal views Three views should be obtained in case of LIMA graft: • The LIMA ostium and body are assessed in a straight view, typically the view used to engage the LIMA (e.g., RAO straight or AP view). • The native LAD is assessed in a view that is good for the LAD, such as AP cranial or LAO cranial view. • The LIMA‐to‐LAD anastomosis may be well seen on the cranial views. However, it is best assessed on a 90° lateral view, a view that is routinely obtained in all LIMA cases (Figure 34.42). Furthermore, when redo CABG or heart surgery is contemplated in a patient with a previously placed LIMA graft, the left lateral view is very important in planning surgery as it shows how close the LIMA is to the sternum. In addition, a straight AP view will be useful to assess how far the LIMA is from the midline.

Chapter 34.  Angiographic Views  685

LIMA-LAD anastomosis on lateral view

Figure 34.42  Left lateral view showing the LIMA‐to‐LAD anastomosis.

XI.  Left ventriculography A.  RAO, LAO, and LAO cranial views The RAO view allows the assessment of the anterior, apical and inferior walls, whereas the LAO view allows the visualization of the septal, posterolateral, and apical walls (Figure 34.43). The LAO cranial view is preferred to the straight LAO view; in fact, the straight LAO view foreshortens the lateral wall and septal wall and overlaps the septal wall with the anterior wall, whereas the LAO cranial, by being orthogonal rather than aligned with the heart, opens up the septal and lateral walls, as well as the base (LVOT) and the LA (Figures 34.44, 34.45, 34.46). The standard views are RAO (30°), LAO (40–60°), and LAO cranial (40–60° LAO, 20–25° cranial). The standard injection is 7–8 ml/s for a total of 20–24 ml (an enlarged LV may require a larger volume). The pigtail catheter should be positioned in the mid‐cavity, midway between the base and the apex, and should be free‐moving. A position too close to the apex induces ventricular ectopy, while a position too close to the LVOT/aorta does not fill the LV appropriately. A position too close to the base/mitral valve, particularly when the catheter feels “stuck” and not freely moving, often implies catheter impingement somewhere in the mitral apparatus (e.g. chordae). This may induce and overestimate mitral regurgitation; it may also lead to myocardial stain wherein the whole volume is injected over the impinged area, with a risk of LV perforation. In the latter situation, the catheter should be pulled out and repositioned before injection. A pigtail multihole catheter is used rather than an end-hole catheter, to avoid the risk of myocardial stain.

Anterior

Septum

RAO Looking in this direction

Inferior LAO

Anterior

Figure 34.43  Top figure: Illustration of how the RAO and LAO views “look” at the heart. Lower figure: RAO view. The left ventriculogram being a two‐dimensional luminogram, the anterior wall and the apex are seen, but the septum and the posterolateral wall are not seen.

Posterior mitral leaflet RAO

Inferior (infero-diaphragmatic)

Apical

686  Part 11.  Cardiac Tests: Invasive Procedures

LAO cranial view looks in this direction. LV walls are well displayed with septal (rather than anterior), apical, and lateral walls, in addition to the LVOT and LA posteriorly. Without the cranial angulation, the walls are foreshortened and overlapped, and the LA is hidden behind the LV.

LAO straight view (foreshortens LV walls) Figure 34.44  LAO straight vs. LAO cranial view. LAO cranial better opens the LV wall without foreshortening. LAO cranial would look from here

Aorta

Pulm Vein LA

LVOT Septal

LA

Lateral

Anterior

Lateral (not foreshortened)

Septal (not foreshortened) LV

Apical Apex LAO view

LAO cranial view

Figure 34.45  Left ventriculogram on LAO straight view vs. LAO cranial view.

Septal

Lateral

Apex Figure 34.46  Left ventriculogram performed in LAO straight view.

If LVEDP or PCWP >25 mmHg, ventriculography is avoided or only performed after giving nitroglycerin, using a small contrast volume. Typically, one RAO view is performed. An LAO cranial view is additionally or alternatively performed when either of the following is suspected: (1) posterolateral MI; (2) VSD; (3) MR; (4) LVOT obstruction (e.g., HOCM, goose‐neck deformity of the LVOT in primum ASD). B.  Mitral valve The two leaflets of the mitral valve are shown in Figure 34.47. While one may get the impression of two leaflets on the RAO view, this often only shows the posterior leaflet, which engulfs the anterior leaflet by virtue of its crescentic shape.

Chapter 34.  Angiographic Views  687

Coronal view of the mitral valve, showing how the RAO and LAO views “see” it

RAO view of the mitral valve

A To the side RAO (a)

RAO view of the mitral valve in case of posterior leaflet prolapse

A

A P

P

P In front LAO

(b)

(c)

Figure 34.47  (a) Illustration of how the RAO and LAO views look at the mitral valve. RAO looks at the mitral valve from the side (right heart side), while LAO looks from in front. (b) Illustration of how the mitral valve is seen on the RAO view (in gray). The anterior leaflet is not often seen on the RAO view, as it is engulfed within the crescent‐shaped posterior leaflet. (c) In posterior prolapse, the mitral valve bulges at the base of the LV (arrow).

Aorta

Location of LA Figure 34.48  RAO view of the LV. Look how the aorta overlaps with the LA. Go steeper RAO to separate the aorta from the LA.

C.  Assessment of mitral regurgitation When the severity of a regurgitation on echo‐Doppler is unclear or not consistent with the clinical presentation, invasive assessment is justified. Left ventriculography and aortography are the most accurate invasive methods of mitral and aortic regurgitation assessment, respectively. In order to appropriately assess mitral regurgitation: 1.  Use a 6 Fr pigtail catheter (rather than 4 Fr) 2.  Inject a large bolus of contrast per second and sustain it for 4 seconds, to allow a steady‐state contrast opacification of the LV and LA (e.g., 12 ml/s for a total of 48 ml). In severe MR, the large LA requires a large amount of contrast to be adequately filled and outlined. 3.  Ectopy should be avoided or minimized 4.  The catheter should be in the mid‐cavity (LVOT placement reduces LV and LA filling) 5.  Use a view that allows full visualization of the LA. In the standard 30° RAO, the LA overlaps with the descending aorta behind it, which blurs how strongly and fully the LA is opacified (Figure 34.48). Hence, it is important to go steeper on the RAO angulation (45–60° RAO) to provide a clear area between the mitral valve and the aorta (Figure 34.49). Alternatively, the LAO cranial view may be used. To grade mitral regurgitation, the extent of LA opacification is compared to the LV opacification during the period of maximal LV filling: 1+ (mild MR): a small puff of regurgitant contrast is seen in the LA but does not fully opacify the LA. 2+ (moderate MR): LA is fully opacified, but faintly (LA  LV), typically within one cardiac cycle; and/or contrast is seen refluxing in the pulmonary veins. In grades 3+ and 4+, LA is enlarged. When LA is so large, larger than the LV, it is difficult to opacify the LA as much as the LV even when 50% of the flow is regurgitant; thus, 3+ severe MR may appear 2 + . Mitral regurgitation may also be graded using the angiographic regurgitant fraction. After calibration of fluoroscopic dimensions using the diameter of the pigtail loop, the LV end‐diastolic and end‐systolic volumes are derived from measurement of the end‐diastolic and end‐systolic areas. The difference between the two is the total stroke volume. Only part of this volume, the forward stroke volume, eventually reaches the systemic circulation and is measured using thermodilution cardiac output. The regurgitant fraction is equal to: (total stroke volume – forward stroke volume)/total stroke volume (>50% is severe).

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Left upper pulmonary vein

MR with gigantic LA Figure 34.49  Steep RAO view shows severe MR with full delineation of the LA, which opacifies at least as much as the LV. Contrast spills back into the pulmonary vein. Thus, MR is graded 4+. LA is aneurysmal and approximates LV size.

XII.  Aortography for assessment of aortic insufficiency Aortography is best performed in the LAO view. This view is orthogonal to the aortic arch and opens the aortic arch without foreshortening and without overlap of the ascending and descending aorta. This allows assessment of the aorta along with AI, aortic dilatation being one of the most common causes or accompaniments of AI. Aortography is performed using a 6 Fr pigtail catheter, with a large injection of 20 ml/s for 50–60 ml. The large per‐second volume of 20 ml is necessary to fill the large aorta. AI is graded similarly to MR: 1+ Small puff of regurgitant contrast is seen in the LV but does not fully opacify it. 2+ LV fills fully but is less opacified than the aorta. 3+ LV fills fully and is as opacified as the aorta. 4+ LV fills fully and is more opacified than the aorta, typically within one cardiac cycle. LV is enlarged in grades 3+ and 4 + .

XIII.  Coronary anomalies Coronary artery anomalies occur in 0.3–0.9% of individuals without structural heart defects, and in 3–36% of those with structural heart defects. Among all patients undergoing coronary angiography, the most common coronary anomalies are the following: 1.  Separate ostia of the LAD and LCx (0.41%). 2.  Origin of the LCx from the RCA or the right sinus of Valsalva (LM only gives LAD and looks unusually long in this case) (0.37%). 3.  Anterior and unusually high origin of the RCA (higher than the sinus of Valsalva) (0.18%). 4.  RCA originating from the left sinus of Valsalva (0.13%). 5.  Left main originating from the right sinus of Valsalva (from the RCA or from a separate ostium) (0.02%). 6.  Less common anomalies: coronary artery fistula (to RV, RA, or PA usually) (0.1–0.2%); anomalous coronary artery originating from the PA. The three most common anomalies are benign and are not, per se, associated with any hemodynamic effect. In the case of anomalous LCx origin, the LCx always courses posterior to the aorta, hence the benign nature of this anomaly. An anomalous LCx origin is suspected when the first left angiographic view shows an unusually long LM, this long LM being in fact the LAD, as the LCx is missing. A.  Anomalous LM or RCA origin and course In the case of anomalous LM or RCA originating from the opposite sinus, the anomalous artery may follow one of the following four courses (Figure 34.50): (1) anterior to the PA; (2) posterior to the aorta; (3) subpulmonic, also called septal (the anomalous coronary artery dives underneath the septal LVOT then re‐emerges more distally); (4) interarterial. Only the interarterial course is associated with myocardial ischemia during exercise, with a subsequent risk of VT/VF and sudden cardiac death during exercise. “Squeezing” of the coronary artery between the aorta and PA is often offered as a simplistic, yet inaccurate, explanation. When the course is interarterial, the anomalous coronary artery has a sharply angled, oblique origin, sharper than seen in the other anomalies. This sharp origin creates a slit‐like ostium which gets stretched when the aorta distends during exercise, and thus it further narrows and leads to exertional ischemia. In addition, this anomalous origin is prone to spasm, torsion, or kinking, or an intramural course through the aortic wall. The interarterial course is the most common course of anomalous LM and even more so anomalous RCA (>75%). The other three anomalous courses have very rarely been associated with sudden death. In order to define the anomalous course, left ventriculography or aortography should be performed in an RAO view, and the anomalous coronary is spotted as a “dot” or an “eye” around the aorta (the eye is a loop anterior to the aorta) (Figures 34.51, 34.52).

Chapter 34.  Angiographic Views  689

Posterior LCx

LCx

LCx NC R L

RCA

NC R L

LV

NC R L

NC R L

LAD PA

LAD

PA

LAD

RV Anterior Interarterial

Retroaortic

Prepulmonic

Septal (subpulmonic)

Anomalous left main originating from the right sinus

NC R L

PA Always retroaortic Anomalous left circumflex originating from the right sinus Figure 34.50  Axial cuts across the aortic cusps and the PA, showing the course of anomalous left main artery and anomalous left circumflex artery originating from the right sinus.

LCx Axial plane

NC R L

NC R L

PA RAO view looks from this angle

LM

NC R L

NC R L

LM

LAD RAO view

Interarterial LM

RAO view

RAO view Retroaortic LM

Anterior-course LM

Subpulmonic LM

LCx LM

Longitudinal plane

PA LCx

Angiography in RAO view: Interarterial LM gives anterior dot

Angiography in RAO view: Retroaortic LM gives posterior dot

LAD

Angiography in RAO view: Anterior loop or eye corresponds to the anterior LM that loops around the PA to give LCx

PA LM LAD

Angiography in RAO view: Anterior loop or eye corresponds to the subpulmonic LM that loops underneath the PA to give LCx.

Figure 34.51  Anomalous origin of LM as visualized on RAO aortography. Always think of the coronary anatomy in the axial plane and imagine how the anomalous coronary artery projects on the RAO angle (dot vs. loop/eye). The eye of an anterior‐course LM is formed by the upward loop of the LM and the downward loop of the LCx. The eye of a subpulmonic LM is formed by the downward loop of the LM and the upward loop of the LCx.

690  Part 11.  Cardiac Tests: Invasive Procedures

Aorta

Anterior dot

Left rather than anterior origin

Right anterior rather than left origin

Left cusp

Right cusp

(a)

RAO 1 and 2

(b)

LAO 1

(c)

LAO 2

L R

L RCA with left origin

Normal RCA

R

Normal RCA LAO

RCA with anterior takeoff LAO

Figure 34.52  Anomalous RCA engaged with AL1. Two cases (1 and 2) are presented. (a) RAO view of both cases 1 and 2. An anterior dot is seen, suggesting that the anomalous RCA has an interarterial course. However, in the particular case of RCA, this takeoff does not necessarily imply a left RCA origin and is, in fact, more commonly seen with an anterior RCA origin. Before presuming that the RCA originates from the left cusp, ensure it is not just an anterior‐origin RCA by looking at a non‐selective LAO 40° view with imaging of the cusps; LAO splays out the left and right cusps and distinguishes a left origin from a right anterior origin. (b) On LAO of case 1, RCA is seen originating from the left cusp and the LM is seen filling next to it, implying a left‐originating RCA rather than an anterior-origin RCA. (c) On LAO of case 2, RCA is seen originating from the anterior surface of the right cusp (arrow) rather than the left cusp, implying an anterior‐origin RCA.

It is most important to remember that an anterior dot implies interarterial course, whereas a posterior dot (retroaortic course) or an eye/loop (subpulmonic or anterior course) are benign. These rules also apply to the anomalous RCA originating from the left sinus and to the anomalous LAD originating from the right sinus. CT or MRI are used to confirm those findings (class I). In the particular case of the RCA, a left RCA origin should be distinguished from the benign anterior RCA origin (Figure 34.52). The sudden death or the exertional symptoms of chest pain or syncope typically manifest before the age of 25, if ever. The risk of sudden cardiac death with anomalous LM is unclear. In autopsy series, 27–80% of patients with anomalous interarterial LM had died suddenly, and up to 30% of patients with anomalous RCA had died suddenly. However, this does not represent the absolute risk of sudden death from an anomalous coronary artery; rather, it is the relative frequency of sudden death among patients with anomalous coronary artery who happened to die and receive an autopsy (selection bias). Stress testing is insensitive for the diagnosis of ischemia or prediction of sudden death related to an anomalous coronary artery and should not be used for risk‐stratifying an anomalous LM. Surgery is indicated in patients with anomalous interarterial LM, regardless of symptoms or stress testing, or anomalous interarterial RCA with documented evidence of ischemia on stress testing. Surgery may consist of coronary reimplantation, but often consists of bypass surgery to the anomalous artery, preferably using a mammary graft; since the artery is only obstructed during exercise, the mammary graft may not mature, and therefore ligation of the native artery is usually performed, the flow becoming totally dependent on the mammary graft. B.  Coronary artery fistula A coronary artery fistula is a communication between a coronary artery and a cardiac chamber (coronary cameral fistula) or a vascular structure such as the PA or the coronary sinus (coronary arteriovenous fistula). Approximately 60% of these fistulas arise from the RCA, 30–40% from the LAD, and 5% involve both coronary arteries and terminate most commonly on the right side of the heart (most ­frequently RV [41%], then RA and PA); only 3% terminate in the LV. LAO view looks at the septum and differentiates a left‐ sided vs. right‐sided termination; RAO view looks at the AV groove and differentiates RV termination (anterior to the AV groove), RA termination (posterior to the AV groove), and PA termination (Figure 34.43).

Chapter 34.  Angiographic Views  691

Acquired fistula may be seen after a penetrating trauma, PCI, RV biopsy, or cardiac surgery. The origin and course of fistulas are delineated by coronary angiography, CT, or MRI. Congenital coronary fistulas are often small and benign; they are often diagnosed in adulthood as a result of a murmur, which is typically continuous but sometimes only heard in systole. However, a fistula may have two major untoward consequences: (1) significant left‐to‐right shunting with O2 step‐up, pulmonary hypertension, and both right‐sided and left‐sided enlargement (fistula to RA or RV); (2) coronary steal, i.e., reduction in blood flow distal to the site of fistulization with myocardial ischemia. The proximal segment of the coronary artery attempts to compensate and undergoes progressive aneurismal dilatation; atherosclerosis, thrombosis, and endarteritis may develop. Small fistulas have an excellent prognosis and ~23% close spontaneously. Fistula‐related complications are present in 11% of patients younger than 20 years and 35% of patients older than 20 years. Many fistulas progressively enlarge over time and insidiously lead to symptoms at a later age. Some fistulas are simple and consist of a single origin and a single track, whereas others are complex (multiple origins or plexiform network). A large fistula (2–3× the caliber of the distal vessel) or any fistula with hemodynamic effect should be closed surgically or percutaneously; percutaneous closure is possible when a single large communication is identified (oversized coil embolization). C.  Anomalous coronary artery originating from the pulmonary artery In this case, a coronary artery originates from the PA. This is different from coronary‐to‐PA fistula, wherein the coronary artery originates normally but communicates with the PA. A coronary artery originating from the PA is one of the most serious coronary anomalies and often leads to death in infancy if untreated, particularly since the coronary artery involved is often the left coronary artery. The main issue is the low pressure in the main PA, which is more dreadful than its low oxygenation. The low PA pressure explains why the flow in the aberrant coronary artery is directed retrogradely towards the pulmonary artery, and is derived via anastomotic vessels from the contralateral, normally arising coronary artery. Severe myocardial ischemia is therefore present. The few patients who are diagnosed in adulthood have an RCA originating from the PA, or a left coronary artery arising from the PA with a relatively small left coronary system and abundant right‐to‐left collaterals.

XIV.  Lower extremity angiography A.  Anatomical tips (see Figures 34.53, 34.54, 34.55) B.  Technical tips Angiography of the abdominal aorta is performed using a 4–5 Fr multihole pigtail catheter or pigtail‐like catheter (e.g., OmniFlush). The catheter is positioned at the level of L1, which coincides with the level of the renal arteries. Angiography is obtained using a 10–12 ml/s injection for a total of 20–24 ml (4 Fr OmniFlush catheter allows the injection of this volume). If bilateral iliofemoral runoff is performed using a bolus‐chase technique, the contrast dose is 7–8 ml/s for 60–70 ml. The bolus fills the patient’s aorta and iliac arteries, and the use of 7 ml vs. 8 ml depends on the size of these vessels. The duration of the injection depends on the patient’s height; less than a 10‐second injection may be done in small patients.

CIA IIA EIA Inferior epigastric artery

CFA Profunda

SFA

Figure 34.53  Right oblique view of the aorta, iliac and femoral arteries. Note how the iliac arteries dive posteriorly, then emerge and become superficial at the level of the inguinal ligament to form the CFA over the head of the femur. The lower loop of the inferior epigastric artery corresponds to the inguinal ligament, and thus defines the point where the deep external iliac artery emerges to the surface and becomes the CFA. A femoral stick above the loop of the inferior epigastric artery is a deep stick in the pelvic area, at a level where the artery cannot be appropriately compressed for hemostasis and where bleeding can seep through loose, non‐concealing pelvic tissue. The internal iliac artery gives gluteal branches to the thigh and deep pelvic branches, and may receive collaterals from the inferior mesenteric artery and the median sacral artery in case of common iliac occlusion. The CFA gives the profunda femoris, which sharply dives posteriorly and laterally in the thigh close to the femur, and the SFA, which continues anteriorly and medially, away from the femur, and is almost as anterior as the CFA early on. The CFA and profunda give circumflex branches to the hip, and the profunda gives perforating branches to the thigh throughout its course. The SFA only gives distal geniculate branches to the knee area. CFA, common femoral artery; CIA, common iliac artery; EIA, external iliac artery; IIA, internal iliac artery; SFA, superficial femoral artery.

692  Part 11.  Cardiac Tests: Invasive Procedures

Superficial circumflex

Circumflex

Inferior epigastric

Common femoral

Profunda SFA in adductor canal

adductor hiatus Popliteal

AT

Tibio-peroneal trunk PT

Peroneal Figure 34.54  Femoropopliteal anatomy. A right lower extremity is shown. Dashed arteries are posterior arteries. SFA runs in the adductor canal, between the sartorius muscle anteriorly and the adductor muscles posteriorly. It dives posteriorly into the popliteal fossa behind the femur at the level of the adductor hiatus, which, in terms of fluoroscopic bony landmarks, coincides with the point at which the SFA intersects with the femur in an AP view. SFA becomes popliteal artery at this adductor hiatus level. Thus the popliteal artery starts much higher than the knee joint space (dashed artery). The popliteal artery is a posterior artery; below the knee, it gives the anterior tibial (AT) artery then continues straight in the posterior leg compartment as the tibioperoneal trunk. The AT artery is an anterior branch that emerges anteriorly by bending below the fibula head (AT genu), lies deep in the anterior leg compartment over the interosseous membrane (deeper than the anterior tibial muscle), supplies the anterior leg compartment, then emerges superficially as the dorsalis pedis artery and the lateral tarsal artery at the foot level. The tibioperoneal trunk gives rise to the posterior tibial (PT) artery and the peroneal artery, both of which supply the posterior compartment of the leg. The peroneal artery ends at the lateral malleolus and communicates with the AT through the anterior perforating branch; the PT runs to the medial malleolus and continues to the plantar foot. Laterally to medially, the infrapopliteal vessels encountered are: AT, peroneal, then PT (distally, the peroneal becomes more lateral than the AT). There are several anatomical variants. Some patients have a trifurcation of AT, PT, and peroneal artery (as opposed to two bifurcations). Other patients have a very high takeoff of the AT close to the knee joint. In ~8% of patients, the AT ends early and the peroneal artery provides the dosalis pedis artery through an anterior perforating branch. In another small proportion of patients, there is no anatomical large dorsalis pedis artery at the level of the foot; the AT ramifies early on and ends as a lateral tarsal artery that supplies the foot. Note about the femoral vein: in contrast to the groin/CFA level, where the vein is medial to the artery, the femoral vein quickly crosses over and becomes lateral to the SFA and to the popliteal artery, up until the mid‐popliteal level at the knee joint level, where the vein becomes posterior to the popliteal artery. Thus, when attempting retrograde popliteal arterial access, the needle should be positioned 3–4 cm above the knee joint to enter the artery 6–7 cm above the knee joint, where the artery and veins are not overlapped. Below the knee, every infrapopliteal artery is surrounded by two veins.

Alternatively, one may selectively engage a contralateral iliac artery using the OmniFlush or IMA catheter with the help of a slippery wire (Glidewire): (1) from a right femoral access, the OmniFlush catheter is torqued towards the left iliac, (2) the Glidewire is then advanced beyond the OmniFlush catheter tip, then torqued and advanced into the left iliac, (3) the catheter and wire are then slightly pulled until the catheter perfectly embraces the aortoiliac bifurcation; the catheter is then advanced over the wire more distally (Figure 34.56). For selective unilateral iliofemoral runoff, the contrast dose is 5 ml/s for a total of 30 ml (alternatively, as low as 4 ml/s for 20 ml may be used in short patients with small arteries) The per‐second dose is adjusted according to the diameter of the vessels (a large vessel needs a large bolus to fill it); the total duration, and thus the total dose, is adjusted according to the height of the patient. C.  Angiographic tips The runoffs are typically performed in AP view. In iliac imaging, a contralateral view is helpful in opening up the bifurcation of the common iliac artery into the external and internal iliac arteries and removing any overlap (20° contralateral oblique ± 20° caudal). In femoral imaging, a 30° ipsilateral view is helpful in opening up the common femoral bifurcation and identifying the ostium of the SFA; the SFA is more ­anterior and medial than the profunda and directed away from the femur. A more oblique view may help open the femoral bifurcation when the profunda is overlapped with the SFA on a shallow oblique view. When the common iliac artery is occluded, collaterals develop through the contralateral internal iliac artery, the inferior mesenteric artery (which anastomoses with the internal iliac artery), or the median sacral artery. When the external iliac artery is occluded, collaterals

Chapter 34.  Angiographic Views  693

SFA Profunda

Mid-SFA

SFA distally

Figure 34.55  Axial CT scan images showing the SFA anatomy. Top: note the anteroposterior relationship between SFA and profunda. Bottom left: SFA in the adductor canal, anterior to the adductor muscles. It becomes progressively more posterior as it goes down the thigh. Bottom right: SFA just proximal then distal to the adductor hiatus.

(a)

(b)

(c)

Figure 34.56  OmniFlush or IMA catheter used to selectively engage the left iliac/femoral artery through a right femoral access. (a) The left iliac is wired through a properly directed OmniFlush catheter, albeit not selectively engaged. A slippery wire (Glidewire) is used. (b) After the wire gains some distance into the left iliac, the whole system (catheter + wire) is pulled back to embrace the aortoiliac curvature, providing support for further wire and catheter advancement, as seen in (c).

develop through the ipsilateral internal iliac artery but also the mammary artery (as it goes down from the chest and anastomoses with the inferior epigastric artery) (Figure 34.57). When the SFA is occluded, the profunda, which is rarely diseased, supplies collaterals to the popliteal artery through the geniculate branches and reconstitutes the SFA distally (Figures 34.58, 34.59). Beware of confusing the profunda with the SFA in a case of ostial SFA occlusion. Unlike the SFA, the profunda provides branches at the thigh level. A medial profunda branch segment may still be mislabeled as proximal SFA when the true SFA is totally occluded; in this case, use a steep ipsilateral oblique view at the common femoral level to see whether this branch has a posterior course directed toward the femur (profunda), or an anterior course that curves away from the femur (SFA). A path too close to the femur on the AP or oblique view indicates that the artery is a profunda rather than SFA (Figures 34.60, 34.61).

694  Part 11.  Cardiac Tests: Invasive Procedures

CFA

Figure 34.57  External iliac occlusion extending into the common femoral artery (CFA), with reconstitution from the internal iliac artery at the level of the CFA. The reconstitution occurs through the superficial circumflex artery (arrowhead), a lateral artery lower than the inferior epigastric artery. The white line indicates the path of the occlusion.

Femoral head

Femoral head

Profunda

Popliteal reconstitution Figure 34.58  Totally occluded left SFA from the ostium to the popliteal level. It reconstitutes through profunda collaterals. The right panel shows the path of the occluded SFA (white line).

Profunda

Proximal and mid SFA Distal SFA occluded up until the popliteal artery

Figure 34.59  Totally occluded right distal SFA with collaterals mostly originating from the profunda; additionally, some bridging collaterals are seen.

Collaterals from profunda

Is this the SFA before it occludes (with a bridging collateral that looks like a branch), or a profunda branch? (RAO view) SFA bridging collateral vs. profunda

SFA reconstitutes beyond the total occlusion Figure 34.60  Differentiate SFA from profunda in the case of SFA occlusion.

Figure 34.61  Same patient as Figure 34.60. An almost lateral view (left panel) shows that the branch in question is actually SFA not profunda, as it is anterior and directed away from the femur, whereas the profunda dives towards the femur. Successful revascularization of this SFA was performed (right panel).

SFA Profunda Steep RAO view (~75°)

696  Part 11.  Cardiac Tests: Invasive Procedures

In moderate iliac or common femoral disease disease, pressure gradients should be obtained across the stenosis. A significant pressure gradient is a peak‐to‐peak gradient > 20 mmHg at rest or with vasodilators (nitroglycerin). Pressure gradients may be obtained by catheter pullback; however, owing to respiratory fluctuations in arterial pressure, this method is often inadequate in assessing moderate instantaneous gradients; in addition, the catheter itself may create an obstruction and worsen the gradient, or a curved catheter may abut the arterial wall and falsely create a damped pressure past a stenosis. The best technique consists of advancing a 0.014” coronary pressure wire through a catheter and positioning it distal to the lesion, followed by simultaneous pressure measurements distal to the lesion (pressure wire transducer) and proximal to the lesion (using any catheter ≥ 5 Fr or a long 4 Fr sheath advanced close to the lesion). Alternatively, simultaneous pressure measurements may be performed using a 6 Fr sheath positioned proximal to the lesion and a straight 4 Fr catheter (e.g., Glidecath) advanced beyond the lesion. Make sure both transducers are zeroed at the same level.

XV.  Carotid angiography A.  Anatomical and technical tips Aortic arch angiography is performed in the view that opens up the aortic arch, that is, the LAO view (20 ml/s for a total of 40 ml). The aortic arch is classified as type I–III, depending on how steep it is, i.e., depending on the distance between the peak of the aortic arch and the origin of the right innominate trunk (Figure 34.62). A true bovine arch is characterized by a left common carotid artery that comes off the innominate artery at least few millimeters beyond its origin, and is seen in 9% of the population. The left common carotid and innominate arteries may share a common bifurcating origin from the aortic arch; this is sometimes erroneously called bovine arch. While vertebral arteries usually originate from the subclavian arteries, the left vertebral artery originates from the aortic arch in 5% of patients. The aortic arch angiogram defines the arch’s anatomy and any disease in the proximal portions of the four major vessels. C C V

V

SC SC

1–2 diameter of CCA

> 2 diameter of CCA Type I

Type II

Type III

Figure 34.62  Aortic arch types I, II, and III. The distance between the top of the aortic arch and the right innominate is referenced to the diameter of the common carotid artery (CCA). C, carotid; SC, subclavian; V, vertebral. Reproduced with permission of HMP Communications from Madhwal S, Rajagopal V, Bhatt D, et al. Predictors of difficult carotid stenting as determined by aortic arch angiography. J Inv Cardiol 2008; 20: 200–4.

(a)

(b)

Figure 34.63  (a) On an LAO view, the JB1 catheter is torqued counterclockwise until it engages the right innominate trunk (goes from solid to dashed). Then a Wholey wire is advanced through the JB1 and torqued into the right common carotid artery; RAO caudal view may help open the common carotid–subclavian bifurcation. Occasionally, the wire may be going up the vertebral artery rather than the carotid artery. (b) The JB1 catheter is subsequently advanced over the Wholey wire to selectively engage the common carotid artery.

Chapter 34.  Angiographic Views  697

(a)

(b)

(c)

Tip “hooked” in the left subclavian

Simmons pushed until it is shaped

Figure 34.64  Simmons catheter used to engage the innominate and carotid arteries. There are several techniques to shape it: (a) it may be advanced over the wire until it is shaped over the aortic valve (solid gray), then pulled back with a counterclockwise rotation until it engages the innominate artery (dashed gray). (b) Alternatively, the Simmons catheter can be shaped in the descending aorta then advanced to engage the vessel of interest. (c) The tip of Simmons may be hooked into the left subclavian artery, then pushed until it is shaped in the aortic arch; a figure of eight may be seen before full shaping of the catheter.

In aortic arch types I, II, and sometimes III, a JR4 catheter may be used to selectively engage the innominate and the left carotid arteries, in an LAO view. After being positioned in the ascending aorta, the JR4 catheter is pulled with a counterclockwise rotation to selectively engage the innominate artery then the left common carotid artery. On the right, after selectively engaging the innominate artery, a Wholey wire or a Glidewire is used to selectively enter the right common carotid artery, followed by advancement of the JR4 catheter over the wire (Figure 34.63). Beware of advancing the Wholey wire distally beyond the common carotid artery. Other catheters with tips longer and straighter than JR4 are preferably used (e.g., JB1 catheter, HeadHunter). RAO caudal view (20°, 20°) opens the right innominate bifurcation into the right common carotid artery and guides selective wiring of the common carotid artery. In a type III arch, the curved catheters (Simmons or Vitek) may need to be used to engage both common carotid arteries. In a bovine arch, the curved catheters may be needed to engage the left common carotid artery (Figure 34.64). The wire is advanced until it is looped over the aortic valve, then the catheter is advanced until its base is on the aortic valve. Subsequently, the wire is removed and the catheter is allowed to take its shape in the ascending aorta over the aortic valve; the catheter is then pulled back until it engages the vessel of interest. B.  Angiographic tips Once a common carotid artery is selectively engaged, the carotid bulb and the internal carotid artery (ICA) are positioned in the field of view; ­typically, the carotid bulb is located at the angle of the jaw. The carotid is then imaged in two views, using a 4–5 ml/s injection for a total of 10 ml per view: 30° ipsilateral oblique and 90° lateral view. A contralateral oblique view and an AP view may be used in case of overlap or unclear lesion severity. Note that the external carotid artery (ECA) is differentiated from the ICA by the fact that the ECA provides branches at the extracranial level, and that the ECA is actually internal to the ICA on an AP view (opposite to what the names may suggest). The ICA does not provide any branch at the cervical level. The right vertebral artery, if accidentally engaged, is distinguished from the right common carotid artery by its smooth straight course in the neck without branches and by the loop it makes at the level of C1. The intracerebral circulation is also imaged in two views: lateral view and AP cranial view (Town view). The first large ICA branch is the ophthalmic artery, seen at the intracerebral level. In unilateral carotid disease, collaterals may be provided by: (i) contralateral ICA (crossover of flow from one ICA side to another through the circle of Willis may be visualized); (ii) ECA (through a communication between the superficial temporal artery and the ophthalmic artery); (iii) vertebral artery (through the circle of Willis and the posterior communicating artery). On the other hand, in a patient with severe vertebrobasilar disease, the posterior circulation may be provided by the ICA through the ­posterior communicating artery. Non‐selective imaging of the vertebral arteries is necessary in severe carotid disease to assess the risk of an intervention.

Q u e s t io n s a n d   a n s w e rs Question 1. On RAO caudal view, in the LAD area, one artery is seen at the border of the heart shadow, another is seen over the heart shadow. Which one is the LAD? Question 2. On RAO caudal view, in the LAD area, one large artery is seen running at the border of the heart shadow. No other large artery is seen. What is the large artery seen? And what is the likely status of the LAD? Question 3. How would you confirm the findings of Question 2? Question 4. On LAO caudal view, the distal LM, proximal LAD, and LCx are overlapped. Is this situation more likely to happen with a vertical or a horizontal heart? How would you open up the LM bifurcation in this case? Question 5. Is there is a situation where a cranial view may show well the proximal LAD and even the distal LM bifurcation? Question 6. A cranial view shows a lot of overlap in the proximal and mid‐LAD area. How can the image be improved? Question 7. A patient has an occluded proximal LAD and a large proximal diagonal branch originating before the occlusion. On LAO cranial view (or any cranial view), how would you avoid miscalling this large diagonal LAD?

698  Part 11.  Cardiac Tests: Invasive Procedures

Question 8. On RAO caudal view, which branches run on the border of the heart shadow? On LAO cranial view and other cranial views, which arteries run on the border of the heart shadow? Question 9. On RAO caudal view, the proximal LCx is foreshortened and overlapped with the distal LM. How can you open the distal LM and proximal LCx? Question 10. A patient has a borderline ostial LM stenosis on the caudal views. What other views allow good delineation of the ostial LM? Question 11. In which case is a cranial view a valuable view for the LCx? Question 12. What is the single best RCA view? Question 13. What part of the RCA is not well seen on the LAO straight view? Question 14. What are, in order, the best views for the distal RCA, i.e., the views that open the distal RCA bifurcation? Question 15. On LAO cranial view, RCA appears to course distally in a straight line, without any bend (Figure 34.33A). What can be said of this RCA? Question 16. Which RCA view looks at the AV grove from its side rather than en face, only allowing assessment of the mid‐RCA, while foreshortening the proximal and distal RCA? Question 17. On LAO straight view, a venous graft appears attached to an artery running on the heart border. What is the grafted artery? Question 18. On RAO straight view, a venous graft appears to be attached to an artery running on the heart border. What is the grafted artery? Question 19. On RAO straight view, a venous graft appears to be attached to an artery running on the lower part of the heart. What is the grafted artery? Question 20. What three views need to be obtained for a LIMA graft? Question 21. In order to assess MR by LV angiography, what view should be used and how much contrast should be injected? Question 22. In order to diagnose the course of an anomalous LM (originating from the right sinus) or RCA (originating from the left sinus), aortography should be performed in what view? Question 23. RCA appears to be originating from the left sinus. What is the other anomalous RCA origin that is sometimes confused with a left‐originating RCA? Which view allows the distinction? Answer 1. The diagonal branch runs on the border of the heart shadow. The artery that is more centered is the LAD (Figures 34.10, 34.11, 34.12). Answer 2. The artery seen is likely a large diagonal branch. The LAD is likely occluded. Answer 3. Obtain LAO cranial view (Figure 34.13). Answer 4. This scenario is more likely to happen with a vertical heart. LAO caudal looks at the heart from underneath it and displays it better if it is horizontal. To open up the LM bifurcation, the LCx needs to be pulled further down and to the right. Thus, change the view to a more caudal and less leftward angle (Figures 34.16, 34.18). Answer 5. Vertical heart. Answer 6. The LAD moves in an opposite direction to the image intensifier. Going more cranial will push the LAD down and separate it from the LCx. Also, imaging in deep inspiration will make the heart more vertical and provide a better cranial view (less overlap) (Figure 34.24). Answer 7. The LAD stays in the center of the heart shadow, and in the LAO cranial view, it runs parallel to the spine. Conversely, the diagonal branch takes a turn and aims towards the border of the heart shadow (Figures 34.13, 34.26). Also, the LAD gives septal branches which are characteristically straight and do not torque in systole. Answer 8. On the RAO caudal view, branches running on the border of the heart shadow are diagonal branches. On the LAO cranial view, branches running on the border of the heart shadow are OM branches; diagonal branches loop and aim towards the heart border, but do not usually run over it. On other cranial views, branches running on the border of the heart shadow can be either OM or diagonal branches (Figures 34.20, 34.21, 34.28). Answer 9. Angle the image more caudally. Answer 10. Cranial views are good for ostial LM. Also, LAO straight and AP straight are good views for ostial LM. Answer 11. When the LCx is dominant, the cranial views show the LCx looping proximally then continuing distally and giving left PLBs and a PDA. The distal LCx, in this case, is well seen on cranial views. If the LCx is not dominant, it is only seen looping proximally without a deep distal continuation. In fact, whenever the LCx is well seen distally beyond its loop on a cranial view, suspect a dominant LCx. On LAO cranial view, the left PDA runs parallel to the LAD. Answer 12. LAO cranial (30° LAO, 15° cranial). Answer 13. The distal RCA bifurcation is not well seen on LAO straight (PDA and PLBs are overlapped). LAO cranial, on the other hand, opens the distal RCA bifurcation.

Chapter 34.  Angiographic Views  699

Answer 14. (1) AP cranial; (2) LAO cranial. Answer 15. This RCA is either occluded in its mid‐segment or non‐dominant. A dominant, patent RCA should have two distal bends on the LAO straight, LAO cranial, and AP cranial views. Answer 16. RAO straight view (Figure 34.35). Answer 17. OM branch (Figure 34.37). In left coronary imaging, LAO straight resembles LAO cranial. Answer 18. Diagonal branch. Answer 19. OM branch. In left coronary imaging, RAO straight resembles RAO caudal. Answer 20. (i) Straight view for the LIMA body (AP or RAO usually); (ii) cranial view for the native LAD (the cranial view may also show the LIMA–LAD anastomosis); (iii) 90° left lateral view for the LIMA–LAD anastomosis. Answer 21. MR should be assessed in an extreme RAO view (e.g., 45–60°), which allows the separation of the large LA from the descending aorta. LAO cranial may also be used. A large injection is used and sustained over 4 seconds, to allow a steady‐state filling of the LV and LA (12–13 ml/s for a total of 48–52 ml). Answer 22. RAO view, which shows the “dot” and “eye” signs. Answer 23. Anterior RCA takeoff from the right sinus may be confused with left RCA takeoff. LAO view allows the distinction. Anterior takeoff is benign, while left takeoff may lead to ischemia (Figure 34.52).

Further reading Anomalous coronaries Chaitman BR, Lesperance J, Saltiel J, Bourassa MG. Clinical, angiographic, and hemodynamic findings in patients with anomalous origin of the coronary arteries. Circulation 1976; 53: 122–31. Kimbiris D, Iskandrian AS, Segal BL, Bemis CE. Anomalous aortic origin of coronary arteries. Circulation 1978; 58: 606–15. Lowe JE, Oldham HN, Sabiston DC. Surgical management of congenital coronary artery fistulas. Ann Surg 1981; 194: 373–80. Serota H, Barth CW, Seuc CA, et al. Rapid identification of the course of anomalous coronary arteries in adults: the “dot and eye” method. Am J Cardiol 1990; 65: 891–8. Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary angiography. Cathet Cardiovasc Diagn 1990; 21: 28–40. Sherwood MC, Rockenmacher S, Colan SD, Geva T. Prognostic significance of clinically silent coronary artery fistulas. Am J Cardiol 1999; 83: 407–11.

35  Cardiac Catheterization Techniques, Tips, and Tricks

I. View for the engagement of the native coronary arteries: RAO vs. LAO  700 II. Design of the Judkins and Amplatz catheters  700 III. Engagement of the RCA  700 IV. How to gauge the level of the RCA origin in relation to the aortic valve level  703 V. What is the most common cause of failure to engage the RCA? What is the next step?  704 VI. JR4 catheter engages the conus branch. What is the next step?  704 VII. Left coronary artery engagement: general tips  704 VIII. Management of a JL catheter that is sub‐selectively engaged in the LAD or LCx  706 IX. Specific maneuvers for the Amplatz left catheter  706 X. If you feel that no torque is getting transmitted, what is the next step?  706 XI. Appropriate guide catheters for left coronary interventions  706 XII. Appropriate guide catheters for RCA interventions  708 XIII. Selective engagement of SVGs: general tips  709 XIV. Specific torque maneuvers for engaging the SVGs  709 XV. Appropriate catheters for engaging SVGs  711 XVI. Engagement of the left internal mammary artery graft  712 XVII. Left ventricular catheterization  713 XVIII. Engagement of anomalous coronary arteries  714 XIX. Specific tips for coronary engagement using a radial approach  714 XX. Damping and ventricularization of the aortic waveform upon coronary engagement  717 XXI. Technique of right heart catheterization  718

I.  View for the engagement of the native coronary arteries: RAO vs. LAO In order to engage a native coronary artery, a view that is orthogonal to its takeoff, i.e., LAO view, should be used (Figure 35.1).

II.  Design of the Judkins and Amplatz catheters (see Figures 35.2–35.7) In general, with any Judkins catheter, a larger arm makes the catheter point down, whereas a shorter arm makes the catheter look up.

III.  Engagement of the RCA (see Figure 35.8) Advance the JR4 catheter to the aortic valve, then pull slightly to free the catheter, then pull and clockwise torque 90–180° in one motion (both the pull and clockwise motions must be coordinated). If the catheter is excessively torqued (>180°), one should be prepared for a slight counterclock as the catheter engages the RCA. The torque is not transmitted to the tip unless the catheter is moved. Torquing the catheter in place does not lead to any torque transmission to the tip; then, immediately as the catheter is pulled, all the excessive torque is transmitted. The key to a successful RCA engagement is a coordinated and simultaneous pull and torque (90–180°). In addition, the catheter tip has a tendency to dive down when the torque gets transmitted, hence the importance of keeping a pulling tension on the catheter as the torque is transmitted. A second technique consists of positioning the catheter 2–3 cm above the ostium, followed by a clockwise torque; the catheter will dive into the RCA ostium. A pulling tension needs to be maintained during the torque maneuver, as the catheter may dive too low upon torque transmission. The RCA courses in the AV groove, which appears as a moving “white band” over the heart shadow. If one watches the cardiac silhouette on fluoroscopy, this white band is seen and is a clue to the course of the RCA. An AR catheter is handled similarly to a JR4, except that the torque transmits to the tip more easily and the catheter has less tendency to dive down upon torque transmission. It points more downward than JR4.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

700

Posterior

NC L R

L R NC LAO

RAO

Anterior Aortic arch opened in a LAO view

(a)

(b)

Figure 35.1  (a) Axial cut at the level of sinuses of Valsalva. R is the right cusp, L is the left cusp, and NC is the non‐coronary cusp. LAO view is orthogonal to the ostia, and therefore displays the coronary arteries in front of the operator, permitting the catheters to be torqued towards the appropriate plane. (b) Aortic arch opened in LAO view. Tip Length of the Judkins Left Catheter

Tip Length of the Judkins Right Catheter S

Judkins Left

4.0

Judkins Right

3.0 S

5.0 P

(a)

Tip Length = P-S distance (cm) P = Primary Curve S = Secondary Curve

3.0 4.0

Tip Length = P-S distance (cm) P = Primary Curve S = Secondary Curve

P 5.0

(b)

Figure 35.2  (a) Judkins left (JL) catheter. The size of the Judkins catheter is the distance between the primary and secondary curve, in cm (JL3 → 6). The secondary curve is what sits on the contralateral aortic wall. (b) Judkins right (JR) catheter. Courtesy of Mark Freed and Robert Safian, Physician’s Press, Royal Oak, MI.

JL5 JL4

Figure 35.3  In the case of an elongated or enlarged aorta (elderly, hypertensive, or tall patient), the JL4 arm may be too short and the catheter may point up and risk dissecting the left main upon contrast injection. In addition, the secondary curve may fall down and the catheter may fold on itself. Use a larger curve (JL5, JL6) to make the catheter look down and be coaxial with the ostium.

Tip Length of the Amplatz Left Catheter Amplatz Left

S

1.0

2.0 3.0

P

Tip Length = P-S distance (cm) P = Primary Curve S = Secondary Curve

Figure 35.4  The Amplatz left (AL) catheter has a “duck” shape. AL may be used to engage the left coronary artery but also a right coronary artery with superior takeoff. Courtesy of Mark Freed and Robert Safian, Physician’s Press, Royal Oak, MI.

702  Part 11.  Cardiac Tests: Invasive Procedures

Figure 35.5  AL sits both on the back wall of the aorta and on the aortic valve (usually contralateral cusp), and thus provides support both from the opposite wall of the aorta and from the cusp. AL points up, but may point down if the AL curve is small relatively to the aorta. In addition, if the AL curve is small, the AL may not sit on the aortic valve. Reproduced with permission of Wolters Kluwer Health from Baim DS. Coronary angiography. In Grossman W, Baim DS. Grossman’s Cardiac Catheterization, Angiography, and Intervention, 7th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2006, pp. 187–221.

Amplatz

Dilated Root Figure 35.6  AL engaging the RCA. AL looks up if the AL curve is proportionate to the aortic size; less frequently, AL looks down if its curve is small in relation to the aorta (e.g., AL1 in a dilated aortic root). Courtesy of Mark Freed and Robert Safian, Physician’s Press, Royal Oak, MI.

Amplatz Right

S

1.0 2.0 3.0

P

Tip Length = P-S distance (cm) P = Primary Curve S = Secondary Curve

Figure 35.7  The primary‐to‐secondary distance distinguishes Amplatz right (AR) 1, 2, and 3. The size of the secondary curve (S), per se, distinguishes AR catheter from AL catheter. AR has a smaller curve than AL. Therefore: (1) AR does not sit on the aortic cusps or the back wall of the aorta, and does not provide support from these structures; (2) as opposed to AL, AR points down. The AR catheters represented in this illustration are AR mod (modified AR) catheters, the only type of AR catheters currently in use. Courtesy of Mark Freed and Robert Safian, Physician’s Press, Royal Oak, MI.

Figure 35.8  Engagement of RCA.

Chapter 35.  Cardiac Catheterization  703

A no‐torque catheter (3DRC or Williams right catheter) is, in a way, a JR4 catheter that is already torqued (Figure 35.9). All the operator has to do is advance it to the aortic valve then pull it to engage the RCA. A slight torque may be necessary if the RCA is not immediately engaged. For experienced operators, this catheter may not offer any advantage over the JR4 catheter, including no advantage in anomalous RCA takeoff. It has a short tip like JR4 and points slightly more upward than JR4. In general, even with a JR4 catheter, less of a pulling tension is required to engage the RCA transradially. The torque does not easily transmit in patients with tortuous iliac arteries and aorta, in which cases a long femoral sheath that straightens the tortuosity and lands in the aorta should be used (e.g., 23 cm or 45 cm sheath). Also, the torque may not easily transmit in patients with a steep aortic arch, where JR4 may prove difficult to use; a catheter that requires less torque, such as AR or no‐torque catheter, is preferred in these patients. JR4

3 DRC or Williams right

Figure 35.9  The 3DRC catheter is, in a way, a JR4 that is already torqued. It simplifies JR4 engagement but does not have any major advantage over JR4 for experienced operators. It may facilitate RCA engagement when the torque does not get well transmitted, e.g., steep aortic arch.

IV.  How to gauge the level of the RCA origin in relation to the aortic valve level In some patients, one may get the impression that the RCA origin is low, very close to the aortic valve. More specifically, in an elderly patient with an elongated, almost horizontal ascending aorta, the origin of the RCA seems to be displaced downward (Figure 35.10). In fact, the distance between the aortic valve and the coronary origin is the same as in a normal aorta; however, the level of this origin is down. That is why, in those patients, one should seek the RCA origin at a level close to the aortic valve. Once the catheter is at the outer curvature of the aorta, it is already too high, above the RCA level; it should be readvanced to the aortic valve and pulled back more slowly. Again, use the white opacity of the AV groove to help localize the RCA.

Elderly patient

Young patient (a)

(b)

Figure 35.10  (a) Origin of the RCA in a young patient. (b) Origin of the RCA in an old patient with elongated ± dilated aorta: RCA seems to be displaced downward and is at the same level as the aortic valve. Tip: the way the catheter body is shaped in the ascending aorta gives an idea about the shape of the aorta. Once the catheter reaches the outer curvature of the aorta (star), it is already too high. Also, the steepness of the aortic arch (arrow) dictates how difficult the torque transmission will be. In a steep arch, a catheter that requires less torque is preferred (AR, Williams right).

704  Part 11.  Cardiac Tests: Invasive Procedures

V.  What is the most common cause of failure to engage the RCA? What is the next step? The most common cause of failure to engage the RCA is an anomalous anterior and high takeoff (Figure 35.11). In this case, use an extreme LAO view, or better, a 90° left lateral view to be orthogonal to the origin of the RCA and attempt engaging in this view, initially using the JR4 catheter. JR4 may fail to engage the RCA because its tip is too short to reach. Alternatively, switch to an AL0.75 or AL1 catheter. Non‐selective contrast injections help identify the level of the RCA. If the above two techniques fail or if the RCA is not seen during contrast injections over the right sinus of Valsalva, RCA may be originating further up or from the left sinus of Valsalva, in which cases a larger AL is needed. For RCA originating from the left, a larger AL (1.5 or 2) may be used and aimed towards the left, or a left Judkins may be used (e.g., JL5 if JL4 is used to engage the left coronary artery).

VI.  JR4 catheter engages the conus branch. What is the next step? The RCA origin is posterior and lower than the conus origin (Figure 35.12). Thus, when the conus is engaged but not deeply so, one may continue to clockwise torque the catheter, aiming more posteriorly. If this fails, switch to a catheter that points down in comparison to the JR4, such as JR5 or AR. Posterior

NC L R

90 degrees lateral

Normal RCA Anterior RCA LAO Anterior Figure 35.11  Axial cut at the level of the sinuses of Valsalva. A 90° lateral view is orthogonal to an anterior RCA and allows easier engagement. AL catheter may be necessary to reach an anterior RCA.

Conus

More anterior and superior takeoff than RCA

RCA

Figure 35.12  Relationship of the conus branch and RCA. If JR4 falls into the conus branch, a catheter with a more inferior takeoff, such as JR5 or AR, will successfully engage the RCA.

VII.  Left coronary artery engagement: general tips In patients with an elongated aorta (widely folding aorta) or a dilated aorta, such as tall or elderly hypertensive patients, the short arm of the JL4 catheter tends to fold on itself even before reaching the left coronary level (Figure 35.13). Even when the ostium is successfully engaged, the catheter tip points up in the left main artery, with a subsequent risk of left main dissection and inappropriate imaging (Figure 35.3). A catheter with a larger arm, i.e., larger primary‐to‐secondary‐curve distance, should be used (e.g., JL5, JL6). Furthermore, in those cases, it is important to advance the catheter over the wire until it reaches the aortic valve before taking out the wire, to prevent the catheter from “flipping” over itself. If, on the other hand, the JL catheter is pointing down underneath the ostium, or the aorta is too narrow for the catheter, a smaller JL arm should be used.

Chapter 35.  Cardiac Catheterization  705

JL4 JL5

(a)

(b)

Figure 35.13  (a) Engagement of the left coronary artery in patients with normal‐size aorta. (b) Engagement of the left coronary artery in patients with elongated aorta. In this case, make sure to advance the catheter all the way to the aortic valve before taking the wire out, otherwise the arm of the JL catheter may fold on itself. Reproduced with permission of Wolters Kluwer Health from Baim DS. Coronary angiography. In Grossman W, Baim DS. Grossman’s Cardiac Catheterization, Angiography, and Intervention, 7th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2006, pp. 187–221.

Other technical tips (Figure 35.14) 1.  When the aorta is too wide, the whole catheter (arm and tip) falls below the coronary origin and points up. a. If the JL4 arm is not too short, one may push the catheter against the aortic valve to reshape it, and keep pushing gently until the tip catches the ostium (step 1 in Figure 35.15). Next, the catheter is slightly pulled until it becomes more coaxial with the ostium (step 2 in Figure 35.15). b. One may pull up the catheter and readvance it with a clockwise torque. Clockwise torque makes the catheter turn up. Asking the patient to take a deep breath may also help, as it straightens the aorta. c. If (a) and (b) do not work, or if the aorta is significantly dilated/elongated, switch to a larger catheter (JL5). 2.  When the aorta is too narrow, only the catheter tip falls below the coronary origin and points down. a. One may pull up and readvance with a clockwise torque to turn the catheter up. b. One may switch to a smaller catheter (JL3.5). Throughout all of these manipulations, the catheter body in the ascending aorta and aortic arch should be monitored. A catheter that is twisted out of its shape indicates an excessive torque that should be reversed.

(i) Elongated wide aorta

(ii) Narrow aorta

Figure 35.14  Two scenarios wherein the JL catheter falls below the left coronary origin and does not engage by a simple pull. In (i), a longer JL arm is needed (e.g., from JL4 to JL5). In (ii), a shorter JL arm is needed (e.g., from JL4 to JL3.5).

1

2

Figure 35.15  JL catheter engagement when it falls slightly below the left coronary ostium in a wide aorta (two steps, 1 and 2).

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VIII.  Management of a JL catheter that is sub‐selectively engaged in the LAD or LCx If the JL4 keeps selectively engaging the LAD in a patient with a short LM or separate ostia for the LAD and the LCx, how can the catheter be directed toward the LCx? Unlike the JR catheter, the JL catheter has a hinge point on the aorta (secondary curve) so that clockwise rotation of the JL catheter moves it posteriorly. Thus, to move the catheter from the LAD to the LCx, which is more posterior, the catheter is typically rotated clockwise. To move the catheter from the LCx to the LAD, the catheter is rotated counterclockwise. In a patient with a large aorta, when the JL4 catheter is not resting on the aorta, the opposite maneuvers may be effective. On the other hand, it is often more effective to switch catheters. Two principles allow the selection of the right catheter: (1) the LAD points up, whereas the LCx points down; (2) a larger JL catheter arm makes the catheter point down and moves the tip from the LAD to the LCx (e.g., JL5 points down in comparison to JL4, EBU4 points down in comparison to EBU3.5). Thus, in order to move the catheter from the LAD to the LCx, one may use a larger JL catheter (JL4 → JL5); in order to move the catheter from the LCx to the LAD, one may use a smaller JL catheter (JL5 → JL4; or JL4 → JL3.5) In addition, when the LM is short, one may use a short‐arm AL catheter to selectively engage the LCx (AL1.5). A short‐arm AL tends to point down (opposite of short-arm JL), and thus would selectively point towards the LCx.

IX.  Specific maneuvers for the Amplatz left catheter A. Engagement Advance a wire until it loops over the aortic valve, then advance the AL catheter all the way over the wire onto the aortic cusp: the tip of the AL must catch the cusp of interest, while the body must sit on the contralateral cusp. Next, push the catheter up with a counterclockwise rotation in order to catch the left coronary ostium, or push with a clockwise rotation in order to catch the RCA ostium (Figure 35.16). During those manipulations, the wire is kept inside the catheter body to improve catheter pushability and torqueability; the wire is pulled out when the catheter is close to the ostium. Once the AL catches the ostium, slightly withdraw the catheter for deeper and more coaxial engagement. When used to engage a SVG, the same AL manipulation is performed, except that the AL catheter is not advanced all the way down to the aortic valve level. The AL is advanced to the ascending aortic level above the native coronary level. The wire is pulled and the AL tip is allowed to catch the aortic wall, then AL is pushed with a clockwise or counterclockwise rotation to catch the appropriate SVG (usually, clockwise torque is used for the left SVG). B. Disengagement If a well‐seated AL is pulled out, the tip has a tendency to be “sucked” in deeper. Thus, in order to disengage an AL, one should push it until it prolapses out of the ostium, then clock it out (push and clock). As opposed to Judkins catheters, AL disengagement should be performed under fluoroscopy. In some cases, pushing the catheter may further advance it inside the artery; therefore, gentle maneuvering under fluoroscopy with a change in strategy may be required. More specifically, when using a small‐curve AL that is not sitting on the valve, i.e. when the tip is not looking upward, pushing the AL catheter may further advance it (Figure 35.17). Also, when an AL guide catheter is used, pushing may further advance rather than retract the catheter; this is because guide catheters are stiffer than diagnostic catheter and are less likely to flip out of the ostium with a push. Thus, when an AL guide is used, one may directly pull it under fluoroscopy, preferably over a balloon catheter.

X.  If you feel that no torque is getting transmitted, what is the next step? 1.  Ensure that the catheter has not been kinked as a result of excessive torquing. A kinked catheter is characterized by a severely damped or erratic pressure tracing. 2.  It is likely that there is severe aortoiliac tortuosity preventing torque transmission. Under fluoroscopy, look at the shape of the catheter in the aortoiliac region to confirm, then exchange the standard short sheath (11 cm) for a long sheath that lands in the distal aorta (23 cm sheath) or better, in the thoracic aorta (45 cm sheath). 3.  A very steep aortic arch may prevent torque transmission. In this case, for the RCA, use a catheter that does not require significant torquing (AR, Williams right).

XI.  Appropriate guide catheters for left coronary interventions Guide catheters have a stiffer shaft but a larger internal diameter than diagnostic catheters. Guide catheters rely on three elements for support: (1) coaxial guide alignment with the coronary takeoff; this is the most important aspect of support and is achieved not just by advancing the catheter into the ostium but by clockwise (RCA guide) or counterclockwise torque; (2) deep engagement; (3) Support from abutting the opposite aorta and/or the aortic valve (AL guides abut both the opposite aortic wall and the aortic valve, while the extra‐ backup guides abut the opposite aortic wall). Guides useful for left coronary interventions (Figure 35.18) • Extra‐backup guides (e.g., EBU, XB, Voda). Those guides have one bend and a long tip, longer than the JL tip, which allows more coaxial and deeper support than JL. While long, the exact tip length varies with the size of the EBU; a relatively shorter tip tends to point towards the upward‐looking LAD, whereas a longer tip points towards the downward‐looking LCx. When the LM is long, an EBU guide with long tip is used and advanced deep into the LM, close to the ostium of the LCx, in order to reduce the non‐supported distance before the sharp LM–LCx angle. • AL guide: AL is particularly useful in patients with a short LM, wherein a short AL guide (AL1.5) points down towards the LCx (Figure 35.19). Outside this, AL1.5 or 2 is useful in cases that require robust support and in transradial cases. An AL guide is also useful in case of a high coronary takeoff (use AL2 or 3, depending on how high the takeoff is and how large the aorta is). • JL guide does not usually provide adequate coaxial support because of the bend at its tip. It is useful for ostial LM intervention or interventions where extra support is not needed (e.g., LM is short and the LAD or LCx is neither calcified nor tortuous). The JL guide has a tip that is even shorter than the diagnostic JL tip.

Left Left

Right

Right (a)

(b)

Left

Left Right

Right (c)

(d)

Figure 35.16  Catheterization of the left coronary artery with an Amplatz left catheter in LAO view, which spreads out the left and right coronary cusps. (a, b) The wire is sent towards the left coronary cusp, then the catheter is advanced over the wire in such a way that its tip catches the left coronary cusp, while its body aims towards the right coronary cusp. The wire is kept inside the catheter for pushability and torqueability. (c) After the tip catches the left cusp, the catheter is pushed with a slight counterclockwise torque until it catches the ostium. (d) The catheter is then pulled for more coaxial engagement.

Figure 35.17  Small‐arm Amplatz catheter. Pushing it may further dive it inside the left coronary artery rather than disengage it.

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-XB 3.5 looks up -Provides support from the opposite aorta (arrow)

XB 4.0 looks down

AL 2 with support from the opposite aortic cusp and the opposite aorta

Figure 35.18  Extra‐backup guides and AL guide for the left coronary artery. XB with the long tip (XB4, as opposed to XB3.5) is useful for LCx intervention (looking down) or for a patient with a long LM. Courtesy of Cordis Corporation.

Figure 35.19  Small‐arm AL guide catheter (AL1) is used to engage the LCx in a patient with a short LM. A small AL arm points down towards the LCx (arrow) and provides good coaxial support for a LCx intervention in a patient with a short LM.

XII.  Appropriate guide catheters for RCA interventions (Figure 35.20) A.  Horizontal RCA takeoff • JR4, hockeystick 1 or 2 (the longer tip of hockeystick 2 may allow deep engagement and extra support in complex cases). B.  Inferior RCA takeoff • First option: multipurpose (multipurpose 2 has a longer tip than multipurpose 1). • Other options: AR1 or 2, right coronary bypass guide (RCB), JR5 or short tip JR4. AL1 may be used if the aorta is dilated, which makes the AL1 point down. C.  Superior RCA takeoff • AL (0.75 or 1) or XB RCA for an upwardly sharp takeoff (“shepherd crook” RCA). These guides provide extra backup support from the opposite aortic wall (Figure 35.21). They are also used in a highly tortuous RCA requiring a lot of support. • Hockeystick 2, internal mammary (IM) guide, 3DRC, left coronary bypass guide (LCB), or JR3.5 may be effective (the shorter arm of JR3.5 points more upward than JR4). They provide support by being coaxial. Hockeystick 2 also allows support through deep intubation of its long tip. D.  High anterior RCA takeoff • AL (0.75 or 1) or hockeystick 2.

Chapter 35.  Cardiac Catheterization  709

Superior RCA takeoff

AL 1

XB RCA

Hockeystick

IM, LCB, 3DRC

Multipurpose for inferior RCA takeoff- May also use AR, RCB, JR 5

Figure 35.20  Guide catheters for superior RCA takeoff and inferior RCA takeoff. Courtesy of Cordis Corporation.

Figure 35.21  AL1 guide catheter engaging the RCA, and providing good backup support from the aortic cusp and the opposite aortic wall.

XIII.  Selective engagement of SVGs: general tips In order to engage SVGs, it is important to understand their locations and takeoffs (Figure 35.22). a.  From bottom to top, one finds SVG‐to‐RCA, then SVG‐to‐LAD or diagonals, then SVG‐to‐OM. b.  The SVG‐to‐RCA originates from the right surface of the aorta, above the RCA and almost in the same plane as the RCA (or slightly more posterior). The SVG‐to‐LAD or SVG‐to‐diagonal branch originates from the anterior surface of the aorta. The SVG‐to‐OM originates from the left posterior surface of the aorta. c.  The SVG‐to‐RCA has a downward takeoff, whereas the SVGs to the left coronary branches have an upward takeoff (particularly upward in the case of SVG‐to‐OM). The SVG‐to‐RCA is best engaged in an LAO view, which is orthogonal to this SVG takeoff. SVGs to the left coronary branches are best engaged in an RAO view, which is orthogonal to the takeoff of these SVGs (Figures 35.22, 35.23) (Right SVG → LAO; Left SVG → RAO). When rings are attached to the SVGs, engage each SVG in a view orthogonal to the ring, i.e., a view where the ring is seen as a straight column.

XIV.  Specific torque maneuvers for engaging the SVGs In order to engage the SVG‐to‐RCA, the catheter is positioned above the level of the RCA, then pulled with a counterclockwise rotation. As opposed to what may make intuitive sense, counterclockwise torquing is used to engage the SVG‐to‐RCA rather than clockwise torquing (this is opposite to native RCA engagement).

710  Part 11.  Cardiac Tests: Invasive Procedures

SVG-to-OM

SVG-toRCA

LCx RCA

RAO

SVG-to-Diagonal

LAO

LAD

Figure 35.22  Location of SVGs: • Down to up: SVG‐to‐RCA, SVG‐to‐LAD or diagonal, then SVG‐to‐OM • Right to left: SVG‐to‐RCA, SVG‐to‐LAD or diagonal, then SVG‐to‐OM • Inferior takeoff for SVG‐to‐RCA. Superior takeoff for SVG‐to‐LAD or diagonal and, more so, SVG‐to‐OM. LAO view is orthogonal to the takeoff of SVG‐to‐RCA, while RAO view is orthogonal to the takeoff of SVG‐to‐left coronary branches.

Figure 35.23  Catheter engaging SVG‐to‐OM graft in RAO view. The ostium of this left SVG is well laid out on an RAO view. The catheter is torqued to aim to the left border of the aorta on this view (dashed line is the aortic contour).

In order to engage an SVG to a left coronary branch, advance the catheter down to the aortic valve, torque it counterclockwise, then pull up and torque clockwise around the expected level of the graft. Overall, a counterclockwise torque is necessary for the right SVG, and a clockwise torque around the graft level is necessary for the left SVG.

If, after engaging one SVG, the catheter keeps falling in this same SVG as one is trying to engage other SVGs, what should be done next? The catheter needs to be moved out of the curvature that keeps leading it into the first SVG. The catheter should be pulled up a few centimeters above this SVG, torqued clockwise or counterclockwise about 90–180° to get out of the same curvature, then advanced to the level where the other SVG is thought to be. Appropriate torquing is then performed at this level. For example, if the catheter keeps falling in the SVG‐to‐diagonal when one is trying to engage the SVG‐to‐OM, withdraw the catheter, torque it counterclockwise at a high level, then advance it and clockwise torque it at the expected SVG‐to‐OM level (above the SVG‐to‐ diagonal level).

Chapter 35.  Cardiac Catheterization  711

XV.  Appropriate catheters for engaging SVGs (see Figure 35.24) A. SVG‐to‐RCA Since this graft has an inferior takeoff, a catheter pointing down is necessary for engagement: 1.  A multipurpose catheter is the most appropriate catheter for this graft. It points down and has a long supportive tip that dives deeply and coaxially into the SVG. 2.  AR1 and right coronary bypass (RCB) catheters are alternatives. The RCB catheter is somewhat similar to JR4, except that its short tip points down. JR4 points slightly up and thus does not usually provide appropriate diagnostic images; the contrast may spill out and give the impression of a non‐filling, occluded graft. Moreover, JR4 is certainly not an appropriate interventional guide for this SVG. B.  SVGs to the left coronary branches JR4 is often an appropriate diagnostic catheter for the left‐sided SVGs. However, since these SVGs have a superior takeoff, JR4 is not an appropriate interventional catheter. Guiding catheters pointing up are usually necessary for SVG intervention: 1.  Hockeystick guide catheter, which is a catheter that has a slightly superior angle. The long‐tip hockeystick 2 guide is preferred to hockeystick 1 for deep engagement and support (Figure 35.25). 2.  AL1.5 or AL2 (depending on the aortic size). 3.  A left coronary bypass (LCB) catheter (short‐tip catheter pointing up), an internal mammary catheter, or JR4 catheter may be used for the SVG‐to‐LAD or diagonal, which tends to have a less superior takeoff than the SVG‐to‐OM. The LCB catheter is somewhat similar to JR4, except that its short tip points up.

Catheters pointing down (SVG-RCA):

JR 4

RCB

AR 1

AL

Hockeystick

Multipurpose 1

Multipurpose 2

Catheters pointing up (SVG-left coronary): LCB

IM

Figure 35.24  Shapes of various catheters.

Figure 35.25  A hockeystick 2 guide catheter is used to engage the SVG‐to‐OM graft in an RAO view. The long arm of the hockeystick 2 points slightly upward, which proves very useful in left‐sided SVG interventions (arrow). It allows both coaxial and backup support.

712  Part 11.  Cardiac Tests: Invasive Procedures

XVI.  Engagement of the left internal mammary artery graft Steps necessary to engage the left internal mammary artery (LIMA) graft (Figure 35.26): 1.  Position a JR4 catheter in the aortic arch, then pull it back with a counterclockwise rotation until the left subclavian is engaged. This is performed in the LAO view, because the LAO view opens up the aortic arch and the origins of the major vessels. 2.  Advance an exchange‐length wire into the left subclavian artery. If the subclavian artery is very tortuous, a polymer hydrophilic wire (Glidewire) is used to maneuver through the left subclavian artery. 3.  Then advance an exchange‐length wire and exchange the JR4 catheter for an internal mammary (IM) catheter. Advance the latter over the wire beyond the bend of the subclavian artery. 4.  An AP or RAO view may be used in order to selectively engage the LIMA. The RAO view foreshortens the subclavian but is orthogonal to the LIMA takeoff. Pull the IM catheter with a slight counterclockwise torque until it engages the LIMA. During this process, inject small puffs of contrast to identify where the LIMA originates. LIMA often originates around the subclavian bend, but it may originate a bit more distally or proximally before the bend. The LIMA is between the vertebral artery and the thyrocervical trunk. Seeing the thyrocervical trunk during a puff injection points to a need to pull the catheter slightly more. Occasionally, if the aorta and the subclavian artery are too tortuous, leave the 0.035” wire in the IM catheter during torque manipulations to provide more stiffness and allow more torque transmission to the catheter. Also, make sure a long 45 cm sheath is advanced in the aorta for support. 5.  After obtaining the LIMA views, the catheter is disengaged and pullback pressure recorded across the ostium of the left subclavian artery. One of the most common causes of ischemia in the LIMA‐to‐LAD territory is left subclavian stenosis, and this should be systematically checked. If the LIMA graft proves difficult to engage, do not persevere in the engagement attempts, as there is a risk of dissecting the LIMA ostium. Perform non‐selective imaging near the LIMA ostium, with a relatively higher volume of contrast (e.g., 5 ml/s for 12 ml). In addition, inflate a blood pressure cuff across the left arm and perform the contrast injection at the peak cuff inflation. This diverts the non‐selective contrast into the LIMA. If the left subclavian artery proves difficult to engage, perform an aortic arch angiogram to analyze its takeoff. It is likely that the aortic arch is a type III arch, with the left subclavian originating more proximally than thought, proximal to the aortic arch bend. When the LIMA needs to be engaged for interventional purposes and difficulty is encountered, a 0.014” hydrophilic or a soft coronary wire is used to selectively enter the LIMA, then the guide is gently tracked over this wire. The right internal mammary artery (RIMA) is engaged using the same steps as the LIMA, with a counterclockwise torque to enter the right innominate in an LAO view. However, an RAO caudal view may be needed to open the subclavian–carotid bifurcation and allow wiring of the subclavian. Once the IM catheter is advanced into the right subclavian, the LAO view is more appropriate to cannulate the ostium of the RIMA, and the catheter needs to be clockwise torqued rather than counterclockwise torqued.

Vertebral artery

Thyro-cervical trunk

Subclavian artery

LIMA RAO view

LAO view LAO view (a)

(b)

(c)

Figure 35.26  (a) Engagement of the left subclavian artery with a JR4 catheter (counterclock), followed by wire advancement into the left subclavian artery, then catheter exchange for an IM catheter, then engagement of the LIMA. (b) LIMA is between the vertebral artery and the thyrocervical trunk, at the subclavian bend. (c) The engaged IM catheter is shown in an RAO view, which foreshortens the subclavian artery but opens up the ostium of the LIMA.

Chapter 35.  Cardiac Catheterization  713

XVII.  Left ventricular catheterization The LAO view may be used, as it displays the right and left coronary sinuses and the aortic orifice in between; it is particularly useful when a wire is used to cross the valve, to ensure that the wire does not go into the coronary arteries. After crossing the aortic valve, RAO view may be used, as it is orthogonal to the long axis of the LV and allows proper catheter positioning in the mid‐LV. In the absence of aortic stenosis, a pigtail catheter is used to access the LV (Figure 35.27). A guidewire is kept inside the pigtail catheter all the way to the tip, but not beyond the tip. This wire provides stiffness and support to the catheter, particularly when a 4 Fr pigtail catheter is used. The valve is crossed with the pigtail catheter itself: the pigtail is advanced over the aortic valve and allowed to loop (figure‐of‐9), then pulled back with a slight clockwise or counterclockwise torque; it may fall into the LV during this pullback. If it does not, slightly torque the catheter to direct it in a different plane, then readvance it and pull it. This maneuver is repeated, each time with a slightly different torque. The loop has to be over the center of the valve, not eccentric over one cusp. If the catheter repeatedly fails to fall into the LV, one may advance the wire beyond the pigtail catheter and use it to access the LV (the wire is directed through catheter torque). If the catheter arm falls in the LV but the pigtail tip is still in the aorta, advance the wire beyond the tip. This will invariably make the whole catheter fall in the LV (Figure 35.28). Aortic stenosis In aortic stenosis, the left ventricle is accessed using an Amplatz left (usually AL1), multipurpose, or Judkins right catheter pointing toward the aortic valve orifice and a straight‐tip 0.035” wire (e.g., straight‐tip, stiff‐shaft Glidewire). The LAO view is used as it opens up the left and right cusps and allows one to aim at the aortic orifice in between and avoid the coronaries, as opposed to the RAO view that superimposes the left and right cusps. The catheter is torqued in a way that looks toward the aortic orifice, and the wire is advanced; the catheter is used to direct the wire in various planes. It is often best to start with an aortic cusp injection (6 ml/s for 12 ml) to localize the exact AS jet, so that one can point the catheter/wire toward it. Serial catheter rotations with wire readvancement are performed until the wire crosses the aortic valve. Beside torquing, the catheter may be slightly advanced and pulled to direct the wire in different planes. The key to successful crossing of a stenotic valve is to aim in the direction of the aortic orifice (Figure 35.29). The valve calcification seen on fluoroscopy is also a useful guide to the location of the aortic orifice. To reduce the risk of stroke during these manipulations, the catheter is flushed every 2 minutes and heparin anticoagulation is provided. After crossing the valve, the Amplatz catheter is exchanged for a double‐lumen pigtail catheter using a long 260 cm Amplatz super‐ stiff wire. Amplatz wire has a soft atraumatic but non‐supportive tip which should be shaped into a large pigtail curve to allow stable positioning in the LV during catheter exchanges. Simultaneous LV and aortic pressures are recorded through the double‐lumen catheter. The cardiac output is simultaneously obtained through a Swan catheter that has been left in the PA, and the valve area is calculated.

Figure 35.27  Pigtail catheter advancement. This is an LAO view, but one may use an RAO view. Advance the wire as far as the tip of the catheter to stiffen it, advance the catheter, then pull back with a slight clockwise or counterclockwise torque. Reproduced with permission of Wolters Kluwer Health from Baim DS. Coronary angiography. In Grossman W, Baim DS. Grossman’s Cardiac Catheterization, Angiography, and Intervention, 7th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2006, pp. 187–221.

The pigtail bend is in the LV but the pigtail tip is not advance a wire the whole system falls all the way in. Figure 35.28  Dealing with a situation when the pigtail bend is in the LV, but the pigtail tip is not.

714  Part 11.  Cardiac Tests: Invasive Procedures

1

2

3

Figure 35.29  Various aortic root shapes, with various locations of the aortic orifice on LAO view. A different catheter is necessary in each case to direct the wire into the aortic orifice: (1) JR4; (2) Multipurpose catheter; (3) AL1 or 2 catheter. This aortic orifice is often indirectly localized using the aortic valve calcifications. Moreover, an aortic cup injection (6 ml/s for 12 ml) helps localize the exact AS jet, so that one can point the catheter/wire toward it. The aortic configuration (3), wherein the aorta is severely elongated and horizontal while the aortic valve is vertical, is commonly seen in elderly patients.

XVIII.  Engagement of anomalous coronary arteries A.  Anomalous LCx originating from the right coronary sinus This anomalous LCx always has a posterior course and an origin posterior to the RCA. It points downward. It may be engaged by: (1) further clockwise rotation of the JR4 catheter beyond the origin of the RCA; (2) use of a catheter pointing down such as AR or RCB, or, better yet, multipurpose (multipurpose being the best guide for anomalous LCx intervention). B.  Anomalous LM originating from the right sinus Unless it takes a less common posterior course, this anomalous LM is usually anterior to the RCA, and has a downward takeoff. It is best engaged with a multipurpose catheter, AR, or a short AL (AL0.75 or 1), with a clockwise rotation from the neutral position. C.  Anomalous RCA originating from the left sinus This RCA is usually anterior and more cephalad than the LM. It can be engaged with a large AL (e.g., AL1.5 or 2) or a long JL catheter (JL5) that is sometimes pushed and looped over the aortic valve. A JL catheter is usually successful when the RCA is close to the LM, while AL may be necessary when the RCA is anterior.

XIX.  Specific tips for coronary engagement using a radial approach A. Tips Four important tips are critical to successful coronary engagement through a radial access (Figure 35.30): • The guidewire should be advanced and looped over the aortic valve. The catheter should then be advanced over the wire all the way until it touches the aortic valve below the coronary ostia. This allows the catheter to be appropriately shaped and prevents it from sliding out of the ascending aorta (the catheter approaches the coronary ostium from below). This is not necessary in femoral manipulations, except if the aorta is large or if AL is used. • The catheter should not only touch the aortic valve, it should be maneuvered to specifically touch the corresponding cusp (e.g., left coronary cusp for left coronary engagement). If the catheter does not fall swiftly into its cusp, the wire is directed toward this cusp and the catheter is then advanced over it. • Engagement of the coronary ostia is facilitated by leaving the guidewire within the catheter to enhance torqueability and prevent the catheter from looping on itself. This is particularly important in the left coronary engagement and in patients with tortuous subclavian vessels or a short ascending aorta (short patients). • A deep breath vertically elongates the aorta and the subclavian artery and attenuates the sharp catheter turn from the subclavian into the aorta, which facilitates engagement. Also, a long sheath (25 cm) may circumvent tortuous radioulnar loops and any spastic area, improving torqueability. A long sheath limits the spasm that may occur later on, during catheter advancement or exchange through the radial artery, and is advised during interventions or when multiple catheters are exchanged. If the wire keeps falling into the descending rather than ascending aorta, the catheter should be used to direct the wire into the ascending aorta, generally with a counterclockwise maneuver, and the patient may be asked to take a deep breath (this vertically elongates the aortic arch and the origins of the left subclavian and right innominate, creating a more vertical angle into the ascending aorta). A Glidewire may be used during these manipulations, as it more easily slips into the ascending aorta. B.  Importance of patient’s height, subclavian tortuosity, right radial vs. left radial Short patients with short and steep aortas are difficult to engage from a right radial access, as the catheter will take a sharp turn from the innominate artery into the ascending aorta, which reduces torqueability and increases the chance of catheter loop and prolapse out of the ascending aorta (Figure  35.30B). A deep breath elongates the aorta and may facilitate coronary engagement; a left Amplatz catheter advanced over the wire onto the aortic valve may prove useful (Figure 35.31).

Chapter 35.  Cardiac Catheterization  715

(a)

(b)

(c)

Figure 35.30  Engagement of a coronary artery through a radial approach. (a) It is best to advance the catheter over the wire all the way down to the valve before starting the manipulations, to ensure appropriate catheter shaping and prevent the catheter from looping on itself or sliding out of the ascending aorta into the arch. (b) A short ascending aorta translates into a sharper catheter turn into the ascending aorta, less support, and more tendency to loop and prolapse out of the ascending aorta. (c) A left radial approach is associated with a less sharp turn at the aortic level, and thus easier catheter maneuvering and support than a right radial approach.

AL sits on the aortic valve

Figure 35.31  AL2 is used to engage the left coronary artery through a right radial approach in a patient with a short aorta. Amplatz left catheters may prove useful if the special radial and Judkins catheters are unsuccessful. They sit on the aortic valve and are less likely to loop and prolapse, providing good support.

In addition, severe tortuosity of the right subclavian and the right innominate–aortic arch junction is much more common than left subclavian tortuosity (10–20% vs. 5%), which further complicates the right radial approach (Figure 35.32). This is particularly common in patients with several of the following four features: short stature, old age (>75), female sex, and hypertension. A left radial access may, thus, be preferred in patients with several of those features (e.g., old patients of short stature) or those with severe right subclavian tortuosity. A hydrophilic Glidewire is frequently needed to cross the subclavian loops. A catheter advanced through the left radial access follows a path close to the femoral path, with a less sharp turn at the ascending aortic level than a right radial access. The support from a left radial access is therefore generally better, and a left radial access is particularly useful in patients with short aortas (Figure 35.30C). A left radial access is more readily feasible in patients with a small body habitus, wherein the operator works from the right side of the patient and leans over to the left, similarly to using a left femoral access.

716  Part 11.  Cardiac Tests: Invasive Procedures

Advance catheter over the wire then pull to straighten the loop

Figure 35.32  Severe right subclavian/ innominate tortuosity or loop is present in ~10–20% of patients, especially elderly (>75), short, hypertensive, and female patients. A hydrophilic 0.035” wire (Glidewire) is used to traverse the tortuosity, ideally as the patient takes a deep breath, then advanced far into the aorta. The catheter is then advanced over the wire as far as possible. The whole system is then pulled back (right image), which allows the tortuosity to straighten.

Tiger catheter

Jackey catheter

Ikari left 3.5 catheter

JL3.5 catheter

Figure 35.33  Specific radial catheters, particularly helpful for a right radial approach. Compare them to JL catheter. (i) Tiger and Jackey: note the long secondary curve that allows the catheter to rest over the contralateral aorta for support (arrows). Tiger’s tip tends to point up, while Jackey’s tip may point down. (ii) Ikari left: unlike the limited aortic contact of JL, Ikari has a long secondary curve that sits on the opposite aortic wall and provides good support (stars). In addition, Ikari left has a natural bend that embraces the right innominate angulation (arrowhead), attenuating the catheter’s tendency to turn over itself (dashed JL catheter).

C.  Judkins catheter sizes in transradial procedures; catheters for diagnostic and interventional transradial procedures • From a left radial approach, no change in Judkins arm size is generally needed for right or left coronary engagement. • From a right radial approach: (1) left coronary engagement usually requires a catheter that is 0.5 smaller than what would be used with the femoral or left radial approach (e.g., JL3.5, XB3 or 3.5); (2) RCA requires the same curve or a larger one (e.g., JR5). • Special radial catheters may be used, and these are particularly useful during a right radial approach. Tiger and Jackey catheters are useful diagnostic catheters; the Tiger catheter points upward, while the Jackey catheter generally points downward (Figure 35.33). • Amplatz left catheters may prove useful if the special radial and Judkins catheters are unsuccessful. They sit on the aortic valve and are less likely to loop and prolapse, which allows them to provide good support, particularly during interventions (Figure 35.31). • For diagnostic procedures: Tiger/Jackey (for both left and right coronary arteries) or Judkins catheters are the initial catheters used. • For simple left coronary interventions, a Judkins catheter or Ikari left catheter may be used. • For complex left coronary interventions, the following may be used: AL catheter (AL1.5 or 2), EBU catheter, or the Ikari left catheter, which is a modified Judkins catheter designed to embrace the brachiocephalic angle and the aortic wall. From a transradial approach, EBU and Ikari left are manipulated somewhat similarly to AL (Figure 35.16): (i) they are initially advanced until their tip catches the left cusp (over the wire); (ii) they are then pushed against the cusp in a U fashion until their tip points up and catches the ostium. Alternatively, Ikari left may just be pulled to engage the ostium, similarly to a Judkins catheter. In a way, Ikari left may be maneuvered either as an EBU‐like or a Judkins‐like catheter. • For simple RCA interventions, JR4 or JR5 may be used. • For complex RCA interventions, AR (especially the longer-tip AR2), hockeystick 2, or AL0.75 catheter may be used.

Chapter 35.  Cardiac Catheterization  717

D.  How to engage the RCA using the Tiger catheter that was used for left coronary engagement After engaging the left coronary and obtaining the images with a Tiger catheter, the catheter is disengaged under fluoroscopy, then slightly pulled with a torque maneuver to get out of the left coronary plane. The catheter is then pushed down to the valve, avoiding the plane of the left coronary ostium. At this point, the catheter is pulled with a slight clock or counterclock maneuver to engage the RCA. It is generally easier to engage the RCA from a radial approach than from a femoral approach, and less torque is generally required. Furthermore, the catheter is less prone to diving down. While the RCA is engaged with a clockwise rotation from a femoral approach, a clockwise or counterclockwise rotation may prove useful from a right radial approach.

XX.  Damping and ventricularization of the aortic waveform upon coronary engagement When a catheter engages a coronary artery, the pressure at its tip may damp or ventricularize. Damping is characterized by flattening of the pressure tracing with significant drop in the systolic and diastolic pressures; it indicates pressure reduction at the tip of the catheter (Figure 35.34). Ventricularization is characterized by a change in pressure from an aortic to a “ventricular‐like” tracing and reflects severe ostial narrowing. The stenotic lesion restricts blood flow into the engaged artery from which the pressure is being recorded; since coronary flow mainly occurs in diastole, the drop in pressure across the stenosis is mainly diastolic. Ventricularization may be obvious and may manifest as a severe drop in diastolic aortic pressure and a change from a triangular to a rectangular shape. Subtle or early ventricularization is more common and is identified by two features: (1) diastolic pressure changes from downsloping (aortic) to upsloping (ventricular); (2) A waves appear on the tracing. Also, in addition to the drop and change in diastolic pressure, the systolic pressure usually decreases during ventricularization. Damping that occurs before engagement of a coronary artery usually alerts to the presence of air or clot in the catheter, or to twisting of the catheter after excessive torquing. Damping upon coronary engagement has several causes: (1) severe ostial disease, with the catheter further reducing or occluding flow across the ostium and leading to reduced pressure in the coronary artery; (2) ostial spasm; (3) small coronary artery engaged with a large catheter that occludes it, particularly when a right coronary catheter selectively engages the small conus branch; (4) catheter against the arterial wall or against a plaque which damps the pressure at its tip. Ventricularization only occurs with ostial narrowing (causes [1] to [3]) and is not seen when a catheter is against the arterial wall. Since damping and ventricularization often signify occlusion of flow across the ostium, injecting contrast while damped or ventricularized replaces the remaining oxygenated blood with contrast. The latter is not quickly cleared because of reduced flow, which further reduces myocardial oxygen supply. Lack of contrast clearance from the coronary arteries or, worse, from the myocardium (myocardial stain) is a serious consequence of damping, which imminently leads to ischemia and ventricular fibrillation and dictates immediate catheter disengagement. In addition, vigorous injection while damped or ventricularized may lead to coronary dissection, since the catheter is surrounded by ostial disease or is against the vessel wall. It may also lead to embolization of thrombus or air if these were the causes of damping. Thus, one should not inject contrast or flush with saline while damped or ventricularized, but should disengage and attempt to re‐ engage after taking a non‐selective image to check for ostial disease, attempt to engage the right coronary if the conus branch was previously engaged, and administer sublingual nitroglycerin if ostial spasm was likely. A catheter with side holes allows contrast clearance, reduces the risk of ventricular fibrillation, and provides some coronary perfusion while the catheter is seated in the coronary artery between coronary injections; it may be useful during a coronary intervention where the guiding catheter has to remain engaged for a prolonged time. Yet, it is important to realize that a catheter with side holes only partly reduces catheter‐related ischemia and does not prevent the dreaded risk of dissection. Moreover, this catheter will transmit a normal pressure recording that is partly related to the transmission of pressure from the side holes positioned in the aorta, rather than from the tip positioned at the ostium, therefore providing a false reassurance. The spilling of contrast in the aorta results in lower image quality and greater contrast use. During a coronary intervention, ventricularization often occurs when the guiding catheter is too deeply engaged, particularly if the artery is small or has moderate ostial disease. Slight pullback or torque is appropriate. Interestingly, the administration of nitroglycerin may induce or worsen ventricularization early on; the increase in flow induced by vasodilators may worsen the drop in pressure across the ostial obstruction, particularly diastolic pressure, leading to ventricularization (drop in pressure = flow × resistance). However, nitroglycerin may improve ventricularization later on, once spasm, a component of ostial obstruction, is relieved.

150

100

50

0

mmHg

Damping

Ventricularization

Figure 35.34  Examples of damping and ventricularization of the aortic pressure upon coronary engagement. In ventricularization, the diastolic pressure does not necessarily drop to levels that are as low as the left ventricular diastolic pressure, but the shape of the tracing changes from an arterial one to a ventricular one, i.e., the diastolic segment between the spikes is upsloping (arrow) and A wave is seen (arrowhead).

718  Part 11.  Cardiac Tests: Invasive Procedures

XXI.  Technique of right heart catheterization 1.  From jugular, subclavian, brachial, or femoral venous access, the right heart catheter is advanced to the RA. At this point, the catheter is connected to the pressure transducer (through the manifold, for example) and flushed, and the RA pressure is recorded after ensuring proper zeroing at the mid‐chest level. 2.  The catheter is then advanced to the RV, then the PA, while the balloon at the tip of the catheter is inflated and pressures are recorded. Special handling is required when a femoral access is used. At the base of the RV (bottom part of the cardiac silhouette), the catheter is pushed, then torqued clockwise with a slight pull until it points superiorly and falls into the PA. Deep inspiration and cough may assist in crossing the pulmonic valve and advancing the catheter distally. Alternatively, the catheter tip may be “hooked” in the ostium of a hepatic vein or directed towards the lateral RA with the balloon inflated. When advanced, it creates a loop in the RA. Once a loop is formed, further catheter push directs the tip of the loop towards the RV, then towards the RVOT and PA (Figure 35.35). A Swan wire or a supportive 0.014” wire may be advanced beyond the catheter tip, with the balloon inflated, and used to cross the pulmonic valve into the PA. This wire is particularly helpful in patients with dilated RV. The wire also provides stiffness to the catheter and helps it track into the distal PA, preventing its prolapse into the RV. The catheter is advanced over the wire while the balloon is inflated, except in TR, where the inflated balloon may project the catheter backward, along the regurgitant flow. 3.  After recording the PA pressure, the catheter is advanced with the balloon inflated until it wedges, i.e., the tip becomes immobile on fluoroscopy and one sees a change from PA pressure to PCWP on the monitor. PCWP is recorded, the balloon is then deflated and the catheter pulled back to the PA position. Avoid flushing in the PCWP position, as this may injure the pulmonary capillaries. 4.  Cardiac output (CO) is measured using the thermodilution technique while the catheter is in the PA. Also, an oxygen sample is obtained from the PA (both for CO calculation using the Fick equation and for detecting a shunt). An oxygen sample is simultaneously obtained from the arterial sheath to calculate Fick CO. 5.  The catheter is then pulled back and SVC and IVC blood samples obtained for oximetry (shunt screen). All oximetry samples should be collected within a few minutes in a calm steady state to avoid fluctuation of O2 consumption and mixed venous O2 saturation in the same patient. If catheterization is performed from a femoral access, the SVC is easily engaged by advancing a multipurpose catheter over a 0.035” wire into the SVC, immediately after removing the Swan catheter. The Swan catheter does not float easily into the SVC.

Swan wire

RA

RV

(b)

RA RV Hepatic vein (a) Figure 35.35  (a) Catheter loop at the lateral RA wall allows advancement into the PA (top image). The catheter tip may also be hooked at the ostium of a hepatic vein (bottom image), pushed until it loops in the RA, then released with balloon deflation. In right HF with dilated hepatic veins, the catheter tends to dive deeply into the hepatic vein (unwanted effect) rather than be “stuck” at its ostium. (b) Alternatively, the catheter is kept straight, and a Swan wire advanced into the PA. These techniques are especially useful in patients with dilated RV and/or TR. Remember that cough and deep inspiration also allow easier catheter tracking into the PA.

Chapter 35.  Cardiac Catheterization  719

6.  Left heart catheterization is performed afterward. 7.  In special settings, simultaneous tracings may be necessary. During simultaneous recordings, “re‐zero” both transducers simultaneously at the same level. After simultaneous recordings, switch catheter–transducer connections and ensure that the measurements and the pressure gradient remain unchanged (indirectly proving proper zeroing) a. When suspecting constrictive pericarditis, standard right heart catheterization is initially performed. Afterward, the LV is accessed and simultaneous LV pressure and PCWP recordings are obtained, followed by simultaneous LV and RV pressure recordings. These recordings may be repeated after a saline challenge. b. When assessing for aortic stenosis, right heart catheterization is performed first and the right heart catheter is left in the PA. The left ventricle is then accessed, using the technique described in Section XVII. Simultaneous LV–aortic pressure tracings are then recorded through the double‐lumen catheter. CO is simultaneously obtained through the Swan catheter that was left in the PA, and the valve area is calculated. c. When assessing for mitral stenosis, right heart catheterization is performed first and the right heart catheter is left in the PA. The left ventricle is then accessed and simultaneous LV pressure and PCWP recordings are obtained. CO is obtained (or repeated) after pulling the right heart catheter into the PA. In order to adequately calculate valve area, make sure CO is performed close to the timing of gradient measurement. Some maneuvers may be performed if needed (e.g., handgrip, exercise), after which LV pressure, PCWP, PA pressure, and CO are evaluated again. d. If pulmonary hypertension is not associated with an increased PCWP, and if pulmonary arterial hypertension is suspected, a vasodilator may be infused and PA pressure, PCWP, and systemic pressure reassessed at each up‐titration. During the last titration of the vasodilator, measure CO and assess RA pressure on pullback. Note The right bundle being a slender bundle, the right heart catheter may produce a transient RBBB. In a patient with LBBB, this may lead to complete AV block. Beware of AV block in any patient with LBBB undergoing right heart catheterization. A temporary pacemaker should be readily available.

36  Hemodynamics

I. Right heart catheter  720 II. Overview of pressure tracings: differences between atrial, ventricular, and arterial tracings  720 III. RA pressure abnormalities  720 IV. Pulmonary capillary wedge pressure (PCWP) abnormalities  720 V. LVEDP 725 VI. Cardiac output and vascular resistances  726 VII. Shunt evaluation  727 VIII. Valvular disorders: overview of pressure gradients and valve area calculation  729 IX. Dynamic LVOT obstruction  733 X. Pericardial disorders: tamponade and constrictive pericarditis  735 XI. Exercise hemodynamics  736 Appendix 1. Advanced hemodynamic calculation: a case of shunt with pulmonary hypertension  737 Questions and answers: Additional hemodynamic cases  738

I.  Right heart catheter (see Figure 36.1) For catheterization technique, see Chapter 35, Section XXI.

II.  Overview of pressure tracings: differences between atrial, ventricular, and arterial tracings (Figures 36.2, 36.3, 36.4) III.  RA pressure abnormalities Summary of RA pressure abnormalities (Figures 36.5, 36.6, 36.7): • Deep X and deep Y descents: constrictive pericarditis, restrictive cardiomyopathy, and, most frequently, severe RV failure. Deep X and deep Y descents reflect loss of atrial and ventricular compliances, wherein atrial pressure goes sharply down and then up; they may also reflect the distension of the pericardium and the functional constriction seen in severe RV dilatation. • Large V wave with deep Y descent: severe TR and/or RV failure. The X that precedes the V wave may be flattened and “carried up” by the large V wave (flat X = systolic flow blunting). • Deep X and flat Y (blunting of diastolic flow): tamponade (mnemonic: Flat Y Tamponade = FYT). In tamponade, not only is chamber compliance impaired, but ventricular filling is totally impeded in diastole, explaining the flat Y. Y may also be flat with sinus tachycardia. • Large V wave: severe TR and/or RV failure. In severe TR, the V wave is not only tall but wide and plateaus throughout systole, approximating the RV systolic pressure; this leads to a ventricularized RA pressure. • Large A wave: impaired RV compliance.

IV.  Pulmonary capillary wedge pressure (PCWP) abnormalities PCWP is obtained by inflating the balloon‐tipped catheter in a distal PA position until it occludes the PA branch. This leads to a stagnant column of blood beyond the balloon, the pressure of which equalizes with the downstream pulmonary venous pressure and thus the LA pressure. Similarly to LA pressure, PCWP has A, X, V, and Y waves. Mean PCWP is equal to mean LA pressure. However, PCWP is delayed ~50–100 ms in comparison to LA pressure because of the delay in retrograde pressure transmission from the LA through the pulmonary vasculature; therefore, PCWP’s A and V waves peak later than LA’s A and V waves. In addition, PCWP has a smoother contour with less steep and deep V downslope than LA pressure, as the pressure waveform gets damped while being transmitted from the LA through the pulmonary capillaries.

Practical Cardiovascular Medicine, First Edition. Elias B. Hanna. © 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.

720

Distal port + thermistor +balloon (deflated) Thermistor port

Balloon port Distal port yellow Proximal port blue

PA

Distal port opening + thermistor

Balloon

Proximal port

Proximal port opening 30 cm from catheter tip

RA

RV Distal Proximal yellow port blue port Balloon port Thermistor Figure 36.1  The Swan–Ganz balloon flotation catheter has four ports. (1) The distal yellow port communicates with the distal tip of the catheter; it is connected to the transducer and used to obtain pressures as the catheter is advanced through the right‐sided chambers (RA → PA → PCWP). (2) The proximal blue port communicates with another lumen, 30 cm proximal to the tip. When the catheter tip is in the PA, the blue port opens in the RA; at this location, the blue port is used to inject saline into the RA and obtain cardiac output by the thermodilution technique. The blue port may also be used to record RA pressure simultaneously with PA pressure, particularly when a Swan–Ganz catheter is used for continuous monitoring in the cardiac unit. (3) The balloon port communicates with the distal balloon and allows wedging of the catheter tip (PA pressure → PCWP). (4) The temperature sensor port also communicates with the distal catheter tip; after cold saline is injected through the blue port (RA), the temperature sensor (PA) analyzes the temperature change over time and allows calculation of CO. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

Arterial pressure (Ao or PA)

Ventricular pressure (LV or RV) Atrial pressure (LA or RA) a

c

v

y

x

R T P S

Systole

Diastole

Figure 36.2  Timing of atrial, ventricular, and arterial pressures in relation to each other and to the ECG. 1. Atrial pressure has an A wave that follows the P wave, and a V wave that peaks at or after the end of the T wave and almost intersects with the ventricular pressure descent (slightly precedes it). Unlike the ventricular and arterial pressures, which peak during the ST–T segment, atrial pressure peaks before the ST–T segment (A wave) and after the ST–T segment (V wave). 2. Ventricular pressure increases in diastole and has an A wave. 3. Arterial pressure decreases in diastole, has no A wave, and has a dicrotic notch (the latter 3 features distinguish it from ventricular tracing). Ventricular end‐diastolic pressure (EDP) is the post‐A ventricular pressure and corresponds to the peak of R wave (black dot).   Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

722  Part 11.  Cardiac Tests: Invasive Procedures

P

T

25 mmHg

a

v

a

v

v

a

a c

c 0 mmHg

x

y

x

X descent and V upslope =systolic events

y

x

y

x

y

V peak, Y and A =diastolic events

Figure 36.3  Atrial pressure tracing (RA or PCWP). A wave corresponds to atrial contraction and follows the electrocardiographic P wave. X descent corresponds to the atrial relaxation and to the downward pulling of the tricuspid annulus in early systole. V wave corresponds to atrial filling during ventricular systole while the tricuspid valve is closed. Y descent occurs in early diastole as the tricuspid valve opens and the RA rapidly empties. Thus, X descent and the upslope of V wave are systolic events (coincide with the pulse), whereas the peak of V wave, the Y descent, and the A wave are diastolic events. V wave corresponds to atrial compliance (a large V wave implies a volume overload that overwhelms the atrial compliance). On the other hand, A wave corresponds to ventricular compliance. In normal individuals, RA pressure is characterized by A wave > V wave. LA is normally less compliant than RA, because it is constrained by pulmonary veins and it is thicker than RA, and thus LA V wave > A wave. The C wave is a small positive deflection on the atrial tracing that sometimes interrupts the X descent; it corresponds to the brief protrusion of the tricuspid valve into the RA in early systole during isovolumic ventricular contraction. The A wave is only seen in sinus rhythm; it is not seen in atrial fibrillation (AF). However, a C wave may be seen in AF and may mimic the A wave. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

EDP EDP a

v a

a

v a v

v

x y

RA

RV

PA

PCWP

LV

Figure 36.4  RA, RV, PA, and PCWP tracings obtained while advancing the catheter from RA to PA. LV pressure from LV catheterization is shown. In general, mean RA pressure is equal to RV diastolic pressure, and mean PCWP is equal to PA diastolic pressure and LV end‐diastolic pressure. RA pressure and RV end‐diastolic pressure are lower than PA diastolic pressure and PCWP, except in cases of “equalization of diastolic pressure” (tamponade, constriction, severe RV failure). Concerning RA and PCWP pressures: note the A, X, V, Y waves and the timing of A and V waves (V peaks after ECG T wave). Concerning PA: in contrast to the RV pressure, which increases throughout diastole (upsloping) and has A wave bump, PA pressure decreases throughout diastole (downsloping), does not have an A bump, and has a dicrotic notch. In contrast to the RA or PCWP tracing, the systolic PA peak occurs during the ST–T interval and the PA pressure is downsloping in diastole. Example of normal pressures (in mmHg): RA pressure (mean) = 5; RV pressure = 25/5; PA pressure = 25/12; PCWP = 12; LV pressure = 120/12 (LVEDP = 12) Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

A.  Differential diagnosis of a large V wave A large V wave is a V wave that is ≥ 2× the mean PCWP, or ≥ 10 mmHg larger than the mean PCWP. While classically associated with severe MR, a large V wave implies volume overload that overwhelms the LA compliance. Thus, V wave may not be large in severe but compensated chronic MR (e.g., asymptomatic MR patients), and may, on the other hand, be large in decompensated HF even in the absence of MR. In fact, the causes of a large V wave are: (1) severe and decompensated MR; (2) decompensated LV failure; (3) mitral stenosis; (4) VSD. In one study, ~40% of patients with a large V wave did not have significant MR, while only 40% of patients with severe MR had a large V wave.2 A gigantic V wave, i.e., a V wave that is ≥ 2.5× the mean PCWP, or >50 mmHg, is usually secondary to MR.

Chapter 36.  Hemodynamics  723

25

a

v

a

c v

a

v

x

x

x

y

y

a

v

v

x y

y

a

a

v

a v

x

y

0 mmHg

Figure 36.5  Typical deep X and deep Y descents on RA tracing, consistent with constrictive pericarditis but also with restrictive cardiomyopathy and severe RV failure. In severe RV failure, a large V wave with a flattened X descent may also be seen. V wave and Y descent become particularly prominent in inspiration (end of the tracing).   Normally, mean RA pressure declines with inspiration. A flat RA pressure without significant inspiratory drop of the mean, as in this case, is characteristic of RV failure and constriction. Only the depth of Y descent changes with inspiration. In severe RV failure, RA and RV compliances are severely overwhelmed, such that RA pressure may paradoxically rise with the inspiratory rise in preload, despite the direct transmission of negative intrathoracic pressure.   Reproduced with permission from Hanna and Glancy (2012).1

a c x

v

a

v

y

y x

Figure 36.6  Deep X with flat Y on RA tracing, suggestive of tamponade. This may also be seen with sinus tachycardia, which shortens diastole and may thus attenuate Y descent. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

v 25

v a

y

0

v a

25

y RA

0

RV

Figure 36.7  Ventricularized RA pressure in a patient with severe TR. The V wave is not only ample but wide and peaks during the ST–T segment, similarly to the RV systolic pressure. Note that Y descent is deep but X descent is flattened. Compare to RV pressure in the same patient. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

B.  Differentiate a large V wave from PA pressure A large V wave may resemble PA pressure (Figures 36.8, 36.9). Five features help differentiate PCWP from PA pressure: • V wave peaks after T wave, whereas systolic PA pressure peaks during T wave. • V wave has a gradual upslope and a sharp downslope, which is opposite to the PA pressure (V wave has a more “peaked,” narrow appearance). • The segment between V waves is rather horizontal or upsloping and an A wave is usually seen, whereas on the PA pressure tracing the segment between the systolic peaks is downsloping, has a dicrotic notch, and does not have an A wave. • Mean PCWP should be ≤ diastolic PA pressure and 95%), whereas PA saturation = mixed venous saturation. This is the best confirmatory method of appropriate wedging, as in rare cases, A and V waves may be seen with a hybrid PA–PCWP tracing. It may, however, be difficult to withdraw blood from a wedged Swan catheter; a balloon flotation catheter with multiple distal side‐holes may be used (Berman catheter).

724  Part 11.  Cardiac Tests: Invasive Procedures

50

0

(i)

(ii)

Figure 36.8  On gross inspection of both figures, they may seem similar. In fact, (i) is the PCWP tracing of a patient with severe MR and gigantic V waves, while (ii) is his PA pressure tracing. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1 Keys to differentiate: 1. Timing: note that in (i) the V wave peaks after the end of the ECG T wave, whereas in (ii) the systolic PA pressure peaks before the end of the T wave (down‐arrows). 2. The segment between V waves is horizontal, whereas the segment between PA peaks, i.e., diastolic PA pressure, is downsloping (arrowheads). 3. PA pressure has a dicrotic notch. PA pressure has a sharp upslope and a slow downslope, which is opposite to the shape of V wave. 4. PA pressure is double‐peaked. The second peak (horizontal arrow) corresponds to the transmission of V wave to the PA pressure. Note that V wave is almost as large as systolic PA pressure, yet the mean PCWP is certainly lower than the mean PA pressure.

100

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50

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0

(a)

PCWP

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(b)

PA pressure

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(c)

Hybrid PA-PCWP

Figure 36.9  (a, b) PCWP tracing shows a large V wave of ~38 mmHg, with a mean PCWP of 26 mmHg. The mean PCWP (left oblique arrow) is lower than the mean PA pressure (right oblique arrow), and is equal to the PA diastolic pressure (bar), all of which is consistent with a true PCWP.   (c) Tracing C is recorded after inflation of the PA catheter balloon. It may mimic a PCWP tracing with a large V wave. However, the mean of this pressure tracing almost approximates the mean PA pressure and exceeds the PA diastolic pressure. Also, the timing does not fit with PA pressure: the presumed V waves peak as early as the PA pressure peaks, during the ECG T waves (vertical arrows), and have a sharp upslope, similar to the PA pressure upslope; the presumed A waves precede the ECG P waves. Thus, this is not a true PCWP tracing. The PA catheter is “underwedged,” which results in a hybrid PA–PCWP waveform.

C.  Case of pulmonary hypertension: differentiate PCWP from a damped PA pressure In severe pulmonary hypertension (PH), two issues arise. First, in severe PH, the segmental PA branches are dilated, which makes it difficult for the catheter to occlude these branches; thus, the wedged PA waveform may be a damped PA waveform and may overestimate the true PCWP (it is a hybrid PA–PCWP waveform with arterial rather than PCWP characteristics) (Figure 36.9). Second, a phasic PCWP depends on appropriate retrograde transmission of LA pressure through the pulmonary vasculature without any anatomical barrier; in case of severely elevated pulmonary arteriolar or venous resistance, retrograde transmission of LA pressure is attenuated, producing a damped and flattened

Chapter 36.  Hemodynamics  725

PCWP that lacks distinct waves and descents. In the latter situation, mean PCWP may approximate mean LA pressure, but the waveform is flat and featureless and falsely creates or overestimates a transmitral gradient. In sum, the PCWP of PH may be a false PCWP (damped PA waveform), or a true PCWP that is, nonetheless, featureless (damped PCWP waveform). Other cases where PCWP lacks A and V waves and potentially overestimates the true PCWP: (i) catheter overwedging; (ii) catheter in the upper lung zone 1, where the pulmonary capillaries are collapsed by the alveolar pressure and where PCWP reflects alveolar pressure rather than capillary pressure (this false PCWP may exceed PA diastolic pressure). In patients with elevated PCWP, it is harder for the alveolar pressure to compress the pulmonary capillaries, and thus zone 1 significantly shrinks and is unlikely to be catheterized. Beside the issue of PCWP–LA pressure correlation, a major pitfall of LA pressure itself is that it is not equivalent to LV preload, which is LV end‐diastolic volume. Patients with a very steep LV pressure–volume relationship, such as patients with acute HF or severe diastolic HF, may have a relatively normal LV preload volume with a high LA pressure.

V. LVEDP LV diastolic pressure slightly increases throughout diastole, and, except in AF, has an A wave that corresponds to the atrial A wave. LVEDP is located at the downslope of the A wave. In normal individuals with compliant LV, LV pressure increases only slightly after A wave, so that post‐A LV pressure is not significantly higher than pre‐A LV pressure. In compensated LV dysfunction, LV pressure is normal throughout diastole but increases only after A wave; similarly, LA pressure is overall normal and increases only after A wave, explaining why mean LA pressure better correlates with pre‐A LV pressure than with LVEDP. In decompensated LV dysfunction, LV pressure is high throughout diastole and increases further after A wave (Figure 36.10, Table 36.1). To identify LVEDP, search for a bump on the LV upstroke; the bump is A wave and the point that follows this bump is LVEDP (Figure 36.11). While LVEDP varies with respiration, the most accurate LVEDP is obtained when the respiratory pressure is 0 mmHg, which, unless the patient actively exhales, corresponds to end‐expiration and coincides with the highest recorded LVEDP point. This end‐expiratory rule applies to all measured pressures. Note: Normal hemodynamic values • RA: mean ≤ 7 mmHg • RV: ≤ 35/8 • PA: ≤ 35/12 (mean PA pressure ≤ 20 mmHg) • LVEDP: ≤ 16 mmHg • PCWP: mean ≤ 12 mmHg. Note that values up to 15–18 mmHg may not lead to congestion in patients with chronic heart failure who have increased pulmonary capillary lymphatic drainage. However, except for patients with poor LV compliance, such as patients with new‐onset acute heart failure or severe diastolic heart failure, PCWP of 15–18 mmHg corresponds to an unnecessary increase in LV volume preload and may be safely reduced to 12 mmHg (see Chapter 5, Figure 5.5).

v a a v S4 E

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Compensated LV dysfunction

Decompensated LV dysfunction

Figure 36.10  Diastolic superimposition of LA pressure (or PCWP, in blue) and LV pressure (in black). Downward arrows point to LVEDP. In compensated LV dysfunction, LV pressure is normal before A wave but increases after A wave (LVEDP). On PCWP tracing, V wave is normal, A wave is increased, but mean PCWP is overall normal and better correlates with the pre‐A LV pressure than the elevated LVEDP (PCWP  PCWP: compensated LV dysfunction, AI • LVEDP ≈ PCWP in decompensated LV failure • LVEDP 30% or 2 l/min, as O2 may increase SvO2 disproportionately to SaO2 and lead to overestimation of cardiac output (compared to SaO2, SvO2 is on a steeper portion of the O2–hemoglobin dissociation curve, which explains the sharper rise with O2 therapy). Thermodilution is measured using a PA catheter that has a thermistor at its distal tip. After the catheter is positioned in the PA, 10 ml of cold (room temperature) saline is injected instantaneously through the blue RA port. The thermistor analyzes how quickly the temperature drops as blood reaches the PA and how quickly it recovers. The higher the cardiac output, the more brief and sharp the temperature change will be with a small area under the curve. The colder the injectate, and the more instantaneously it reaches the RA, the more accurate the measured cardiac output. Usually three measurements are obtained to average the slight variability of cardiac output (~10%) that occurs with various levels of wakefulness. When used for valve area calculation, the cardiac output and pressure gradient should be measured almost simultaneously to account for this variation. This method is valid in most cases, and has  RV pressure at other times). Equalization of RV and LV end‐diastolic pressures may be seen in RV failure as well, except that RV supersedes LV pressures at times. 3. While (1) and (2) correspond to the analysis of diastolic RV and LV pressures, the third feature corresponds to the analysis of systolic RV and LV pressures. Discordance of peaks, wherein the systolic peaks of RV and LV move in opposite directions, is very specific for constrictive pericarditis. This contrasts with restrictive cardiomyopathy or decompensated ventricular failure, wherein the peaks are concordant. There is discordance on this recording, as RV peak increases when LV peak decreases. The two black lines illustrate this concept. Reproduced with permission of Demos Medical from Hanna and Glancy (2012).1

XI.  Exercise hemodynamics In patients with unexplained exertional dyspnea, a Swan catheter may be placed and exercise performed on a supine cycle ergometer mounted on the catheterization table. Invasive PA pressure, PCWP, and CO are measured during exercise. This may unveil occult LV diastolic dysfunction as a cause of the patient’s dyspnea. On the bicycle, the work is started at 25 watts (W), and increased by ~25 W every 2 minutes (mild exercise ~50 W, heart rate 110 bpm; moderate exercise ~100 W, heart rate 130 bpm; maximal exercise ~150–200 W). At each stage, the patient must pedal at 60–80 rpm to achieve the estimated work. During exercise, venous return increases and stroke volume increases as a result of the increased preload (Frank–Starling mechanism) and the inotropic reserve. Normally, in early exercise, LV end‐diastolic volume increases (preload increases) while end‐systolic volume decreases (EF increases). At high levels of tachycardia, as diastole shortens, the rising LV end‐diastolic volume plateaus or even declines, while stroke volume continues to rise from the reduction of end‐systolic volume. Even in normal individuals, PCWP and PA pressure increase to some extent with exercise, and PCWP frequently exceeds 15 mmHg. PA pressure increases as a result of the increased cardiac output (similarly to the exertional rise of systemic arterial pressure). The normal values of exertional PA pressure and PCWP are shown in Table 36.3.3 Whether in normal individuals or in those with LV diastolic dysfunction, most of the rise of PCWP (≥80%) already occurs at a low level of exercise (at 1.5 minutes of 25 W).4 In diastolic dysfunction, PCWP will rise sharply early on, then continue the rise, but the early rise already gives a good idea of the final response. In fact, in diastolic dysfunction, PCWP already rises with passive leg elevation, before cycling (~40% of the eventual rise).4 Two studies found that PCWP adjusted to the workload in W/kg provides a more accurate assessment of diastolic function (normal PCWP is 120 bpm reduces diastolic time, and thus reduces balloon filling and inflation during this brief time. The reduced diastolic time during each cardiac cycle is the main issue, rather than a limited ability to circulate gas at high rates; switching to 1:2 does not necessarily help. 4. Balloon kinking may lead to poor augmentation or poor deflation. Check the catheter and tubing for a visible kink, ensure the balloon has fully exited the sheath and get an X‐ray, and position the patient flat, as bending the groin area may kink the catheter. 5. Gas leak due to loose connections or balloon leak/rupture. The latter may result from inflation against calcified aortic plaques and may lead to clotting inside the balloon and balloon entrapment. The blue, balloon inflation waveform is abbreviated and blood is seen coming out of the gas lumen. IABP should be placed on standby and removed quickly (