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The Echo Manual [4 ed.]
 1496312198, 9781496312198, 9781975117559, 1975117557

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Table of contents :
Cover
Title Page
Copyright
Dedication
List of Contributors
Preface
Contents
Abbreviations
1: Transthoracic M-mode and Two-Dimensional Echocardiography
2: Transthoracic Three-Dimensional Echocardiography
3: Transesophageal Echocardiography
4: Doppler Echocardiography and Color Flow Imaging: Comprehensive Noninvasive Hemodynamic Assessment
5: Tissue Doppler and Strain Imaging
6: Contrast Echocardiography
7: Quantification of Left-sided Cardiac Chambers: Mass, Volumes, and Ejection Fraction
8: Assessment of Diastolic Function
9: Right Heart Assessment and Pulmonary Hypertension
10: Cardiomyopathies
11: Heart Failure, LVAD, and Transplantation
12: Pericardial Diseases
13: Native Valvular Heart Disease
14: Prosthetic Valve Evaluation
15: Infective Endocarditis
16: Stress Echocardiography
17: Coronary Artery Disease, Acute Myocardial Infarction, Takotsubo Syndrome
18: Cardiac Diseases Due to Systemic Illness, Genetics, or Medication
19: Cardiac Tumors and Masses
20: Diseases of the Aorta
21: Congenital Heart Disease
22: Interventional Echocardiography
23: Adult Intraoperative Echocardiography
24: Intracardiac and Intravascular Ultrasound
25: Vascular Tonometry and Imaging for Cardiovascular Risk Assessment
26: Handheld Cardiac and Point-of-Care Ultrasound
27: Physics of Ultrasound
28: The Future of Echocardiography
29: Artificial Intelligence and Echocardiography: Current Status andFuture Directions
Appendix
Index

Citation preview

The Echo Manual FOURTH EDITION Jae K. Oh, MD Samsung Professor of Cardiovascular Diseases, Mayo Clinic Director, Echocardiography Core Lab, Mayo Clinic Co-Director, Integrated CV Imaging, Mayo Clinic Director, Heart Vascular Stroke Institute, Samsung Medical Center, Korea President, Asian-Pacific Association of Echocardiography

Garvan C. Kane, MD, PhD Professor of Medicine, Mayo Clinic Director, Stress Echocardiography, Mayo Clinic Co-Director, Echocardiography Laboratory, Mayo Clinic Vice Chair, Division of Cardiovascular Ultrasound, Mayo Clinic

James B. Seward, MD Nasseff Professor of Cardiology (Emeritus) in Honor of Dr. Burton Onofrio, Mayo Clinic Director (Emeritus) Mayo Echocardiographic Laboratory Professor of Adult and Pediatric Cardiology (Emeritus), Mayo Clinic Professor (Emeritus) Department of Cardiovascular Medicine, Mayo Clinic

A. Jamil Tajik, MD Thomas J. Watson Jr Professor (Emeritus) in Honor of Dr. Robert L. Frye, Mayo Clinic Chairman (Emeritus), Department of Cardiovascular Medicine, Mayo Clinic Director (Emeritus), Mayo Echocardiographic Laboratory Director, Cardiac Specialty Center, Aurora St. Luke’s Medical Center, Milwaukee, Wisconsin

Senior Acquisitions Editor: Sharon Zinner Development Editor: Elizabeth Schaeffer Editorial Coordinator: John Larkin Marketing Manager: Rachel Mante Leung Production Project Manager: Joan Sinclair Design Coordinator: Holly McLaughlin Manufacturing Coordinator: Beth Welsh Prepress Vendor: SPi Global Fourth Edition Copyright © 2019 by Wolters Kluwer © 2019 Mayo Foundation for Medical Education and Research. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, recording, or otherwise, without written permission from Mayo Foundation, Section of Scientific Publications, Plummer 10,200 First Street SW, Rochester, MN 55905. Nothing in this publication implies that Mayo Foundation endorses any of the products mentioned in this book. 9 8 7 6 5 4 3 2 1 Printed in China Cataloging in Publication data available on request from publisher ISBN 978-1-4963-1219-8 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. shop.lww.com

To Pioneers of Echocardiography To our Echo Colleagues To our Families

List of Contributors Sahar S. Abdelmoneim, MD Research Associate/Collaborator, Echo Core Lab Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Karima Addetia, MD Assistant Professor of Medicine, Section of Cardiology University of Chicago Medical Center Chicago, Illinois

Naser Ammash, MD Professor of Medicine Consultant, Division of Structural Heart Disease Director, Heart Brain Clinic, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Lori A. Blauwet, MD, MA Associate Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Allison K. Cabalka, MD Associate Professor of Pediatrics Consultant, Division of Pediatric Cardiology Mayo Clinic Rochester, Minnesota

Frank Cetta, MD Professor of Medicine and Pediatrics Division of Pediatric Cardiology Department of Cardiovascular Medicine Mayo Clinic

Rochester, Minnesota

Sung-A Chang, MD, PhD Associate Professor Division of Cardiology Department of Medicine Heart Vascular Stroke Institute Imaging Center Samsung Medical Center Sungkyunkwan University School of Medicine Seoul, Republic of Korea

Thais Coutinho, MD Chief, Division of Cardiac Prevention and Rehabilitation Chair, Canadian Women’s Heart Health Centre Division of Cardiology University of Ottawa Heart Institute Ottawa, Ontario, Canada

Michael W. Cullen, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Raúl E. Espinosa, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Covadonga Fernández-Golfín, MD Director, Cardiac Imaging Unit Department of Cardiology University Hospital Ramón y Cajal Madrid, Spain

David A. Foley, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

William K. Freeman, MD Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic

Scottsdale, Arizona

Jeffrey B. Geske, MD Associate Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Ariana González, MD Director, Valvular Heart Diseases Department of Cardiology University Hospital Ramón y Cajal Madrid, Spain

Donald J. Hagler, MD Professor of Medicine and Pediatrics Consultant, Division of Pediatric Cardiology Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Kyle W. Klarich, MD Professor of Medicine Vice Chair, Department of Cardiovascular Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Iftikhar J. Kullo, MD Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Roberto M. Lang, MD President (Emeritus), American Society of Echocardiography Professor of Medicine, Section of Cardiology University of Chicago Medical Center Chicago, Illinois

Grace Lin, MD Associate Professor of Medicine Director, Heart Failure Clinic Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Lieng-H Ling, MBBS, MD Associate Professor, Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Senior Consultant Department of Cardiology National University Heart Centre Singapore

Joseph F. Maalouf, MD Professor of Medicine Director, Interventional Echocardiography Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Joseph J. Maleszewski, MD Professor of Laboratory Medicine & Pathology and Medicine Departments of Laboratory Medicine & Pathology, Cardiovascular Medicine, and Clinical Genomics Mayo Clinic Rochester, Minnesota

Sunil V. Mankad, MD Associate Professor of Medicine Consultant, Department Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Robert B. McCully, MD Professor of Medicine Director (Emeritus), Stress Echocardiography Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Hector I. Michelena, MD Professor of Medicine Director, Intraoperative Echocardiography Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Fletcher A. Miller, MD Professor of Medicine Director (Emeritus), Echocardiography Laboratory Consultant, Department of Cardiovascular Medicine Mayo Clinic

Rochester, Minnesota

William R. Miranda, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Victor Mor-Avi, PhD Research Professor Department of Medicine, Section of Cardiology University of Chicago Medical Center Chicago, Illinois

Sharon L. Mulvagh, MD Professor of Medicine Dalhousie University Halifax, Nova Scotia, Canada Professor (Emeritus), Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Vuyisile T. Nkomo, MD, MPH Professor of Medicine Director, Valvular Heart Diseases Clinic Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Patrick O’Leary, MD Professor of Pediatrics Division of Pediatric Cardiology Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Sungji Park, MD, PhD Professor Director, Imaging Center Heart Vascular Stroke Institute Samsung Medical Center Sungkyunkwan University School of Medicine Seoul, Republic of Korea

Patricia A. Pellikka, MD President (Emeritus), American Society of Echocardiography

Professor of Medicine Director, Echocardiography Laboratory Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Sorin V. Pisralu, MD, PhD Professor of Medicine Vice Chair, Division of Cardiovascular Ultrasound Consultant, Department of Cardiovascular medicine Mayo Clinic Rochester, Minnesota

David Playford, MBBS, PhD Professor University of Notre Dame Fremantle, Australia Mount Hospital, Western Australia

Peter M. Pollak, MD Director of Structural Intervention Consultant, Department of Cardiovascular Medicine Mayo Clinic Jacksonville, Florida

Guy S. Reeder, MD Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Charanjit S. Rihal, MD William S. and Ann Atherton Professor of Cardiology Chair (Emeritus), Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Hartzell V. Schaff, MD Stuart W. Harrington Professor of Surgery Consultant, Department of Cardiovascular Surgery Mayo Clinic Rochester, Minnesota

Peter C. Spittell, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine

Mayo Clinic Rochester, Minnesota

Geoff Strange, BN, PhD Professor University of Notre Dame, Fremantle Western Australia, Australia Royal Prince Alfred Hospital Sydney, New South Wales, Australia

Rakesh M. Suri, MD, DPhil Professor of Surgery Cleveland Clinic Foundation and Cleveland Clinic Abu Dhabi

Jeremy J. Thaden, MD Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Yan Topilsky, MD Associate Professor Sackler University of medicine Tel Aviv, Israel Director of Echo and Non Invasive Cardiology Tel Aviv Medical Center

Hector R. Villarraga, MD Associate Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

Brandon M. Wiley, MD, MS Assistant Professor of Medicine Consultant, Department of Cardiovascular Medicine Mayo Clinic Rochester, Minnesota

José Luis Zamorano, MD Vice President, European Society of Cardiology Head of Cardiology University Hospital Ramón y Cajal Madrid, Spain

Preface The first edition of the Echo Manual was originally written in early 1990s as an internal manual at Mayo Clinic to standardize the acquisition and the interpretation of echocardiography, which was rapidly developing. When it was published, we were thrilled by readers’ encouraging response, which has motivated us to update this Manual few times to the current fourth edition. The first edition took 4 years to complete. At that time, all echocardiography images were stored in video tapes. We created a list of educationally valuable illustrative images, which were later retrieved and photographed using 38-roll film per each image. When each roll-film was developed, the best image was selected to be labeled and cropped. The revised images were photographed again to create figures shown in the first edition of the Manual. When echocardiography images were acquired and stored digitally, it became much easier to locate and create images. But, it is remarkable that images created by photography were frequently better than digitized images, some of which are still shown in this edition. The Echo Manual has lived through remarkable growing periods of echocardiography with development of Doppler hemodynamics, color flow imaging, transesophageal imaging, stress echocardiography, contrast (ultrasound enhancing) agent, tissue Doppler, strain imaging, 3D echocardiography and hand-held ultrasound imaging. Echocardiography has matured to have become the most practical and the most widely available imaging and hemodynamic diagnostic tool for the entire field of cardiovascular diseases. Consequently, the utilization of echocardiography is now in the hands of not only cardiologists, but any physicians who have a need to assess cardiac structure, function, and hemodynamics in their outpatient office, bedside, emergency department, critical care unit, interventional suite, and operating room. The bedside ultrasound imaging by a hand-held device was recommended to be the fifth pillar to bedside physical examination in addition to inspection, palpation, percussion, and auscultation (1). There is, however, a large gap between what echocardiography

can do and how it is used in clinical practice. Optimal utilization of echocardiography requires dedicated training and it is our sincere hope that this fourth edition of the Echo Manual can help to close the gap for all physicians and sonographers who perform and interpret echocardiography to provide the best care for their patients. Echocardiography has become an amazing tool not only for diagnosis but also guiding many innovative device therapies and procedures. We hope that the Manual also helps interventionalists and cardiac surgeons to use echocardiography for obtaining the best result for their procedures. As the field of echocardiography has expanded tremendously since the last edition, several new chapters (3D echocardiography, interventional echocardiography, echocardiography for heart failure and LVAD, hand-carried ultrasound, and artificial intelligence in echocardiography) were added. Previous chapters were updated with new information, recent references, and new images with corresponding real-time images. We thank all contributing authors for their passion and expertise for echocardiography and for their sacrifice in precious time. We continued to emphasize the interpretation of echocardiography information in clinical context since our ultimate goal of performing echocardiography is to provide the best care for our patients. A creation of this fourth edition of the Echo Manual would not have been possible without support and understanding from our families. Most of echocardiography cases and images in this manual came from the extensive clinical materials at Mayo Clinic. We thank Mayo Clinic Echocardiography Laboratory and the Department of Cardiovascular Medicine for providing an amazing environment for practice, education, and research as well as collegiality and friendship. Mark A. Zang, Jeffrey R. Stelley, and Jeffrey W. Gansen of our Echocardiography Laboratory visual section helped creating still and video images used for the Manual. Paul W. Honerman of Illustration and Design revised and created all illustrative figures. Tessa Flies helped me with administrative duties and made sure that I do have a time to complete this Manual in time. We could not thank enough the Wolters Kluwer for their support and patience for having this fourth edition of the Echo Manual published almost 10 years after the third edition. Finally, we are grateful to echocardiography and numerous pioneers in this field for making our professional life filled with new discoveries, better diagnostic methods, many memorable trips, wonderful meetings, international cousins, mentoring fellows, making friends all around the world, and the most

importantly, opportunities to improve the care for our patients. Jae K. Oh On behalf of all authors

REFERENCE 1. Narula J, Chandrashekhar Y, Braunwald E. Time to add a fifth pillar to bedside physical examination: Inspection, palpation, percussion, auscultation, and insonation. JAMA Cardiology, 2018;3(4): 346–350.

Contents List of Contributors Preface Abbreviations 1 Transthoracic M-mode and Two-Dimensional Echocardiography Jae K. Oh and Joseph J. Maleszewski 2 Transthoracic Three-Dimensional Echocardiography Karima Addetia, Victor Mor-Avi, and Roberto M. Lang 3 Transesophageal Echocardiography Jeremy J. Thaden, Joseph F. Maalouf, and Jae K. Oh 4 Doppler Echocardiography and Color Flow Imaging: Comprehensive Noninvasive Hemodynamic Assessment Jae K. Oh and William R. Miranda 5 Tissue Doppler and Strain Imaging Hector R. Villarraga, Garvan C. Kane, and Jae K. Oh 6 Contrast Echocardiography Sahar S. Abdelmoneim and Sharon L. Mulvagh 7 Quantification of Left-sided Cardiac Chambers: Mass, Volumes, and Ejection Fraction Garvan C. Kane 8 Assessment of Diastolic Function

Jae K. Oh 9 Right Heart Assessment and Pulmonary Hypertension Garvan C. Kane and Sung-A Chang 10 Cardiomyopathies Jeffrey B. Geske and Jae K. Oh 11 Heart Failure, LVAD, and Transplantation Yan Topilsky, Grace Lin, and Jae K. Oh 12 Pericardial Diseases Jae K. Oh, Raúl E. Espinosa, and Lieng-H Ling 13 Native Valvular Heart Disease Jae K. Oh, Sungji Park, Sorin V. Pisralu, and Vuyisile T. Nkomo 14 Prosthetic Valve Evaluation Lori A. Blauwet, Fletcher A. Miller, and Jae K. Oh 15 Infective Endocarditis William K. Freeman 16 Stress Echocardiography Robert B. McCully, Patricia A. Pellikka, and Jae K. Oh 17 Coronary Artery Disease, Acute Myocardial Infarction, Takotsubo Syndrome Sunil V. Mankad and Jae K. Oh 18 Cardiac Diseases Due to Systemic Illness, Genetics, or Medication Garvan C. Kane 19 Cardiac Tumors and Masses Kyle W. Klarich, Jae K. Oh, and Joseph J. Maleszewski 20 Diseases of the Aorta

Peter C. Spittell 21 Congenital Heart Disease Patrick O’Leary, Naser Ammash, and Frank Cetta 22 Interventional Echocardiography Jeremy J. Thaden, Brandon M. Wiley, Peter M. Pollak, and Charanjit S. Rihal 23 Adult Intraoperative Echocardiography Hector I. Michelena, Rakesh M. Suri, and Hartzell V. Schaff 24 Intracardiac and Intravascular Ultrasound Donald J. Hagler, Allison K. Cabalka, and Guy S. Reeder 25 Vascular Tonometry and Imaging for Cardiovascular Risk Assessment Thais Coutinho and Iftikhar J. Kullo 26 Handheld Cardiac and Point-of-Care Ultrasound Michael W. Cullen and Brandon M. Wiley 27 Physics of Ultrasound David A. Foley 28 The Future of Echocardiography José Luis Zamorano, Ariana González, and Covadonga FernándezGolfín 29 Artificial Intelligence and Echocardiography: Current Status and Future Directions David Playford and Geoff Strange Appendix Index

Abbreviations

A a′ Aa ACT or AT Ao AS AVP AVR CHF CI CO CSA CW D DT E e′ Ea E/A ECG ERO IVC IVCT

late diastolic filling due to atrial contraction late diastolic velocity of the mitral anulus (same as a′) Acceleration time aorta aortic stenosis aortic prosthetic valve aortic valve replacement congestive heart failure cardiac index cardiac output cross sectional area continuous wave diastolic forward flow velocity deceleration time peak velocity of early diastolic filling of mitral inflow peak early diastolic velocity of the mitral anulus mitral anulus early diastolic velocity (same as e′) ratio of E and A velocities electrocardiogram (-graphy) effective regurgitant orifice inferior vena cava isovolumic contraction time

IVRT LA LV LVEF LVOT MR MS MV MVP PFO PHT PISA PVR PW Qp Qs RA RV S S′ SV SVC SVR TAVR TEE TR TTE TVI TVP 2D 3D

isovolumic relaxation time left atrium (-ial) left ventricle (-icular) left ventricular ejection fraction left ventricular outflow tract mitral regurgitation mitral stenosis mitral valve mitral valve prosthesis patent foramen ovale pressure half-time proximal isovelocity surface area pulmonary vascular resistance posterior wall or pulsed wave pulmonary stroke volume systemic stroke volume right atrium (-ial) right ventricle (-icular) systolic forward flow velocity systolic velocity of the mitral anulus stroke volume superior vena cava systemic vascular resistance transcatheter AVR transesophageal echocardiography tricuspid regurgitation transthoracic echocardiography time velocity integral tricuspid valve prosthesis two-dimensional three-dimensional

VS

ventricular septum

CHAPTER

1

Transthoracic M-mode and TwoDimensional Echocardiography Jae K. Oh and Joseph J. Maleszewski

TWO-DIMENSIONAL ECHOCARDIOGRAPHY Even with a great advance in three-dimensional (3D) echocardiography, twodimensional (2D) transthoracic echocardiography, currently, remains as the main tool for a comprehensive echocardiography study. Hence, an echocardiography examination begins with transthoracic 2D scanning from four standard transducer positions: the parasternal, apical, subcostal, and suprasternal windows. The parasternal and apical views usually are obtained with the patient in the left lateral decubitus position (Fig. 1-1A), and the subcostal and suprasternal notch views are obtained with the patient in the supine position (Fig. 1-1B). A patient may need to flex or bend the knee to relax the abdomen during the subcostal examination. An examiner may sit at the left or right side of a patient and scan with the right or left hand, respectively. From each transducer position, multiple long- and short-axis tomographic images of the heart are obtained by manually rotating and angulating the transducer (Table 1-1); hence, a multiplane examination is performed (Fig. 1-2) (1–4). The long-axis view represents a sagittal section of the heart, bisecting the heart from the base to the apex. The short-axis view is perpendicular to the longaxis view and is equivalent to sectioning the heart like a loaf of bread. Real-time 2D echocardiography provides high-resolution images of cardiac structures and their movements so that detailed anatomic and functional information about the heart can be obtained. Quantitative measurements of cardiac dimensions, area, and volume are derived from 2D images or 2D-derived M-mode (see below). In addition, 2D echocardiography provides the framework for Doppler and color flow imaging. These standard long and short tomographic imaging planes are acquired as described in the following sections. Newer matrix transducers allow visualization of multiple tomographic views from a single 3D image of the heart

(see Chapter 2). Biplane or X-plane imaging allows visualization of two tomographic views, which are orthogonal to each other, from the same acquisition. This shortens the duration of the examination and minimizes variation in the acquisition of cardiovascular images. With more advances and clinical experiences in 3D or multidimensional echocardiographic imaging, visualization and quantitation of cardiovascular structure, function, and hemodynamics will improve. While ultrasound technology is able to provide 3D and 4D imaging of the heart, echocardiography unit is being miniaturized to be held in a hand to provide a point-of-care imaging in various clinical situations including physician’s office, critical care unit, emergency department, and medical school education (5). Comprehensive knowledge about cardiovascular anatomy provided by multiple tomographic images from 2D transthoracic echocardiography is essential for medical staff utilizing the miniaturized echocardiography unit (see Chapter 26).

Parasternal Position The examination is begun by placing the transducer in the left parasternal region, usually in the third or fourth left intercostal space, with the patient in the left lateral decubitus position (Fig. 1-1A). From this position, sector images can be obtained of the heart along its long and short axes.

FIGURE 1-1 Four standard transthoracic transducer positions. A: The parasternal (1) and apical (2) views usually are obtained with the patient in the left lateral decubitus position. The parasternal view usually is obtained by placing the transducer at the left parasternal area in the third or fourth intercostal space. The apical view is obtained with the transducer at the maximal apical impulse (usually slightly lateral and inferior to the nipple, but it may be substantially displaced laterally and inferiorly because of cardiac enlargement or rotation or both). These views may be imaged best during held expiration, especially in patients who have chronic obstructive lung disease. The apical view can be difficult to obtain in a thin young person, and the transducer may need to be tilted superiorly. B: The subcostal (3) and suprasternal notch (4) views are obtained with the patient in the supine position. For subcostal imaging, relaxing the abdominal muscles by flexing the patient’s knees and forced inspiration frequently

improve the views. For suprasternal notch imaging, the patient’s head needs to be extended and turned leftward so the transducer can be placed comfortably in the suprasternal notch without rubbing the patient’s neck.

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Video 1-1A

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Video 1-1B Long-Axis View of the Left Ventricle The long-axis view of the left ventricle (LV) is recorded with the transducer groove facing toward the patient’s right flank and the transducer positioned in the third or fourth left intercostal interspace so that the ultrasound beam is parallel with a line joining the right shoulder to the left flank. The image obtained represents a section through the long axis of the LV (Fig. 1-3A). The image is oriented so the aorta is displayed on the right, the cardiac apex on the left, the chest wall and right ventricle (RV) anteriorly, and posterior structures posteriorly (Fig. 1-3B). Therefore, the long-axis view of the LV is displayed as a sagittal section of the heart viewed from the left side of a supine patient.

TABLE 1-1 Transducer Positions and Cardiac Views Parasternal position Long-axis view LV in sagittal section RV inflow LV outflow Short-axis view LV apex Papillary muscles (midlevel) Mitral valve (basal level) Aortic valve–RV outflow Pulmonary trunk bifurcation Apical position Four-chamber view Five-chamber (or long-axis) view Two-chamber view Subcostal position Inferior vena cava and hepatic vein RV and LV inflow LV-aorta RV outflow Suprasternal notch position Long-axis aorta–short-axis pulmonary artery Short-axis aorta–long-axis pulmonary artery Long-axis aorta and superior vena cava LV, left ventricle; RV, right ventricle.

The long-axis view of the LV allows visualization of the aortic root and aortic valve cusps. The chamber behind the aortic root is the left atrial (LA) cavity. Usually, the left inferior pulmonary vein, appearing as a round structure, also can be seen immediately posterior to the lower part of the LA. The long-axis view allows good visualization of the anterior and posterior leaflets of the mitral valve and their chordal and papillary muscle attachments (Fig. 1-4A). The coronary sinus appears as a small, circular echo-free structure and usually can be recorded in the region of the posterior atrioventricular groove (Fig. 1-3A). If the coronary sinus is enlarged, a persistent left-sided superior vena cava, increased right atrial (RA) pressure, or rarely coronary sinus atrial septal defect should be suspected (Fig. 1-4B). The left-sided superior vena cava can be confirmed by opacification of the coronary sinus with the administration of agitated saline through a vein in the left arm (see Chapter 6). The LV outflow

tract (LVOT), bounded by the ventricular septum anteriorly and the anterior leaflet of the mitral valve posteriorly, is well seen and normally is widely patent during systole. Subaortic membrane may be seen as a subtle bulge near the junction between the LVOT and the ventricular septum and can be suspected by turbulent flow before the aortic valve (see Chapter 21). The LVOT diameter, which is used to calculate systemic stroke volume, is measured from this view. However, the measurement of actual LVOT area by 3D echocardiography is more accurate for calculation of stroke volume. In this view, the descending thoracic aorta appears as a circular structure behind the LA (Fig. 1-4A) and LV posterior wall true- or pseudoaneurysm may be seen well from the parasternal long-axis view (Fig. 1-4C). RV enlargement or RV pressure overload as well as asymmetric ventricular septal hypertrophy in hypertrophic cardiomyopathy can be assessed in this view (Fig. 1-4D and E). With this view, color flow imaging is useful for screening for aortic and mitral valve regurgitation as well as subaortic obstruction.

FIGURE 1-2 A: Drawings of the longitudinal views from the four standard transthoracic transducer positions. Shown are the parasternal long-axis view (1), parasternal right ventricular inflow view (2), apical four-chamber view (3), apical fivechamber view (4), apical two-chamber view (5), subcostal four-chamber view (6), subcostal long-axis (five-chamber) view (7), and suprasternal notch view (8). B: Drawings of short-axis views. These views are obtained by rotating the transducer 90 degrees clockwise from the longitudinal position. Drawings 1 to 6 show parasternal short-axis views at different levels by angulating the transducer from a superomedial position (for imaging the aortic and pulmonary valves) to an inferolateral position, tilting toward the apex (from level 1 to level 6 short-axis views). Shown are short-axis

views of the right ventricular outflow tract and pulmonary valve (1), aortic valve and left atrium (2), right ventricular outflow tract (3), and short-axis views at the left ventricular basal (mitral valve level) (4), the left ventricle midlevel (papillary muscle) (5), and the left ventricle apical level (6). A good view to visualize the right ventricular outflow tract is the subcostal short-axis view (7). Also shown is the suprasternal notch short-axis view of the aorta (8). Ao, aorta; LA, left atrium; LV, left ventricle; MV, mitral valve; RA, right atrium; RPA, right pulmonary artery; RV, right ventricle; RVO, right ventricular outflow. (B: From Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

FIGURE 1-3 A: Anatomic section (left) and drawing (right) of the heart. B: Corresponding still frame of 2D echocardiographic image of the parasternal long-axis view. The parasternal long-axis view allows visualization of the right ventricle (RV), ventricular septum (VS), posterior wall (PW) aortic valve cusps, left ventricle (LV), mitral valve, left atrium (LA), and ascending thoracic aorta (Ao). Parasternal long-axis view starts with a long field-depth to visualize any abnormal structures posterior to the heart such as pleural effusion, descending thoracic aneurysm, or a mass. *Pulmonary artery. (A from Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

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Video 1-3A

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Video 1-3B Long-Axis View of Right Ventricular Inflow With the transducer in the same intercostal interspace (third or fourth), a longaxis view of the RV and RA is obtained by tilting the transducer inferomedially and rotating it slightly clockwise. In this view, the image is oriented with the chest wall anterior, the RA on the right and posterior, and the RV apex anterior and to the left. This view shows the RA cavity, tricuspid valve, coronary sinus entry into the RA, and the RV inflow up to the apex of the RV (Fig. 1-5). This view is good for recording the velocity of tricuspid regurgitation. The entry of the coronary sinus into the RA along with the posterior leaflet of the tricuspid valve may be seen clearly in this view. Short-Axis Views With the transducer placed in the parasternal position (third or fourth left

intercostal space), short-axis views of the heart are obtained by rotating the transducer clockwise so the plane of the ultrasound beam is approximately perpendicular to the plane of the long axis of the LV. The groove on the transducer is pointed superiorly to face the right supraclavicular fossa, and the beam is roughly parallel with a line joining the left shoulder and right flank. With the transducer pointed directly posteriorly, a cross section is obtained of the LV at the level of the mitral leaflets. From this position, the transducer is tilted inferiorly toward the LV apex to obtain a transverse section of the ventricular apex. The images are displayed as if viewed from below (looking from the apex of the heart up toward the base). In this format, the cross-sectional view of the LV is displayed posteriorly and to the right side of the image and the RV is displayed anteriorly and to the left.

FIGURE 1-4 A: Parasternal long-axis view from a 64-year-old patient with acute pulmonary edema demonstrating a flail posterior mitral leaflet (arrow). Also, the left atrium (LA) is enlarged. A round structure posterior to the LA is the descending thoracic aorta of normal dimension. B: Another parasternal long-axis view demonstrating a large coronary sinus (*). Because of a persistent left superior vena cava, the coronary sinus is quickly opacified after agitated saline is injected into a leftarm vein. C: A large posterior wall pseudo-aneurysm (*) with a relatively small mouth (arrow) very close to the posterior mitral leaflet. D: A female patient with pulmonary hypertension and small amount of pericardial effusion (PE). The most prominent finding from this parasternal long-axis view is a dilated right ventricle (RV) with the flattened ventricular septum toward the left ventricle. E: A marked increase in ventricular septal (VS) thickness from a patient with hypertrophic cardiomyopathy. Ao, ascending aorta; LA, left atrium; LV, left ventricle; RV, right ventricle.

FIGURE 1-5 A: Right ventricular (RV) inflow view demonstrating a tricuspid leaflet (arrow) during systole. The coronary sinus (CS) enters the right atrium (RA). This RV inflow view is good for visualizing tricuspid leaflet morphology and for obtaining tricuspid regurgitation velocity. B: Right ventricular inflow view during systole demonstrating inadequate coaptation of the tricuspid leaflets (arrow). The RA and CS are dilated. This is a good view to guide a catheter into the CS. LV, left ventricle; VS, ventricular septum.

A cross section of the cardiac apex can be obtained also by placing the transducer directly over the point of maximal (apical) impulse (apical short-axis view). This view is helpful in the assessment of apical wall motion, apical hypertrophic cardiomyopathy, noncompaction of the apex, apical stress cardiomyopathy, and apical mass. As the ultrasound beam is tilted superiorly, a cross section is obtained at the level of the papillary muscles. The papillary muscles, namely, the anterolateral and posteromedial muscles, project into the LV cavity at approximately the 3 and 8 o’clock positions, respectively (Fig. 1-6). By tilting the transducer further superiorly so it is nearly perpendicular to the chest wall, the ultrasound beam transects the body of the LV at the level of the mitral leaflets. In this view, the mitral anterior (A) and posterior (P) leaflets are seen in cross section and, during diastole, look like a fish mouth. A1 and P1

scallops are seen on the right side of the image, which represents the lateral aspect of the LV, and A3 and P3 scallops are seen near the ventricular septum. This view is good for measuring the mitral valve area in a patient with mitral stenosis, and it is the view to identify a cleft mitral valve. By tilting the transducer further superiorly, the great arteries are sectioned transversely. At this level in normal subjects, the aorta appears as a circle with a tricuspid aortic valve that has the appearance of the letter “Y” during diastole (Fig. 1-7). Coronary ostia may be seen in this view. The RV outflow tract (RVOT) crosses anterior to the aorta from the left to the right of the image, wrapping around the aorta; in cross section, it has a sausage-like appearance anterior to the circular aorta. The pulmonary valve is observed anterior and to the right of the aortic valve. The origins of the right (anteriorly) and left main coronary arteries also can be seen in this view.

Apical Position This view is obtained with the patient turned in the left lateral decubitus position (Fig. 1-1A). The apical impulse is localized, and the transducer is placed at or in the immediate vicinity of the point of maximal impulse. With the apical transducer position, a four-chamber view of the heart or a right anterior oblique equivalent view of the LV usually is recorded. The notch on the transducer is placed pointing up or down, depending on whether the goal is to display the LV on the right or on the left side of the image, respectively (Fig. 1-8). Because the views obtained with the apical transducer position represent long-axis views of the heart, particularly of the LV, it is desirable that the orientation of the image of these views be similar to that of the long-axis view of the LV. For this reason, pioneers in the Mayo Clinic Echocardiography Laboratory chose to display the apical views with the LV on the left side and the RV on the right side of the image. However, more commonly, the LV is displayed on the right side and the RV on the left side of the image. For the four-chamber view, the ultrasound beam is directed superiorly and medially toward the patient’s right scapula. This view displays all four chambers of the heart, the ventricular and atrial septa, and the crux of the heart (Fig. 1-8A). While recording the apical four-chamber view, we usually tilt the beam in a slightly anterior and posterior direction to scan a greater portion of the atrial septum. The image is oriented so the apex is at the top and the atria at the bottom. Two different image displays of the apical fourchamber view are shown in Figure 1-8B. The ventricular and atrial septa are connected by a membranous septum. The left (mitral) atrioventricular groove

normally is slightly higher (more toward the atria) than the right (tricuspid) atrioventricular groove. The anterior leaflet of the mitral valve inserts into the left atrioventricular groove and near the cephalic end of the membranous septum, whereas the septal leaflet of the tricuspid valve inserts near the midportion of the membranous septum. Therefore, the insertion of the septal leaflet of the tricuspid valve is somewhat inferior (5–10 mm in the hearts of older children and adults) to the insertion of the anterior mitral leaflet. This is an important anatomic distinction because it can be useful in identifying ventricular chambers. In Ebstein anomaly, the apparent insertion of the septal tricuspid leaflet is displaced more apically.

FIGURE 1-6 Parasternal short-axis views. Multiple tomographic planes have been obtained by angulating the transducer from the level of the aortic and pulmonary valves to the left ventricular apex. A: Anatomic section (left) and drawing (right) of a parasternal short-axis view at the papillary muscle level. B: Corresponding still frame of a 2D echocardiographic image in the parasternal short-axis view at the papillary muscle level (AL, anterolateral papillary muscle; PM, posteromedial papillary muscle). This view is particularly useful in measuring left ventricular (LV) cavity dimension and wall thickness and in assessing wall motion. C: Superior and rightward tilting of the transducer obtains a parasternal short-axis view at the basal level showing the mitral valve (MV). A1, lateral anterior leaflet; A2, middle anterior leaflet; A3, medial anterior leaflet; P1, lateral posterior leaflet; P2, middle posterior leaflet; P3, medial posterior leaflet; RV, right ventricle; VS, ventricular septum. (A from Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great

vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

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Video 1-6A

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Video 1-6B

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Video 1-6C

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Video 1-6D

FIGURE 1-7 By tilting the transducer further superiorly, the short-axis view of the aortic valve is obtained. In this view, the right ventricular outflow tract and pulmonary valve are visualized. Below the aortic valve lies the left atrium; the connection of all four pulmonary veins with the left ventricle is usually seen. A: Anatomic section (left) of the heart and drawing (right) of this view. B: Corresponding 2D echocardiographic image. LA, left atrium; PV, pulmonary valve; RA, right atrium; RVOT, right ventricular outflow tract. (A from Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional realtime ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

In the apical view, the atrial septum usually can be seen in its entirety without any thinning or dropout if the ultrasound beam is directed slightly anteriorly; however, echoes do drop out in its midportion, which is the region of the fossa ovalis, if the ultrasound beam is directed further posteriorly. This view also allows visualization of the emptying of the right and left inferior pulmonary veins into the LA, and with further posterior angulation of the ultrasound beam, the course of the coronary sinus as it enters the right atrium. With a slight clockwise rotation of the transducer (Fig. 1-8C), the aortic root and valve are imaged in addition to the four chambers (apical long-axis or fivechamber view). The aortic root occupies the region where the crux of the heart was recorded in the previous section. In this view, color flow imaging allows quantitative assessment by the proximal isovelocity area method as well as qualitative assessment of aortic regurgitation. Pulsed-wave Doppler echocardiography from this view at the aortic annulus region measures velocity and time velocity integral of the LVOT required for calculating stroke volume. With further clockwise rotation of the transducer, the apical two-chamber view with anterior and inferior walls of the LV along with the mitral valve (P1 scallop near the anterior wall and P3 scallop near the inferior wall with P2 in between) is obtained (Fig. 1-8D). All three apical views are essential for analysis of regional myocardial contractility and, hence, for stress echocardiography. Apical views provide another opportunity to visualize all 16 LV segments. The aortic, mitral, and tricuspid valves are seen from the apical views. The LV apex harbors diagnostic clues for cardiomyopathy, apical thrombus, hypereosinophilia, and aneurysm (Fig. 1-9). Apical views also are important for obtaining measurements of chamber volumes and several essential Doppler echocardiographic recordings. LV volumes are quantified with the biplane Simpson method from apical four- and two-chamber views of the LV, although 3D echocardiography is a preferred method for obtaining LV volume. LA volume is measured from the apical four-chamber and apical two-chamber views. LVOT velocity, which is used to calculate stroke volume, is recorded from the apical long-axis view. Mitral inflow, pulmonary vein, and mitral annulus tissue velocities, essential measurements for the assessment of diastolic function, also are obtained from the apical view (see Chapter 8).

FIGURE 1-8 A: Anatomic section (left) and drawing (right) of apical four-chamber view. B: Corresponding 2D echocardiographic image of the apical four-chamber view in two different imaging display formats with LV on the left (left) or on the right (right). The apical view is obtained by placing the transducer in the immediate vicinity of or at the point of maximal apical impulse. This view displays all four cardiac chambers, the ventricular and atrial septa, and the crux of the heart. Note that the insertion of the septal leaflet of the tricuspid valve (arrow) is slightly inferior to the insertion of the anterior mitral leaflet in two different imaging displays; this is an important anatomic distinction in the identification of the correct ventricle and image display format. C: By

rotating the transducer clockwise, the five-chamber or long-axis apical view (left) allows visualization of the left ventricular (LV) outflow tract and aortic valve (AV). Further rotation of the transducer clockwise produces the two-chamber view (right), which is useful for visualizing the entire posterior or inferior (Inf) wall and in analyzing anterior (Ant) wall motion. Ao, aorta; AS, anteroseptum; AV, aortic valve; IL, inferolateral wall; LA, left atrium; LV, left ventricle; MV, mitral valve; RA, right atrium; RV, right ventricle. (A from Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

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Video 1-8A

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Video 1-8B

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Video 1-8C

Subcostal Position In certain patients, especially those who have chronic obstructive lung disease and emphysema, the usual precordial ultrasonic window may become obliterated because of hyperinflated lungs. This necessitated a search for other locations for imaging the heart and led to the discovery of the subcostal region, a good ultrasonic window in these patients. The subcostal examination is performed by placing the transducer in the midline or slightly to the patient’s right, with the transducer groove pointed down toward the patient’s spine (Fig. 1-1B). The transducer head is tilted inferiorly and slightly toward the patient’s right. With this position, the liver parenchyma, hepatic vessels, and inferior vena cava (IVC) are visualized (Fig. 110). Based on the diameter and the collapsibility with respiration or sniff of the IVC, RA pressure is estimated (see Chapter 9). M-mode of the IVC may be helpful in measuring IVC diameter and its variability with respiration (Fig. 110C). With a slight superior tilt of the transducer, the drainage of the hepatic veins into the IVC can be identified. To record the IVC along its long axis, the transducer is rotated so that its groove points toward the patient’s right flank. The hepatic veins again can be recognized by their draining into the IVC. Color flow imaging (Fig. 1-11) and pulsed-wave Doppler recording of the hepatic veins (see Chapter 4) should be a routine part of the echocardiography study in all patients because severe tricuspid regurgitation, pulmonary hypertension, restrictive right-side filling, and constrictive pericarditis produce distinct Doppler signals in the hepatic veins.

FIGURE 1-9 Various lesions seen in apical views. A: Apical four-chamber view (left) showing noncompaction cardiomyopathy characterized by prominent noncompacted trabeculations (arrowheads) resulting in deep recesses (arrows). Color flow imaging (right) shows flow within the recesses. B: Apical four-chamber view (left) showing increased wall thickness at the midportion to apex (*) in left ventricle (LV). Contrast administration demonstrated midcavitary obstruction with apical cavity (*) (right). C: Intracavitary masses (*) attached to the LV septal and the lateral walls at the apex (left). Contrast administration demonstrate typical thrombus with no perfusion (*) consistent with eosinophilic thrombus in hypereosinophilia (right). LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

The transducer is tilted further superiorly so that it points roughly between the

patient’s suprasternal notch and the left supraclavicular fossa. The tomographic view of the heart that is obtained is nearly similar to the four-chamber view obtained from the apical position (Fig. 1-12), except that in this view the apices of the two ventricles can be visualized by tilting the transducer head slightly toward the patient’s left. The two atria, and especially the atrial septum, are visualized best in this section. Although dropout of echoes of the atrial septum in the region of the fossa ovalis may be noted from the parasternal and apical transducer positions, the atrial septum can be seen in its entirety from the subcostal position. Therefore, this is the best view to visualize abnormalities of the atrial septum with transthoracic echocardiography. To identify the sinus venosus portion of the atrial septum, the transducer needs to be rotated clockwise slightly to visualize the (dis)continuity between the atrial septum and the superior vena cava. Also, atrial septal motion can be well evaluated in this view. For orientation of the image in this view, we have followed the same format as for the similar view from the parasternal position, that is, the atria are displayed on the right and the cardiac apex on the left. From this position, the transducer is rotated clockwise and tilted slightly superiorly to visualize the ascending aorta and its relation to the mitral valve and LV. In this tomographic section, a foreshortened view of the LV long axis is recorded. Both leaflets of the mitral valve and the aortic leaflets as well as the LVOT usually can be well visualized.

FIGURE 1-10 A: Subcostal view with the transducer angulated toward the liver and normal inferior vena cava (IVC). The IVC is small and collapses with inspiration. The hepatic vein is small (arrow). B: IVC is markedly dilated. The diameter (solid line) is measured perpendicular to the long axis of the IVC at end expiration, just proximal to the junction of the hepatic veins that lie approximately 0.5 to 3.0 cm proximal to the ostium of the right atrium (RA). (Reprinted from Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults. J Am Soc Echocardiogr, 2010;23(7):685–713. Copyright © 2010 Elsevier. With permission.) C: M-mode echocardiogram of the IVC with simultaneous respirometer recording.

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Video 1-10A

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Video 1-10B Further clockwise rotation and superior tilting of the transducer show a cross section of the heart (Fig. 1-12C and D). In this view, the LV is visualized in the short axis, with portions of the mitral valve in its cavity. More importantly, this view is used to show the long axis of the entire RVOT. The orifice of the tricuspid valve usually appears directly end on. On the video monitor, the heart appears upside down, with RV inflow and RVOT along the right side of the image, the cross section of LV to the left, liver tissue anterior, and the pulmonary valve inferior.

FIGURE 1-11 A and B: Color flow imaging of the hepatic vein shows antegrade (blue with aliasing orange in A) and reversal (orange-red in B) flow.

FIGURE 1-12 Subcostal view. A: Anatomic section (left) and drawing (right) of the heart in the long-axis view. B: Corresponding 2D echocardiographic image. C: Anatomic section (left) and drawing (right) of the heart in the short-axis view. D: Corresponding 2D echocardiographic image. The subcostal view allows better definition of certain cardiac structures, including the atrial septum (arrows in B), left atrium (LA), right atrium (RA), right ventricular free wall, right ventricular outflow tract and pulmonary valve (arrow in D), hepatic vein, and abdominal aorta. This view may be the only satisfactory echocardiographic window for patients who have chronic obstructive lung disease and emphysema. AV, aortic valve; LV, left ventricle; PA, pulmonary artery; RV, right ventricle. (A and C from Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303. By permission of Mayo Foundation for Medical Education and Research.)

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Video 1-12A

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Video 1-12B Another important structure to scan routinely from the subcostal view is the abdominal aorta, which can be imaged accurately in most patients (Fig. 1-13). A prospective study showed that the screening examination detected an occult abdominal aortic aneurysm in 6.5% of hypertensive patients older than 50 years (6). Although atherosclerosis has a lower incidence in Asia, a routine subcostal imaging in 920 patients in Korea with coronary artery disease identified abdominal aortic aneurysm in 2.2% (7). A pulsed-wave Doppler examination of the abdominal aorta in this view is also helpful in identifying coarctation of the aorta by demonstrating persistent diastolic flow. Coarctation of the aorta and severe aortic regurgitation produce a characteristic pulsed-wave Doppler recording in the abdominal aorta (Chapters 4 and 21).

FIGURE 1-13 A: Normal abdominal aorta (Ao) from the subcostal view. LA, left atrium; RA, right atrium. B: Long-axis view of the abdominal aorta (Ao) from the subcostal view demonstrating a large abdominal aortic aneurysm, half of which is filled with thrombus (*).

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Video 1-13

Suprasternal Notch Position For visualization of the left aortic arch in the long axis, the transducer head is positioned in the suprasternal notch (Fig. 1-1B), with the long axis of the transducer to the left and parallel with the trachea and the transducer groove directed toward the right supraclavicular region. With this transducer position (Fig. 1-14A), the ascending aorta, aortic arch, origin of the brachiocephalic vessels, and descending thoracic aorta are visualized. Occasionally, cusps of the aortic valve also can be seen in the aortic root. The orientation of the image of this view is similar to that of a lateral view of an angiogram; thus, the ascending aorta is on the left of the figure and the descending aorta on the right. The right pulmonary artery is visualized in the short axis posterior to the ascending aorta and beneath the aortic arch. Inferior to the right pulmonary artery, the LA can be seen. For visualization of the long axis of the aorta in the presence of a right

aortic arch, the transducer is rotated counterclockwise, with the groove directed toward the right breast.

FIGURE 1-14 Drawing (left) and corresponding 2D echocardiographic image (right) of suprasternal notch long-axis (A) and short-axis (B) views. A: This transducer position (right) allows visualization of the ascending aorta (Asc), aortic arch (Arch), origin of the brachiocephalic vessels (arrows), descending thoracic aorta (Dsc), and right pulmonary artery (*). B: The short-axis view of the aortic arch (right) is obtained by rotating the transducer clockwise, which also allows visualization of the right pulmonary artery (RPA) in its long-axis format, located inferiorly to the aortic arch (Arch). Inferior to RPA is the left atrial (LA) cavity with connections of the four pulmonary veins (arrows).

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Video 1-14A

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Video 1-14B

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Video 1-14C

FIGURE 1-15 A: Color flow imaging of the descending thoracic aorta shows torrential diastolic flow reversals (red color indicated by an arrow) from severe aortic regurgitation. B: Color flow imaging of the descending thoracic aorta demonstrates turbulent flow (arrow) from coarctation. C: Color flow imaging from the suprasternal notch demonstrates flow (*) outside of the descending aorta moving toward the head, in a patient with RV volume overload, the typical finding of the vertical vein as anomalous pulmonary venous return.

The short-axis view of the aortic arch is obtained by rotating the transducer clockwise so the transducer groove faces posteriorly toward the patient’s trachea (Fig. 1-14B). In this view, the cross section of the ascending aorta is superior and the right pulmonary artery, in its long axis, is inferior. Occasionally, the first bifurcation of the right pulmonary artery can be visualized on the left of the image. By rotating the transducer slightly clockwise and tilting it toward the patient’s left and slightly anteriorly, the distal main pulmonary artery can be visualized. From this position, the left pulmonary artery can be seen occasionally by tilting the transducer posteriorly and to the left. Inferior to the pulmonary artery is the LA cavity. Immediately beneath the distal part of the right pulmonary artery, the right superior pulmonary vein connects with the LA. Color flow imaging from the suprasternal notch view is an essential part of a comprehensive echocardiogram since it can provide normal and abnormal blood

flow information from severe aortic regurgitation, coarctation of the aorta, anomalous pulmonary venous return, or obstruction of the superior vena cava (Fig. 1-15).

FIGURE 1-16 A: The superior vena cava (SVC) is visualized by further clockwise rotation; it appears along the right side of the aorta or can be imaged separately from the right supraclavicular area. B: Color flow imaging of the SVC shows increased flow velocity with aliasing (arrow). C: The SVC obstruction (left) is caused by a mediastinal mass (lymphoma), which also obstructed a near-by arterial circulation with a heart shape (*). Color flow imaging of the heart shape artery due to a mediastinal mass (right).

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Video 1-16A

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Video 1-16B The superior vena cava can be recorded in this view as an echo-free space alongside the aorta on the left of the image (Fig. 1-16). The left innominate vein can be visualized traversing superior to the aorta to its junction with the superior vena cava. With a slight counterclockwise rotation and anterior tilt of the transducer, the long axis of the superior vena cava can be recorded alongside the long axis of the ascending aorta. In this view, the superior vena cava can be scanned to its junction with the RA. An example of SCV abnormality is shown in Figure 1-16B and C. This same view of the superior vena cava occasionally can be obtained also with the transducer placed along the upper right sternal border.

M-MODE ECHOCARDIOGRAPHY M-mode echocardiography complements 2D echocardiography by recording detailed motions of cardiac structures. It is best derived with guidance from a 2D echocardiographic image by placing a cursor through the desired structure (8) (Fig. 1-17). M-mode is used for the measurement of dimensions and is essential for the display of subtle motion abnormalities of specific cardiac structures as well as the timing of their motion. Methods for measuring cardiac dimensions from M-mode are shown in Figure 1-18. Normal values for cardiac dimensions in adults are well established. Sex-specific reference M-mode values in adults were determined from a healthy subset of the Framingham Heart Study (Table 12) (9,10). For these measurements, the M-mode cursor is drawn as a straight line from the transducer position to any direction in the sector to record the

movement of the cardiac structure of interest. Many of us who learned echocardiography invlate 70s to early 80s obtained phonocardiogram recording simultaneously with M-mode recording by nonimaging transducer sweeping from the base to the apex of the heart (Fig. 1-19). We assessed not only structural changes, but hemodynamic significance of cardiac structural abnormalities from M-mode echocardiography (11). M-mode recordings of various cardiac lesions are shown and some of them with corresponding Doppler signals to demonstrate hemodynamic assessment by M-mode echocardiography in Figure 1-20. Some of these findings are of historical interest only because in our contemporary clinical practice, the diagnosis is usually made from 2D, 3D, and Doppler echocardiographic information. However, subtle motion of cardiac structures can be appreciated from M-mode recordings. M-mode can be utilized with colorflow imaging to create color M-mode. Color M-mode is used for timing of cardiac flow and also for measuring intracardiac flow propagation velocity to assess the status of myocardial relaxation (see Chapter 4).

FIGURE 1-17 A: An M-mode cursor is placed along different levels (1, ventricular; 2, mitral valve; 3, aortic valve level) of the heart, with parasternal long-axis 2D echocardiographic guidance. B–D: Representative normal M-mode echocardiograms

at the midventricular (B), mitral valve (C), and aortic valve levels (D), respectively. B: EDd and ESd are end-diastolic and end-systolic dimensions, respectively, of the left ventricle (LV). C: M-mode echocardiogram of the anterior mitral leaflet: A, peak of late opening with atrial systole; C, closure of the mitral valve; D, end systole before mitral valve opening; E, peak of early opening; F, middiastolic closure. D: Double-headed arrow indicates the dimension of the left atrium (LA) at end systole. Ao, aorta; AV, aortic valve; LA, left atrium; LV, left ventricle; PW, posterior wall; RV, right ventricle; RVOT, right ventricular outflow tract; VS, ventricular septum.

FIGURE 1-18 Diagram of M-mode echocardiogram of the left ventricle, aortic root, and left atrium (LA). The left ventricular internal dimension (LVD) at end diastole (D) was measured at the onset of the QRS complex, and the systolic internal dimension [LVD(S)] was measured at the maximal excursion of the ventricular septum, which normally occurs before the maximal excursion of the posterior wall. These measurements correspond, respectively, to the maximal (max) and minimal (min) internal dimensions between the ventricular septum and the posterobasal LV free-wall endocardium. Septal thickness (ST) and posterior wall thickness (PWT) were measured at end diastole (D) at the onset of the QRS complex. The aortic root

dimension (AO) was measured at the onset of the QRS complex from the leading edge to the leading edge of the aortic walls. The LA dimension was measured at end systole as the largest distance between the posterior aortic wall and the center of the line denoting the posterior LA wall. Their normal values are given in the Appendix. ECG, electrocardiogram. (From Gardin JM, Henry WL, Savage DD, et al. Echocardiographic measurements in normal subjects: Evaluation of an adult population without clinically apparent heart disease. J Clin Ultrasound, 1979;7(6):439–447. Copyright © 1979 Wiley Periodicals, Inc., A Wiley Company. Reprinted by permission of John Wiley & Sons, Inc.)

TABLE 1-2 Normal Values from M-Mode Echocardiographya

Men (n = 288)



Mean

SD

Mean

SD

Age, yr

35.7

6.1

35.9

5.5

Height, m

1.77

0.06

1.63

0.06

Weight, kg

74.1

6.9

59.3

6.1

Body mass index, kg/m2

23.5

1.6

22.1

1.7

Body surface area, m2

1.91

0.11

1.64

0.10

Systolic blood pressure, mm Hg

117.0

9.1

110.0

10.5

Diastolic blood pressure, mm Hg

74.8

6.8

70.9

7.5

LV diastolic dimension, mm

50.8

3.6

46.1

3.0

LV systolic dimension, mm

32.9

3.4

28.9

2.8

LV wall thickness, mmb

18.1

2.0

15.5

1.5

LA dimension, mm

37.5

3.6

33.1

3.2

Women (n = 524)

LA, left atrium; LV, left ventricle. aThese reference values were derived from a healthy subset of the Framingham Heart Study. These values were obtained by M-mode measurement with two-dimensional echocardiographic guidance. bLV wall thickness is the sum of the ventricular septum and posterior wall thickness. Reprinted from Lauer MS, Larson MG, Levy D. Gender-specific reference M-mode values in adults: Population-derived values with consideration of the impact of height. J Am Coll Cardiol, 1995;26(4):1039–1046. Copyright © 1995 American College of Cardiology. With permission.

FIGURE 1-19 A: A continuous recording of M-mode echocardiogram from the basal to the midportion of the heart from a parasternal location using a nonimaging probe in a patient with a large left atrium (LA) and thick mitral valve (MV) leaflets (arrows) with stenosis. A phonocardiogram was obtained simultaneously, and arrows indicate an early diastolic sound of “opening snap.” B: M-mode echocardiogram of mitral stenosis (left) with flattened EF slope (arrows). Corresponding continuous wave Doppler recording of mitral inflow velocity, which is increased (right).

FIGURE 1-20 A: M-mode echocardiogram of mitral valve prolapse (left). Mitral leaflets are thickened, and there is late systolic posterior motion (prolapse) of the posterior mitral leaflet below the C-D line (arrows). Corresponding continuous wave Doppler of mitral regurgitation (right) due to mitral valve prolapse (arrow). There is no flow velocity recorded during the first half of the systole (*) since mitral regurgitation usually starts at midsystole (with click) in mitral valve prolapse. B: M-mode echocardiogram of hypertrophic obstructive cardiomyopathy (left) showing systolic anterior motion (SAM, arrowheads) of mitral valve responsible for obstruction of the LV outflow tract. Corresponding continuous wave Doppler recording from the LVOT

(right). The Doppler has a scooped “dagger” shape with a late peaking. C: M-mode echocardiogram of left atrial myxoma recorded from the parasternal transducer position. During diastole, the mitral orifice is filled with increased echodensity (arrows) representing protruding atrial myxoma. D: M-mode echocardiogram of the mitral valve with fluttering (arrowheads) from aortic regurgitation. However, this M-mode sign may not be present if the aortic regurgitation jet is eccentric toward the ventricular septum rather than toward the mitral valve. The left ventricle (LV) is enlarged and systolic function is reduced. E: M-mode echocardiogram of a dilated LV with increased E-point septal separation (EPSS). Normal value for EPSS is less than 7 mm, but this patient has EPSS greater than 20 mm due to systolic dysfunction and LV enlargement. There is also “B” bump (arrow) of the mitral valve, which usually indicates increased LV diastolic filling pressure. B bump can also be seen in patients with prolong PR interval. F: M-mode from a patient with RV enlargement. G: M-mode of the mitral valve (left) which is thick (arrow). Ventricular septum (VS) is also increased in its thickness. With the increased septal thickness, early mitral valve opening is greater than late opening characteristic for restrictive diastolic filling. The restrictive filling is confirmed by pulsed-wave Doppler recording of mitral inflow velocity with E/A ratio close to 2 (right). H: M-mode of the aortic valve. The maximal opening tapers off during midsystole (arrowheads) when cardiac output is severely reduced. I: Aortic valve opening is only 4 mm, with thickened cusps. Also, multiple dense echoes (arrow) are noted in the aortic root during systole and diastole. These findings suggest severe aortic stenosis, but a Doppler study is required to determine how severe the stenosis is. J: M-mode echocardiogram (left) with normal-appearing aortic valve (AV). With Valsalva, there is a midsystolic closure of the AV in this patient with dynamic LVOT obstruction and systolic anterior motion of the mitral valve (right). Usually, this is from hypertrophic cardiomyopathy, but in this case, the patient had an early stage of cardiac amyloidosis. K: M-mode passing through the midportion of the heart demonstrating moderate size posterior pericardial effusion (PE) along with subtle respiratory variation in ventricular cavity size (left). Mitral inflow PW Doppler recording (right) demonstrates respiratory variation of LV filling with early filling (E) decreases with inspiration (upward respirometer recording) due to tamponade. L: Characteristic respiratory variation of ventricular septum (VS) as well as ventricular chamber size due to interventricular dependence seen in constrictive pericarditis (left). Posterior wall M-mode shows abrupt filling during early diastole followed by flattening of the wall. This is a characteristic finding of constrictive pericarditis. PW mitral inflow velocity recording (right) demonstrates typical respiratory variation seen in constrictive pericarditis (see Chapter 12). M: Normal pulmonary valve (PV) M-mode echocardiogram with prominent “a” wave (a). The valve closure is smooth (arrowheads). N: Midsystolic closure (arrows) of PV, producing a W shape in pulmonary hypertension (left). There is no “a” wave. Corresponding PW Doppler of the RV outflow demonstrating midsystolic closure (arrow) creating the characteristic “W” shape from pulmonary hypertension (right). Ao, aorta; AV, aortic valve; LA, left atrium; LV, left ventricle; MS, mitral stenosis; PV, pulmonary valve; RV, right ventricle.

REFERENCES 1. Tajik AJ, Seward JB, Hagler DJ, et al. Two-dimensional real-time ultrasonic imaging of the heart and great vessels: Technique, image orientation, structure identification, and validation. Mayo Clinic Proceedings, 1978;53:271–303.

2. Bansal RC, Tajik AJ, Seward JB, et al. Feasibility of detailed two-dimensional echocardiographic examination in adults: Prospective study of 200 patients. Mayo Clinic Proceedings, 1980;55:291–308. 3. Edwards WD, Tajik AJ, Seward JB. Standardized nomenclature and anatomic basis for regional tomographic analysis of the heart. Mayo Clinic Proceedings, 1981;56:479–497. 4. Henry WL, DeMaria A, Gramiak R, et al. Report of the American Society of Echocardiography Committee on nomenclature and standards in two-dimensional echocardiography. Circulation, 1980;62:212–217. 5. Chamsi-Pasha MA, Sengupta PP, Zoghbi WA. Handheld echocardiography: Current state and future perspectives. Circulation, 2017;136(22):2178–2188. 6. Spittell PC, Ehrsam JE, Anderson L, et al. Screening for abdominal aortic aneurysm during transthoracic echocardiography in a hypertensive patient population. Journal of the American Society of Echocardiography, 1997;10:722–727. 7. Lee SH, Chang SA, Jang SY, et al. Screening for abdominal aortic aneurysm during transthoracic echocardiography in patients with significant coronary artery disease. Yonsei Medical Journal, 2015;56(1):38–44. 8. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 2015;28(1):1–39 e14. 9. Lauer MS, Larson MG, Levy D. Gender-specific reference M-mode values in adults: Populationderived values with consideration of the impact of height. Journal of the American College of Cardiology, 1995;26:1039–1046. 10. Vasan RS, Larson MG, Benjamin EJ, et al. Echocardiographic reference values for aortic root size: The Framingham Heart Study. Journal of the American Society of Echocardiography, 1995;8:793–800. 11. Feigenbaum H. Role of M-mode technique in today’s echocardiography. Journal of the American Society of Echocardiography, 2010;23(3):240–257.

CHAPTER

2

Transthoracic Three-Dimensional Echocardiography Karima Addetia, Victor Mor-Avi, and Roberto M. Lang

INTRODUCTION Three-dimensional echocardiography (3DE) began with the cumbersome off-line reconstruction of multiple 2D acquisition planes, first reported in the 1980s. In the 1990s, advancements in technology led to the development of the matrixarray transducer, which was capable of scanning a pyramidal volume instead of a single plane. In subsequent years, further advancements allowed miniaturization of the matrix-array transducers, which improved the spatial and temporal resolution of the images. These pyramidal data sets are now analyzed with semiautomated software facilitating the integration of this novel 3D imaging modality into the clinical setting (Fig. 2-1). Recent studies have shown that when cardiac chamber sizes are quantified using 3DE, their volumes approximate those obtained with cardiovascular magnetic resonance imaging (cMRI) more closely than do measurements obtained with 2D ultrasound imaging. It is therefore not surprising that the recent chamber quantification guidelines recommend for the first time the use of 3DE for the evaluation of right and left ventricular volumes (1).

3D Image Acquisition Three different types of acquisition modes are available with current 3DE technology: 1) multi-plane imaging; 2) real-time or live 3D imaging (narrow angle); and 3) EKG-gated multi-beat acquisition that can be performed using either a full-volume (wide-angle) or zoom mode (Fig. 2-2). Full-volume acquisitions have the largest sector width together with the highest spatial and temporal resolution (>30 vps). This acquisition mode is the optimal choice for quantification of cardiac chambers and detailed diagnosis of complex pathologies. The “zoom” mode displays a smaller, magnified pyramidal volume

of data that may vary from 20° × 20° up to 90° × 90°. This mode is optimal for visualization of fast-moving structures such as valves, although it is limited by a reduction in spatial and temporal resolution when compared to full-volume data sets (Fig. 2-3). Multi-plane imaging is unique to the matrix-array transducer and allows simultaneous side-by-side display of the 2D reference plane being scanned and a user-defined rotated plane from the reference plane. This allows additional visualization of targeted structures from different angles simultaneously. Realtime or live 3D imaging enables acquisition of narrow pyramidal data sets in a single heartbeat. This narrow volume can be visualized in real time and is particularly useful during the guidance of interventional procedures when wires and catheters need to be located and tracked with ultrasound. While this imaging mode is limited by poor temporal and spatial resolution, it is useful in patients with rhythm disturbances and, unlike multi-beat acquisitions, is not influenced by breathing motion. Multi-beat 3D imaging combines subvolumes of data that are scanned during consecutive cardiac cycles (usually ranging from 2 to 6) using ECG gating and stitched together to create a single data set (Fig. 2-4A and B). Gated image acquisition is prone to “stitch” artifacts created by patient or respiratory motion or irregular cardiac rhythms (Fig. 2-4C). Yet, this mode results in the highest temporal and spatial resolution. In order to help minimize breathing artifacts, multi-beat acquisition should be performed during held endexpiration. Patients with irregular heartbeats (e.g., premature ventricular contractions [PVCs] or atrial fibrillation) may not be adequately imaged using multi-beat acquisition methods, due to the presence of “stitch” artifacts.

FIGURE 2-1 Evolution of 3D echocardiography over time. Top: Acquisition techniques of multiple ECG- and respiration-gated 2D acquisitions, resulting in off-line 3D reconstruction. Bottom: Major advances relevant to matrix array technology. (Adapted with permission from Caiani E. Transthoracic and transesophageal matrix transducers and image formation. In: Lang RM, Shernan SK, Shirali GS, et al., eds. Comprehensive Atlas of 3D Echocardiography, 1st ed. Philadelphia, PA: Wolters Kluwer Health, 2013:1–12.)

3DE imaging systems can also generate 3D color Doppler data sets by superimposing flow velocity data onto a 3D zoom or full-volume data sets. Currently these color data sets have narrower sector widths and lower frame rates so that color jet quantification using parameters such as vena contracta area, 3D PISA, and effective regurgitant orifice area (EROA) remain challenging.

FIGURE 2-2 Illustration of acquisition modes available with current 3DE technology: 1) narrow-volume or live 3D imaging (far left) and 2) EKG-gated multi-beat acquisition that can be performed using either a full-volume (wide-angle) or zoom mode (middle and far right). The full volume is preferred for cardiac chamber assessment while the zoom mode is preferred for fast-moving structures such as the valves.

An inherent limitation of 3DE imaging is a trade-off between spatial and temporal resolutions (volume rate or frame rate). To improve spatial resolution, an increased number of scan lines (or subvolumes) need to be acquired to “stitch” together the 3D data set. Volume rates can be optimized by reducing the sector width and/or imaging depth to reduce the volume size of the data set, the disadvantage being limited visualization of the specific structure of interest. Figures 2-5 and 2-6 list the anatomic structures that are most commonly imaged with transthoracic echocardiography together with the corresponding best choice of acquisition mode and image display as outlined by the current guidelines (2).

FIGURE 2-3 Multi-plane and narrow-volume acquisitions are limited to a single beat and therefore can be used for live scanning. Multi-beat acquisitions are built over a series of consecutive beats and have higher temporal and spatial resolution.

The Left Ventricle Quantification of left ventricular (LV) volumes and ejection fraction (EF) is one of the cornerstones of clinical echocardiography, since these estimates provide important diagnostic and prognostic information in multiple clinical scenarios. The main LV parameters that can be evaluated using 3DE include volume, function, mass, and shape. The accuracy of traditional 2D methodology for LV volume quantification is limited by acquisition of foreshortened apical views and reliance on geometric modeling. Foreshortening occurs when the imaging plane does not pass through the true LV apex resulting in an oblique view of the LV cavity. When these oblique views are used to calculate LV volumes, the resultant volumes are underestimated. In this regard, 3DE offers a number of advantages. Firstly, it eliminates errors associated with ventricular foreshortening by allowing the user to select from the pyramidal data set anatomically correct, nonforeshortened apical views. The validity of this concept first became apparent when LV mass measurements acquired using 2D and 3D echocardiography were compared with cMRI (3). Because in most patients, LV apical views were foreshortened with 2D imaging, the calculated LV mass was significantly underestimated compared to cMRI reference values. In contrast, 3D imaging resulted in more accurate measurements. In addition, 3DE eliminates the need for geometric assumptions

when calculating ventricular volumes. When LV volume is measured using the biplane Simpson technique from long-axis 2D images, it is assumed that LV shape can be approximated by a prolated ellipse, an assumption that may be inaccurate in the presence of wall motion abnormalities and aneurysms.

FIGURE 2-4 A: Multi-beat 3D imaging (both full-volume and zoom) combines subvolumes of data scanned during consecutive cardiac cycles. B: The data are then “stitched” together to create a single data set. C: Gated image acquisition is prone to “stitch” artifacts created by patient or respiratory motion or irregular cardiac rhythms (black arrows).

LV volume quantification using 3DE echocardiography can be performed using two different approaches (Fig. 2-7).

FIGURE 2-5 Full-volume acquisitions of the left ventricle (A), right ventricle (B), left atrium (C), and right atrium (D). These data sets were acquired by first using the biplane mode to confirm the absence of wall dropout in orthogonal planes (first two panels on left) and then acquiring the full-volume 3D data set during a (1–6 beat) breath-hold (third and fourth panel). The chamber is then displayed after cropping. Ideally, frame rates of these data sets should be >20 vps.

1. 3D-guided biplane technique. With this technique, nonforeshortened anatomically correct 2D views are selected from the pyramidal data set from which LV volumes are measured using the biplane Simpson approximation. This approach eliminates foreshortening errors, but geometric assumptions can still confound volume calculations. 2. Direct volumetric quantification. This technique is based on the semiautomated detection of LV endocardial surfaces throughout the cardiac cycle. Direct phase-by-phase volumetric analysis based on pixel counts

contained within the 3D endocardial surface results in LV volume over time curve. With this approach, both foreshortening and geometric assumptions are eliminated.

FIGURE 2-6 Zoom acquisitions of the aortic, pulmonary, mitral, and tricuspid valves (top to bottom). Each valve is initially displayed in orthogonal planes to ensure the absence of dropout (first two panels on left). The valve is then acquired as a (1–6 beat) zoom data set during breath-hold (third panel). The 3D valve is displayed in the recommended orientation: from the aortic perspective for the aortic valve, from the main pulmonary artery perspective for the pulmonary valve, from the left atrial perspective (also called the “surgeon’s view”) for the mitral valve with the aortic valve in the 12 o’clock position, and from the right ventricular perspective for the tricuspid valve with the septal leaflet in the 6 o’clock position.

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Video 2-6 When the 3D-guided biplane approach is compared with the 3D surface analysis volumetric method, LV volumes obtained with the latter method correlate better with cMRI-derived reference volumes, with smaller biases and narrower limits of agreement (4–6), underscoring the superior accuracy of this methodology, especially in distorted ventricles. Because 3DE avoids apical foreshortening and circumvents the need for geometric assumptions, when compared side-by-side with 2D biplane Simpson with and without contrast, 3D volumes and EF have the lowest inter- and intraobserver variability and test/retest variability (5). In one study, noncontrast 3D EF had an observer and test-retest variability of 5% to 8%, while 2D biplane methods showed a variability of 10% to 15% (5). In this study, 3D contrast enhancement did not improve observer variability. This is important because it means that 3D imaging is able to detect smaller volume and EF changes in patients requiring serial assessments. This is clinically useful in patients receiving potentially cardiotoxic chemotherapeutic agents or in patients with regurgitant valvular lesions, where small changes may prompt more frequent evaluations or changes in medical strategy.

FIGURE 2-7 LV volume quantification using 3D echocardiography can be performed using one of two approaches. The first approach is called the 3D-guided biplane technique (left panels). This method uses user-defined, nonforeshortened, orthogonal 2D views of the left ventricle, which have been extracted from the 3D data set in end-diastole (left panel, top row) and end-systole (left panel, bottom row). The length of the left ventricle in these orthogonal views should be close to identical in end-diastole and end-systole (see length measurements). Left ventricular volumes and ejection fraction are then measured using the biplane Simpson method. This approach eliminates foreshortening errors, but geometric assumptions can still impact volume calculations. The second approach is called direct volumetric quantification method (right panels). This technique is based on the semiautomated detection of left ventricular endocardial surfaces throughout the cardiac cycle (two columns, far right). Volume over time curves are generated (bottom left). Volumetric analysis is based on pixel counts contained within the 3D endocardial surface (top, left). With this approach, both foreshortening and geometric assumptions are eliminated.

One of the difficulties associated with the widespread application of 3DE lies in the ability to obtain good quality 3D data sets with optimal temporal and spatial resolution in which the entire left ventricle is contained within the 3D pyramidal volume. This is challenging in 1) patients with dilated ventricles, 2) patients with poor acoustic windows, 3) patients with arrhythmias, and 4) patients who are unable to hold their breath. Feasibility for adequate LV 3DE imaging in nonselected patients is between 70% and 90%. Despite the superiority of 3DE chamber quantification, its integration into daily practice has also been hampered by the added time required for 3DE analysis. New adaptive analytic algorithms based on machine learning technology allow quantification of 3D data sets by way of automated border detection. With this new technology, limited input is required to trace endocardial borders because the software is capable of contouring the endocardium automatically. The user only needs to make final adjustments. With this type of technology, it may become easier to

incorporate 3D quantification into the daily clinical routine (7) (Fig. 2-8).

Validation Against cMRI Despite its improved accuracy and reproducibility, 3D echocardiography consistently underestimates LV volumes when compared with cMRI. In addition to foreshortening, correct tracing of the endocardial border has been identified as a major source of ventricular volume underestimation (8). The standard convention is to trace the border at the interface between the compacted and noncompacted myocardium, while including the trabeculae within the LV cavity. Due to the limited spatial resolution of 3D images in some patients, accurate detection of this interface is challenging, more so when considering that small inaccuracies in the endocardial tracing may adversely influence the accuracy of the volume calculation. It is interesting to note that while 3D imaging is more accurate than 2D imaging for volumetric quantification, calculation of EF tends to be similar between techniques, because the volume underestimation at endsystole and end-diastole by 2D echocardiography are of similar magnitude. Normal values for 3D LV volumes and EF from selected studies are reported in Table 2-1. Women have higher 3D LVEF than do men and smaller indexed LV volumes (9–13).

FIGURE 2-8 Novel adaptive analytic algorithms based on machine learning allows quantification of 3D data sets by way of automated border detection. Limited input from the user is required to trace endocardial borders because the software is capable of contouring the endocardium automatically.

Left Ventricular Mass In population-based studies, LV hypertrophy is an important predictor of cardiovascular events (14) and an integral part of LV remodeling in multiple diseases. Traditionally, LV mass has been quantified using M-mode or 2D measurements of wall thickness, together with end-diastolic LV cavity dimensions (1). 3D LV mass can be determined using either the 3D-guided biplane technique or the direct volumetric analysis method, in both cases at enddiastole. 3D methods have the advantage of direct measurement without geometrical assumptions about cavity shape and hypertrophy distribution. These measurements have been proven to be more accurate than M-mode or 2D measurements with higher intermeasurement and test/retest reproducibility. Due to these advantages, 3D mass measurements are able to better discriminate small changes in mass over time in the same patient. In addition to accurate detection of the endocardial boundaries, LV mass

measurements heavily rely on the accurate detection of the epicardial border, which can be extremely challenging. Measurements obtained using 3DE have been shown to closely approximate LV mass obtained with cMRI, in explanted hearts and animal experiments (15). Further improvements in 3D technology and additional studies ascertaining prognostic value of 3D over 2D mass are needed in order to usher 3DE LV mass measurements into the clinical arena. Currently, this methodology is very dependent on image quality, and normal values are less well established.

3D Speckle Tracking Echocardiography Speckle tracking echocardiography (STE) is an off-line technique that allows quantification of LV deformation parameters (i.e., strain and strain rate) by tracking the motion of distinct acoustic markers throughout the cardiac cycle. The concept has been recently integrated into 3DE, enabling 3D deformation measurements. The main advantage of 3D over 2D STE is that while with the latter, speckles ere “lost” when they move out of the imaging plane, with 3D tracking, speckles can be followed in all directions as they move within the thicker pyramidal imaging volume. Additionally, when 2D global LV longitudinal strain is measured, speckle-tracking information is collected from nonsimultaneous beats in different views, and thus beat-to-beat variability could impact measurements. Normative values for 3D STE derived parameters collected from select recent studies are reported in Table 2-1. The main limitation of 3D STE at this time is its relatively low spatial and temporal resolution, which may impact the accuracy and reproducibility of 3D speckletracking results. Furthermore, significant intervendor variability has been reported when comparisons are made on the same patient using different vendor platforms (16,17). Importantly, a recent intersocietal taskforce in collaboration with the major manufacturers has been able to standardize these measurements and minimize this problem (18). TABLE 2-1 Normal Values for 3D Chamber Size and Functional Parameters from Selected Recent Publications



Studies

N

Men

Women

Left ventricle

EDVi, (mL/m2) ESVi, (mL/m2) EF (%)

Fukuda et al.

410

50 (7) 19 (5) 61 (4)

46 (9) 17 (4) 63 (4)

Aune et al.



66 (10) 29 (6) 57 (4)

58 (8) 23 (5) 61 (6)

Chahal et al. (European)

499

40 (9) 19 (5) 61 (6)

42 (8) 16 (4) 62 (5)

Chahal et al. (Asian)

479

41 (9) 16 (5) 62 (5)

39 (8) 15 (4) 62 (5)

Muraru et al.

226

63 (11) 24 (5) 64 (4)

56 (8) 20 (4) 65 (4)

Bernard et al.

440

69 (14) 29 (7) 59 (4)

60 (10) 24 (5) 60 (5)

Mizukoshi et al.

390

70 (9)

61 (8)

Muraru et al.

265

77 (10)

73 (8)

Fukuda et al.

410

64 (12)

56 (11)

Radial strain (%) Kleijn et al. Circumferential strain (%) Longitudinal strain Bernard et al. (%)

303

35 (10) −31 (3) −16 (2)

36 (11) −31 (3) −16 (2)

440

42 (5) −30 (4) −20 (3)

44 (4) −31 (4) −21 (2)

Muraru et al.a

265

51 (46;58) −19 (−20;−16) −18 (−19;−16)

54 (48;59) −18 (−20;−17) −20 (−21;−18)

Maffessanti et al.b 507

107 (17) 44 (11) 60 (8)

81 (12) 30 (8) 63 (7)

Tamborini et al.

245

56 (9) 22 (6) 62 (7)

51 (7) 18 (5) 64 (7)

Badano et al.c

276

31 (19;52) 11 (4;21) 66 (51;80)

31 (27;45) 10 (5;18) 68 (63;71)

Fukuda et al.

410

23 (6) 10 (3) 58 (6)

24 (6) 10 (3) 58 (6)

Peluso et al.

200

31 (8) 12 (4) 61 (6)

27 (6) 9 (3) 65 (8)

Indexed mass (g/m2)

Right ventricle

Left atrium

EDVi, (mL/m2) ESVi, (mL/m2) EF (%)

EDVi, (mL/m2) ESVi, (mL/m2) EF (%)

Right atrium EDVi, (mL/m2) ESVi, (mL/m2) EF (%)

EDV, end-diastolic volume; ESV, end-systolic volume; EF, ejection fraction. a This study reported first quartile and third quartile (in brackets). No standard deviation was reported. b This study did not report indexed values for EDV and ESV. cThis study reported median (25th percentile; 75th percentile).

Left Ventricular Shape Alterations in LV shape, size, and wall thickness and function induced by changes in cardiac load, tissue injury, and other factors define LV remodeling. Remodeling can be unfavorable as in progressive heart failure, where the heart size and mass increase as function deteriorates, and favorable (i.e., reverse remodeling), which occurs for example after successful valve surgery. Clinically, LV remodeling is assessed using 2D echocardiographic evaluation of chamber size and mass, both of which are limited by the use of foreshortened views and geometric assumptions. Newer methods based on 3D imaging have overcome these limitations. With 2D echocardiography, the sphericity index is calculated as the ratio between LV volumes calculated using the biplane Simpson method of disks and the volume of a sphere with a diameter equal to the LV long axis in the apical 4-chamber view (19). With 3DE, the sphericity index is calculated as a ratio of LV volume and the volume of a sphere with a diameter measured from the nonforeshortened 2D plane extracted from the 3D data set (20) (Fig. 2-9).

FIGURE 2-9 Methodologies for the assessment of left ventricular shape. The sphericity index is the simplest way to estimate left ventricular shape. The index is calculated as the ratio between left ventricular volume measured using 2D or 3D echocardiography and the volume of a sphere calculated using a diameter (D) equal to the long axis of the left ventricle in the four-chamber view. The 2D method is

illustrated on the far left. The calculated left ventricular volume is obtained using the 2D biplane Simpson formula. The diameter of sphere (D) is equal to the long axis of the left ventricle in the four-chamber view (dotted yellow line, top left). The 3D-based method is illustrated in the middle panel. In this formula, the 3D left ventricular volume is used while the diameter (D) is obtained from a manually extracted, nonforeshortened apical four-chamber view (dotted yellow line, center panel). On the far right panel, a newer method based on curvature indices is illustrated. Colorcoded curvature values are superimposed on the endocardial surface of the left ventricle; red hues correspond with more convex surfaces, blue hues correspond with more concave surfaces, and the green/yellow hues correspond with flatter surfaces.

More intricate and complex indices for LV shape have been developed using custom software to reflect the resemblance of the LV shape to a sphere or cone. Adverse alterations in LV shape frequently have a negative impact on outcomes. Patients with dilated cardiomyopathy and more spherical ventricles have worse outcomes. Patients with degenerative mitral valve disease with severe mitral regurgitation and normal LV EF have been shown to have more spherical ventricles, which revert to a more conical shape after mitral valve surgery (21). Surgical techniques designed to restore the post–myocardial infarction ventricles with aneurysmal dilatation to a more physiological conical shape have been shown to result in improved outcomes. Therefore, analysis of LV shape, in addition to an insight into LV remodeling, likely provides additional prognostic information to that provided by ejection phase indices. While sphericity does provide additional information about LV remodeling, it remains a global parameter. It does not account for regional changes in LV shape, which are known to occur in common disease states, such as ischemic heart disease. Regional assessment of LV shape is possible using curvature indices. Curvature is defined as the magnitude by which a surface deviates from being flat. It is calculated as the reciprocal of the radius of a circle that tangentially fits the curved surface of interest. A large radius represents a small curvature (flatter surface), while a small radius represents a larger curvature (a more round or convex surface). Regional curvature analysis of 3DE data sets of the left ventricle has been used to describe regional LV remodeling in dilated cardiomyopathy as well as other pathologies (22) (Fig. 2-9). It is widely accepted that LV EF is an important prognostic parameter. LV volumes obtained using 2D echocardiography underestimate true volumes and therefore have not been useful in providing outcome-related information for decision-making in patient care. Recent data, however, suggest that this may not be true for 3DE-derived LV volumes. Both larger 3D volumes and lower LV EF have been shown to be associated with higher mortality. When compared

alongside 2D parameters, 3D LV EF and 3D end-systolic volume have been shown to correlate more strongly with outcomes than do 2D parameters (23).

The Right Ventricle Although right ventricular (RV) volumes and EF are also of prognostic importance in a variety of disease states, including ischemic and nonischemic cardiomyopathy, pulmonary arterial hypertension, and right-sided valve disease, objective quantification of 3D RV size and function has been elusive for years. Estimation of RV size and function using 2D imaging is challenging due to its asymmetrical and complex crescent shape and retrosternal location, making it difficult to visualize the entire RV chamber from a single 2D echocardiographic view. While it is possible to calculate LV volumes and EF by 2D echocardiography using the biplane method of discs, it is not possible to approximate RV volumes in this way because the RV chamber shape cannot be approximated by a prolated ellipse. Additionally, it is difficult to obtain orthogonal long-axis views of the right ventricle around a common axis, such that the use of the Simpson biplane or area-length methods is technically not feasible. Segments such as the RV outflow tract, which account for up to 30% of the RV volume, are not measured by 2D analysis, resulting in poor correlations between RV volumes and those obtained with angiographic studies. Functional analysis of the right ventricle from 2D echocardiography has therefore been limited to visual assessment, fractional change in RV areas, and assessment of RV longitudinal motion using parameters such as tricuspid annular plane systolic excursion or TAPSE and tissue Doppler S-wave velocity. Recently, 3DE has provided a unique opportunity for the quantification of RV volumes and EF from full-volume RV data sets obtained from the RV-focused view without the need for geometric assumptions. Because the right ventricle is asymmetrical, RV fullvolume data sets must be obtained with particular care to include all three RV regions, namely the inflow, outflow, and body, in order to avoid RV free wall dropout, which is most frequently seen in the anterior free wall (Fig. 2-5). Once a 3D full-volume data set of the right ventricle is obtained, there are two approaches for volume assessment (24) (Fig. 2-10). 1. Disk summation or method of disks. When using this technique, the operator traces the contour of the RV endocardial border at end-systole and end-diastole in a stack of short-axis views with known thickness spanning the right ventricle from base to apex. The software then computes the end-systolic and

end-diastolic volumes by adding the slice volumes. 2. Direct volume quantification. This technique is based on the semiautomated detection of the RV endocardial surface, followed by calculation of the volume contained within this surface. The operator uses end-diastolic and end-systolic frames obtained from a full-volume 3DE data set in the long- and short-axis views to trace the endocardial border such that trabeculae are included within the RV cavity. Over time, it has been recognized that the disc summation method is less accurate than is the volumetric technique, because it fails to accurately account for the volume contained in the basal slice and therefore tends to overestimate RV volumes when compared with known-volume phantoms (24). This is because the tricuspid valve and RV outflow tract are not in the same plane. The more accepted approach for RV volume and EF quantification using 3DE today is the direct volume quantification or the volumetric approach. This volumetric approach has been validated using in vitro as well as in vivo models against cMRI reference (24–26).

FIGURE 2-10 There are two approaches for 3D quantification of right ventricular volume and ejection fraction. The first (top row) is the disk summation method. In this technique, the user traces the contour of the RV endocardial border in a stack of short-axis views with known thickness spanning the right ventricle from base to apex at end-diastole and end-systole. The software computes the end-systolic and enddiastolic volumes and provides a value for the ejection fraction. The second (bottom panel) is the volumetric analysis method. In this technique, the operator uses enddiastolic and end-systolic planes obtained from a full-volume 3DE data set in both the long- and short-axis views to trace the endocardial border. Volume estimates are based on pixel counts contained within the 3D endocardial surface.

Similar to the left ventricle, RV volumes are underestimated on 3DE when

compared with cMRI. 3DE measurements also result in wider margins of error with higher inter- and intraobserver variability than cMRI. This is probably due to the lower spatial resolution and prominent RV trabeculae, which make the identification of the endocardial border challenging. Currently, 3D analysis is the only echocardiographic technique that provides a reliable measurement of RV EF (Fig. 2-10). However, clinical use of 3DE for RV volume and functional assessment is limited due to the learning curve required for the acquisition and measurements of 3D RV data sets.

Right Ventricular Shape RV shape varies in different disease states. Due to its crescent shape on crosssectional views and asymmetrical inflow and outflow tracts, the right ventricle cannot be viewed in its entirety in any single 2D plane, and hence the difficulty in characterizing and quantifying changes in RV shape with 2D echocardiography. Until recently, quantification of changes in RV shape has been limited to the use of the eccentricity index and assessment of septal flattening and regional apical geometry. In contrast, with 3DE imaging, the entire right ventricle can be contained in a single data set. This provides a unique opportunity for evaluating the entire RV surface morphology. A recently described methodology for the assessment of RV shape divides the RV endocardial surface into six regions. It has been reported that patients with severe pulmonary arterial hypertension have rounder RV outflow tracts, flatter apical free walls, and a septum that tends to bulge into the LV cavity, when compared with normal subjects. The study of the RV shape together with functional measures remains an area of increasing interest and promise (27).

THE LEFT ATRIUM Left atrial (LA) enlargement is a marker of chronic elevation of LV filling pressure. It is also a powerful predictor of adverse cardiovascular outcomes, including stroke, atrial fibrillation, congestive heart failure, and death (28). LA volume measurements are preferred over linear dimensions because they allow more accurate assessment of the asymmetric remodeling of the atrium. However, left atrial volumes remain grossly inaccurate when measured using the 2D arealength or 2D biplane method of discs approaches, which are based on geometric assumptions. The accuracy of these volumes is even further compromised if

dedicated views of the left atrium are not acquired. Analogous to the left ventricle, where it is important to avoid foreshortening in order to minimize volume underestimation, care must also be taken to maximize the long-axis dimension of the left atrium during imaging in both the apical 4- and 2-chamber views. This is important because the long axes of the left ventricle and left atrium almost always lie in different planes (Fig. 2-11). Hence the need for nonforeshortened “focused” acquisitions of the left atrium. If acquired correctly, the length of the left atrium in the two apical views should be nearly identical (29). 3DE intrinsically eliminates this problem, similar to volumetric analysis of the ventricles, by allowing the operator to manually select nonforeshortened orthogonal planes from the 3D data set prior to quantification. This is in addition to minimizing inaccuracies associated with geometric assumptions, which are not needed with 3DE analysis. The two approaches available for LA volume quantification with 3DE are the same as those described for the left ventricle, that is, the biplane Simpson method and the volumetric method (see section on The Left Ventricle). Of note, LA volumes obtained using 3DE more closely approximate those measured with cMRI, probably because the differentiation between compacted and noncompacted myocardium does not apply to the left atrium (30). When 3Dderived LA volumes are compared with 2D volumes in the same subjects, 3D volumes are larger (31). A number of recent studies have reported normal values for 3D LA volumes (Table 2-1). The left atrium has three main functions: reservoir, conduit and “booster.” During ventricular systole, the left atrium functions as a reservoir, accepting blood from the pulmonary veins; in early diastole, it serves as a passive conduit, accepting blood from the left ventricle; and in late diastole it contracts, serving as a pump to complete LV filling. 3DE allows calculation of time-volume curves, which may prove in the future to have prognostic implications. Some data suggest that with age, LA reservoir function decreases and booster function augments (29). A similar pattern is seen with increasing severity of diastolic dysfunction.

3D IMAGING OF THE VALVES The superiority of 3DE over 2D imaging lies in its realistic imaging of native heart valves, visualization of their anatomical relationships, and geometry, including nonplanarity. With transthoracic 3DE, it is possible to obtain 3D views

of all the valves (Fig. 2-6) from different perspectives. Perhaps the most difficult valve to image is the pulmonary valve. There are two particular areas where transthoracic 3DE provides incremental benefit over 2D imaging (32). These include 1) the quantitative assessment of mitral stenosis and 2) the visualization of the tricuspid valve. Recent studies have also suggested value in the quantification of valvular regurgitation using full-volume 3D color Doppler to visualize and measure the vena contracta area and 3D PISA–derived EROA. 3D PISA assessment is especially attractive in cases where the hemispheric principle is not applicable. Limitations of 3D color Doppler imaging at this time include challenging acquisition and low frame rate of data sets, which limit the accuracy of measurements. Finally, at this time, there are no official guidelines to assist in the categorization of 3D color Doppler measurements.

FIGURE 2-11 A–C are images taken from the same patient. The left atrium does not enlarge symmetrically so that a single dimension in the parasternal long-axis view (A) does not necessarily correlate with left atrial enlargement. In B left atrial volume is obtained from the apical-four chamber view while in C left atrial volume is being obtained from the focused left atrial view. The volume obtained in C is larger than that obtained in B. In order to accurately measure left atrial volumes, the atrial-focused view must be used. This view maximizes left atrial dimensions in order to avoid foreshortening of the left atrium (C). With 3D echocardiography, the operator can choose the anatomically correct, nonforeshortened left atrial views so that calculated volumes are more accurate (E).

Mitral Stenosis The mitral valve (MV) is best assessed using transesophageal echocardiography. The proximity of the valve to the ultrasound probe and the superior spatial resolution of the transesophageal 3DE images allow MV assessment with great anatomical detail. From a transthoracic perspective, the MV can be imaged from 1) parasternal short-axis view and 2) the apical four-chamber view, using both zoom and full-volume acquisition, when higher spatial and temporal resolution are required (Fig. 2-12). Rheumatic MV stenosis (Fig. 2-12c) continues to be an important public health concern. As discussed in greater detail in Chapter 13, the severity of rheumatic MV stenosis on 2D echocardiography is approximated by measuring the MV orifice area using the pressure half-time method, the continuity equation method, and/or 2D planimetry. The Doppler-based methods are heavily influenced by hemodynamic variables, LV and LA compliance, and associated valvular lesions. Accordingly, direct measurements of MV orifice area (e.g., 2D planimetry) are sometimes more accurate. However, 2D planimetry of the mitral valve orifice is not easy to perform. It requires that the ultrasound beam be perpendicular to the leaflet tips in the short axis views, in order to trace the MV orifice area. An incorrect imaging plane can result in overestimation of the MV orifice area. 3DE enables the echocardiographer to select the anatomically correct plane on which to perform the MV orifice area measurement at the leaflet tips (Fig. 2-13). This methodology is feasible and has shown the best agreement with the invasively determined MV area, particularly after percutaneous mitral valvuloplasty. 3D planimetry is the most accurate method for measuring MV orifice area in the immediate period following percutaneous balloon mitral valvuloplasty and can be used to estimate MV orifice area in patients with calcific mitral stenosis (33).

FIGURE 2-12 Panel A shows transthoracic imaging of the mitral valve. The mitral valve should be displayed with the aorta in the 12 o’clock position. From this perspective, the left atrial appendage is in the 9 o’clock position. Panel B shows the mitral valve from the left atrial perspective in a patient with prolapse of P2 (arrow). Panel C displays the mitral valve in a patient with mitral stenosis form the left atrial and left ventricular perspective depicting commissural fusion and thickening of the mitral leaflets.

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Video 2-12A

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Video 2-12B

FIGURE 2-13 3D of the mitral valve can be acquired from the parasternal long-axis view (top row) and the apical four-chamber view (bottom row). Multiplanar reconstruction can be used to obtain orthogonal views of the mitral valve (green and red boxes). After careful alignment of these orthogonal planes, the third plane (blue line) can be used to cut through the leaflet tips to allow planimetry of the mitral valve orifice area (blue boxes, far right). The resultant mitral valve area (MVA) can then be traced.

The Tricuspid Valve The tricuspid valve (TV) is a complex structure with three leaflets of varying sizes that are attached to the fibrous tricuspid annulus. With 2D echocardiography, no more than two leaflets can be reasonably identified in each

of the standard views. Transthoracic 3DE allows simultaneous visualization of all three TV leaflets from a single acquisition (Fig. 2-14). Unlike the mitral valve, 3D images of the TV are best acquired from the transthoracic approach. The close proximity of the tricuspid apparatus to the anterior wall of the chest makes it readily available to the 3D transthoracic probe. Transthoracic acquisitions of the TV can be performed from the 1) apical four-chamber RVfocused views, 2) parasternal long-axis RV inflow views, and 3) parasternal basal short-axis views. Using the 3D zoom mode, the TV can be visualized from the right atrial and RV perspective. This view can be useful in delineating the mechanism of tricuspid regurgitation or identifying the leaflet (leaflets) involved in the pathology (Fig. 2-14). Tricuspid regurgitation due to endocardial lead implantation or implantable cardioverter defibrillators is a known complication of these procedures. Together with 2D imaging and full-volume RV imaging, the zoom view of the tricuspid valve can sometimes be used to determine whether a device lead is impinging on the TV leaflets (34,35).

FIGURE 2-14 Transthoracic imaging of the tricuspid valve. The tricuspid valve should be displayed with the septal leaflet in the 6 o’clock position. A: Normal tricuspid valve displayed from the right ventricular perspective. Note the thin leaflets. B: Tricuspid valve in a patient with severe pulmonary hypertension. Note the thickened leaflets. C: Bicuspid tricuspid valve with only two leaflets. D: Tricuspid valve as seen from the

right atrial perspective. All leaflets are prolapsed. E and F: Tricuspid valve as seen from the right atrial (E) and right ventricular (F) perspective in a patient with a pacemaker. The lead is in the commissure between the posterior and septal leaflets. G: A quadricuspid tricuspid valve as seen from the right ventricular perspective. H and I: Tricuspid valve in a patient with malcoaptation seen in end-diastole (H) and end-systole (I) from the right ventricular perspective. J: tricuspid valve seen from the right ventricular perspective in a patient with malcoaptation between the anterior and posterior leaflets (A, anterior leaflet; P, posterior leaflet; S, septal leaflet; PM, pacemaker; PS, posteroseptal commissure).

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Video 2-14A

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Video 2-14B

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Video 2-14C

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Video 2-14D Recently, increasing attention has been given to the TV in patients undergoing MV surgery. It has been shown that a dilated tricuspid annulus (based on a single 2D diameter) with or without the presence of significant tricuspid regurgitation is associated with worse outcomes post MV surgery, suggesting that tricuspid annular dilatation may be a better indicator of TV dysfunction than the presence or absence of tricuspid regurgitation. This is largely because tricuspid regurgitation varies markedly with RV loading conditions. However, because of its oval shape, nonplanar morphology, and dynamic behavior throughout the cardiac cycle, a single 2D diameter of the annulus cannot fully characterize tricuspid annular size. With transthoracic 3DE, it has been shown that it is possible to obtain accurate measurements of the tricuspid annulus area, perimeter, and dimensions and to track these measurements dynamically.

SUMMARY 3D imaging has the potential to radically modify the manner in which we routinely quantify cardiac chambers on transthoracic echocardiography. It eliminates geometric assumptions and diminishes foreshortening, thereby resulting in volume measurements that are more reproducible and accurate. Further analysis of the endocardial surfaces and time-volume curves will open the doors to the characterization of chamber shape, interchamber relationships, and 3D deformation. Transthoracic 3DE also holds promise for comprehensive evaluation of cardiac valves. It is currently recommended in the evaluation of mitral stenosis when planimetry is required and has recently been shown to be valuable in the evaluation of the tricuspid valve.

REFERENCES 1. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 2015;28(1): 1–39.e14. 2. Lang RM, Badano LP, Tsang W, et al. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. Journal of the American Society of Echocardiography, 2012;25(1):3–46. 3. Mor-Avi V, Sugeng L, Weinert L, et al. Fast measurement of left ventricular mass with real-time threedimensional echocardiography: Comparison with magnetic resonance imaging. Circulation, 2004;110(13):1814–1818. 4. Jacobs LD, Salgo IS, Goonewardena S, et al. Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data. European Heart Journal, 2006;27(4):460–468. 5. Thavendiranathan P, Liu S, Verhaert D, et al. Feasibility, accuracy, and reproducibility of real-time fullvolume 3D transthoracic echocardiography to measure LV volumes and systolic function: a fully automated endocardial contouring algorithm in sinus rhythm and atrial fibrillation. JACC Cardiovascular Imaging, 2012;5(3):239–251. 6. Nesser HJ, Mor-Avi V, Gorissen W, et al. Quantification of left ventricular volumes using threedimensional echocardiographic speckle tracking: comparison with MRI. European Heart Journal, 2009;30(13):1565–1573. 7. Tsang W, Salgo IS, Medvedofsky D, et al. Transthoracic 3D Echocardiographic Left Heart Chamber Quantification Using an Automated Adaptive Analytics Algorithm. JACC Cardiovascular Imaging, 2016;9(7):769–782. 8. Mor-Avi V, Jenkins C, Kuhl HP, et al. Real-time 3-dimensional echocardiographic quantification of left ventricular volumes: Multicenter study for validation with magnetic resonance imaging and investigation of sources of error. JACC Cardiovascular Imaging, 2008;1(4):413–423. 9. Aune E, Baekkevar M, Rodevand O, et al. Reference values for left ventricular volumes with real-time 3-dimensional echocardiography. Scandinavian Cardiovascular Journal, 2010; 44(1):24–30. 10. Bernard A, Addetia K, Dulgheru R, et al. 3D echocardiographic reference ranges for normal left

ventricular volumes and strain: Results from the EACVI NORRE study. European Heart Journal Cardiovascular Imaging, 2017;18(4):475–483. 11. Chahal NS, Lim TK, Jain P, et al. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction. JACC Cardiovascular Imaging, 2012;5(12): 1191–1197. 12. Fukuda S, Watanabe H, Daimon M, et al. Normal values of real-time 3-dimensional echocardiographic parameters in a healthy Japanese population: The JAMP-3D Study. Circulation Journal, 2012;76(5):1177–1181. 13. Muraru D, Badano LP, Peluso D, et al. Comprehensive analysis of left ventricular geometry and function by three-dimensional echocardiography in healthy adults. Journal of the American Society of Echocardiography, 2013;26(6): 618–628. 14. Bluemke DA, Kronmal RA, Lima JA, et al. The relationship of left ventricular mass and geometry to incident cardiovascular events: The MESA (Multi-Ethnic Study of Atherosclerosis) study. Journal of the American College of Cardiology, 2008;52(25):2148–2155. 15. Gopal AS, Schnellbaecher MJ, Shen Z, et al. Freehand three-dimensional echocardiography for determination of left ventricular volume and mass in patients with abnormal ventricles: Comparison with magnetic resonance imaging. Journal of the American Society of Echocardiography, 1997; 10(8):853–861. 16. Badano LP, Cucchini U, Muraru D, et al. Use of three-dimensional speckle tracking to assess left ventricular myocardial mechanics: Inter-vendor consistency and reproducibility of strain measurements. European Heart Journal Cardiovascular Imaging, 2013;14(3):285–293. 17. Gayat E, Ahmad H, Weinert L, et al. Reproducibility and inter-vendor variability of left ventricular deformation measurements by three-dimensional speckle-tracking echocardiography. Journal of the American Society of Echocardiography, 2011;24(8):878–885. 18. Yang H, Marwick TH, Fukuda N, et al. Improvement in Strain Concordance between Two Major Vendors after the Strain Standardization Initiative. Journal of the American Society of Echocardiography, 2015;28(6):642–648.e7. 19. Lamas GA, Vaughan DE, Parisi AF, et al. Effects of left ventricular shape and captopril therapy on exercise capacity after anterior wall acute myocardial infarction. American Journal of Cardiology, 1989;63(17):1167–1173. 20. Mannaerts HF, van der Heide JA, Kamp O, et al. Early identification of left ventricular remodelling after myocardial infarction, assessed by transthoracic 3D echocardiography. European Heart Journal, 2004;25(8):680–687. 21. Maffessanti F, Caiani EG, Tamborini G, et al. Serial changes in left ventricular shape following early mitral valve repair. American Journal of Cardiology, 2010;106(6):836–842. 22. Salgo IS, Tsang W, Ackerman W, et al. Geometric assessment of regional left ventricular remodeling by three-dimensional echocardiographic shape analysis correlates with left ventricular function. Journal of the American Society of Echocardiography, 2012;25(1):80–88. 23. Stanton T, Haluska BA, Leano R, et al. Hemodynamic benefit of rest and exercise optimization of cardiac resynchronization therapy. Echocardiography, 2014;31(8):980–988. 24. Sugeng L, Mor-Avi V, Weinert L, et al. Multimodality comparison of quantitative volumetric analysis of the right ventricle. JACC Cardiovascular Imaging, 2010;3(1):10–18. 25. Medvedofsky D, Addetia K, Patel AR, et al. Novel Approach to Three-Dimensional Echocardiographic Quantification of Right Ventricular Volumes and Function from Focused Views. Journal of the American Society of Echocardiography, 2015;28(10):1222–1231. 26. Muraru D, Spadotto V, Cecchetto A, et al. New speckle-tracking algorithm for right ventricular volume analysis from three-dimensional echocardiographic data sets: Validation with cardiac magnetic

resonance and comparison with the previous analysis tool. European Heart Journal Cardiovascular Imaging, 2016;17(11):1279–1289. 27. Addetia K, Maffessanti F, Yamat M, et al. Three-dimensional echocardiography-based analysis of right ventricular shape in pulmonary arterial hypertension. European Heart Journal Cardiovascular Imaging, 2016;17(5):564–575. 28. Tsang TS, Abhayaratna WP, Barnes ME, et al. Prediction of cardiovascular outcomes with left atrial size: Is volume superior to area or diameter? Journal of the American College of Cardiology, 2006;47(5):1018–1023. 29. Badano LP, Miglioranza MH, Mihaila S, et al. Left Atrial Volumes and Function by Three-Dimensional Echocardiography: Reference Values, Accuracy, Reproducibility, and Comparison with TwoDimensional Echocardiographic Measurements. Circulation Cardiovascular Imaging, 2016;9(7). 30. Mor-Avi V, Yodwut C, Jenkins C, et al. Real-time 3D echocardiographic quantification of left atrial volume: Multicenter study for validation with CMR. JACC Cardiovascular Imaging, 2012;5(8):769– 777. 31. Miyasaka Y, Tsujimoto S, Maeba H, et al. Left atrial volume by real-time three-dimensional echocardiography: Validation by 64-slice multidetector computed tomography. Journal of the American Society of Echocardiography, 2011;24(6): 680–686. 32. Lang RM, Tsang W, Weinert L, et al. Valvular heart disease. The value of 3-dimensional echocardiography. Journal of the American College of Cardiology, 2011;58(19):1933–1944. 33. Zamorano J, Cordeiro P, Sugeng L, et al. Real-time three-dimensional echocardiography for rheumatic mitral valve stenosis evaluation: An accurate and novel approach. Journal of the American College of Cardiology, 2004;43(11):2091–2096. 34. Addetia K, Maffessanti F, Mediratta A, et al. Impact of implantable transvenous device lead location on severity of tricuspid regurgitation. Journal of the American Society of Echocardiography, 2014;27(11):1164–1175. 35. Mediratta A, Addetia K, Yamat M, et al. 3D echocardiographic location of implantable device leads and mechanism of associated tricuspid regurgitation. JACC Cardiovascular Imaging, 2014;7(4):337–347.

CHAPTER

3

Transesophageal Echocardiography Jeremy J. Thaden, Joseph F. Maalouf, and Jae K. Oh

INTRODUCTION In 1987, clinical transesophageal echocardiography (TEE) was introduced at Mayo Clinic (1). This technology has inexorably changed the diagnostic strategy for numerous cardiovascular diseases and, in many circumstances, has become the diagnostic procedure of choice. The principal reason for this change in practice is that TEE provides superb clarity and easily interpretable images. TEE is relatively easy to perform, uncomplicated, and capable of providing unique insight into cardiothoracic structures anywhere at the patient’s bedside, even in critically ill patients or during interventional/surgical procedure. TEE incorporates all the functionality of transthoracic echocardiography (TTE), including three-dimensional imaging, which can reliably interrogate cardiovascular anatomy, function, hemodynamics, and blood flow. Before the introduction of TEE, echocardiography was frequently used as a screening tool that had to be complemented by other diagnostic modalities. Definitive management of valvular disease, aortic dissection, endocarditis, atrial fibrillation, congenital heart disease, and intracardiac masses and tumors can be accomplished on the basis of a complete echocardiography examination, including TEE (2–10). In this clinical context, TEE will continue to have a major role in the management of virtually all cardiovascular diseases. Approximately 5% to 10% of patients who have a TTE examination require the addition of TEE. Also, TEE has become an integral part of cardiovascular surgery and a growing list of transcatheter structural heart procedures where it is useful to assess candidacy for an operation, guide the operation, and assess the results of the operation (see Chapter 23). As in the earlier editions of The Echo Manual, TEE is discussed throughout the text in relation to the diagnosis and management of specific cardiovascular diseases.

INDICATIONS The indications for TEE procedures at Mayo Clinic are listed in Table 3-1. The distribution of indications for TEE varies from institution to institution, depending on the patient population. The most common indication has been for evaluation of a potential cardiac source of embolism (35%) and atrial fibrillation (34%). Besides these indications, TEE is now considered essential in the evaluation of mitral valve lesions, left atrial (LA) or LA appendage thrombus, intracardiac mass, atrial septal defect, endocarditis and its complications, thoracic aortic lesions (in particular, aortic dissection), and critically ill patients (11–16). Because of 1) an increasing number of patients with atrial fibrillation, 2) a well-established practice model for TEE-guided cardioversion, and 3) ablation procedures, atrial fibrillation has become one of the more common reasons for referral for TEE.

PREPARATION AND POTENTIAL COMPLICATIONS TEE is a semiinvasive procedure that can be uncomfortable in unprepared patients. Patients should be informed about the potential risks and benefits and be familiarized with the TEE procedure. The preprocedure discussion should include even uncommon complications (70% methemoglobin), exchange transfusion or dialysis

may be needed. A short-acting sedative or amnestic agent such as midazolam (Versed), 1 to 10 mg (mean dose, 3.6 ± 2.3 mg), and fentanyl, 25 to 100 mg intravenously, are used almost routinely to make the TEE examination more comfortable for the patient. These agents should be used with caution in debilitated or elderly patients because of potential respiratory suppression or hypotension. However, midazolam can be rapidly reversed in about 60 seconds with flumazenil, 0.2 to 0.4 mg intravenously. Naloxone at an initial dose of 0.4 mg can be given intravenously to reverse the effect of fentanyl. Occasionally, it has been necessary to paralyze an agitated critically ill patient. A nasogastric or endotracheal tube usually does not interfere substantially with esophageal intubation with the TEE probe or prohibit the acquisition of satisfactory images. Esophageal perforation is a rare but disastrous complication of TEE (19). TEE should not be performed in patients with dysphagia without further evaluation of the esophagus. Intubation of a TEE probe should not be forced. Prolonged intubation of a TEE probe during an operation may increase the risk of perforation. When the TEE probe is not used intraoperatively, it may be disconnected from the machine to reduce thermal injury. Also, the TEE probe should not be left in the esophagus or the stomach in a locked position.

INSTRUMENTATION The TEE probe is a modified gastroesophageal endoscopy probe, typically with a 3- to 7-MHz ultrasound transducer at the tip. It can be maneuvered to various positions in the esophagus and stomach, from which the heart and other cardiovascular and surrounding structures can be visualized. The diameter of the adult transducer tip is 9 to 14 mm, and this is miniaturized to less than 3 mm for pediatric, neonatal, and even fetal use. All adult probes use multiplane transducers that can be rotated 180 degrees. The transducer usually is rotated by a switch at the proximal operator end. The tip of the probe also can be anteflexed (anterior flexion) or retroflexed (posterior flexion) or moved laterally (side to side) by larger knobs at the proximal end. When performed electively, the examination begins with the patient in the left lateral decubitus position. The procedure room is equipped with oral suction, oxygen supply, pulse oximeter, and cardiopulmonary resuscitation capabilities. In critically ill patients for whom transfer is difficult, the examination is performed at the bedside. If the patient is mechanically ventilated, the TEE probe is often introduced with the patient

supine. We use a bite guard to protect the TEE scope, unless the patient is edentulous. When the scope is introduced, the imaging surface of the transducer faces the tongue, which directs the ultrasound beam from the posteriorly located esophagus anteriorly toward the heart. A digital technique may be used for esophageal intubation. When the probe is introduced, the posterior portion of the tongue is depressed with the left index finger to minimize tongue movement, and the tip of the transducer is placed over the left index finger to a position at the center of the tongue. After the transducer is in the correct position, the left index finger is placed over the distal shaft or tip of the probe and depressed directly downward onto the tongue. This places the tip of the probe in direct alignment with the posteriorly located esophagus and away from the anteriorly located trachea. The tip of the transducer is advanced smoothly and slowly posteriorly toward the esophagus. At this time, the patient is asked to swallow. The tip of the TEE transducer should be advanced into the esophagus without force or notable resistance. The distance from the incisors to the midesophagus, adjacent to the LA, is approximately 30 cm.

TRAINING OF PHYSICIANS AND THE ROLE OF SONOGRAPHERS TEE complements the TTE examination. Therefore, it is advised that a physician who performs TEE has competency in TTE, which includes personally performing more than 300 documented surface echocardiograms before performing TEE. It is critical that the physician knows the function of all knobs to be able to capture all appropriate images and Doppler signals within the shortest time possible. The physician also needs to learn the technique of esophageal intubation under the supervision of an endoscopist or other echocardiologist experienced in TEE procedure. We consider a minimum of 50 esophageal intubations necessary to provide adequate training in intubation. The sonographer or trained assistant has an essential role in preparing patients for TEE and in assisting the physician during the examination. The role of the sonographer or assistant in TEE is summarized in Table 3-3 (Table 3-2). In our laboratory, a registered nurse or nurse sonographer coordinates and assists with TEE examinations. Because TEE is semiinvasive, the skills of a registered nurse are preferred for closely monitoring the patient, that is, for obtaining vital signs,

administering medications, inserting intravenous catheters, and using suction, oxygen, or other emergency equipment. A properly trained assistant can perform these functions except for intravenous administration of medications. Because TEE has a small but definite risk for the patient, it generally is considered necessary for the procedure to be performed by a physician. Also, physicians and allied health personnel involved in performing TEE are required to have annual training in conscious or moderate sedation. TABLE 3-2 Preparation for Transesophageal Echocardiography Preparation Inquiry about history of dysphagia or esophageal abnormality Reduce risk of pulmonary aspiration For healthy patients undergoing elective procedures 6 hours fasting (light meal consisting of toast and clear liquids) 6 hours milk 2 hours clear liquids No restriction if patient is tracheally intubated In very urgent situations, tracheal intubation and/or upper esophageal suction is necessary Local anesthesia spray Intravenous access with three-way stopcock Medications Drying agent (optional) to reduce salivation Glycopyrrolate (Robinul), 0.2 mg intravenous 2–3 min before examination Sedation Midazolam hydrochloride (Versed), 1–10 mg (low doses in older patients) Reversal: flumazenil (Romazicon), 0.2–0.4 mg, if needed for rapid reversal of midazolam hydrochloride Analgesia Fentanyl, 25–100 mg* intravenous (lower dosage in older patients) Reversal: Naloxone (Narcan) (1 mg/mL vial), up to 0.1 mg/kg For treatment of methemoglobinemia (most often associated with benzocaine products used for local anesthesia) Methylene blue, 1–2 mg/kg intravenously Muscle relaxant (occasional use in special circumstances) Paralyzing agent in conjunction with sedation for agitated patient on mechanical ventilator *Higher doses are rarely necessary.

MULTIPLANE TRANSESOPHAGEAL ECHOCARDIOGRAPHY IMAGING VIEWS

The multiplane TEE transducer consists of a single array of crystals that can be rotated electronically or mechanically around the long axis of the ultrasound beam in an arc of 180 degrees (Fig. 3-1). With rotation of the transducer array, multiplane TEE produces a continuum of transverse and longitudinal image planes (22). TABLE 3-3 Summary of the Role of the Sonographer/Assistant in Transesophageal Echocardiography Before procedure Preparation of equipment and supplies Assemble supplies Medications, normal saline flushes, and contrast medium Intravenous supplies (angiocatheter, three-way stopcock) Lidocaine spray and tongue blade Scope lubricant: lubricating jelly or viscous lidocaine Gloves, safety glasses, TEE probe, and bite block Maintain and check suction, oxygen, and basic life-support equipment Patient preparation Confirm that patient has had no oral intake for at least 6 hours before TEE Obtain brief history of drug allergies and current medications Explain procedure to patient Obtain baseline vital signs and monitor rhythm Remove patient’s dentures, oral prostheses, and eyeglasses Establish intravenous catheter for administration of medications Place patient in the left lateral decubitus position with wedge support and safety restraints Assist patient during esophageal intubation, such as head position, breathing, and reassurance Drugs Pharyngeal anesthesia (see Table 3-2) Drying agent (optional) Sedation and/or analgesia (see Table 3-2) During procedure Position and maintain bite block Monitor vital signs: rhythm, respiration, blood pressure, and oxygen saturation Use oral suction if necessary Have basic life-support equipment available After procedure Optional reversal of midazolam sedation with flumazenil (see Table 3-2) Assist patient during recovery period (patient must be fully awake and/or accompanied at departure) Remove intravenous catheter Instruct patient not to drive for 12 hours if sedation was used Record vital signs and patient’s condition on dismissal Arrange for escort if patient is not completely recovered

Clean scope with enzyme solution and glutaraldehyde disinfectant

Multiplane images are identified by an icon to indicate the degree of transducer rotation (Fig. 3-2). This designation helps the operator to understand the orientation of the ultrasound beam and to conduct the TEE examination more efficiently. The transverse esophageal plane, which is in the short axis of the body, is designated as 0 degrees. The longitudinal esophageal plane, which is in the long axis of the body, is designated as 90 degrees. The TEE transducer can be rotated in a continuum throughout 180 degrees, resulting in versatility of the examination and ease of understanding. Normally, from the midesophagus, the short axis of the heart is imaged at 45 degrees of rotation and its long axis at 135 degrees. By convention, the transducer location is displayed at the top of the page (20), although, if preferred, the transducer location can be displayed at the bottom of the screen to replicate transthoracic image format (22).

FIGURE 3-1 Array rotations of selected degrees (0, 45, 90, 135, and 180 degrees) permit a logical sequence of standard transducer orientations and resultant images. Such a display helps the examiner acquire the desired views: 0-degree transverse orientation, which is horizontal to the chest at the midesophageal level; 45-degree short-axis orientation to the base of the heart from the midesophagus; 90-degree longitudinal orientation, which is in the sagittal plane of the body; 135-degree longaxis orientation to the heart from the midesophagus; and 180-degree rotation, which produces a mirror-image transverse plane. (From Seward JB, et al. Mayo Clin Proc, 1993;68:523–551. Used with permission of Mayo Foundation for Medical Education and Research.)

Primary Views Standard TEE imaging windows include the upper esophagus, the midesophagus, and transgastric views (Fig. 3-3). The heart and its anatomy can

be completely visualized from these primary imaging windows by advancing the probe, withdrawing the probe, anteflexion (anterior flexion), retroflexion (posterior flexion), lateral flexion, rightward (clockwise) and leftward (counterclockwise) rotation of the probe, and adjustment of the multiplane transducer angle.

Upper Esophageal Views The upper esophageal window is adjacent to the great vessels and aortic arch and thus provides high-resolution images of these structures and adjacent anatomy. From this position, the ascending aorta long axis can be reliably visualized at a multiplane angle of 90 to 110 degrees with the imaging plane oriented anteriorly and frequently with slight anteflexion of the probe (Fig. 3-4A). From this view of the midascending aorta long axis, decreasing the transducer angle to 0 to 30 degrees allows visualization of a short-axis view of the ascending aorta and the bifurcation of the pulmonary artery (Fig. 3-4B). By rotating the transducer shaft clockwise, the long axis of the right pulmonary artery and the short axis of the superior vena cava and the right upper pulmonary vein are viewed adjacent to the ascending aorta. This is the best view for identifying an anomalous connection of the right upper pulmonary vein with the superior vena cava (11). By rotating the transducer shaft counterclockwise, the proximal portion of the left pulmonary artery can be visualized.

FIGURE 3-2 Four multiplane transesophageal echocardiographic (TEE) images obtained by rotating the transducer array from 0 to 135 degrees. The icon (in the corner) indicates the position of the transducer. A: Four-chamber view (0 degrees with retroflexion of the transducer tip). B: Short-axis view (45–60 degrees) of the aortic valve. Asterisk, Left atrial (LA) appendage. C: Two-chamber view (65–100 degrees with leftward rotation of TEE shaft). Arrow, LA appendage. D: Long-axis view (125–140 degrees) of the left ventricle (LV). Ao, aorta; RA, right atrium; RV, right ventricle; RVOT, right ventricular outflow tract.

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Video 3-2A

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Video 3-2B

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Video 3-2C

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Video 3-2D Further leftward (counterclockwise) rotation from the left main pulmonary artery with a transducer angle of 0 to 10 degrees results in visualization of the descending thoracic aorta in short axis (Fig. 3-5). The anatomic relationship

between the thoracic aorta and the esophagus is intimate. The proximity between these two structures allows superb visualization of the aorta with TEE. The aortic arch and the distal portion of the ascending aorta may not be accessible with transverse imaging because of the interposed trachea, but multiplane TEE usually allows complete visualization of the remainder of the thoracic aorta. While keeping the descending thoracic aorta in view, advance the probe and rotate the shaft to visualize sequentially the lower thoracic and upper abdominal aorta. With similar care to keep the aorta continuously in view, withdraw the probe to visualize the upper thoracic aorta. Conversely, with the transducer array at 90 to 100 degrees, the longitudinal view of the aorta is obtained (Fig. 3-5). With this transducer orientation, it is usually possible to visualize the takeoff of the left subclavian, left carotid, and innominate arteries from an upper esophageal window adjacent to the aortic arch.

FIGURE 3-3 Standard transesophageal echocardiographic (TEE) imaging windows. The upper esophageal window lies in close proximity to the aortic arch, pulmonary artery bifurcation, and the upper descending thoracic aorta, making it an ideal position to image these structures. The midesophageal window is ideal for imaging the cardiac valves, left atrium, left atrial appendage, the interatrial septum, and is also useful to assess biventricular function. The transgastric and deep transgastric views are frequently useful for visualization of left ventricular function and regional wall motion, the tricuspid valve, and for spectral Doppler assessment of the aortic valve. (Copyright Mayo Foundation for Medical Education and Research.)

FIGURE 3-4 Ascending aorta and the pulmonary artery bifurcation. A: At a transducer angle of 90 to 110 degrees with the transducer directed anteriorly, a longitudinal view of the ascending aorta is seen. B: From this transducer position, reducing the transducer angle to 0 to 30 degrees provides visualization of the pulmonary artery bifurcation. Ao, aorta; LPA, left main pulmonary artery; PA, main pulmonary artery; RPA, right main pulmonary artery.

Midesophageal Views When the transducer is in the midesophageal imaging window, it resides immediately posterior to the left atrium. This close proximity allows for highresolution images of the left atrium, LA appendage, pulmonary veins, mitral valve, and interatrial septum. From the midesophageal window, one can also readily evaluate biventricular function and the function of all four cardiac valves. Four primary multiplane TEE views can be obtained by rotating the transducer array from 0 to 135 degrees from the midesophageal window: 1) 0 degrees (transverse plane): oblique view of basal structures including LA appendage and the four-chamber view by retroflexion and anteflexion of the transducer tip, 2) 45 degrees: short-axis view of the aortic valve, 3) 90 degrees: this produces images oblique to the long axis of the heart including the atrial septum, both vena cavae and 2 chamber view of the LV; and 4) 135 degrees: the standard left ventricular outflow tract (LVOT) view.

FIGURE 3-5 Descending thoracic aorta. Biplane imaging shows simultaneous transverse (left) and longitudinal (right) views of the descending thoracic aorta.

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Video 3-5 A typical four chamber view of the heart is visualized with the transducer angle at 0 to 10 degrees (Fig. 3-6A). Slight retroflexion from this position is frequently required to avoid foreshortening the left ventricular apex. Rightward (clockwise) rotation results in a dedicated right ventricular view, while leftward (counterclockwise) rotation results in a dedicated left ventricular view. Frequently, visualization of the tricuspid valve is optimized from this position by advancing the transducer to a lower esophageal window. With the left ventricle

centered in the frame, increasing the transducer angle to 80 to 100 degrees creates a two-chamber view (Fig. 3-6B) and further increasing the angle to approximately 120 to 140 degrees provides a long-axis view of the left ventricle and LVOT (Fig. 3-6C).

FIGURE 3-6 Left ventricular function and regional wall motion. From the midesophagus, multiplane imaging angles of 0 to 10 degrees (A), 80 to 100 degrees (B), and 120 to 140 degrees (C) produce the left ventricular four chamber, two chamber, and long-axis views, respectively. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

Zoomed, high-resolution views of the mitral valve can be obtained from the midesophageal window. Interrogation of the mitral valve from multiple imaging planes is critical to be sure the valve is visualized in its entirety (Fig. 3-7). In our lab, this is typically accomplished by scanning the mitral valve from 0 to 120 to 140 degrees (or the angle of a typical long-axis view) in 30-degree increments. Precise localization of mitral leaflet pathology can be achieved in two steps (Fig. 3-8). The first step involves determining whether the pathologic lesion involves the anterior or posterior leaflet. This can be determined in any view but often is readily apparent in the long-axis view (110 to 140 degree transducer angle) (Fig. 3-8A) or in the four- or five-chamber view with the transducer angle at 0 to 10 degrees. In each of these views, the leaflet associated with the aortic valve is

identified as the anterior mitral leaflet. The second step involves determining the medial to lateral location of the leaflet pathology, and this is typically best determined in the mitral commissural view with a transducer angle of 50 to 70 degrees (Fig. 3-8B). This view typically provides visualization of the P1, A2, and P3 scallops from right to left (lateral to medial) (Figs. 3-7 and 3-8B). Lateral leaflet pathology (A1 or P1) is seen on the right side of the image (adjacent to the LA appendage), medial pathology (A3 or P3) is seen on the left side of the image (adjacent to the atrial septum), and middle leaflet pathology (A2 or P2) is seen in the middle. This is also one of the views to detect and visualize mitral prosthetic paravalvular leak (Fig. 3-9). From the level of the mitral valve with the transducer angle at approximately 35 to 55 degrees, slight withdrawal of the probe will allow visualization of the aortic valve in short axis (Fig. 3-2B). Increasing the transducer angle further to 120 to 140 degrees provides a typical long-axis view of the aortic valve (Fig. 32D). From this long-axis view, leftward (counterclockwise) rotation will result in visualization of the LA appendage. The LA appendage is normally multilobed and therefore should be interrogated at multiple angles to ensure it is visualized in its entirety.

FIGURE 3-7 A: Anatomic specimen of the mitral valve (Courtesy of J. Maleszewski, MD). B: A schematic diagram of the mitral valve viewed from the left atrium

(surgeon’s view). The mitral valve is bisected by multiplanar imaging from the midesophageal window. From this position, the entirety of the mitral valve visualized by rotating the multiplane imaging angle between 0 and 140 degrees. C: Mitral leaflet pathology as viewed from the midesophageal imaging window at approximately 60 degrees (commissural view). The corresponding location of various posterior leaflet flail scallops is shown.

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Video 3-7 When viewing the LA appendage at approximately 90 to 110 degrees, further leftward (counterclockwise) rotation allows simultaneous visualization of the left upper and left lower pulmonary veins as a “Y” configuration entering the left atrium (Fig. 3-10, left). For the right pulmonary veins, set the transducer array to 45 to 70 degrees and rotate the shaft of the transducer to the patient’s extreme right (clockwise rotation of the transducer shaft); this allows the right upper and lower pulmonary veins to be visualized simultaneously, which appear as a “Y” configuration, where they enter the left atrium (Fig. 3-10, right). Sometimes, we see more than 2 (Inferior and superior) pulmonary veins at each side. The connection of the pulmonary veins with the left atrium are also visualized from the transverse view (0 degrees) with the transducer behind the left atrium. The upper pulmonary veins are easier to see, but the lower veins also are seen by slightly advancing the probe from the position used for the upper pulmonary veins. Increasing the transducer angle back to 90 to 110 degrees and rotating the transducer leftward (counterclockwise) from the right-sided veins results in a bicaval view providing visualization of the atrial septum and the superior and inferior vena cava simultaneously (Fig. 3-11). This is the best TEE imaging view to assess patent foramen ovale by 2-D, color flow imaging, and administration of agitated saline.

FIGURE 3-8 Mitral leaflet scallops by transesophageal echocardiography. A: Discrimination between anterior and posterior mitral leaflet pathology is readily apparent from the long-axis view at 120 to 140 degrees. In this view, the anterior mitral leaflet (AML) is seen to the right, adjacent to the aortic valve (AV) and a flail posterior mitral leaflet (PML) is seen to the left (arrow). B: Medial-lateral discrimination of the leaflet pathology is typically best performed from the mitral valve commissural view at 50 to 70 degrees. In this view, the most lateral portion of the posterior leaflet, the P1 scallop, is seen on the right and the medial most scallop of the posterior leaflet, P3, is seen on the left. The middle scallop of the anterior leaflet, A2, is typically seen in the middle. In this case, a short-axis view of the flail posterior leaflet is also seen posterior to the A2 scallop, corresponding to a P2 flail segment (arrow). A2, A2 mitral scallop; AML, anterior mitral leaflet; AV, aortic valve; LA, left atrium; P1, P1 mitral scallop; P2, P2 mitral scallop; P3, P3 mitral scallop; PML, posterior mitral leaflet.

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Video 3-8A

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Video 3-8B The proximal portions of the coronary arteries are normally seen with TEE. The left coronary artery is visualized best from the transverse basal short-axis view (0 degrees). The left main coronary artery is located immediately below the level of the LA appendage. From the transverse LA appendage view, the probe needs to be withdrawn slightly to demonstrate the left main coronary artery and its bifurcation into the left anterior descending and circumflex coronary arteries (Fig. 3-12). At 90 degrees of transducer orientation and leftward rotation of the probe, a short-axis view of the left main coronary artery is obtained. With further leftward rotation, a long-axis view of the left anterior descending and short-axis to long-axis view of the circumflex coronary artery can be obtained. The proximal right coronary artery is visualized best in the longitudinal plane (90 to 135 degrees), arising from the anteriorly located right aortic sinus, about 1 to 2 cm above the aortic valve (Fig. 3-12B). Anomalous coronary arteries, coronary aneurysms, and coronary fistulas can be diagnosed with TEE.

FIGURE 3-9 Color flow imaging from midesophageal TEE view of severe mitral periprosthetic regurgitation.

Transgastric Views From the midesophageal views, one can straighten the probe and advance the probe into the stomach. With the transducer tip in the fundus of the stomach (about 40 to 45 cm from the incisors) and the transducer array at 0 to 10 degrees, a short-axis view of the LV and right ventricle (RV) is seen (Fig. 3-13A). Frequently, some degree of anteflexion is required in this position to maintain adequate contact with the stomach wall. Further anteflexion (or withdrawal) creates a basal short-axis view of the left ventricle, and retroflexion (or advancement) creates an apical short-axis view of the left ventricle. Similar to the midesophageal views, a two chamber view is created with a transducer angle of 90 to 110 degrees (Fig. 3-13B) and a long-axis view is created with a transducer angle of approximately 120 to 140 degrees (Fig. 3-13C). From a left ventricular two chamber view, rightward (clockwise) rotation of the transducer will create a tricuspid inflow view (Fig. 3-13D). From this longaxis view, decreasing the transducer angle to 0 to 20 degrees results in a shortaxis view of the tricuspid valve. The tricuspid valve is frequently best visualized from a shallow transgastric or deep esophageal window.

FIGURE 3-10 Pulmonary veins. Left-sided pulmonary veins are typically viewed in a “Y” configuration at a transducer angle of 90 to 110 degrees (A) and right-sided pulmonary veins are typically viewed at a transducer angle of 45 to 60 degrees (B). Color flow imaging of the left-sided PV (C) and right-sided PV (D). Please note the three different right-sided PVs. LLPV, left lower (inferior) pulmonary vein; LUPV, left upper (superior) pulmonary vein; RLPV, right lower (inferior) pulmonary vein; RUPV, right upper (superior) pulmonary vein.

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Video 3-10

CAVEATS

TEE has improved the visualization not only of cardiovascular structures previously seen with TTE but structures that were not well appreciated with TTE. Understanding unfamiliar but normal structures helps to minimize misinterpretation of TEE findings. Previously unrecognized normal structures seen with TEE are the most frequent reasons for misinterpretation. The most frequently misinterpreted TEE images are shown in Figure 3-14. A large hiatal hernia, pneumopericardium, or a mechanical valve prosthesis may interfere with imaging the heart with TEE.

FIGURE 3-11 Bicaval TEE view. IVC; inferior vena cava; SVC; superior vena cava.

3D Transesophageal Echocardiography: Basic Concepts and Clinical Applications Introduction of the matrix array transducer into clinical practice has allowed for acquisition of 3D volumetric echocardiographic datasets. 3D TEE is increasingly utilized during routine clinical practice to assess complex cardiac anatomy and pathology, to evaluate candidacy for structural heart procedures, to guide a growing list of transcatheter heart procedures, and for echocardiographic quantitation.

FIGURE 3-12 A: Transverse view above the aortic valve showing the left main (large arrow) coronary artery and its bifurcation into the circumflex (Cx) and left anterior descending (LAD) coronary arteries. B: Long-axis view of the aorta (Ao) showing the ostium of the right coronary artery in apex-down format (arrow). (See Chapter 7 for transesophageal imaging of abnormal coronary arteries.) LA, left atrium; RV, right ventricle; SVC, superior vena cava; VS, ventricular septum.

FIGURE 3-13 Transgastric views of the left and right ventricle. A: A midventricular short-axis view is shown with a transducer angle of 0 to 20 degrees. Increasing the transducer angle to 90 to 110 degrees produces a transgastric two-chamber view (B) and further increasing the angle to 120 to 140 degrees produces a transgastric longaxis view (C). D: Rotation of the transducer shaft to the right (clockwise) and decreasing the angle to 90 to 110 degrees allows visualization of the transgastric right ventricular inflow view. AV, aortic valve; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

FIGURE 3-14 Frequently encountered normal variants with transesophageal echocardiography. A prominent eustachian valve (A, arrow) is frequently seen at the junction of the inferior vena cava (IVC) and right atrium (RA) in the bicaval view. The eustachian valve is a remnant of the fetal valve of the inferior vena cava, which functions to facilitate right-to-left shunting during fetal development. A Chiari network (B, arrows) is another structure frequently seen at the junction of the IVC and RA. This structure is characterized by multiple thin, filamentous, and highly mobile projections arising from the eustachian or thebesian valves (arrows). Prominent lipomatous hypertrophy of the atrial septum (C, arrows) is commonly encountered and can be mistaken for an intracardiac mass or tumor. Lipomatous hypertrophy of the atrial septum typically spares the fossa ovalis, resulting in a “dumbbell” appearance of the atrial septum (C). The warfarin ridge, or “Q-tip,” is a normal structure (D, arrows) that separates the left superior pulmonary vein (LSPV) from the left atrial appendage (LAA). Particularly early in the experience with transesophageal echocardiography, this was occasionally mistaken for an intracardiac mass or thrombus. A prominent crista terminalis (E, arrows) can also be mistaken for a right atrial mass, often seen

arising near the confluence of the right atrium with superior vena cava or inferior vena cava (E, left panel). However, rotation of the transducer shaft to the right (E, right panel) creates an off-axis view, which confirms that this is a continuous ridge extending from the superior vena cava to the inferior vena cava, which is characteristic of the crista terminalis. Panel F is a basal short-axis view showing several soft tissue masses (arrow) in a space between the left atrium (LA) and aorta (Ao). The space is the transverse sinus. The soft tissue masses are either fibrin or fat material in pericardial effusion or the tip of the LA appendage. Ao, aorta; IVC, inferior vena cava; LA, left atrium; LAA, left atrial appendage; LSPV, left superior pulmonary vein; RA, right atrium; RVO, right ventricular outflow tract.

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Video 3-14A

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Video 3-14B

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Video 3-14C Currently available 3D transesophageal echocardiographic systems, compared to 2D imaging modes, are limited in spatial and temporal resolution. In contrast to 2D echocardiographic imaging modes that acquire planar images of the heart, 3D imaging systems acquire pyramidal-shaped volumetric datasets consisting of information in the axial, lateral, and elevation dimensions (Fig. 3-15). Spatial resolution of current 3D echocardiographic systems is approximately 0.5 mm in the axial dimension. Resolution in the lateral and elevation dimensions is typically 2 to 3 mm but varies with imaging depth, with near-field resolution being better than far-field resolution. Acquired datasets are then cropped as necessary to visualize anatomy of interest or analyzed to obtain quantitative measurements. Increasingly, systems are utilizing automated or semiautomated techniques to improve the efficiency, accuracy, and reproducibility of quantitative 3D analysis.

FIGURE 3-15 Three-dimensional transesophageal echocardiography using a matrix array transducer. The matrix array transducer facilitates acquisition of threedimensional, pyramidal-shaped volumetric datasets. The three dimensions in the acquired volume are denoted as axial, lateral, and elevation dimensions.

Currently utilized 3D echocardiographic imaging modes include single-beat (real time) and multibeat (ECG-gated) acquisitions. Single-beat acquisitions have the advantage of showing cardiac structures in real time, but compared to 2D imaging modes, they are limited by relatively low temporal resolution (low volume rates). Limited volume rates of 3D imaging can be overcome by decreasing the spatial resolution, which sacrifices the “crispness” of the image

for better volume rates (Fig. 3-16). Alternatively, some machines have the capability to acquire ECG-gated multibeat acquisitions, which improve volume rate without compromising image quality (Fig. 3-17). Multibeat acquisitions typically require a breath-hold and a regular cardiac rhythm to avoid stitch artifact. The addition of color Doppler not only provides 3D visualization of blood flow in the context of the surface-rendered 3D image but also further limits temporal resolution. 3D color Doppler imaging is helpful to precisely locate regurgitant lesions, differentiate dropout artifact from a true defect, and the datasets can be used for quantitative analysis of regurgitant lesions. Many of the imaging artifacts encountered in 2D echocardiography are also encountered in 3D echocardiography, but 3D echocardiography also has frequently encountered artifacts which are unique (Fig. 3-18). Stitch artifact, mentioned previously, is commonly encountered in the multibeat acquisition imaging mode whenever there is movement of the heart in relationship to the transducer during the acquisition. This commonly occurs as the result of an irregular heart rhythm or respiratory motion and appears as straight lines within the acquired volume corresponding to each wedge-shaped subvolume. A second commonly encountered artifact in 3D echocardiography is dropout artifact. Acoustic shadowing can result in tissue dropout and can give the false impression of a tissue defect when one is not truly present. Dropout artifact frequently occurs in situations where there are structures that cause significant acoustic shadowing, such as prosthetic valves or bulky calcification. Dropout artifact can also occur when attempting to image thin structures, particularly if they are at a poor insonation angle (e.g., parallel to the ultrasound beam). The addition of color Doppler imaging can be employed to interrogate for blood flow through the apparent defect to help differentiate dropout artifact from a true defect. There are several important principles that will facilitate acquisition of highquality 3D datasets. Given the somewhat limited spatial and temporal resolution of current 3D imaging, structures of interest should be imaged in the near-field whenever possible to optimize resolution. Gain levels should typically be in the midrange; if gains are too high, this can degrade image quality and cause noise artifact, and if gains are too low, this can cause dropout artifact. Biplane-guided image acquisition can also be employed to optimize volume size to 1) ensure that all structures of interest are within the 3D volume and 2) to more precisely reduce the volume size to optimize spatial and temporal resolution. 3D TEE is particularly suited for evaluation of complex mitral valve anatomy

given the close proximity of the mitral valve to the midesophageal imaging window. While 2D echocardiography provides a general understanding of the mitral valve anatomy, 3D echocardiography provides a more comprehensive understanding of mitral valve pathology and 3D spatial relationships. This information is often critical for the preprocedural assessment and guidance of procedures such as transcatheter edge-to-edge mitral valve repair (Fig. 3-19). 3D echocardiography has also shown utility for characterization of mitral prosthesis paravalvular regurgitation and guidance of transcatheter paravalvular leak closure procedures (Fig. 3-20). Additionally, 3D volumetric datasets can be manipulated using multiplanar reconstruction to obtain a number of quantitative measurements. 3D echocardiographic measurements of mitral valve stenotic orifice area (Fig. 3-21), mitral valve regurgitant orifice area (Fig. 3-22), aortic annulus dimensions (Fig. 3-23), and LA appendage dimensions (Fig. 3-24) have already been validated in comparison to reference techniques (23–26). It is likely that the future applications of 3D echocardiography will grow as the technology continually improves.

FIGURE 3-16 Spatial resolution in three-dimensional echocardiography. This illustration represents a surface-rendered image of the mitral valve using a low scan line density, seen in the left panel, versus a higher scan line density, seen in the right panel. The spatial or detail resolution of a three dimensional, surface-rendered image is defined by the ultrasound scan line density, which is directly related to number of 2D sectors in the volume of interest and number of ultrasound lines in a 2D sector. Scan line density can be reduced (left panel) to improve temporal resolution, but this is at the expense of spatial resolution or the “crispness” of the image. A higher scan line density (right panel) produces a more crisp image, but this is at the expense of temporal resolution, which is often limited with current generation three-dimensional echocardiographic systems.

FIGURE 3-17 ECG-gated multibeat acquisition. One method to overcome the limited spatial and temporal resolution of currently available three-dimensional echocardiographic systems is to perform an ECG-gated multibeat acquisition. In this imaging mode, multiple wedge-shaped subvolumes are captured during each cardiac cycle and are then “stitched” together to form the full volume dataset. Advantages of this imaging mode include improved spatial and temporal resolution with the ability to acquire larger datasets. Note that the 3D volume rate in multibeat acquisition is determined by the time needed to acquire a subvolume.

FIGURE 3-18 3D transesophageal echocardiographic imaging artifacts. An ECGgated, multibeat acquisition provides improved spatial and temporal resolution but introduces potential for stitch artifact. When the imaged cardiac structure moves in relationship to the ultrasound transducer during acquisition, stitch artifact is produced. Despite careful attention to minimize probe movement and during held patient respiration, subtle stitch artifact is observed over the mitral valve as straight lines

marking the edges of the wedge-shaped subvolumes (A, arrows). Dropout artifact can also be observed when imaging thin structures, particularly when the tissue lies at a poor insonation angle (e.g., perpendicular to the ultrasound beam) which further reduces reflection of ultrasound waves. For these reasons, dropout artifact is relatively common when imaging a normal aortic valve from the midesophageal imaging window (B, asterisks).

FIGURE 3-19 3D TEE for mitral valve assessment. All mitral leaflet scallops can be examined with a thorough, multiplane 2D TEE exam. The long-axis, zoomed view of the mitral valve typically displays the A2 and P2 scallops (A, arrows). In panel A, bileaflet mitral valve prolapse involving A2 and P2 is shown. 2D color Doppler imaging (B) reveals a complex jet of mitral regurgitation with a small anteriorly directed jet (B, single arrow) and a larger posteriorly directed jet (B, double arrows). Panel C shows an en face view of the mitral valve from the perspective of the left atrium, the “surgeon’s view.” This view demonstrates that the mitral valve prolapse is not confined to A2-P2 but instead involves the entire medial portion of the anterior and posterior leaflet scallops (C, arrows). Mitral annular calcification is also appreciated in the lateral portion of the mitral annulus (C, asterisk). 3D color Doppler imaging confirms the larger posteriorly directed jet (D, double arrows) occurs at A2-P2 but also extends as a broad, continuous jet to the medial commissure. The smaller anteriorly directed jet seen on the 2D imaging is confined primarily to the A2-P2 region (D, single arrow). 3D TEE offers incremental information beyond that obtained by 2D TEE, which can be helpful in planning both surgical and transcatheter mitral valve repair. AV, aortic valve; LA, left atrium; LAA, left atrial appendage; LV, left ventricle.

FIGURE 3-20 3D TEE for mitral paravalvular regurgitation. 2D TEE with color Doppler demonstrates a large anterolateral jet of paravalvular regurgitation (A, asterisk) adjacent to the left atrial appendage (LAA) and a second posterolateral jet of paravalvular regurgitation (B, arrow). C: 3D TEE with color Doppler imaging provides more precise localization and visualization of the circumferential extent of the anterolateral (asterisk) and posterolateral (arrow) paravalvular regurgitant jets. D: Live 3D TEE can be used for procedural guidance to assist with cannulation and deployment of percutaneous closure of mitral paravalvular regurgitation. Panel D shows 2 plugs (arrows) deployed in the posterolateral paravalvular jet and the guide catheter (asterisk) crossing the atrial septum in good position to cannulate the anterolateral defect adjacent to the left atrial appendage (LAA). Ao, aorta; LA, left atrium; LAA, left atrial appendage; LV, left ventricle.

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Video 3-20A

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Video 3-20B

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Video 3-20C

FIGURE 3-21 Mitral valve area by 3D planimetry. 3D echocardiography volumetric datasets with multiplanar reconstruction allow for alignment of the mitral stenotic orifice in two orthogonal planes (panels A and B). By aligning with the tip of the mitral leaflets, a short-axis view of the stenotic orifice is produced in panel C. This allows for direct planimetry of the stenotic orifice in short axis (C, asterisk). Simultaneous display of the tomographic planes and their spatial relationships are shown in panel D. LA, left atrium; LV, left ventricle.

FIGURE 3-22 3D color Doppler planimetry of the mitral regurgitation vena contracta area. 3D color Doppler datasets are utilized to perform direct planimetry of the mitral regurgitation vena contracta area. Orthogonal planes are used to align with the vena contracta (A and B), resulting in a short-axis view of the vena contracta by color Doppler (C, arrow). A surfaced-rendered 3D image of the mitral valve and systolic flow convergence from the perspective of the left ventricle is shown in panel D. Note the elliptical shape of the vena contracta in this patient with secondary mitral regurgitation. LA, left atrium; LV, left ventricle.

FIGURE 3-23 Aortic annular measurement by 3D TEE. A 3D echocardiographic dataset of the aortic annulus is used to align with the aortic annulus (Ann) in two orthogonal views (panels A and C). Proper alignment with the nadir of the aortic leaflets results in a short-axis view of the aortic annulus in panel B, which allows for direct planimetry and measurement of the minimum and maximum diameters. Simultaneous display of the tomographic planes and their spatial relationships are shown in panel D. Ann, aortic annulus; Ao, aorta; LA, left atrium; LVOT, left ventricular outflow tract.

FIGURE 3-24 Left atrial appendage ostial measurement by 3D TEE. Given the close proximity of the left atrial appendage to the midesophageal window, high-resolution 3D echocardiographic images can be obtained (D). 3D datasets can be aligned with the ostium of the left atrial appendage in two orthogonal views (A and B) to produce a short-axis view of the ostium for planimetry (C). A surfaced-rendered 3D image of the ostium of the LA appendage from the perspective of the LA is shown in panel D.

REFERENCES 1. Seward JB, Khandheria BK, Oh JK, et al. Transesophageal echocardiography: Technique, anatomic correlations, implementation, and clinical applications. Mayo Clin Proc, 1988;63: 649–680. 2. Erbel R, Engberding R, Daniel W, et al. Echocardiography in diagnosis of aortic dissection. Lancet, 1989;1:457–461. 3. Freeman WK, Schaff HV, Khandheria BK, et al. Intraoperative evaluation of mitral valve regurgitation and repair by transesophageal echocardiography: incidence and significance of systolic anterior motion. J Am Coll Cardiol, 1992;20:599–609. 4. Randolph GR, Hagler DJ, Connolly HM, et al. Intraoperative transesophageal echocardiography during surgery for congenital heart defects. J Thorac Cardiovasc Surg, 2002;124: 1176–1182. 5. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med, 2001;344:1411–1420. 6. Daniel LB, Grigg LE, Weisel RD, et al. Comparison of transthoracic and transesophageal assessment of prosthetic valve dysfunction. Echocardiography, 1990;7:83–95. 7. de Bruijn SF, Agema WR, Lammers GJ, et al. Transesophageal echocardiography is superior to transthoracic echocardiography in management of patients of any age with transient ischemic attack or stroke. Stroke, 2006;37:2531–2534. 8. Eltzschig HK, Rosenberger P, Loffler M, et al. Impact of intraoperative transesophageal echocardiography on surgical decisions in 12,566 patients undergoing cardiac surgery. Ann Thorac Surg, 2008;85:845–852.

9. Wiet SP, Pearce WH, McCarthy WJ, et al. Utility of transesophageal echocardiography in the diagnosis of disease of the thoracic aorta. J Vasc Surg, 1994;20:613–620. 10. Shapiro SM, Young E, De Guzman S, et al. Transesophageal echocardiography in diagnosis of infective endocarditis. Chest, 1994;105:377–382. 11. Pascoe RD, Oh JK, Warnes CA, et al. Diagnosis of sinus venosus atrial septal defect with transesophageal echocardiography. Circulation, 1996;94:1049–1055. 12. Karalis DG, Bansal RC, Hauck AJ, et al. Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis. Clinical and surgical implications. Circulation, 1992;86:353– 362. 13. Agmon Y, Khandheria BK, Meissner I, et al. Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population. Am J Cardiol, 2002;89:262– 267. 14. Klein AL, Murray RD, Becker ER, et al. Economic analysis of a transesophageal echocardiographyguided approach to cardioversion of patients with atrial fibrillation: The ACUTE economic data at eight weeks. J Am Coll Cardiol, 2004;43:1217–1224. 15. Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med, 2001;345:1740–1746. 16. Sohn DW, Shin GJ, Oh JK, et al. Role of transesophageal echocardiography in hemodynamically unstable patients. Mayo Clin Proc, 1995;70:925–931. 17. Brinkman WT, Shanewise JS, Clements SD, et al. Transesophageal echocardiography: Not an innocuous procedure. Ann Thorac Surg, 2001;72:1725–1726. 18. Novaro GM, Aronow HD, Militello MA, et al. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr, 2003;16:170–175. 19. Min JK, Spencer KT, Furlong KT, et al. Clinical features of complications from transesophageal echocardiography: A single-center case series of 10,000 consecutive examinations. J Am Soc Echocardiogr, 2005;18:925–929. 20. Hahn RT, Abraham T, Adams MS, et al. Guidelines for performing a comprehensive transesophageal echocardiographic examination: Recommendations from the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists. J Am Soc Echocardiogr, 2013;26:921–964. 21. Sharma SC, Rama PR, Miller GL, et al. Systemic absorption and toxicity from topically administered lidocaine during transesophageal echocardiography. J Am Soc Echocardiogr, 1996;9:710–711. 22. Seward JB, Khandheria BK, Freeman WK, et al. Multiplane transesophageal echocardiography: Image orientation, examination technique, anatomic correlations, and clinical applications. Mayo Clin Proc, 1993;68:523–551. 23. Nucifora G, Faletra FF, Regoli F, et al. Evaluation of the left atrial appendage with real-time 3dimensional transesophageal echocardiography: Implications for catheter-based left atrial appendage closure. Circ Cardiovasc Imaging, 2011;4:514–523. 24. Little SH, Pirat B, Kumar R, et al. Three-dimensional color Doppler echocardiography for direct measurement of vena contracta area in mitral regurgitation: In vitro validation and clinical experience. JACC Cardiovasc Imaging, 2008; 1:695–704. 25. Schlosshan D, Aggarwal G, Mathur G, et al. Real-time 3D transesophageal echocardiography for the evaluation of rheumatic mitral stenosis. JACC Cardiovasc Imaging, 2011; 4:580–588. 26. Khalique OK, Kodali SK, Paradis JM, et al. Aortic annular sizing using a novel 3-dimensional echocardiographic method: Use and comparison with cardiac computed tomography. Circ Cardiovasc

Imaging, 2014;7:155–163.

CHAPTER

4

Doppler Echocardiography and Color Flow Imaging: Comprehensive Noninvasive Hemodynamic Assessment Jae K. Oh and William R. Miranda

Hemodynamic assessment is an integral part of cardiac evaluation for diagnosis, monitoring, and management decision process. Doppler echocardiography and color flow imaging, which provide reliable hemodynamic assessment, not only have replaced many invasive hemodynamic procedures but can also be superior to them under certain circumstances (1). Before discussing all major clinical impacts of echocardiographic hemodynamic assessment in our daily practice, it is important to recognize pioneers who have advanced a pure theory of “Doppler effect” by the Austrian physicist Christian Doppler in 1842 to a standard hemodynamic tool. The Norwegian cardiologist Liv Hatle and her colleagues should be credited as the most responsible individuals for making Doppler echocardiography a clinical tool (2) and the Japanese cardiac surgeon, Dr. Omoto, and his team for color flow imaging (3). There are numerous clinicians and scientists who subsequently validated and applied their observations in Doppler echocardiography and color flow imaging (4–9). Consequently, we can now calculate and assess stroke volume (SV), cardiac output, intracardiac pressures, pressure gradients, regurgitant volume, effective orifice area, vascular resistance, and intracardiac blood flow pattern reliably. Because many therapeutic decisions, including surgical and transcatheter interventions, are based on echocardiography, it is critical that everyone involved in the care of cardiac patients as well as in performing echocardiography understand how a hemodynamic assessment is performed by echocardiography and know its advantages and potential limitations.

DOPPLER ECHOCARDIOGRAPHY Doppler echocardiography measures velocities of blood flow and myocardial tissue according to the Doppler effect (2). The Doppler effect describes the phenomenon that sound frequency increases as a sound source moves toward the observer (or the transducer) and decreases as the source moves away from the observer. In the heart, the moving target can be the red blood cell or myocardial tissue such as mitral annulus. When an ultrasound beam with known frequency (fo) is reflected by the red blood cells (RBSs) or myocardial tissue, the frequency of the reflected ultrasound waves (fr) increases when the red blood cells or the myocardium is moving toward the source of ultrasound. Conversely, the frequency of reflected ultrasound waves decreases when the red blood cells are moving away from the source. The change in frequency between the transmitted sound and the reflected sound is termed the frequency shift (Δf) or the Doppler shift (fr − fo). The Doppler shift depends on the transmitted frequency (fo), the velocity of the moving target (v), and the angle (θ) between the ultrasound beam and the direction of the moving target as expressed in the Doppler equation (Fig. 4-1):

where c is the speed of sound in blood (1,540 m/s). If the angle θ is 0 degree (i.e., the ultrasound beam is parallel with the direction of blood flow), the maximal frequency shift is measured because the cosine of 0 degree is 1. Note that as angle θ increases, the corresponding cosine becomes progressively less than 1, and this will result in underestimation of the Doppler shift (Δf) and hence peak velocity, because peak flow velocity is derived from Δf by rearranging the Doppler equation:

Blood flow velocities determined by the Doppler echocardiography are used, in turn, to derive various hemodynamic data (see below). Doppler echocardiography is performed either by the pulsed wave or by the continuous wave (Fig. 4-2). In the pulsed wave mode, a single ultrasound crystal sends to and receives sound beams from a single location by placing the “sample

volume.” The crystal emits a short burst of ultrasound at a certain frequency (pulse repetition frequency). The ultrasound is reflected from moving red blood cells and is received by the same crystal. Therefore, the maximal frequency shift that can be determined to one direction by pulsed wave Doppler is one-half the pulse repetition frequency; this is called the Nyquist frequency. If the frequency shift is higher than the Nyquist frequency, aliasing occurs; that is, the Doppler spectrum or recording is cut off at the Nyquist frequency, and the remaining frequency shift (translated into velocity) is recorded on the top or bottom of the opposite side. In other words, when the highest velocity a pulsed mode can measure is 130 cm/s in one direction, any velocity higher than the aliasing velocity is recorded from the top (when the actual flow moves away from the transducer) or from the bottom (when the actual flow moves toward the transducer) of the recording screen or paper (Fig. 4-3). The pulsed repetition frequency varies inversely with the depth of the sample volume: the shallower the location of the sample volume, the higher the pulsed repetition frequency and the Nyquist frequency (or Doppler velocity).

FIGURE 4-1 Diagram of the Doppler effect (see text for explanation). RBCs, red blood cells.

FIGURE 4-2 Drawing of pulsed wave and continuous wave Doppler echocardiography from the apical view (see text for explanation). Black rectangle in left indicates the sample volume in the left ventricular outflow tract. Ao, aorta; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

In the continuous wave mode, the transducer has two crystals: one to send and the other to receive the reflected waves continuously. Therefore, the maximal frequency shift that can be recorded is not limited by the pulsed repetition frequency or the Nyquist phenomenon. Unlike pulsed wave Doppler, continuous wave Doppler measures all the frequency shifts (i.e., velocities) present along its beam path; hence, it is used to detect and record the highest flow velocity accessible. Occasionally, recording of a high-velocity flow is the first clue to an unsuspected lesion within the path of a continuous wave Doppler beam. Continuous wave Doppler is usually performed with either an image-guided or a nonimaging transducer. A small nonimaging transducer (PEDOF: Pulsed Echo Doppler Flow velocity meter) (10) is more suitable for interrogation of a highvelocity jet from multiple windows, including areas between the ribs. PEDOF probe was designed to record continuous wave Doppler velocities. An imageguided continuous wave examination is more helpful when the direction of blood flow is eccentric or the amount of desired blood flow is trivial. The

characteristics and clinical applications of these Doppler modalities are summarized in Table 4-1. Table 4-2 lists the mean and range of maximal velocities recorded from normal subjects by Doppler echocardiography. Echocardiographers should be familiar with the characteristic configuration and timing of normal and abnormal Doppler signals (Figs. 4-4 and 4-5).

FIGURE 4-3 Representative pulsed wave and continuous wave Doppler spectra from a 60-year-old patient who has aortic stenosis (AS) and aortic regurgitation (AR). (Top) The pulsed wave Doppler sample volume is placed at the left ventricular outflow tract (LVOT), and the Doppler spectrum shows systolic LVOT velocity and turbulent diastolic signal of aortic regurgitation (AR) recorded on both sides of the baseline. Although AR flow is toward the transducer, aliasing (velocity wraparound from the bottom of the recording) occurs because of the high velocity (4–5 m/s). (Bottom)

Continuous wave Doppler detects flow velocities all along its beam (LVOT and aortic valve) and is able to record high velocity. Systolic flow away from the transducer (spectrum below the baseline) represents flow across AS, and diastolic flow is from AR. Peak AS velocity across the stenotic valve varies (5.0–5.5 m/s) because of atrial fibrillation.

PULSED WAVE DOPPLER ECHOCARDIOGRAPHY Pulsed wave Doppler echocardiography measures blood pool or tissue velocities at a designated location by placing the sample volume whose size can be changed. Following locations provide clinically useful hemodynamic data (11). TABLE 4-1 Comparison of Pulsed Wave and Continuous Wave Doppler Pulsed Wave

Continuous Wave

Measures specific blood flow velocity by placing Measures blood flow velocities along the axis of the “sample volume” at the region of interest the entire ultrasound beam (range ambiguity) Maximal measureable velocity without aliasing is usually 15 cm/s in young healthy subjects) than that from the medial annulus (normally >10 cm/s) (Fig. 51). The most recent 2016 guidelines (4) recommends the use of averaged e’ velocity from both annuli, but the use of e’ from one location is acceptable in most clinical situations. Situations where an averaged value is preferred are LBBB (Fig. 5-3), pacemaker rhythm, pulmonary hypertension, and septal or lateral myocardial infarction. Regional wall motion abnormalities or valvular surgery involving the mitral annulus may affect mitral annulus velocities. A localized disease process, such as lateral myocardial infarction, can result in mitral annulus velocities being lower at the lateral annulus than at the septal annulus. In our laboratory, mitral annulus velocities are usually obtained from both locations, but the medial e’ velocity is used for the assessment of LV filling pressure (see Chapter 8). Comparison of e’ from the medial and lateral annulus is also helpful in the diagnosis of constrictive pericarditis (see Chapter 12). Late diastolic velocity (a′) of the mitral annulus at the time of atrial contraction increases during early diastolic dysfunction, as is the case for the mitral inflow A wave, but decreases as atrial function deteriorates. a’ has been correlated with left atrial (LA) function (11).

Evaluation of Regional and Global Systolic Function The extent of systolic movement of the mitral annulus correlates with LV systolic function and stroke volume. Normally, the systolic velocity (S′) of the

mitral annulus is more than 6 cm/s. Although TDI of the mitral annulus reflects the global systolic and diastolic function of the LV, segmental or regional function can be assessed by performing TDI of various LV segments by placing the sample volume (2–5 mm) in the region of interest. The size of the sample volume depends on the location and intensity of the signal and is usually between 2 and 5 mm. Further clinical experience with this variable will determine if s’ can replace other more commonly used systolic variables. However, it appears that the s’ is dependent on the extent of diastolic motion of the respective annulus and it is also increased in patients with constrictive pericarditis, which has decreased stroke volume despite increased medial e’ velocity.

Cardiac Time Intervals Cardiac time intervals are regulated by the mechanics and functions of the myocytes; therefore, these intervals could be utilized as a measure of cardiac function. TDI is well suited for determining the timing of myocardial events. The precise timing of these events is helpful in understanding the mechanism of myocardial relaxation and myocardial suction during early diastolic filling (12–14). In healthy hearts, in which efficient myocardial relaxation is used effectively to suck blood from the LA into the LV during early diastole, the time of onset of mitral inflow (E) coincides with that of myocardial early diastolic motion (relaxation) of the mitral annulus (e’). However, in hearts with delayed myocardial relaxation and increased filling pressure, diastolic filling (onset of the E wave) depends more on the increased LA pressure and occurs earlier than the onset of the early diastolic motion of the mitral annulus (e’). Therefore, the time interval between the onset of mitral E velocity and that of the mitral annulus diastolic motion (e’) increases, and this increased interval has been proposed as another variable to assess LV filling pressures (see Chapter 8).

FIGURE 5-2 Tissue Doppler recordings of the septal mitral annulus from normal (A), borderline normal in the elderly (B), and markedly abnormal with reduced relaxation in cardiomyopathy (C).

FIGURE 5-3 Tissue Doppler recording of (A) the septal or medial mitral annulus with e’ of 5 cm/s (arrow) and (B) lateral mitral annulus with e’ of 9 cm/s (arrow) from a patient with left bundle branch block.

A limitation of measuring cardiac time intervals by pulsed-wave Doppler echocardiography is nonsimultaneity because different cardiac cycles are usually needed to measure various intervals, which in turn are used together. One solution is to have the capability of obtaining multiple pulsed-wave Doppler recordings simultaneously. Another creative means to measure cardiac intervals from a single cardiac cycle is to use tissue Doppler anatomic color M-mode from the anterior mitral leaflet (15) (Fig. 5-4). From this technique, isovolumic

contraction time, isovolumic relaxation time, and LV ejection time can be measured reliably from a single cardiac cycle.

Evaluation of Thick Walls The ventricular walls become thick for several reasons including LV hypertrophy, hypertrophic cardiomyopathy (HCM), hypertension, infiltrative cardiomyopathy, restrictive cardiomyopathy, and athletic heart. These entities can usually be differentiated on the basis of clinical and laboratory findings, but differentiating them can occasionally be difficult. The evaluation of myocardial relaxation with TDI is able to distinguish between a thick athletic normal heart and other disease conditions (16). Mitral annulus motion is well preserved in the athletic heart because myocardial relaxation is preserved, but it is reduced in all other conditions that have impaired relaxation. Strain should also be normal or mildly abnormal (17,18) in athlete’s heart with increased wall thickness. However, strain is reduced in all forms of myopathies with characteristic patterns in HCM, cardiac amyloidosis, Fabry disease, and sarcoidosis (see below).

FIGURE 5-4 Tissue Doppler anatomic M-mode of the anterior mitral leaflet was obtained from color tissue Doppler imaging. Mitral motion recorded the timing of mitral valve closure (MVC), aortic valve opening (AVO), aortic valve closure (AVC), and mitral valve opening (MVO).

E/e’ as a prognostic tool Because E/e’ can estimate LV filling pressures and patients with increased filling

pressures have higher rates of morbidity and mortality, it is expected that a high E/e’ predicts a poor outcome (19). E/e’ was correlated with simultaneously obtained intra-atrial LA pressure (20). LA pressure was higher than 15 mm Hg most of times when E/e’ greater than 15. An E/e’ more than 15 was found to be associated with increased mortality of patients with acute myocardial infarction (21). By itself, e’ is also a good predictor for clinical outcome. In various clinical conditions, patients who have an e’ less than 5 cm/s are more likely to have a much higher mortality than those with an e’ more than 5 cm/s (19). E/e’ is also elevated in a subset of asymptomatic stage A individuals. Whether these patients can be reclassified as stage B heart failure needs further clinical investigations (22). In asymptomatic patients, increased E/e’ was found to be one of major predictors for developing heart failure (23).

2-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY (2D-STE) In the last decade, myocardial strain (S) and strain rate (SR) imaging has become a useful tool for the quantitative assessment of regional and global myocardial mechanics (19,24,25). Strain rate is the rate of change in length calculated as the difference between two velocities normalized to the distance between them; it is expressed as seconds−1 (19–22) (Fig. 5-5A). By convention, shortening is represented by negative values and lengthening by positive values for both strain and strain rate: Strain rate = (Va − Vb)/d where Va − Vb is the instantaneous velocity difference at points a and b, and d is the distance between the two points. Strain (ε) is the percentage change in length during myocardial contraction and relaxation and is expressed as a percentage (Fig. 5-5B):

where L0 is the original length, L1 is the final length, and ΔL is the change in length.

Strain can be derived echocardiographically by the following:

where strain (ε) is the sum of the instantaneous strain rate (SR) values from starting time (t0) to ending time (t).

FIGURE 5-5 A: Diagram for the concept of strain imaging. A narrow sector width was used to attempt to align the direction of myocardial movement in parallel with the direction of the ultrasound beam. (See text for details about how to obtain strain and strain rate.) B: Schematic diagram of LV at the end diastole with the myocardial length of Lo (arrow in the left) and at the end systole with the myocardial length of L (arrow in the right).

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Video 5-5 While strain imaging based on tissue Doppler is angle dependent, 2D-STE is an angle-independent method and has become the technique of choice for strain imaging. It utilizes frame-by-frame tracking within a region of interest of small

patterns of echo densities in the gray-scale B mode images. These unique myocardial features are called “kernels,” “markers,” or “speckles” (26,27) (Fig. 5-6). An important advantage of 2D-STE is the semiautomated and quantitative approach by which regional and global ventricular function is measured from two-dimensional images. Global systolic strain (S) refers itself to the average strain value from all individual segments contained in a designated direction (longitudinal, circumferential, or radial direction) (Fig. 5-7) with its peak value almost always coinciding with aortic valve closure in normally contracting heart (Fig. 5-6). Strain rate is the rate of change in length calculated as the difference between two velocities normalized to the distance between them, expressed as seconds−1. It can provide more information for the whole cardiac cycle and can be calculated from different portions of cardiac cycle such as systolic (SRs) and early (SRe) and late diastolic (SRa) (Fig. 5-8). Another advantage is that it reflects regional function and is independent of translational motion (28), being therefore able to provide local information on the deformation and rate of deformation of a particular segment, segments or territories (i.e., LAD, RCA, etc.).

FIGURE 5-6 A: Apical long-axis view showing multiple (white) speckles in the anterior ventricular septum (VS) and inferolateral (posterior) wall. These speckles or kernels are the white dots seen inside the myocardial wall (left). The region of interest was drawn, and different colors represent separate wall segments. The width of the strain imaging can be adjusted (right). B: LV strain values are displayed by color map with

blue color demonstrating lengthening and red color representing shortening. However, the color map can be different for another vendor (see below). White color demonstrates the lack of contraction. The strain curve along the time-line and its value as well as direction is displayed (upper right), and color M-mode of the strain is also shown (lower right). Inferolateral segments at the basal and the mid level do have blue color indicating bulging. Apical and midventricular septal strain is best preserved in this example from cardiac amyloidosis. C: An example of normal strain with a composite bull’s-eye display (lower right). Note that peak systolic longitudinal strain of all walls occurs at the time of aortic valve closure (AC).

Since strain value indicates the amount of deformation, systolic longitudinal and circumferential strain normally has negative values with shortening of myocardium in the respective direction, while radial strain is positive with lengthening of myocardium in that direction.

FIGURE 5-7 Types of strain.

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Video 5-7A

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Video 5-7B For longitudinal or circumferential strain, if the final length (L) is 10 and the initial length is 8, the deformation would be −20%; for radial strain, if L is 15 and Lo is 10, the deformation would be 50% (5-5B).

FIGURE 5-8 A: Strain imaging (left) and strain rate imaging (right) of a patient with

postsystolic shortening (arrow). Postsystolic shortening was present in the midseptum (aqua color). AVC, aortic valve closure; AVO, aortic valve opening. B: Example of longitudinal strain rate curves from the endocardial surface. Note the first peak that is defined as SRs or systolic strain rate. Second peak SRe is early diastolic strain rate and SRa is late diastolic strain rate. The strain curve resembles pulsed-wave Doppler recording from LVOT (systole) and mitral inflow (diastole) velocities.

In vivo and in vitro models of two-dimensional (2D) S and SR have demonstrated good correlation and agreement with tagged magnetic resonance imaging (MRI) and sonomicrometry as well as with the previous TDI-derived technique (29). In general for the everyday use in a busy echocardiography laboratory, frame rates between 40 and 80 frames/s would not alter too much the peak strain value in an individual with a normal heart rate (30). S and SR measurement by 2D-STE can be performed with vendor-specific and vendorindependent software with different myocardial tracking algorithms. Recognizing that 2D-STE is an important tool in the evaluation of regional and global LV and RV myocardial mechanics, a task force from the EACVI/ASE/Industry (28) has invited representatives to participate in a concerted effort to standardize deformation imaging across all existing platforms and reduce intervendor variability for GLS. A total of 1,302 echocardiograms were performed with seven ultrasound systems on 62 volunteers, and endocardial GLS was measured by nine different softwares (7 from the respective manufacture company and 2 from the independent software only vendors). Absolute values are detailed in the normal values section below. There was moderate intervendor variability, and the inter- and intraobserver reproducibility was superior or equal to that of LV EF. A final recommendation of the task force was that GLS measurements should be interpreted relative to previous exam and hopefully performed in the same machine or software. Image acquisition is very important, and special emphasis on the depth and sector size is very important as well as avoiding any foreshortening of the apex. The size of the region of interest should be at least 85% to 90% of the myocardium thickness, and since tracking occurs in systole and diastole, a space of at least 5 mm should be left between the epicardium in diastole and the sector width (Fig. 5-6A).

RV and LV Function The LV myocardium is a structure that has two geometric helical fibers with the subendocardial in a right-handed helical configuration while the subepicardial

has a left-handed pattern. The fibers are mainly longitudinally oriented in the subendocardium with fibers in the midwall in the circumferential direction and to an oblique orientation in the subepicardium (31,32). These layers contract simultaneously from base to apex with clockwise rotation at the base and counterclockwise in the apex (when viewed from the apex) with a greater deformation at the endocardial level and less at the epicardium (Fig. 5-9) (33). On the other hand, the RV has a more defined anatomy composed mainly of longitudinal fibers at the base and mid, sharing the apex with the LV, with less degree of radial fibers (34) (Fig. 5-10). In strain images analyzed, vendor-specific software utilizes its own images or DICOM (Digital Imaging and Communications in Medicine) format to derive strain and strain rate. Some are specific for the US machine and some are independent with the only requirement of having imported images in DICOM format.

FIGURE 5-9 Example of different regions of interest and different placement of the regions of interest. A: Full-thickness region of interest. Notice the values and average of −19.9 and the region of interest is at least 90% of the full myocardial thickness. B: Region of interest mainly localized in the endo- and midmyocardium. Note the values are similar to the previous figure, which are endocardial values of longitudinal deformation. C: Midmyocardial region of interest. Note the values that are still similar to A and B. D: Epicardial region of interest. Note the lower values due to the lower deformation of these fibers.

Longitudinal, circumferential, and radial strain and strain rate can be derived as well as twist, untwist, and torsion. In clinical practice, however, longitudinal strain is most well validated and it can be measured easily and reliable during a routine echocardiography examination, with good inter- and intraobserver

variability once the team has had an adequate run-in phase to practice on the acquisition and analysis methodology. The degree of torsion and twisting can be assessed by strain imaging, but it is time-consuming with no significant clinical application.

FIGURE 5-10 Strain imaging of normal RV with color display (left), strain curve (right upper), and color M-mode (right lower).

Normal Values It is very important when you are starting 2D-STE to have a dedicated team for its implementation. To gain confidence and decrease inter- and intraobserver variability, it is suggested to analyze normal patients and define normal values in your laboratory first. Normal values for the more frequent used software are shown in Table 5-1 (30). In general, the subendocardial strain values are higher than the epicardial (35) as well as an apex to base gradient with higher values at the apex; some platforms have demonstrated different values for men and women and changes in SRe as age progresses. The ASE/EACVI industry task force defined absolute values for GLS with a range from −18.0% to −21.5%, with an absolute difference between vendors of 3.7% strain units (36). Values for the most common software are displayed in Table 5-1. TABLE 5-1

Normal Values of Strain and Systolic Strain Rate (S and SRs) with Standard Deviation (SD) for Different Vendors

Radial Longitudinal Longitudinal Circumferential Circumferential Radial Strain % Strain % Strain % SRs sec SRs sec−1 SRs sec−1 −1

GE

−18.6 ± 5.1



−22.9 ± 4.4



54.6 ± 12.6



VVI

−17.3 ± 2.5

−1.0 ± 0.1

−21.9 ±4.0

−1.3 ± 0.3

44.8 ± 21.7

2.3 ± 0.7

TOMTEC (54 FPS)

−18.4 ± 2.0

−0.99 ± 0.1

−22.1 ± 4.1

−1.4 ± 0.3

43.9 ± 12.1

2.2 ± 0.6

Toshiba

−19.9 ± 2.4



−30.5 ± 3.8



51.4 ± 8.0



Philips

−18.9 ± 2.5



−22.2 ± 3.2



36.3 ± 8.2



SRs, systolic strain rate.

RV Function The right ventricle is an easier structure to evaluate for strain since it is composed mainly of longitudinal fibers in its endocardium (70%) and circumferential epicardial fibers in its free wall at the base and midlevel, and shares the apical fibers with the LV (34). In general, the longitudinal strain is obtained most frequently from the apical 4-chamber view. The strain values from the septum and the free wall can be averaged, but the latter is the most frequently utilized for expressing RV systolic function (Fig. 5-10). Its application in RV function is discussed in more detail in Chapter 9. Pulmonary arterial hypertension (PAH): Right ventricular free wall longitudinal strain (RVFWS) has been correlated with pulmonary pressures, pulmonary vascular resistance, survival, and response to therapy (37,38). In a group of patients who were serially followed, there was a mean increase in RV systolic strain after PAH treatment. The group of patients who had worsening of RV free wall strain despite treatment to less than −12.5% had poorer survival (39). In those patients with RV dysfunction, if LV deformation is impaired despite normal LV ejection fraction, a value of GLS less than −13% has been associated with increased mortality over 2 years (40). In some clinical scenarios, it is important to differentiate between acute pulmonary emboli and chronic PAH. In a study (41) of 45 patients with acute PE (with CT scan within 48 h of the echocardiogram) compared to 45 patients with

mild PAH, RVFWS had a better discrimination power than did the McConnell sign; a cutoff value of −17.9% had a sensitivity of 87.5% and a specificity of 62.5% COPD: Early in the natural history of the disease, there is an asymptomatic increase in pulmonary pressures; probably due to an increase in arterial stiffness, (42) subtle changes in free RV wall strain and systolic strain rate have been described (37,42).

LV Function Abnormalities in LV strain in the three domains of contractility have been shown to be present in patients despite normal ejection fraction, and this has been more robust for longitudinal strain since the endocardial layer is the one initially compromised. In the pyramidal approach of patients with predisposition for heart failure, 2DSTE plays a pivotal role in those patients in stage A (presence of risk factors, i.e., hypertension, coronary artery disease) and stage B (structural changes as decreased EF or abnormal tissue Doppler velocities or strain/strain rate values, without symptoms) for early identification of an underlying cardiomyopathy. In asymptomatic patients with nonischemic cardiomyopathy older than 65 years (23) in stage B HF (SBHF), GLS was a strong predictor of the occurrence of HF with an incremental value to other parameters after a follow-up period of up to 18 months. This has also been validated in a community setting (43) and in AL amyloid patients in SBHF who have an increased mortality when compared to those in stage A (44). In stage C or D, (45) when symptoms of HF are present, a recent meta-analysis (45) of over 5,000 patients showed that GLS was superior to LVEF in predicting major adverse cardiac events.

Hypertrophic Cardiomyopathy In general, longitudinal systolic strain values are lower in the regions where the myocardium is thicker (Fig. 5-11). Strain curve morphology can also be abnormal, in some cases showing elongation or lengthening instead of shortening (Fig. 5-11B) with positive curves or strain values in these regions. Fibrosis in HCM is mainly limited to the septum at the basal and mid regions (46,47). Longitudinal strain was found to correlate well with the presence of fibrosis derived from delayed enhancement quantifiable by cardiac MRI in a group of over 200 patients (48). Different characteristic bull’s-eye patterns can

also provide insight in the type of HCM (Fig. 5-11A and B). RV strain of the free wall is also frequently abnormal in patients with HCM (49).

Athlete’s heart Remodeling of the athlete’s heart depends on whether the type of exercise is isometric or isotonic (17). One of the key clinical points is its differentiation from HCM. Doppler tissue velocities and strain values are significantly lower in HCM patients than in athletes. Usually, systolic strain values are normal in all three directions (18,50). All components of strain were significantly reduced in pts with HCM (GLS: −8.1 ± 3.8%; P < 0.001) when compared with athletes (−15.2 ± 3.6%) and control subjects (−16.0 ± 2.8%). In general, there was no significant difference between the strain values of the athletes and the control group, but in some of the segments, the strain values of the control group were significantly higher than those in the athletes. A cutoff value of GLS less than −10% for the diagnosis of pathologic hypertrophy (HCM) resulted in a sensitivity of 80.0% and a specificity of 95.0% (40). Using segmental strain in professional soccer players, a cutoff value of inferoseptal longitudinal strain of less than −11% had a sensitivity of 60% and specificity of 96% to identify pathological hypertrophy.

Amyloid Heart Disease: (See Chapter 18) Primary light-chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the extracellular deposition of insoluble fibrillary amyloid proteins in multiple organs. In the heart, it is characterized by amyloid deposition in the interstitium, resulting in marked increase of wall thickness; in general, these by-products infiltrate the heart from endocardium to epicardium and from base to apex, this region of the heart being the last to be compromised (apical sparing). Classically, amyloid heart disease has been defined as an increase in wall thickness greater than 12 mm (septum plus posterior wall/2), but other entities could also increase myocardial thickness (51). Ideally, a technique that can aid in the diagnosis when the LV EF is still normal would be of great clinical help. In patients with AL amyloidosis with or without increased LV wall thickness, basal segments are affected first, followed by midsegments with a relative apical sparing (44) (Fig. 5-12). In patients with confirmed TTR and senile amyloid with normal ejection fraction, longitudinal strain will also follow this pattern and at a later stage especially when EF is less than 40% circumferential and radial strain will be compromised. Longitudinal RV and LV values in patients with AL amyloid heart disease and normal EF have been correlated with survival (52–54). LV longitudinal strain values less than −15.5% and RV less than −12% were significantly associated with 5-year mortality (44,54). Strain imaging may be more sensitive in monitoring the response to therapy (see Chapter 18).

FIGURE 5-11 Hypertrophic cardiomyopathy. A: 2-D parasternal short-axis view at the basal level (left) and strain imaging (right) of a patient with hypertrophic cardiomyopathy. There is asymmetric septal hypertrophy (*) and marked reduction of longitudinal strain in the anteroseptal and anterior wall at the base. B: 2-D apical 4chamber view (left) and characteristic strain display in bull’s-eye format (right) in apical hypertrophic cardiomyopathy. Note a small apical strain with blue color indicating lengthening of the region instead of thickening. The region appears to be dyskinetic in 2-D apical views.

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Myocarditis

Classically, myocarditis involves all the layers of the myocardium. Therefore, all domains of contractility (longitudinal, circumferential, and radial) would be compromised (55). In patients with suspicion of coronary artery disease, strain is of particular help since only the longitudinal domain would be affected in the former group when compared to myocarditis patients (56). Strain values can also predict complications in this disease group.

FIGURE 5-12 Amyloidosis Strain imaging bull’s-eye display in cardiac amyloidosis 2 years apart. Strain is reduced first in the basal portion (left), progressed to the midlevel sparing the apex (right).

Coronary Artery Disease/Ischemia In patients with established CAD, different researchers have described a decrease in longitudinal strain, but probably the most important finding is postsystolic shortening (PSS), which has been demonstrated to occur before ischemia and also as a marker of viability (Figs. 5-8A and 5-13) (57,58). In the acute chest pain setting, strain could be of value as it can detect changes in longitudinal strain when the EKG and cardiac enzymes are not diagnostic and could also suggest the affected coronary territory (59) (Fig. 5-14). In women with documented significant CAD and normal EF, the presence of longitudinal dyssynchrony (>45 ms SD of the time to peak) had a sensitivity of 97% and sensitivity of 89% (AUC 0.96) for its diagnosis (60). Diastolic dysfunction is one of the earliest manifestations of myocardial ischemia and stays for up to 24 hours after resolution of wall motion abnormality (Fig. 5-15). Mayo Clinic has performed a prospective study to assess the clinical role of diastolic strain imaging in 300 patients. Normal diastolic strain in patients with chest pain syndrome was found to have an excellent negative predictive value, but its positive predictive value was low (Sasaki et al. Unpublished). We, however, confirmed that diastolic strain of ischemic region remains abnormal for 24 hours

after the disappearance of chest pain (Fig. 5-16). If we are able to assess diastolic strain online during the echocardiography examination, it may have an incremental diagnostic and triage role for the patients with chest pain syndrome in the office and the emergency department.

FIGURE 5-13 Normal circumferential strain values on the left; notice that all curves are peaking at the same time. On the right, the different peaks that the strain curves have with postsystolic shortening and evidence of dyssynchrony.

Hypertension In general, longitudinal strain values are close to normal in patients with normal geometry, while in those with concentric or eccentric hypertrophy and concentric remodeling, GLS and GLSRs are lower (61). These values are still above the ones defined for HCM.

FIGURE 5-14 A: Bull’s-eye strain display from a 73-year-old male who presented with heart failure and troponin elevation. There were no ECG abnormalities, and 2-D echocardiography showed no obvious regional wall motion abnormalities. There was moderate reduction in longitudinal strain values in most areas except for the basal inferior wall. Coronary angiography demonstrated severe three-vessel coronary artery disease with 50% left main, 90% left anterior descending, 100% obtuse marginal, and 90% midright coronary artery stenosis. B: Bull’s-eye strain display from a patient with

ischemic cardiomyopathy with left ventricular ejection fraction of 30%. Anterior and anteroseptal segments are akinetic, and inferior/lateral wall motion is preserved.

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Chronic Renal Failure Sometimes it is difficult to differentiate this entity from amyloid heart disease since both have the same sparkling appearance to the myocardium and there is increased wall thickness. In general, values of longitudinal strain are lower than normal but not as compromised for the same degree of wall thickness as amyloid heart disease.

FIGURE 5-15 Transverse strain curve demonstrating normal (a) and abnormal (b) diastolic radial strain. A: When diastolic function is normal, normal myocardial relaxation lengthens the myocardium rapidly so that the radial stain is quickly reduced (from A to B) during the initial one-third of the diastole. B: When diastolic function is abnormal, relaxation is delayed and the extent of myocardial lengthening is reduced during the initial one-third of the diastole.

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Cardiac Transplant After cardiac allograft transplantation, there is myocardial thickening due to the graft versus host reaction. Deformation variables in normal transplanted hearts are lower than normal due to this reason, (62) especially longitudinal strain. In patients with severe vasculopathy (ISHLT 3), strain is also compromised when compared with normal transplanted hearts (63). This also holds true for severe

rejection with normal EF were besides (64).

FIGURE 5-16 Transverse strain imaging from an apical long-axis view demonstrating delayed diastolic relaxation at the apical septal (AS) indicated by an arrow and apical lateral (AL) segments (left). The strain curve (right) demonstrated delayed diastolic relaxation in those areas (arrow), while other segments do relax rapidly during the initial one-third of the diastole. This was obtained 24 hours after termination of chest pain in an elderly male with normal ECG and troponin when presented to the emergency department. Subsequent coronary angiography showed a critical mid–left anterior descending coronary artery stenosis.

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Cardio-Oncology In the past two decades, there has been a remarkable improvement in the

management of cancer patients. The combination of early diagnosis, use of novel targeted therapies, new chemotherapeutic agents, proton and photon radiation therapy, and better surgical techniques have decreased cancer-related mortality significantly, and therefore the number of survivors has increased. Patients with breast cancer and lymphoma are the main group who as part of their regimen receive anthracyclines, +/− trastuzumab, and radiotherapy and account for up to 20% of cardiac toxicity and later in life the development of congestive heart failure. It is crucial in these patients to follow the imaging algorithms suggested by the expert consensus statement from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular imaging (EACVI) (65). The document defined cardiotoxicity as a drop of greater than 10% in EF to a value less than 53% (65) and incorporates the evaluation of strain as part of the protocol (Fig. 5-17), since many studies have shown that a change in strain or strain rate values can predict a future drop in EF. We and others have shown that a decrease of longitudinal, circumferential, or radial strain or circumferential or longitudinal early diastolic strain rate either alone or in combination can predict cardiotoxicity before a drop in ejection fraction occurs (53,66,67). The expert consensus paper (65) also recommended the use of strain to monitor patients receiving chemotherapeutic agents with potential type I cardiotoxicity (mainly anthracyclines) or type II (trastuzumab more frequently used in this category), and it is suggested that a drop of greater than 15% or an absolute of 3% decrease in GLS below the lower limit of normal based on vendor, gender, and age could suggest early myocardial dysfunction. A major impact of strain imaging in this patient population is in the early detection of cardiotoxicity and also developing a strategy to prevent or minimizing the cardiotoxicity. Several clinical trials are under way using strain imaging this area.

FIGURE 5-17 Bull’s-eye displays of longitudinal strain from the same patient at baseline (left) and after chemotherapy (right) while there was no obvious reduction in LV ejection fraction or appearance of regional wall motion abnormality.

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Cardiorheumatology Patients with rheumatoid arthritis have a higher incidence of CAD at an earlier age; longitudinal strain could be abnormal in this patient population, suggesting to the clinician that additional testing should be performed to rule out this condition (68).

Valvular Heart Disease In general, its biggest value would be in patients with severe stenosis or insufficiency when the conventional clinical or echocardiographic criteria are

still misleading. Aortic Stenosis In this group of patients, there is collagen deposition with development of fibrosis from subendocardium to epicardium; therefore, depending on the extension of fibrosis, the domains of contractility will be compromised. The detection of systolic myocardial dysfunction when the gradient or the velocity is high in an asymptomatic patient with normal EF could be of aid in the clinical decision algorithm (69). A subset of patients in whom it could be more beneficial is those with low-flow low-gradient normal EF aortic stenosis where the valvuloarterial impedance is high with reduced longitudinal systolic function, (70) again also as a tool for better clinical decision-making. Aortic Insufficiency Volume overload associated with this disease can alter the mechanics of the LV, thereby leading to abnormal deformation. (71) LV and RV strain has helped in asymptomatic patients in the triage for surgery (72). For mitral stenosis, mitral insufficiency, and tricuspid insufficiency, algorithms are being developed to incorporate strain in these valvular diseases.

Evaluation of Dyssynchrony and Positive response to CRT The PROSPECT multicenter trial did not show a very good sensitivity and specificity of mechanical dyssynchrony to predict CRT response using Doppler tissue imaging and tissue-derived strain (73). Mechanical dyssynchrony is measured by time intervals between peak ejection systolic velocities or peak strain of multiple myocardial segments, as discussed below. Up to 4% to 6% of normal hearts can experience systolic intraventricular dyssynchrony manifested as abnormal segmental contraction after aortic valve closure. This systolic mechanical dyssynchrony can be defined as the uncoordinated timing of contraction in different regions of the heart. That is, myocardial segmental contractions do not occur simultaneously. Systolic dyssynchrony is commonly manifested as prolongation of the QRS duration on surface electrocardiography (ECG), but it has also been demonstrated in patients with normal QRS duration. QRS prolongation (>120 milliseconds) has been described in one-fourth to one-half of patients who have heart failure (74). Systolic dyssynchrony can be divided into intraventricular (within the LV) and interventricular (between the LV and right ventricle [RV]) dyssynchrony.

Intraventricular dyssynchrony results in a fragmented profile of ineffective contraction, with prolongation of the isovolumic contraction and relaxation times. The regional “shifting” rather than ejection of blood from the LV worsens regional wall stress and aggravates mitral regurgitation. These factors, in combination with activation of neurohormonal and proinflammatory cytokine pathways, accelerate cardiac dilatation, resulting in progressive LV dilatation and cardiac remodeling. However, mechanical dyssynchrony purely based on the difference between segmental contractions does not incorporate the viability or contractility of the underlying myocardial segments. If the dyssynchronous underlying myocardium does not have myocardial viability, correction of the dyssynchrony does not improve cardiac function. Therefore, it is critical to incorporate the assessment of viability when we try to identify the patients who can benefit from cardiac resynchronization therapy. Interventricular dyssynchrony, especially in the presence of paradoxical septal motion in systole, may adversely affect RV function, further impeding venous return to the LV. RV dyssynchrony on the other hand can also affect LV function by the same mechanism. A new method to evaluate LV intraventricular dyssynchrony has been termed LV mechanical discoordination that uses radial, longitudinal, circumferential strain rate curves and averages thickening (normal systolic event) and thinning (abnormal discoordination) of the different segments during systole or ejection time (75). When LV is perfectly coordinated mechanically, all segments contract and relax almost simultaneously (Fig. 5-18). The rationale to use mechanical discoordination metrics to identify the patients who most likely benefit from CRT is that there is dyssynchronous activation of the failing heart with discoordinated contraction and relaxation between early- and late-activated segments (Fig. 5-19) (75,76). In patients with dyssynchronous activation due to left bundle branch block, the ventricular septum contracts first during isovolumic contraction. If other walls are viable, they dilate or stretch during the isovolumic contraction time while the septum gets activated. During the ejection, the out-ofphase relaxation (thinning or stretching) of early-activated segments counteracts the stroke work of late-activated segments (thickening or shortening). Mechanical discoordination index measures the overall inefficiency of the heart by comparing the counteracting deformation with the amount of contractile deformation (Fig. 5-18). In ischemic cardiomyopathy, decreased regional contractility or elasticity in early-activated segments due to myocardial ischemia or scar diminishes the counteracting force, and therefore a low value of

mechanical discoordination is usually observed. Quantitative measurements of discoordination allow integration of all amplitude information within critical timing (ejection period) into one index and therefore appear to be useful in CRT. The degree of mechanical dis-coordination can be easily detected by color Mmode of radial strain rate (Fig. 5-20). Our study demonstrated that the mechanical discoordination index obtained from radial strain at the midventricular level of greater than 38% could predict reverse remodeling clinical response and mortality (75). Another potential application of strain imaging for CRT is to identify an optimal location for left heart lead location. The TARGET study randomized the patients with LBBB to radial strain–guided versus routine unguided lead placement (77). The left heart lead placement was attempted at the site with the latest activation having greater than absolute value of 10% strain value. The speckled strain-guided lead placement yielded better response to CRT and better clinical outcome. No subsequent studies, however, have validated the data in terms of improved clinical outcome (78).

FIGURE 5-18 An example of normal radial strain (left) and strain rate (right). There is no stretching during the ejection.

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FIGURE 5-19 A: An example of discoordination computation in a responder. Tracings of the strain and strain rate of six ventricular segments are presented as colored lines (left). B: Strain rate signals are separated into positive (thickening on top in red) and negative (thinning on bottom in blue) signals and averaged separately. The average positive and negative strain rate signals are represented as red and blue lines. C: Myocardial thinning and thickening are represented as blue and red areas, respectively (top). The radial discoordination index (RDI) is calculated as the ratio of myocardial thinning to thickening during ejection (bottom). (With permission from Wang CL, Powell BD, Redfield MM, et al. Left ventricular discoordination index measured by speckle tracking strain rate imaging predicts reverse remodelling and survival after cardiac resynchronization therapy. Eur J Heart Fail, 2012;14(5):517– 525. Published on behalf of the European Society of Cardiology. All rights reserved. © 2012 the Authors.)

FIGURE 5-20 Color M-mode of the radial strain rate: a quick way to identify significant ventricular discoordination. Yellow-orange color represents thickening, and blue color represents thinning. The area occupied by blue color during the ejection period (from AVO to AVC) correlates with the amount of discoordination. The orange area during isovolumic contraction at the septal segment is analogous to septal flash. Left: The early termination of septal contraction (orange color) and discoordinated septal thinning (blue color) during the ejection period can be easily identified in a patient with reverse remodeling after CRT. Right: No significant ventricular discoordination (i.e., very little blue color during ejection period) is shown in a patient without reverse remodeling after resynchronization therapy. AVO, aortic valve opening; AVC, aortic valve closure. (With permission from Wang CL, Powell BD, Redfield MM, et al. Left ventricular discoordination index measured by speckle tracking strain rate imaging predicts reverse remodelling and survival after cardiac resynchronization therapy. European Journal of Heart Failure, 2012;14:517–525.)

Prediction of Clinical Outcome or Ventricular Arrhythmia Although LV ejection fraction is a strong predictor for cardiovascular outcome when it is reduced, a subset of the patients with preserved LV EF have a similarly poor outcome. It has been shown that particularly in patients with LV EF greater than 35%, global longitudinal strain (GLS) value has an independent and incremental prognostic value. When 428 asymptomatic stage B heart failure patients with preserved ejection fraction were followed, global longitudinal strain, LA volume index, LV mass, and E/e’ were independent predictors for new heart failure, but global longitudinal strain was found to have the best incremental predictive value (23). A meta-analysis of 5,721 subjects demonstrated that GLS is a more powerful predictor than LV EF of all MACEs and cardiac deaths. (45). VALIANT trial also showed that strain rate was an independent prognostic parameter in patients with acute myocardial infarction (79). GLS is reduced in asymptomatic patients with diabetes mellitus,

hypertension, coronary artery disease, valvular heart disease, chemotherapy, or underlying cardiomyopathy. Further clinical investigations will demonstrate how GLS data can be used to prevent and manage development of heart failure or other cardiovascular outcomes. Indications for strain imaging for GLS are well illustrated by Potter and Marwick (80) (Fig. 5-21). Postsystolic shortening considered to reflect myocardial dysfunction is easily evaluated by strain imaging. Postsystolic shortening is defined as greater than 20% postsystolic index, which is [(maximum strain in cardiac cycle_peak systolic strain)/(maximum strain in cardiac cycle)]. When 1296 low-risk individuals in general population were followed for 11 years, the presence of PSS in greater than or equal to two segments was associated with significant increase in the MACE and cardiac death (81).

LA and 3-D Speckled LV Strain Speckled strain imaging has been applied to the left atrium to determine its longitudinal negative (contraction) and positive (filling) as well as its total strain (Fig. 5-22) (82). Preliminary data suggest that LA strain is useful in estimating LV filling pressure, but it is not mature enough to be used clinically without further investigations. Speckled imaging is also used for 3-D strain. To obtain 3D strain, 3-D speckle-tracking software is used to track speckles from 3-D LV created from apical-4, apical-2, apical long-axis, and 3 short-axis views. Nagata and Otsuji et al. reported that 3-D GLS was the most robust predictor for future cardiac events in asymptomatic patients with severe aortic stenosis (83). This technique needs to be made easier, to be made more practical, and requires more clinical investigations.

FIGURE 5-21 Prognostic and management implications of abnormal strain measurement in common clinical scenarios. (AR, aortic regurgitation; AS, aortic stenosis; AVR, aortic valve replacement; CAD, coronary artery disease; CTRCD, cancer therapeutics–related cardiac dysfunction; CV, cardiovascular; DD, diastolic dysfunction; GLS, global longitudinal strain; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HCM, hypertrophic cardiomyopathy; ICA, invasive coronary angiography; LV, left ventricular; LVD, left ventricular dysfunction; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; MR, mitral regurgitation; post-op, postoperative; RWMA, resting wall motion abnormality; SBHF, stage B heart failure.) (Reprinted from Miglioranza MH, Badano LP, Mihăilă S, et al. Physiologic Determinants of Left Atrial Longitudinal Strain: A Two-Dimensional Speckle-Tracking and Three-Dimensional Echocardiographic Study in Healthy Volunteers. J Am Soc Echocardiogr, 2016;29(11):1023–1034.e3. Copyright 2016 by the American Society of Echocardiography. With permission.)

FIGURE 5-22 LA LS measurement using 2D STE. Color coding of the six myocardial segments of the LA region of interest for the measurement of LA strain in dedicated four- and two-chamber views (A and D, respectively). Individual LA segment LS values in dedicated four- and two-chamber views (B and E, respectively). Average LA LS/time curve obtained (white dotted lines) from the four- and the two-chamber views using the peak of the P wave on the electrocardiographic tracing (yellow dots and yellow vertical lines) as the zero-reference point for the generation of the strain curves (C and F, respectively). Measurements (double-headed arrows) of LSneg, LSpos, and LStot are shown for the dedicated four-chamber view (C). (Reprinted from Potter E, Marwick TH. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc Imaging, 2018;11(2 Pt 1):260–274. Copyright © 2018 by the American College of Cardiology Foundation. With permission.)

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CHAPTER

6

Contrast Echocardiography Sahar S. Abdelmoneim and Sharon L. Mulvagh

Contrast use in ultrasound has been available since the early stage of echocardiography, when indocyanine green and agitated saline were used to identify cardiac structures seen on M-mode and two-dimensional (2D) echocardiography by enhancement of the returning echoes from within the blood pool (1,2). The advent and evolution of clinically useful, commercially available ultrasound contrast agents (UCA) consisting of microbubbles containing high molecular weight gases encapsulated by insoluble shells, and capable of traversing the pulmonary circulation, expanded the clinical applications of contrast echocardiography to include improved delineation of the endocardial border, augmentation of Doppler velocity signals, and assessment of myocardial perfusion. In an echocardiography practice, agitated saline or a commercially available contrast agent is used daily in 10% to 15% of all studies and in 30% to 40% of stress tests. This chapter discusses the routine clinical use and potential future applications of contrast echocardiography including both agitated saline contrast echocardiography and UCA-enhanced echocardiography. The term UCA was changed to ultrasound enhancing agent (UEA) in 2018 Guideline(3), and UEA is used in this Manual.

AGITATED SALINE CONTRAST ECHOCARDIOGRAPHY Agitated saline contrast echocardiography has long been used for detection of intracardiac shunting with right-to-left flow or pulmonary arteriovenous fistulae that may occur in chronic liver disease, detection of residual shunts after cardiac defect closure, enhancement of right-sided intracardiac Doppler signals, and needle localization during percutaneous drainage of pericardial effusion (4). The most commonly used contrast agent for the detection of shunts is agitated saline.

EVALUATION OF SHUNTS The most frequent shunt lesion evaluated in an echocardiography laboratory is an atrial shunt through a patent foramen ovale (PFO), which is a common finding, occurring in approximately 25% of the population. The evaluation can be made with either transthoracic or transesophageal echocardiography (TEE) (Figs. 6-1 and 6-2). With transthoracic echocardiography, either the apical fourchamber view or subcostal view is used. With TEE, the 0-degree transverse or 90-degree bicaval view is optimal for imaging. The use of tissue harmonics is recommended to optimize the agitated saline bubble reflections and improve the sensitivity for shunt detection. An intravenous catheter is required (usually in an arm vein), with a three-way stopcock and two 12-mL syringes to agitate the saline immediately before it is injected. Bubbles created by agitated saline do not normally cross the pulmonary circuit and do not appear in the left side of the heart unless there is a communication between the right and left chambers. With a three-way stopcock, 10 mL of saline (9 mL of bacteriostatic normal saline agitated with 0.5–1.0 mL of room air) can be squirted back and forth (i.e., agitated) between two syringes at least five times before the saline is injected into the venous circulation. To facilitate the saline injection, the upper arm is massaged with two hands soon after the injection is made. The injection should be coordinated with the person who performs echocardiography so that the most optimal imaging view for identifying a suspected shunt lesion is shown on the screen when the saline is injected. If an atrial shunt is present, bubbles from the agitated saline will appear immediately (within 2–3 cardiac cycles) in the left atrium after initially being seen in the right atrium (“positive contrast” effect). In case of a left-to-right shunt, a “negative contrast” effect may be seen as a sharply desalinated washout phenomenon (black area) appearing on the right atrial side of the atrial septum in continuity with the contrast-free left atrium. If the patient has an intrapulmonary shunt, more than three cardiac cycles are needed for the bubbles to go through the pulmonary circulation before they appear in the left atrium and thus is characterized by the late (seen after >3–4 cardiac cycles in the right atrium) appearance of bubbles in the left atrium (see Figure 18-27). During TEE, an intrapulmonary shunt can be located by visualization of the appearance of contrast within the pulmonary veins as they enter the left atrium (Fig. 6-3). The degree of right to left shunt is graded as following: Grade I (mild) if few microbubbles were visualized in the left heart without appreciable change in density of the left ventricular cavity, Grade II (moderate) if microbubbles were

visualized in left heart with less than 50% of comparable density in the right heart, or Grade III (severe) if microbubbles were visualized in the left heart with ≥50% of comparable density in the right heart.

FIGURE 6-1 Left and right: Transthoracic echocardiograms demonstrating, with agitated saline, a right-to-left shunt. Because of a shunt through a patent foramen ovale, the contrast microbubbles (arrows) appear immediately in the left atrium (LA) after appearing in the right atrium (RA). In contrast, if the patient has a pulmonary atrial ventricular shunt, the microbubbles appear in the LA several cardiac cycles after they appear in the RA. The apical four-chamber view is best for evaluating an atrial shunt, but a subcostal view may be used. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

FIGURE 6-2 With agitated saline, transesophageal echocardiography can demonstrate a patent foramen ovale and right-to-left shunt. A: No shunt through the atrial septum (arrows) with the transducer at the bottom of the screen. B: Large rightto-left shunt via patent foramen ovale (arrow in the left) shown by contrast from right atrium to left atrium (arrows in the right) with the transducer at the top of the screen. A pacemaker catheter is seen in the right atrium. The echocardiography probe is set at a 60- to 90-degree angle to obtain the atrial septal–superior vena cava (SVC) view. The connection of the SVC with the right atrium (RA) is well visualized, as is the patent foramen ovale and atrial septum. Agitated saline is injected. After the agitated saline is injected into an arm vein, it appears in the SVC and then the RA. Because of a patent foramen ovale, agitated saline microbubbles appear immediately in the left atrium (LA). Some patients may have a right-to-left shunt only when they perform a Valsalva maneuver or cough. Therefore, imaging should be done with agitated saline and with the patient’s cough or upon release of the Valsalva maneuver.

Another indication for agitated saline is the evaluation of a persistent left superior vena cava. In this case, agitated saline injected into a left arm vein will appear as opacification in the dilated coronary sinus, which is seen in the left

atrioventricular groove (Fig. 6-4), although both the left and right superior vena cava can drain into the coronary sinus. Assessment for potential residual shunt after device closure of an atrial or ventricular septal defect (ASD or VSD) or PFO is also done with agitated saline contrast echocardiography (5) (Fig. 6-5).

FIGURE 6-3 Visualization of left pulmonary vein. Left: Left upper pulmonary vein (arrow). Right: Contrast (arrows) demonstrates the location of an intrapulmonary shunt. PA, pulmonary artery.

Pitfalls of agitated saline contrast echocardiography for shunt detection can occur in cases where there are inadequate contrast injections and hence inadequate right atrial opacification. This can be corrected by increasing the contrast injection dose or by optimizing the machine settings using harmonics. Additionally, false-negative results can occur if there is failure of performance of an adequate Valsalva maneuver (to increase right atrial pressure above left atrial pressure), or when injected agitated saline contrast is streamed along a large Eustachian valve directly into the right ventricle (6).

AUGMENTATION OF THE DOPPLER VELOCITY SIGNAL Bubbles created by agitated saline strengthen Doppler velocity signals from the right heart chambers. To estimate right ventricular (RV) and pulmonary artery systolic pressure, it is necessary to record tricuspid regurgitation velocity, which may not be detectable in 30% of patients. In some patients, the tricuspid regurgitation signal is faint and a stronger signal is needed to provide a reliable estimate of RV systolic pressure. Agitated saline (prepared as described above) improves the chance of obtaining tricuspid regurgitation signals (see Chapter 9).

However, if tricuspid regurgitation is not detected with color flow imaging, its signal is not likely to appear even with the injection of agitated saline. Augmentation of the Doppler velocity signal from the left heart chambers requires gas-filled microbubbles. A good example is augmentation of the Doppler signal from aortic stenosis or a coronary artery (7–9).

FIGURE 6-4 Left: Parasternal long-axis view showing a large coronary sinus (arrow). LA, left atrium; LV, left ventricle; RV, right ventricle. Center: Agitated saline injected into the right arm opacifies the RV, but no contrast in the coronary sinus (arrow). Right: Agitated saline injected into the left arm opacifies the coronary sinus before RV, indicating a persistent left superior vena cava. Arrows, Opacification of the coronary sinus.

MISCELLANEOUS INDICATIONS FOR AGITATED SALINE CONTRAST ECHOCARDIOGRAPHY The echocardiographic guidance of catheter localization into the pericardial space during percutaneous drainage of pericardial effusion can be confirmed by the injection of agitated saline. The appearance of contrast in the pericardial sac confirms the catheter position (10) (Fig. 6-6).

FIGURE 6-5 Left: Transesophageal echocardiogram at 93 degree showing bicaval view demonstrating patent foramen ovale closure with occluder device (arrow) between right atrium (RA) and left atrium (LA). Center: With agitated saline administration, contrast enters RA via superior vena cava (SVC). Pacification of SVC is shown. Right: The entire RA is opacified with no residual shunt postpatent foramen ovale closure as no contrast microbubbles appear in the left atrium (LA) after

appearing in the right atrium.

ECHOCARDIOGRPAHY WITH ULTRASOUND ENHANCING AGENT (UEA) To enhance images of the left heart, UEAs must be small enough to traverse the pulmonary circulation intact and also be durable to have a lasting effect for detection throughout the echocardiographic examination. UEA microbubbles are 2- to 5-μm spheres and have an intravascular rheology and similar velocity profile to red blood cells. They can pass freely through pulmonary and systemic capillaries, do not coalesce or aggregate, are biologically inert, remain entirely within the vascular space, and are eliminated from the body via the reticuloendothelial system with their gas escaping from the lungs (11). The microbubble shell consists of lipid, polymer, galactose, surfactant, albumin, or a combination of these (12). The gas contents are usually perfluorocarbons and sulfur hexafluoride. Microbubbles undergo volumetric oscillations upon exposure to ultrasound waves. These oscillations create the acoustic signals that opacify cardiac chambers or other areas of blood flow (13). Currently, the most frequent indication (per American Society of Echocardiography [ASE] 2008 updated guidelines (11) for the use of UEA) is to enhance the definition of the endocardial border detection (EBD) by left ventricular opacification (LVO) (11,12,14).

FIGURE 6-6 Left: Transthoracic echocardiograms parasternal long axis view demonstrating pericardial effusion (asterisk). Right: Agitated saline contrast injection for assessment of position of catheter during pericardiocentesis demonstrating opacification of the pericardial space (asterisk) after saline contrast injection. LA, left atrium; LV, left ventricle; VS, ventricular septum. RV, right ventricle.

The United States (US) Food and Drug Administration (FDA) has approved

two commercially available UEAs, both containing perfluoropropane (PFC) and indicated for EBD and LVO in patients with suboptimal baseline images: Optison (GE Healthcare Inc., Princeton, NJ), approved in 1998, and Definity (Lantheus Medical Imaging, North Billerica, MA), approved in 2001. Optison contains octafluoropropane gas inside albumin microspheres, whereas Definity contains octafluoropropane gas inside a phospholipid shell (11). Recently, Lumason UEA (known in Europe as SonoVue, Bracco Diagnostics Inc. Princeton, NJ, USA) was approved by the FDA in 2014. Lumason contains sulfur hexafluoride gas inside a lipid type A shell (15).

FIGURE 6-7 Diagram demonstrating second harmonic imaging. A: Ultrasound beam with fundamental frequency fo is aimed at a blood cavity containing microbubbles. B: When the fundamental frequency ultrasound beam is reflected by the microbubbles, not only the fundamental frequency but also the resonating harmonic frequency ultrasound beam returns because of the oscillation of the microbubbles and their nonlinear behavior. Depending on the power of the ultrasound beam, the size of microbubbles changes nonlinearly, which is important for the development of second harmonic imaging.

CONTRAST AGENT–ULTRASOUND INTERACTION Ultrasound generates positive and negative (sinusoidal) pressures, and microbubbles are compressed and expanded by the ultrasound acoustic energy in a nonlinear fashion if the acoustic pressure is sufficiently high at the resonant frequency of the microbubbles. This nonlinear property of microbubbles generates harmonic signals when the microbubbles are contacted by ultrasound waves (Fig. 6-7). When ultrasound waves are transmitted at high frequency (fundamental frequency) to the microbubbles, returning signals have not only the fundamental frequency, fo, but also a second harmonic frequency, 2 fo (frequency twice that of the fundamental frequency) (Fig. 6-8). Myocardial

tissue also generates signals with a second harmonic frequency but a much smaller amount than the nonlinearly behaving microbubbles. Therefore, modifying the imaging device to receive the signals with the second harmonic frequency (second harmonic imaging) enhances the detection of microbubbles. Even without microbubbles in the cardiac chambers, second harmonic imaging of tissue also improves the image quality of myocardial structures. Although the second harmonic imaging signals increase with higher ultrasound power, the microbubbles are deformed by higher positive and negative pressures to the point of being destroyed.

FIGURE 6-8 A: Acoustic signal returning from contrast gas-filled microbubbles. Imaging was at a fundamental frequency of 3.75 MHz; returning signals contain both fundamental fo and second harmonic (2fo) signals. B: Improved microbubble signal relative to tissue and received as second harmonic (2fo) rather than as fundamental frequency fo. Signal amplitude is greater from microbubbles than from tissue at the second harmonic frequency. (A Reprinted from Burns PN, Powers JE, Simpson DH, et al. Harmonic Imaging: Principles and preliminary results. Clin Radiol, 1996;51(Suppl I):50–55. Copyright © 1996 Elsevier. With permission. B Reprinted from Lindner JR. Contrast echocardiography. Curr Probl Cardiol, 2002;27(11):454– 519. Copyright © 2002 Elsevier. With permission.)

The ultrasound acoustic power is expressed as the mechanical index, which is proportional to the acoustic pressure and inversely proportional to the square root of the ultrasound frequency.

Mechanical index (MI) is a major parameter affecting microbubble oscillation. These oscillations can result in weak nonlinear backscatter at a very low MI ( PVd) (Fig. 8-10). With a reduced LV filling during early diastole, flow from the pulmonary vein to the LA is reduced. With atrial contraction, increased LA pressure pumps the large amount of blood from the LA to the LV. The duration and velocity of PVa are usually normal as long as LVEDP is not elevated, but they may be increased if the LVEDP is high (without an increase in mean LV diastolic pressure). At the onset of LV contraction, the

LA is relatively empty with reduced pressure, allowing increased filling or velocity from the pulmonary vein to the LA. In a subgroup of patients with E/A ≤ 0.8, e′ velocity or myocardial relaxation is markedly reduced, and E/e′ is >14 with mitral E velocity usually higher than 50 cm/s (Fig. 8-21). This pattern has been designated as grade 1a diastolic dysfunction at Mayo Clinic to emphasize that filling pressure is increased in the presence of a typical grade 1 mitral inflow velocity pattern (E/A ≤ 0.8). In the ASE/EACVI recommendation, this pattern is classified as grade 2 dysfunction since the prognosis of the patients with this pattern is similar to that of more typical grade diastolic dysfunction (39).

FIGURE 8-21 A composite of mitral inflow, tricuspid regurgitation velocity, and mitral annulus velocity in grade 1A (at Mayo) dysfunction or grade 2 according to ASE/EACVI recommendation. E = 60 cm/s, A = 75 cm/s with E/A = 0.8. Medial e′ = 5 with E/e′ = 12 and lateral e′ = 7 with E/e′ = 8. However, TR velocity is 3 m/s and LA is enlarged.

Grade 2 Diastolic Dysfunction As diastolic function deteriorates, the mitral inflow pattern goes through a phase that resembles a normal diastolic filling pattern, that is, the E/A ratio is 0.8 to 2.0, and DT is normal at 160 to 240 milliseconds. This is the result of a mild to moderately increased LA pressure superimposed on a relaxation abnormality. This is referred to as the “pseudonormalized” mitral flow filling pattern, and it represents a moderate stage of diastolic dysfunction. This can be a challenging

pattern to be classified since it resembles and needs to be distinguished from a true normal pattern. ASE/EACVI guideline recommends in this situation that 3 following criteria be evaluated: E/e′, TR velocity, and LAVI, especially when LVEF is reduced or diastolic dysfunction is already known to be present (Fig. 819). It should be emphasized that it is assumed in this situation that myocardial relaxation or e′ velocity is reduced. Therefore, unless LVEF is marked reduced (≤40 %), we need to make sure that e′ velocity is reduced. Again, the majority decides the diastolic function grading and filling pressure. If ≥2 of 3 criteria (E/e′ > 14 or 15, TR velocity > 2.8 m/s, and LAVI > 34 mL/m2) are positive, LV filling pressure or LA pressure is elevated as grade 2 diastolic dysfunction (Fig. 8-22). If ≥2 are negative or normal, LA pressure is normal as grade 1 diastolic dysfunction. If only two of those 3 criteria are available and their values are split between normal and abnormal values (e.g., E/e′ is 16, TR velocity is 2.6 m/s, and LAVI could not be measured when E/A ratio is 1.2), additional parameters should be evaluated. In above situation, PVs/PVd < 1.0 favors grade 2 diastolic dysfunction with increased filling pressure. One pitfall in this algorithm of assuming diastolic dysfunction is that the assumption may not be correct since a young subject with HCM or EF of 40% after acute myocardial infarction can still maintain clinically normal or adequate myocardial relaxation, although reduced for one’s age (Fig. 8-23). To avoid this pitfall, we recommend always using 4 parameters including mitral annulus e′ velocity especially when LVEF is preserved. Following information can be also helpful in determining grade 2 diastolic dysfunction.

FIGURE 8-22 A: A composite of mitral inflow, tricuspid regurgitation velocity, and mitral annulus velocity in grade 2 diastolic dysfunction. Medial e′ = 3 cm/s and lateral e′ = 6 cm/s with E/e′ of 40 and 20, respectively. TR velocity is higher than 2.8 m/s. B: (Left) Pulmonary vein velocities are lower during systole compared to diastole. (Right) With Valsalva maneuver, E/A decreases from 1.0 to 0.5.

1. When myocardial relaxation is markedly prolonged and LA pressure is elevated, there is a mid-diastolic mitral inflow termed “L wave” due to a middiastolic drop in LV diastolic pressure after the early diastolic rise in LV pressure (23,40) (Fig. 8-22). L wave is also frequently seen in healthy young subjects with a slow heart rate, but its peak velocity is usually 30 cm/s (Fig. 8-24). L wave can be also seen in mitral annulus velocity and PV flow velocity (Fig. 8-24C). 2. A decrease in preload, by having the patient sit, perform the Valsalva maneuver, or take sublingual nitroglycerin, may be able to unmask the

underlying impaired relaxation of the LV (Figs. 8-6 and 8-22B), causing the E/A ratio to decrease by 0.5 or more and reversal of the E/A ratio. In normal subjects, both the E and A velocities decrease more proportionally with a decrease in filling. 3. If LA pressure is elevated, LVEDP is always high. Therefore, mitral A duration is shorter than PVa duration. 4. Normally, active myocardial relaxation initiates LV diastolic filling so that the onset of e′ velocity precedes few milliseconds or almost is simultaneous with the onset of mitral inflow. When LA pressure is elevated, the increased LA pressure opens the mitral valve initiating LV filling followed by myocardial relaxation (Fig. 8-25). Hence, the onset of mitral inflow E velocity is earlier than that of mitral annulus e′ velocity (Fig. 8-26) (35,42,43).

FIGURE 8-23 A: Mitral inflow and annulus velocity in a 23-year-old man with hypertrophic cardiomyopathy with septal thickness of 20 mm (*). If diastolic dysfunction is assumed because of hypertrophic cardiomyopathy, then E/A ratio suggests grade 3 diastolic dysfunction. However, medial and lateral e′ velocities are normal, although lower than expected for 23 year old. This is an example of normal filling pressure and low-normal diastolic function in the setting of a massive hypertrophic septum. Normal “L” wave is seen (arrow). B: Mitral inflow and PV Doppler velocities in this 23-year-old patient with hypertrophic cardiomyopathy demonstrate that PV atrial reversal (PVar) duration is longer than the duration of mitral A flow (arrows pointing the ending of mitral A and PV atrial reversal in relationship to the timing of QRS) indicating that LV end-diastolic pressure is increased while mean LV or pre-A diastolic pressure is not elevated.

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Video 8-23

FIGURE 8-24 A: A composite of mitral inflow, color M mode, and mitral annulus velocities demonstrating “L” wave (arrows). L wave is generated by delayed myocardial relaxation. B: A prominent “L” wave with Valsalva maneuver. C: Upper panel shows pulmonary vein Doppler with “L” wave (arrow after diastolic flow velocity. Lower panel shows corresponding “L” wave in the mitral inflow (arrow).

Grade 3 Diastolic Dysfunction (Restrictive Filling) The term restrictive diastolic filling, or restrictive physiology, should be distinguished from restrictive cardiomyopathy. Restrictive physiology can be present in any cardiac abnormality or in a combination of abnormalities that produce decreased LV compliance and markedly increased LA pressure.

Examples include decompensated congestive systolic heart failure, advanced restrictive cardiomyopathy, severe coronary artery disease, acute severe aortic regurgitation, and constrictive pericarditis. Increased LA pressure shortens IVRT, and high E velocity. Early diastolic filling in a noncompliant LV causes a rapid increase in early LV diastolic pressure, with rapid equalization of LV and LA pressures producing a shortened DT. Atrial contraction increases LA pressure, but A velocity and duration are shortened because LV pressure increases even more rapidly. When LV diastolic pressure is markedly increased, there may be diastolic mitral regurgitation during mid-diastole or with atrial relaxation. Therefore, restrictive physiology or grade 3 diastolic dysfunction is characterized by mitral flow velocities that show increased E velocity, decreased A velocity (E/A ≥ 2.0), and shortened DT (2.8 m/s (Fig. 8-28) and LAVI is >34 mL/m2. It is possible that E/A ratio is ≥2.0 in healthy individuals and normal myocardial relaxation or well-preserved e′ is expected (usually medial e′ ≥ 10 cm/s or lateral e′ ≥ 15 cm/s) with E/e′ ≤ 8.0. Systolic forward flow velocity in the pulmonary vein (PVs) is decreased because of increased LA pressure and decreased LA compliance. Pulmonary vein forward flow stops at mid to late diastole, reflecting the rapid increase in LV pressure; at atrial contraction, the increase in LA pressure can produce a prolonged PVa; however, PVa may not be seen if atrial contraction occurs when the pulmonary vein flow velocity is relatively high (Fig. 8-27). The Valsalva maneuver is rarely necessary in classifying grade 3 diastolic dysfunction except that it may reverse a restrictive filling pattern to a grade 1 or 2 pattern, indicating the reversibility of high filling pressure. However, even if the restrictive filling pattern does not change with the Valsalva maneuver, reversibility cannot be excluded because the Valsalva maneuver may not be adequate or filling pressure may be too high to be altered by the maneuver. Therefore, the grade 4 dysfunction indicating

“irreversible restrictive” filling is not included in the ASE/EACVI recommendation.

FIGURE 8-25 A figure demonstrating that increased LA pressure pushes the mitral valve open (arrow toward the left) with minimal annulus motion (arrow toward the right or LA) because of reduced myocardial relaxation.

FIGURE 8-26 A composite of mitral inflow (top) and annulus (bottom) Doppler velocities demonstrating (A) a simultaneous onset of both flows in a subject with normal filling pressure and (B) earlier onset of mitral inflow in a subject with increased filling pressure. Arrows indicate the onset of each flow, and straight line is drawn to align the timing of both flow at the same QRS complex.

The classification of diastolic filling patterns based on mitral inflow and tissue Doppler velocity pattern is summarized in Figure 8-28.

FIGURE 8-27 A composite of 2D, mitral inflow, medial annulus (e’ of 5 cm/s) and pulmonary vein velocities in a patient with advanced cardiac amyloidosis and restrictive or grade 3 diastolic dysfunction.

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Video 8-27

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Video 8-25

Strain Imaging for Diastolic Function Assessment Diastolic function is intimately coupled with systolic function, and LV systolic strain is usually abnormal in patients with preserved EF and diastolic dysfunction (Fig. 8-29). In RELAX trial, the baseline LV global longitudinal strain was −14.6% and abnormal (≥−16%) in almost 2/3 of the patients with HFpEF (44). There was a modest linear relationship between LV longitudinal systolic strain and NT-proBNP, but not with 6-minute walk distance or peak VO2. We will need additional clinical investigations to know whether systolic strain can help classify diastolic dysfunction. LV torsion was measured in patients with diastolic dysfunction, and it was interesting that it was found to be increased in grade 1 diastolic dysfunction compared with control and then normalized in moderate and reduced in severe diastolic dysfunction (45). Whether increased LV torsion is a compensatory mechanism for reduced myocardial relaxation or a consequence of reduced filling in the early stage of diastolic dysfunction is not clear, but it probably does not add greatly to the classification of diastolic dysfunction. Left atrial function also depends on LV diastolic function and filling. Its reservoir, conduit, and booster functions depend on LA size, pressure, and mitral regurgitation. Since LA volume increases with diastolic dysfunction, it is one of 4 principal variables to evaluate diastolic dysfunction, but has a significant overlap among different gradings or stages of diastolic dysfunction. It has been shown that peak LA strain allows a more accurate categorization of diastolic dysfunction with progressive reduction with worsening of diastolic dysfunction (Fig. 8-30) (46).

FIGURE 8-28 A summary of grading diastolic function based on mitral inflow, tissue Doppler recoding of mitral annulus velocity, tricuspid regurgitation velocity, and LA volume index. Please note that LAVI can be normal or increased in grade 1 diastolic dysfunction (*).

Whether peak LA strain has incremental value to other simpler echocardiography measurements in the evaluation of LV diastolic function requires further clinical observations and investigations.

FIGURE 8-29 A composite of mitral inflow, longitudinal global strain bull’s eye pattern, mitral annulus velocity, and tricuspid regurgitation velocity demonstrating grade 3

diastolic dysfunction. The global longitudinal strain is severely reduced in the base and midlevel of the LV, and e′ velocity is severely reduced (4 cm/s) with severe pulmonary hypertension. There is also “L” wave in the mitral inflow (arrow).

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Video 8-29

FIGURE 8-30 A: The apical 4-chamber view with the entirety of the left atrium (LA) is pictured, with the endocardium of the LA traced (left). LA strain overtime curve and an electrocardiogram signal are shown on the right. B: At the 4 corners, composite LA strain curves are depicted as mean of each subgroup (solid lines) with standard deviation (dotted lines) in normal and 3 diastolic gradings. Center panel shows all 4 LA strain curves in a single plot to facilitate comparisons. (From Singh et al. (46), with permission.)

Evaluation of Diastolic Function in Specific Situations Not all diastolic Doppler velocity patterns fit conveniently or perfectly into one particular filling pattern. The spectrum is wide because of the different contributions and degrees of the underlying disease, abnormal relaxation,

changes in compliance, and volume status. The same degree of decrease in compliance or volume change will produce different mitral flow velocity curves depending on whether relaxation is abnormal. If LV hypertrophy is marked, DT still can be prolonged even with increased LA pressure, whereas a similar increase in pressure in other patients shortens DT. This may help explain why the use of mitral filling patterns in estimating filling pressures works less well in HCM (see below). In severe LV hypertrophy, a triphasic mitral flow pattern with prominent mid-diastolic flow can result from a markedly prolonged relaxation continuing into mid-diastole (23,40). Even if the initial slope of E gives a short DT, the continued filling indicates that abnormal relaxation, not a decrease in compliance, is the main problem. This mid-diastolic delay in myocardial relaxation is also evident from the mitral annulus mid-diastolic velocity (Fig. 824). An opposite example is constrictive pericarditis, in which decreased compliance due to thick pericardium may result in markedly shortened mitral DT while e′ velocity is normal or even increased. These variations illustrate the importance of evaluating the diastolic filling pattern by integrating all available information instead of relying on a single variable to characterize it. This approach helps avoid interpretive errors made by trying to fit all patients into rigid diagnostic algorithms.

FIGURE 8-31 A: Pulsed wave Doppler recording of mitral inflow velocity in an asymptomatic patient with atrial fibrillation after aortic replacement. All E velocities were completed before the onset of QRS, and their deceleration time ranges from 200 to 230 ms. B: Pulsed wave Doppler recording of mitral inflow velocity from an elderly woman with congestive heart failure in the setting of atrial fibrillation. Peak E velocity and deceleration time (DT) vary depending on cardiac cycle length. When E velocity is terminated before the onset of QRS (third, fifth, and sixth signals), DT is shorter (100–110 ms) than that (120–140 ms) of mitral inflow velocity, which was completed before the QRS (first, second, fourth, and seventh signals).

Atrial Fibrillation and Sinus Tachycardia The usual criteria for classifying diastolic filling patterns cannot be applied to

patients with atrial fibrillation and varying cycle lengths. There is no A wave in mitral inflow, and systolic forward flow in the pulmonary vein is almost always diminished. Peak velocity and DT of mitral E vary with the length of the cardiac cycle. Peak acceleration rate of E velocity (≥1,900 cm/s2) was found to correlate well with increased LV filling pressure, (46) but it is difficult to measure. It appears from clinical observations that DT is shortened with increased LV filling pressure, as in patients with sinus rhythm, especially when LV systolic function is decreased (47,48). DT ≤ 160 milliseconds is associated with increased filling pressure. However, DT should be measured only when E velocity ends before the onset of QRS (Fig. 8-31A). When the diastolic filling period is too short, E velocity is terminated prematurely with a shorter DT (Fig. 8-31B). In patients with atrial fibrillation, diastolic flow is predominantly pulmonary vein forward flow. The duration and initial DT of pulmonary vein diastolic flow (≤220 milliseconds) may be useful in predicting increased LV filling pressure (48). E/e′ ≥ 11 (using medial e′) correlates well with increased PCWP in patients with atrial fibrillation (Fig. 8-32) (49). ASE/EACVI guideline also recommends using the difference between the onset of E and e′ (TE-e′), but it is often difficult and time-consuming to measure with a significant variability. In sinus tachycardia, E and A velocities frequently fuse, which makes it difficult to determine the diastolic filling pattern. Even in this situation, E/e′ ≥ 15 usually indicates increased PCWP (50,51). It is also worthwhile trying a gentle carotid sinus massage to slow the heart rate down if there is no carotid bruit (Fig. 8-33).

FIGURE 8-33 Fused mitral inflow (top) and annulus velocities (bottom), which are separated by a gentle carotid massage.

FIGURE 8-32 A: Mitral inflow and annulus velocity from a patient with atrial fibrillation. There is also “L” wave (arrow left). Mitral annulus e′ velocity varies (arrows in right) due to different cardiac cycle lengths. E′ values need to be averaged over 3 to 5 cycles. B: E/e′ > 11 indicates LV filling pressure >15 mm Hg. (Reprinted from Sohn DW, Song JM, Zo JH, et al. Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation. J Am Soc Echocardiogr, 1999;12(11):927–931. Copyright © 1999 American Society of Echocardiography. With permission.)

Hypertrophic Cardiomyopathy Almost all patients with HCM have a significant diastolic dysfunction with abnormal myocardial relaxation; hence, e′ velocity is reduced. Because HCM has multiple phenotypes and hemodynamic abnormalities of LVOT obstruction, mitral regurgitation, or apical pouch affecting diastolic function, it is challenging to perform diastolic function assessment. Simultaneous studies of invasive hemodynamic measurements and echocardiographic diastolic function assessment in symptomatic patients showed that there was no significant correlation between E/A, DT, or IVRT and pre-A or mean LA pressure, but there was a moderate correlation between E/e′ (using medial e′) and diastolic pressures (52,53). In Geske’s study, almost all patients with HCM had E/e′ > 8, and 25% of the patients with E/e′ > 15 were found to have normal filling pressure (Fig. 834). This is quite opposite to the situations without HCM where E/e′ > 15 is relatively specific for increased filling pressure. However, in HCM, E/e′ ≤ 15 is

usually associated with normal filling pressure due to marked reduction in e′ velocity with hypertrophy. When 132 patients with HCM were followed for a mean of 3.8 years, E/e′ > 15 was associated with a higher incidence of major adverse cardiac events (death, heart failure hospitalization, stroke, and atrial fibrillation) (54). It was a better predictor than BNP. Studies have demonstrated a significant improvement in e′, E/e′, and PASP after myectomy (55,56). When patients with HCM are classified according to PASP, patients with pulmonary hypertension do have increased filling pressures (E/A 1.6 vs. 1.0, E/e′ medial 25 vs. 15, and LAVI 65 vs. 44 mL/m2) compared to the patients without pulmonary hypertension although there was no difference in e′ velocity (5 cm/s for medial and 6 cm/s for lateral annulus) (55). Therefore, it is recommended to use E/e′ ratio, LAVI, TR velocity, and PVar velocity (Fig. 8-35). 1) Diastolic filling pressure is decided by the majority rule. LA strain, early diastolic vortices, torsion, and untwisting have been related to diastolic function in HCM, but they are difficult to apply in clinical practice, and there are no definite data showing incremental value to the standard parameters mentioned.

FIGURE 8-34 A: Mean LA pressure versus mean E/e′ ratio in patients with HCM. (Reprinted with permission from Geske JB, Sorajja P, Nishimura RA, et al. Evaluation of left ventricular filling pressures by Doppler echocardiography in patients with hypertrophic cardiomyopathy: correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation, 2007; 116(23):2702–2708.) B: LV filling pressure vs. E/e′ ratio in patients without HCM. (From Ommen SR, et al. Circulation, 2000;102(15):1788–1794, with permission.)

Restrictive Cardiomyopathy Vs Constrictive Pericarditis Both restrictive cardiomyopathy and constrictive pericarditis are predominantly a problem with limited diastolic filling, the former related to abnormal and fibrosed ventricles and the latter related to noncompliant and scarred pericardium. Their characteristic hemodynamic and echocardiographic features are detailed in the cardiomyopathy and the pericardial disease chapter. A major

distinguishing diastolic feature is the mitral annulus velocity, which is markedly reduced in restrictive cardiomyopathy and is preserved or even augmented in constrictive pericarditis (18,20). In addition, respiratory variation in ventricular septal motion and hepatic vein Doppler velocities are unique to constrictive pericarditis (see Chapters 10 and 12).

Valvular Heart Diseases Estimation of filling pressure is important in all valvular heart diseases, but can be challenging in some conditions due to the impact of valvular disease on diastolic parameters. In mitral regurgitation, mitral E velocity increases with increasing amount of regurgitant volume so that E/e′ may not be reliable in estimating LV diastolic pressures. Significant mitral regurgitation reduces systolic component of pulmonary vein flow. However, studies have shown a good correlation between DT of mitral inflow and LV filling pressure (57). In addition, E/e′ > 15 was found to be associated with increased PASP and clinical outcome (58). It also had a significant correlation with LA pressure when LVEF is reduced. Other useful parameters are IVRT and the ratio of IVRT to TE-e′. The same parameters can be used in patients with mitral stenosis (1). Usually, LV diastolic pressure is normal in patients with MS, but in a subset of patients with MS, LV diastolic pressure is also elevated due to underlying myocardial and diastolic dysfunction. Most of the patients with aortic stenosis do have diastolic dysfunction since it occurs in the elderly, especially with tricuspid degenerative aortic valve disease. With LV pressure overload, LV hypertrophy occurs and myocardial relaxation becomes abnormal; hence, mitral annulus e′ velocity is usually reduced. As aortic stenosis becomes more severe, diastolic function becomes also worsened with grade 2 or 3 dysfunction. When patients with AS develop dyspnea, diastolic filling pattern is at least grade 2 while diastolic function is less severe in patients who present with chest pain or syncope (58). E/e′ has been shown to be prognostic in symptomatic as well as asymptomatic patients with aortic stenosis and patients may continue to experience dyspnea after aortic valve replacement if diastolic dysfunction is progressed to severe degree at the time of valve replacement (59). In chronic aortic regurgitation, LV becomes compliant due to its gradual dilatation, and diastolic pressure does not increase for a long time. However, in acute or subacute aortic regurgitation where LV is not dilated, LV diastolic filling pressure rises rapidly resulting in grade 2 or 3 filling pattern

(60). The rapid rise in filling pressure may force the mitral valve to close prematurely.

FIGURE 8-35 A: Apical HCM in 73-year-old woman. E′ velocity is markedly reduced, more so in the medial location than from lateral location. Hence, E/e′ is 40 using the medial e′ and 15 using the lateral. In HCM, we need to see more data to be sure about filling pressure in this situation. B: Systolic strain is reduced in the apex and anterolateral areas. TR velocity is 3 m/s indicating that her filling pressure is elevated.

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Video 8-35A

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Video 8-35B

Mitral Annulus Calcification In patients with mitral annulus calcification, E/e′ ratio can be falsely elevated due to increased mitral E from slightly narrowed mitral orifice and decreased mitral annulus e′ velocity (Fig. 8-36A). It was reported that e′ velocity is about 20% lower and E/e′ is about 40% higher in patients with moderate to severe mitral annulus calcification compared to individuals with no significant calcification (61). Therefore, parameters other than E/e′ should be used in patients with moderate to severe degree of mitral annulus calcification. Figure 836B shows an algorithm to use E/A and IVRT to assess LV filling pressure in the setting of significant mitral annulus calcification. Pulmonary vein velocity along with TR velocity is another reliable way to assess LV filling pressure in this situation.

FIGURE 8-36 From a 76-year-old woman with severe mitral annulus calcification. A: Mitral inflow (left), mitral annulus velocities from medial (center), and lateral location (right). E velocity is 100 cm/s and E/e′ is 33 and 25 using medial and lateral e′ velocity, respectively. B: Pulmonary vein Doppler velocity (left) and tricuspid regurgitation velocity of 2.4 m/s indicate normal filling pressure despite the increased E/e′ ratio. C: A proposed algorithm for evaluation of LV filling pressure in patients with mitral annulus calcification using E/A ratio and IVRT. (From Abudiab MM, et al. JACC Cardiovasc Imaging, 2017 Dec;10(12):1411-1420, with permission.)

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Video 8-36

Diastolic Exercise Test When diastolic function is normal, LV filling augments without a significant increase in filling pressure to meet bodily demands with stress or exertion due to appropriately increased myocardial relaxation and suction. As diastolic worsens, adequate LV filling may occur with exertion, but at the expense of increased filling pressure resulting in dyspnea, or LV filling is limited even with increased filling pressure. However, filling pressure may not be elevated at resting state. An analogous situation is when we evaluate patients for coronary artery disease. Normal wall motion or coronary perfusion at resting state does not mean there is no coronary stenosis. We perform a stress test in that situation to see whether an individual develops new wall abnormality or perfusion defect. Therefore, an ability to determine LV filling pressure with a form of exercise is helpful to evaluate a patient with exertional dyspnea who has normal filling pressure with an evidence of diastolic function (i.e., grade 1 diastolic dysfunction) (1,62) (see diastolic evaluation algorithm in Fig. 8-20). It has been well proven to be feasible and reliable to estimate PCWP with exercise by recording mitral inflow and annulus velocity with exercise as well as at resting state (63–66). In the normal population with normal diastolic function, filling pressure increases slightly with exercise. Mitral inflow E velocity and annulus e′ velocity increase same percentage with exercise in normal subjects so that E/e′ ratio remains unchanged with exercise (Fig. 8-37). Our initial study in middle-aged healthy individuals and a subsequent study in young normal subjects yielded a very similar E/e′ ratio at rest and with exercise (67,68) (Table 8-3).

FIGURE 8-37 Mitral inflow (left) and medial mitral annulus velocity (right) at rest (top) and with exercise (bottom) in an elderly normal subject. E velocity increases from 75 cm/s to 108 cm/s, and e′ increases from 6.7 cm/s to 10.8 cm/s. E/e′ is 11 and 10, respectively.

TABLE 8-3 Normal Values of Mitral E, e’ and E/e’ For Middle Aged and Young at rest and with exercise Variables

Rest

Exercise

Rest

Exercise

Mean Age (y)

59 ± 14



29 ± 6



Mitral E (cm/s)

73 ± 19

90 ± 25

81 ± 14

132 ± 15

Medial e′ (cm/s)

12 ± 4

15 ± 5

14 ± 3

20 ± 3

E/e′ ratio

6.7 ± 2.2

6.6 ± 2.5

6.7 ± 1.4

7.1 ± 1.1

In subjects with diastolic dysfunction, myocardial relaxation or mitral annulus e′ velocity does not improve much, compared to normal individuals, with exercise or with increased preload while mitral E velocity increases due to increased LV filling (Figs. 8-38 and 8-39). As a result, E/e′ increases with exercise. Several studies have shown that E/e′ ratio correlates well with LA or pulmonary capillary wedge pressure with exercise as well as at rest (63–66).

Although our initial feasibility study was performed using a supine bike in order for us to record changes in individual parameters at various stages of exercise, (69) we now perform most of diastolic exercise tests using treadmill exercise protocol since most of our patients also need to have an evaluation for coronary artery disease. We have shown that once diastolic filling pressure is increased with exercise, it takes several minutes for the pressure to return to resting level (Fig. 8-40). With peak exercise, mitral inflow or annulus early and late diastolic velocities are frequently fused due to tachycardia. Therefore, LV wall motions are captured first immediately after termination of treadmill exercise, and other hemodynamic variables are obtained for evaluation of diastolic filling pressure and PASP. Increased TR velocity with exercise supports diastolic dysfunction and increased filling pressure with a higher specificity, and TR velocity is an integral part of diastolic exercise test. Table 8-4 shows diastolic exercise test procedure at Mayo Clinic.

FIGURE 8-38 A: Positive diastolic exercise test using a supine bike. Mitral inflow (top) and annulus velocity (bottom) were obtained serially at rest, 25 W, 50 W, 75 W, and recovery. At rest, E = 50 cm/s and medial e′ = 5 cm/s with E/e′ = 10. There was no significant increase in e′ with exercise, but E velocity increased to 80 cm/s with mild exercise and then to 90 cm/s at 75 W yielding E/e′ = 18. The patient was having

dyspnea from 50 W level of exercise. Mitral inflow returned to the baseline gradually. B: Another example of positive diastolic exercise test using treadmill exercise. Mitral inflow was obtained at rest (top left) and postexercise (top right). Corresponding tricuspid regurgitation velocities are shown (bottom). E velocity increased from 35 cm/s to 90 cm/s with no major change in e′ 4 cm/s (not shown) yielding E/e′ of 8 and 23, respectively, at rest and exercise. TR velocity increased from 2.2 m/s to 4.0 m/s.

Although ASE/EACVI guidelines recommend average value for mitral annulus e′ velocity, it is challenging to obtain both values with exercise test since several parameters need to be acquired in a short period. Mayo Clinic continues to use the medial e′ velocity alone for both resting and exercise diastolic function evaluation since there has been no study demonstrating a definite advantage or superiority of using the average value compared to one location for most of clinical situations. Another simple diastolic stress test can be done with elevation of legs for 3 minutes, which increases venous return to the heart. In patients with significant diastolic dysfunction, filling pressure would increase and E/e′ ratio increases. However, this is not a very sensitive way to detect diastolic dysfunction although can be performed simply at the examination table. We do not recommend dobutamine stress test for evaluation of diastolic function with stress although a persistent restrictive filling with dobutamine infusion was found to be predictive of a poor clinical outcome in patients with ischemic cardiomyopathy (70). Dobutamine is a vasodilator and tends to decrease filling pressure and is not physiologic when we assess patients with exertional dyspnea.

FIGURE 8-39 Another treadmill diastolic exercise test in a patient with exertional dyspnea. Resting mitral annulus, mitral inflow, and TR velocity are shown in the top. With exercise, there was no change in e′ velocity of 5 cm/s, but mitral E increased

from 48 cm/s to 94 cm/s and TR velocity increased from 2.6 m/s to 3.5 m/s.

FIGURE 8-40 Mitral inflow and annulus velocity from a positive exercise diastolic stress test showing marked increase in mitral inflow with 25 W of exercise and it took 10 minutes to return to baseline.

Dyspnea is the most common referral reason for exercise test, and the patients with dyspnea have worse prognosis than do the patients with referral reason of chest pain (71). Many of the patients with dyspnea do have normal stress test for myocardial ischemia. When diastolic evaluation is incorporated into an exercise echocardiography, the yield for a positive study is doubled in patients with referral reason of dyspnea at Mayo Clinic (Fig. 8-41). Several studies have reported that exercise diastolic function test predicts long-term outcome (72–74) and helpful for diagnosing patients with HFpEF (66,74). A time has come to incorporate this simple and helpful diagnostic test into our routine clinical practice to evaluate the patients with exertional dyspnea (75,76). TABLE 8-4 Diastolic Exercise Test 1. Prepare for an exercise test with ECG and pulse oximetry as well as vital signs 2. Resting echocardiogram a. LV size, EF, and wall motion b. Mitral inflow velocity c. Mitral annulus velocity d. TR velocity e. Color flow imaging for MR (if exercise-induced MR is suspected) 3. Exercise protocol (treadmill or supine bike) with monitoring 4. Immediately after (treadmill) or peak (supine bike) exercise a. Obtain LV size, EF, and wall motion (within 60 to 90 s) b. Repeat Doppler measurements c. Obtain TR velocity first d. Mitral inflow and annulus velocity when E and A unfused

5. Positive diastolic exercise test a. Reduced e′ at rest (13 (using lateral e′) c. TR velocity > 2.8 m/s

Clinical Applications of Diastolic Function Evaluation Management of Heart Failure Noninvasive estimates of PCWP allow more optimal treatment of heart failure. The diastolic filling pattern and filling period can provide a guide to a more selective management of heart failure. Grade 1 diastolic dysfunction: this is the best diastolic filling pattern in patients with diastolic dysfunction or clinical heart failure. E/A ratio between 0.6 and 0.8 appears to be the best filling pattern for the patients with ischemic cardiomyopathy (Fig. 8-42), and probably for other heart failure conditions. The patients in this group are usually asymptomatic as long as the diastolic filling period is sufficiently long to accommodate the delay in necessary myocardial relaxation. The key to management is the prevention of exercise-induced tachycardia or the development of atrial fibrillation. β-Blocker therapy is helpful in minimizing tachycardia, and the control of factors that further aggravate diastolic dysfunction is helpful (i.e., management of hypertension, obesity, diabetes mellitus, ischemia). Grade 2 diastolic dysfunction: patients in this group have a moderate increase in filling pressure in addition to impaired relaxation. Hence, a decrease in preload or venous congestion is required as well as neurohormonal modulation with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. Grade 3 diastolic dysfunction: patients in this group have a markedly increased filling pressure, and diastolic filling occurs mostly during early diastole, with a relatively fixed stroke volume. Patients may not tolerate β-blockade since stroke volume cannot be augmented wit bradycardia. Diuresis is the initial treatment of choice, and treatment with an ACE inhibitor or angiotensin receptor blocker can be titrated. Patient’s prognosis and symptoms improve if the diastolic filling pattern can be changed to grade 1 (optimally) or 2. Diastolic function assessment can also identify more stage B heart failure patients, compared to the current recommendation of using LVEF and LVH (77,78).

FIGURE 8-41 A pie diagram demonstrating the result of exercise test in 421 patients ≥ 60 years of age who were evaluated for dyspnea. Positive test for ischemia was found in 32%, but it increased to 63% if diastolic test result was included. (Courtesy of Kane G. and McCully R.)

FIGURE 8-42 A 5-year mortality rate based on E/A ratio in patients with ischemic

cardiomyopathy. (From STICH Trial.)

Prognosis Diastolic echocardiographic variables (E, E/A, DT, E/E′) and LA volume are powerful prognostic indicators for various conditions (79). Even in asymptomatic patients, the presence of diastolic dysfunction portends a poor clinical outcome (80). When the initial Olmsted asymptomatic patients were followed for 4 years, the prevalence of diastolic dysfunction increased from 24% to 39%. Diastolic function was worsened in 24% of the population, which was related to older age. Heart failure incidence increased when diastolic function became worse while it happened only in 2.6% when diastolic function was remained normal or normalized (Fig. 8-43) (81). Maintaining normal diastolic function may be the key to cardiac immortality. Although diastolic filling is affected by various factors, the direction of its change or progression is predictable in patients with known heart disease. Therefore, an assessment of the diastolic filling pattern allows LV filling pressures and LV compliance and relaxation to be estimated and understood so that optimal treatment strategies can be provided to symptomatic patients with diastolic dysfunction. Another important application is to provide a prognosis in cases of various cardiac diseases. A restrictive filling pattern indicates a poor prognosis, and treatments aimed at making diastolic filling less restrictive improve the clinical outcome of patients. The Doppler echocardiographic evaluation of the diastolic filling pattern may be helpful in assessing the response to treatment of patients with heart failure.

FIGURE 8-43 Progression of left ventricular diastolic dysfunction and risk of heart failure. (With permission from Kane et al. JAMA, 2011;306(8):856–863.)

Diagnosis of Diastolic Heart Failure, Cardiomyopathies, and Constrictive Pericarditis Knowledge of diastolic filling pattern and filling pressures allows the detection of cardiac diseases that are frequently missed or not suspected clinically, especially when the LVEF is normal. The evidence is strong that tissue Doppler evaluation of myocardial relaxation can be used to diagnose various forms of cardiomyopathy (HCM, Fabry disease, amyloidosis) even before any frank phenotypic manifestation. With the use of echocardiographic diastolic variables, it has been much easier to detect constrictive pericarditis. Comprehensive 2D and Doppler echocardiography can assess abnormal relaxation, detect changes in compliance or stiffness, and differentiate the level of filling pressure from the rate of change in pressure during diastole, which together with the structural information obtained from 2D echocardiography provides a clinically relevant assessment of diastolic function (82) (Fig. 8-44). The interplay between the basic diastolic properties and the filling pressure can be appreciated by the combined assessment of mitral inflow, tissue Doppler, and 2D imaging. Many myocardial and nonmyocardial conditions can cause heart failure in a patient with normal LVEF. However, abnormal diastolic function is

the most common cause of heart failure with normal LVEF, which is easily diagnosed by echocardiography with evidence of abnormal relaxation, increased filling pressure, and decreased compliance as well as normal (or decreased) LV dimension and preserved LVEF. This is what diastolic heart failure represents. Currently, echocardiography is the diagnostic method of choice for identifying such patients with diastolic heart failure or HFpEF. Recommendation for Diastolic Function Assessment As long as we understand the physiology of diastolic function and which component of diastolic variables determines each echo-Doppler parameter, we should be able to assess diastolic function or filling pressure reliably in most patients. Following is a summary of our approach to diastolic function assessment in clinical practice, which differs slightly from the ASE/EACVI recommendation. 1. Since the sine quo non or a prerequisite of diastolic dysfunction is abnormal or reduced myocardial relaxation, normal myocardial relaxation, hence, truly normal e′ velocity (medial e′ ≥ 8 cm/s) with E/A ratio > 0.8 should indicate truly normal diastolic function, except for in the case of constrictive pericarditis. In this situation, TR velocity should be normal, but LAVI can be increased if stroke volume is increased for a well-trained heart, bradycardia, or high-output heart failure without myocardial disease. 2. The easiest diastolic dysfunction to recognize is the grade 1 pattern characterized by E/A ≤ 0.8 and E ≤ 50 cm/s, regardless of underlying LVEF. This indicates normal filling pressure in the setting of abnormal myocardial relaxation or reduced e′. The current guideline makes this pattern as normal diastolic function if E/e′, TR velocity, and LAVI are less than the cutoff value. The reason for this is that the guideline considers age-related reduced myocardial relaxation as normal, but we should call that as early stage of diastolic dysfunction (with normal filling pressure) or reduced diastolic reserve. Another way to report this pattern is normal LV filling pressure with abnormal myocardial relaxation (Fig. 8-17). 3. We recommend that the first parameter to review for diastolic function assessment is to see whether there is an abnormality in myocardial relaxation. If e′ velocity is lower than age-related normal values, the ASE/EACVI algorithm for reduced EF or known diastolic dysfunction can be used (Fig. 819). We want to emphasize that we must have an evidence that myocardial relaxation is reduced. Patients (especially young) with a clinical history of

hypertension, coronary artery disease, cardiomyopathy, diabetes or increased wall thickness may have normal myocardial relaxation, hence normal diastolic function. Make sure that e’ is reduced before using the recommended algorithm for known diastolic dysfunction. 4. E/e′ > 15 (medial e′) or >14 (average e′) is very specific for increased LV filling pressure especially if combined with TR velocity ≥ 2. 8 m/s. However, we should not use E/e′ for the patients with at least moderate degree of mitral annulus calcification or mitral valve prosthesis. 5. If diastolic function assessment is indeterminate after reviewing e’, E/e’, LAVI and TR velocity, pulmonary vein velocity pattern is very useful. IVRT can be helpful also if it is significantly shortened (120 milliseconds) for delayed relaxation and normal filling pressure. Comparison of the onset of mitral inflow E velocity and the onset of mitral annulus e′ can be helpful. If well done, the Valsalva maneuver can also help differentiate normal from pseudonormalized mitral inflow velocity.

FIGURE 8-44 Top: Three similar mitral inflow velocity recordings from a normal subject (center column), a patient with diastolic heart failure (left column), and a patient with left ventricular (LV) remodeling after myocardial infarction (right column). It is difficult to identify their diastolic function or filling pressures by mitral inflow velocity pattern alone. Middle: Tissue Doppler velocity recording from the septal corner of respective individuals with mitral inflow velocities shown on the top panel. In the middle column, mitral annulus early diastolic velocity (Ea) is normal (11 cm/s), indicating that myocardial relaxation is normal with normal filling pressure (E/Ea = 80/11 ≤ 8). In the left column, Ea is markedly reduced to 5 cm/s, with E/Ea of 20 (=100/5). In the right column, Ea is also reduced to 3 cm/s with E/Ea of 33 (=90/3). Based on mitral inflow velocity and tissue Doppler mitral annulus velocity, the patients in the left and right columns were found to have increased filling pressure and

abnormal relaxation of LV. However, the underlying reason for increased filling pressure is not clear without structural information shown at the bottom. Twodimensional echocardiography shows completely normal cardiac structures for normal subject in the center, abnormal heart (increased wall thickness and enlarged LA size), but normal LV size and ejection fraction (EF) (in real time) in the left column, typical of diastolic heart failure, with leftward/upward-shifted end-diastolic pressure-volume relationship, and abnormal heart (enlarged LV size and reduced EF in real time) in the right column, typical of remodeling with rightward/ downward-shifted end-diastolic pressure-volume relationship.

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CHAPTER

9

Right Heart Assessment and Pulmonary Hypertension Garvan C. Kane and Sung-A Chang

Echocardiographic evaluation of the right heart is hampered by the complex shape of the right ventricle (RV), the proximity to the sternum, the thinness of the RV wall, and the complexity of RV function. Yet, there is increased recognition of the importance of the right heart in various disease states including those that primarily affect the left heart, such as heart failure with reduced or preserved ejection fraction (EF) as well as valvular heart diseases, and those acquired heart diseases that primarily affect the right side such as pulmonary hypertension (PH). Transthoracic echocardiography plays an integral part in the assessment of the patient with known or suspected PH. Echocardiography provides a reasonably accurate estimation of pulmonary artery (PA) hemodynamics, often providing information that helps with the determination of the mechanism of pulmonary hypertension, and most importantly conveys data on many critical prognostic variables. These measures of disease severity may include measures of right heart size, RV systolic function, and integrative hemodynamic variables.

RIGHT ATRIAL SIZE The right atrium (RA) is most commonly measured from an apical four-chamber view, by a monoplane method of discs. The RA area and length measures are taken at ventricular end systole, when the RA is largest, just prior to tricuspid valve opening. The chamber area is traced at the blood-tissue interface starting at the medial tricuspid annulus and finishing at the medial annulus. The length is measured parallel to the long axis of the RA. The intra-atrial septum is measured in a neutral position excluding any component of an atrial septal aneurysm, inferior vena cava (IVC), superior vena cava (SVC), appendage, and the area

between the leaflets and the annular plane (Fig. 9-1). Image optimization includes avoiding a foreshortened image and optimization of the focus depth and gain. Our laboratory reports RA volumes in patients with known or suspected right heart disease but not in those patients who have undergone mechanical tricuspid valve replacement or cardiac transplantation. The American Society of Echocardiography (ASE) recommends the upper limit of normal of the RA volume, as measured by this method, as 33 mL/m2 in women and 39 mL/m2 in men (1). RA volumes may also be measured directly by 3D echocardiography (see Chapter 2). Unlike the left atrium, data regarding the association of RA size with clinical outcomes are less well established (2,3) but may be helpful in the serial assessment of patients. Emerging data assessing RA function have identified impairments in both reservoir and passive conduit functions in pulmonary arterial hypertension (4).

RIGHT VENTRICLE A number of key features distinguish the RV from the left ventricle (LV), and these must be kept in mind when assessing RV anatomy and pathophysiology. The RV supplies a high-flow, low-pressure pulmonary circuit with a resistance one-tenth that of the systemic resistance, with the RV poised to tolerate changes in volume loading better than pressure loading. Located anterior to the LV, the RV free wall is thin and compliant forming a hemiellipsoid shape that wraps around the LV, sitting largely behind the sternum. The RV is composed of three components: the inlet, apical trabecular, and outlet portions. Unlike the LV, the RV lacks fibrous continuity between the inlet (tricuspid) and outflow (pulmonary) valves. The main portion of the RV is much more trabeculated than the LV and has a moderator band, a band of muscular tissue that stretches from the base of the anterior papillary muscle to the ventricular septum. While a dedicated right heart–focused four-chamber view is very helpful in the assessment of the RV, it is important that all available views are used to provide a comprehensive integrated echocardiographic assessment of the RV. These include the parasternal short and long axis in addition to the RV inflow and outflow views as well as apical and subcostal views (1).

FIGURE 9-1 Measurement of right atrium (RA) from the apical four-chamber view. The RA is measured by the monoplane method of disc technique, with the maximum area and length measured at ventricular end systole.

RIGHT VENTRICULAR WALL THICKNESS The normal RV free wall is thin, approximately 2 to 3 mm in thickness. An increase in RV wall thickness, a reflection of RV hypertrophy, typically occurs in response to an increase in RV afterload such as with PH; however, it may also be seen in hypertrophic and infiltrative cardiomyopathies. Thinning of the RV wall may occur with primary cardiomyopathy such as RV dysplasia. The thickness of the RV wall is best measured from the subcostal view at the peak of the R wave (Fig. 9-2) with care taken to distinguish the RV free wall carefully from the trabeculations, epicardial fat, and pericardium. Where possible, fundamental imaging is preferred over harmonic imaging. A true wall thickness in excess of 5 mm is considered thickened.

FIGURE 9-2 The subcostal view is used to measure RV wall thickness (arrows), which needs to be differentiated from the chamber trabeculations. This image is from a patient who has cardiac amyloidosis, with thick walls and enlarged atria, and a small pericardial effusion (PE). Ao, aorta; LV, left ventricle; RA, right atrium; SVC, superior vena cava.

RIGHT VENTRICULAR LINEAR DIMENSIONS Using two-dimensional (2D) echocardiography, the RV can be visualized in many views. However, it is recommended that the linear measures are performed from the RV-focused apical four-chamber view, preferred over the standard apical four-chamber view. To obtain the RV-focused view, the transducer is angled medially. While the LV apex remains at the apex of the imaging plane, the mitral annulus is swung outward with the tricuspid lateral annulus brought more centrally in the imaging window. This brings the whole RV into view (Fig. 9-3). From this view, three linear measurements should be obtained at end diastole (the frame when the RV is largest). The three measures are 1) the basal RV diameter, 2) the mid RV cavity diameter, and 3) the RV length. The basal diameter is not the tricuspid annular diameter but rather the maximum short-axis dimension of the basal one-third of the RV seen on this RV-focused fourchamber view. It is typically in the midportion of the basal segment. The mid diameter is measured in the middle of the RV at the approximate level of the LV

papillary muscles. The longitudinal dimension is drawn from the plane of the tricuspid annulus to the RV apex (Fig. 9-4). While the linear dimensions are prone to interstudy variation, it is particularly helpful to compare studies side by side for comparison to ensure the measurements were taken from similar views. It is also important to visually compare the RV to the LV. While the RV volume is greater than the LV volume, in the apical four-chamber view, the RV should appear approximately two-thirds the size of the LV. When the RV enlarges, it is typically the apical segments that dilate first. Hence, if the RV shares the apex in short axis with the LV, then the RV is typically at least mildly enlarged. If the RV appears as large as the LV in the apical four-chamber view, the RV is typically moderately enlarged. While views of the RV outflow tract (RVOT) can be obtained from parasternal imaging, measures particularly in the long axis are not reproducible and, hence, are not recommended. RV area measures can be taken from the RV-focused apical four-chamber view and may be of some value in a serial assessment of a patient with RV disease. While the assessment of pulmonary hemodynamics is discussed later in this chapter, the detection of RV dilatation may be the first clue to RV pressure or volume overload.

FIGURE 9-3 Right ventricular (RV)-focused apical four-chamber view (right) is preferred over the standard apical four-chamber view (left) for assessing RV chamber size. To obtain the RV-focused view, the transducer is angled medially.

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Video 9-3A

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Video 9-3B

FIGURE 9-4 (A) Schematic of linear dimension measurement of the RV, (B) RV linear dimension measurement from the RV centered apical four-chamber view. The RV length is the linear dimension taken from the midpoint of the tricuspid annular plane to the RV apex. The midchamber dimension is taken at the level of the midpoint of long axis and perpendicular to the long axis of the ventricle (center in A). The RV basal dimension is the short-axis dimension of the basal one-third of the RV (right in A).

RIGHT VENTRICULAR VOLUMES Three-dimensional (3D) echocardiography, now available on a number of commercial clinical systems, is poised to revolutionize the echocardiographic assessment of the RV (Fig. 9-5). Discussed in detail in Chapter 2, 3D volumes of the RV are feasible and reproducible and have been validated against animal specimens, cast models, as well as computed tomography– and magnetic resonance imaging–derived RV volumes. As with the assessment of LV volumes, it is important not to undermeasure RV volumes particularly due to the increased degree of trabeculation. Volume should be measured at the interface between a compacted and noncompacted myocardium to obtain the most reliable measures to reduce the degree of volume underestimation (5). Emerging data suggest that it is best to index RV end-diastolic volumes for body surface area (5,6). Guidelines suggest the upper reference limit for an index RV end-diastolic volume is 89 mL/m2, with index volume being 10% to 15% lower in women than in men (1).

FIGURE 9-5 The right ventricular end-diastolic (EDV) and end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF) can be measured with the use of semiautomated software that constructs a three-dimensional surface model after the echocardiographer defines a series of two-dimensional landmarks. A: RV 3D models from normal (left) and pulmonary hypertension (right). B: RV volume curve with calculated EDV, ESV, SV, and RVEF.

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Video 9-5A

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Video 9-5B

RIGHT VENTRICULAR SYSTOLIC FUNCTION Normal RV systolic function is a complex process with a number of contributing features, which include inherent myocardial contractility, systemic venous return determining preload, pulmonary vascular status determining RV afterload, interventricular septal contraction, and pericardial compliance. Unlike the LV, which has a significant proportion of endocardial and epicardial transverse myocardial fibers, the RV myocardial fibers are predominantly aligned in the longitudinal plane. Hence, a much greater proportion of RV contractility is longitudinal with the base of the ventricle moving down toward the apex in systole. It is this distinction that is highlighted by the value of echocardiographic measures of longitudinal motion such as tricuspid annular plane systolic excursion (TAPSE), annular peak velocity, and longitudinal systolic strain. As

RV afterload is low in the normal pulmonary vasculature and the RV wall thickness is thin, the RV stroke work in a normal patient requires only 15% to 20% of the energy expenditure of the LV. Unlike the LV, which handles changes in afterload with relative ease, the RV is highly sensitive to increases in afterload typically resulting in RV dilatation and a reduction in systolic function.

LONGITUDINAL MEASURES OF RIGHT VENTRICULAR SYSTOLIC FUNCTION TAPSE and S′ In the normal RV, the majority of contraction occurs with the base moving toward a stationary apex during systole. Hence, measurements of the longitudinal contractility serve well to reflect overall RV systolic function. Simple measures include the peak velocity of tricuspid annular motion and the absolute distance traveled in systole of the free wall tricuspid annulus. The former is measured by placing the sample volume on the lateral tricuspid annulus and measuring peak systolic forward velocity by tissue Doppler, socalled S prime or S′ (Fig. 9-6). A normal S′ velocity of the RV is greater than 10 cm/s. Similarly, placing the cursor on the tricuspid annulus and measuring the distance of systolic annular motion by M-mode provides the TAPSE. The TAPSE is measured as the vertical distance of the lateral tricuspid annulus between end diastole and end systole (7) (Fig. 9-7A). Color M-mode may be helpful to distinguish end diastole and end systole and allow measurement of TAPSE (Fig. 9-7B). Due to its simplicity and relative reproducibility, the ASE recommends TAPSE as a routine simple method of estimating RV systolic function. A lower reference value of impaired function is 16 mm (1). While these measures are relatively easy to perform, they have some limitations. Apart from the potential of poor cursor alignment, these measures are intrinsically measures of regional annular systolic function. Frequently, the RV will have regional variation in dysfunction, and it is not uncommon to see a patient with robust annular motion but relatively impaired generalized contractility. Furthermore, in the setting of normal LV contractility, frequently there will be a leftward shift of the RV apex and RV free wall leading to relatively normal S′ and TAPSE measures even in the setting of quite significant impairment of RV contractility.

FIGURE 9-6 Obtained from pulse wave Doppler sampling from the lateral tricuspid annulus, the peak systolic velocity (S′) is a measure of right ventricular longitudinal systolic function.

FIGURE 9-7 Placement of the cursor on the lateral tricuspid annulus allows measurement of the systolic distance of annular motion by M-mode, the tricuspid annular plane systolic excursion, or TAPSE. A: The TAPSE is measured as the vertical distance of the lateral tricuspid annulus between end diastole (ED) and end systole (ES). B: Color M-mode may be helpful to distinguish ED and ES and allow measurement of TAPSE.

RV Strain Imaging Two-dimensional strain imaging of the myocardium provides a regional and

global quantitative assessment of ventricular systolic motion (see Chapter 5). Automated techniques that track unique myocardial speckles, frame by frame, allow assessment of myocardial deformation. This technique, established in the assessment of the LV, has been applied more recently to the RV (Fig. 9-8). Having the advantages of angle independence and not subject to the effects of tethering, strain imaging has the capacity to measure the regional and more global free wall longitudinal contractility. Longitudinal systolic strain of the RVfocused four-chamber view should be used with a default region of interest (ROI) width of 5 mm (8). Although the interventricular septum contributes significantly to RV systolic performance, strain assessment of the septum predominantly reflects the LV, with septal strain being lower than free wall strain (9,10). Hence, assessment of the RV free wall is preferred (Fig. 9-8B) (8,9). Studies in a variety of conditions including various congenital and acquired heart diseases, most notably PH, have suggested measures of RV systolic strain may serve as measures of RV systolic performance that may predict right heart failure decompensation and outcome better than other measures including TAPSE (9,11–13). Due to the current vendor-to-vendor variation, it is recommended that serial assessment with strain imaging be performed on the same platform each time (1).

MYOCARDIAL PERFORMANCE INDEX The right ventricular index of myocardial performance (RIMP) or Tei index is a global estimation of myocardial function reflecting both systolic and diastolic function of the RV. It is a reflection of a comparison of the work of nonejection (i.e., the isovolumic time) to ejection (reflected in the ejection time). It is relatively independent of heart rate. Originally it was felt to be independent of loading conditions, but more recently, it has become clear that RIMP is unreliable in the setting of elevated RV preload. As the RA pressure (RAP) increases, particularly acutely, there is more rapid equalization of pressures between the RA and RV, which shortens the isovolumic relaxation time resulting in pseudonormalization of the myocardial performance index. Traditionally measured using the continuous-wave Doppler signals of tricuspid valve regurgitation and the systolic profile through the RVOT (Fig. 9-9), RIMP may also be measured using the pulse wave tissue Doppler profile. This has the advantage of all measures being taken from the same R-R interval. The upper normal value for RIMP by pulse wave Doppler is 0.43 and by tissue Doppler

0.54 (1), however RIMP should not be used as the singularly assessment of right heart function.

RV 2D FRACTIONAL AREA CHANGE Fractional area change, that is, the percent change in RV area as measured in the four-chamber view, provides an estimate of global RV systolic function. It has the advantage of incorporating changes in both the longitudinal and radial motion. As with area tracings, it is important to measure the compactednoncompacted myocardial interface and include the trabeculations (Fig. 9-10). An RV fractional area of change (FAC) less than 35% indicates systolic dysfunction.

RV 3D EJECTION FRACTION RV EF may be calculated accurately by 3D echocardiography (see Fig. 9-5), being extensively validated against cardiac magnetic resonance imaging. The limitations of EF include the dependency on loading conditions, the need for good image quality, and a regular rhythm as generally a multibeat acquisition is required. While demonstrated to correlate well with other measures of RV EF, the prognostic value of RV EF in many disease states is not well established. One potential reason for this might be the high prevalence of severe functional tricuspid valve regurgitation in patients with significant RV dysfunction, leading to a pseudonormalization of EF and hence an underestimation of disease severity.

FIGURE 9-8 A: Longitudinal systolic strain of the RV is obtained by applying the left ventricle strain package to the right heart in the apical four-chamber view. Care is made to ensure all segments track correctly with the three free wall segments reported separately and as an average. RV was placed in the left side of the apical image. B: Only RV free wall strain was obtained in a patient with pulmonary hypertension. RV was placed in the right side of the apical image.

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Video 9-8 FAC and EF may have particularly advantage in patients who have undergone cardiac surgery. As conventional measures of longitudinal RV systolic function, such as TAPSE, S′, or longitudinal strain tend to be reduced following pericardiotomy (14,15) and hence less well reflect systolic function. There typically is a compensatory increase in radial motion.

FIGURE 9-9 The right index of myocardial performance (RIMP) is a global measure of right ventricular function that is a ratio of the isovolumic relaxation (IVRT) and contraction (IVCT) times to the time of right ventricular ejection (RV ET). The sum of isovolumic times is calculated by the difference between tricuspid valve closure to opening time (TVCOt) taken from the continuous-wave Doppler tricuspid regurgitation profile and the RV ET from sampling of the RV outflow tract.

PULMONARY ARTERY IMAGING On transthoracic echocardiography, the main PA, bifurcation, and the proximal

portions of the left and right branches can be seen from the parasternal basal short-axis view. In this view, the main PA will be shown in long axis and is roughly perpendicular to the ascending aorta. Transesophageal echocardiography (TEE) provides a similar view and typically provides superb visualization of the main pulmonary trunk, right PA, and proximal portion of the left PA (see Chapters 3–4).

FIGURE 9-10 Tracing of RV endocardium to measure RV area during diastole (left) and systole (right).

PULMONARY VEINS Normally, four pulmonary veins (two from the right side and two from the left side) are connected with the LA, typically two upper veins and two that are lower. However, there is significant variability with the most common normal variant having three right-sided veins, with a third vein draining from the right middle lobe. Congenitally, from one to all four pulmonary veins can be connected with or drain into the right side of the heart instead of the left side. The anomalous venous connection(s) can occur in isolation or in association with other congenital defects. Although transthoracic echocardiography may be sufficient to visualize the connections of all four pulmonary veins, TEE provides better visualization of the pulmonary veins. The pulmonary veins can be seen of transthoracic echocardiography from a number of different views. The inferior veins, particularly the right inferior pulmonary vein, are well seen from the apical four-chamber view (Fig. 9-11). The best transthoracic view for visualizing the connections of all four pulmonary veins to the LA is the suprasternal short-axis view (see Fig. 1-14). Color flow imaging can help identify pulmonary vein drainage into the LA. This view is

also best for visualizing anomalous connections with the RA or SVC. One of the pulmonary veins may drain into the vertical vein, which connects with the innominate vein, and is also best seen from the suprasternal view. Color flow imaging demonstrates flow toward the transducer position in the vertical vein, next to the aorta (see Fig. 1-15C). TEE demonstrates all pulmonary veins in all patients. Pulmonary veins may be seen draining into the LA from a neutral 0-degree view with slight counterclockwise rotation to bring in the left-sided veins and clockwise rotation to see the right-sided veins. At 0 degree, typically a slight up and down or rotational movement of the probe in the esophagus, will demonstrate the upper and lower veins. To visualize the veins in the same plane, the right pulmonary veins are seen typically from a 60- to 70-degree transducer position with the probe rotated clockwise, and left-sided pulmonary veins are seen from 120 to 140 degrees with the probe rotated counterclockwise. The left upper vein is seen beside the left atrial appendage and the right upper vein beside the SVC. Doppler and color flow imaging of the pulmonary veins is useful in assessing the severity of mitral regurgitation, diastolic filling pressures, and pulmonary vein stenosis.

FIGURE 9-11 A: (Left) Color flow imaging of normal right inferior pulmonary vein, as it drains into the left atrium on transthoracic apical four-chamber view, shows red color. (Right) Color flow imaging of the right pulmonary vein shows brighter yellow and turbulent color due to mild pulmonary vein stenosis. B: Doppler demonstrates increased pulmonary vein velocities during both systole and diastole.

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Video 9-11A

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Video 9-11B

Pulmonary Vein Stenosis Pulmonary vein stenosis may be associated with congenital defects but may rarely be acquired following left atrial catheter ablation for the treatment of atrial arrhythmia particularly atrial fibrillation. Ablation in the region of the pulmonary veins may result in scarring and hemodynamically significant pulmonary stenosis (16). Actual narrowing of the pulmonary vein may be difficult to visualize with surface 2D echocardiography, but increased flow velocity from a stenotic pulmonary vein is easily recognized with color flow imaging (Fig. 9-11), followed by Doppler examination from an apical, or sometimes parasternal, view (Fig. 9-11B). All four pulmonary veins are clearly visualized, and their hemodynamics are easily assessed with TEE (17,18) (Fig. 9-12) and intraprocedural intracardiac echocardiography. Indeed, due to the increasing use of intracardiac ultrasonography and changes in ablation

techniques, there has been a reduction in the incidence of pulmonary vein stenosis.

PULMONARY ARTERY HEMODYNAMICS The determination of PA pressure is a routine part of an echocardiographic examination. Although certain 2D echocardiographic features suggest pulmonary hypertension, Doppler echocardiography is the primary method for determining actual pulmonary pressures. A comprehensive assessment of PA hemodynamics involves the assessment of systolic, diastolic, and mean PA pressures as well as integrative measures of pulmonary vascular resistance (PVR) (see Fig. 4-42) and capacitance.

PA Systolic Pressure The most frequently assessed measure of PA hemodynamics is the estimation of PA systolic pressure. Color flow and continuous-wave Doppler interrogation of the RVOT is required to exclude evidence of a Doppler gradient between the RV and the PA. In the absence of pulmonic stenosis or RVOT obstruction with a peak CW Doppler velocity of less than or equal to 1 cm/s, RV systolic pressure is equal to PA systolic pressure. Tricuspid regurgitation velocity (TRV) reflects the pressure difference during systole between the RV and the RA (see Figs. 4-19 and 4-20) (19–21). The RV systolic pressure is estimated from the simplified Bernoulli equation to estimate the transtricuspid pressure gradient. This pressure gradient between the RA and peak RV systolic pressure is acquired from the equation that is transtricuspid gradient = 4 × (peak TRV)2, which can be simplified to also be equal to (2 × peak TRV)2. The TRV usually is obtained with continuous-wave Doppler (using either an imaging duplex transducer or a nonimaging transducer) from the RV inflow or the apical four-chamber view position. From the apical position, the transducer needs to be angled more medially and inferiorly from the mitral valve signal. The PA systolic pressure is then estimated as the sum of the transtricuspid gradient and an estimation of RAP. If this is not known, it should be estimated based on the integration of the size and respiratory motion of the IVC and the Doppler profile in the hepatic veins (see below). The normal TRV is 1.7 to 2.3 m/s at rest. A higher velocity indicates pulmonary hypertension, RVOT obstruction, or pulmonic stenosis. Four different

TRV recordings are shown in Figure 9-13. TRV may be less than 2.0 m/s when RAP is markedly increased because of RV infarct, RV failure, or severe tricuspid regurgitation (Fig. 9-14). Therefore, increased TRV represents increased RV systolic pressure, not the severity of tricuspid regurgitation. TRV usually varies with respiration, being lower with inspiration, which increases the volume of tricuspid regurgitation and decreases the transtricuspid gradient. Right ventricular pressure falls much greater than right atrial pressure with inspiration (Fig. 9-15). To avoid respiratory variation, TRV usually is obtained with a patient in held expiration. As TRV increases, there is a greater potential to miscalculate PA systolic pressure by making a slight error in TRV measurements.

FIGURE 9-12 A: Transesophageal echocardiographic view (left) of the left pulmonary veins (asterisk), with stenosis of the vein on the right treated with a stent (arrows). Color flow imaging (right) shows increased flow velocity. LA, left atrium. B: Continuous-wave Doppler recorded peak pulmonary vein velocity of 1.8 m/s. Mean gradient is 10 mm Hg. C: More severe stenosis of two separate pulmonary veins with 2.9 and 1.9 m/s.

It is critically important that the “fuzz” or “beard” on the Doppler profile related to the intrinsic spectral broadening is not measured, and thereby, pressure measurement is not overestimated (see Fig. 4-21) (22). So that this can be

accomplished, it is important to ensure that the Doppler gain is not too high, the reject is turned up, and the modal signal profile, that with the maximum spectral intensity, is measured as to ensure that the true peak velocity is measured (22).

FIGURE 9-13 Representative tricuspid regurgitation velocities (2.5, 2.9, 4.3, 5.3). The numbers in parentheses are pressure gradients derived from peak velocities using the simplified Bernoulli equation.

FIGURE 9-14 Continuous-wave Doppler velocity of severe tricuspid regurgitation with its peak velocity less than 1.5 m/s.

Tricuspid regurgitation is present in more than 75% of the normal adult population and greater than 90% of patients with pulmonary hypertension (23). When the tricuspid regurgitation jet is trivial and its continuous-wave Doppler

spectrum is suboptimal, injection of agitated saline solution or echo contrast into an arm vein enhances the TRV signal (Fig. 9-16) and may aid in Doppler assessment. Recent reported data are consistent with the ASE guidelines, which state that a TRV greater than 2.8 to 2.9 m/s usually corresponds to a PA systolic pressure of approximately 36 mm Hg, assuming a RAP of 3 to 5 mm Hg (22,24). The echo assessment of PA systolic pressure may be challenging in the setting of severe tricuspid valve regurgitation (Fig. 9-14). Often in this setting, RAP will exceed 20 mm Hg that is, generally, the recommended upper limit of noninvasively estimated RAP (Fig. 9-17). Therefore, if RAP is underestimated than RV, systolic pressure will be underestimated in this setting. Furthermore, in the setting of a large effective regurgitant orifice in very severe tricuspid valve regurgitation, there can be “ventricularization” of the atrial pressures. This will render the simplified Bernoulli equation unsuitable, as the proximal velocity is no longer significantly less than the distal velocity and therefore cannot be discounted. Therefore, in torrential tricuspid valve regurgitation, the classic estimation of RV systolic pressure cannot be relied upon, and an alternative method should be considered.

FIGURE 9-15 Simultaneous continuous Doppler recording of tricuspid valve and right heart pressure tracings with inspiration (Insp) and expiration (Exp). RA, right atrium; RV, right ventricle.

Pulmonary pressures increase modestly with exercise in normal subjects (25,26). With increasing cardiac output, there is increasing transpulmonary flow and slightly higher pressure. However, in healthy high-performance athletes, the increase in cardiac output with exercise may be so significant that one may see a TR velocity in excess of 3.1 m/s without disease (27). Also, perhaps due to aging effects on the pulmonary vasculature, asymptomatic older patients may also

display a TR velocity in excess of 3.1 m/s without evidence of disease (25,26).

FIGURE 9-16 Continuous-wave Doppler recording of tricuspid regurgitation velocity without (left) and with (right) injection of agitated saline.

Right Atrial Pressure RAP is best estimated using a combination of 2D imaging of the IVC and pulsed-wave Doppler imaging of the hepatic vein (HV). The IVC is imaged in long axis from the subcostal view. Measurement of the IVC, in the setting of free breathing with a comparison of maximum and minimum dimensions, provides an insight into RAP. The normal IVC dimension is less than 17 to 20 mm and should reduce in size by at least 50% (Fig. 9-17) (1). It is recognized the IVC maybe dilated in young people. If one sees an otherwise distended IVC without other features to suggest an elevated RAP, it is advisable to reassess the IVC size and collapsibility in the left lateral position. Indeed, some advocate that the IVC should be assessed in this position in all patients. In the setting of a normal or low RAP, there is a significant systolic pressure gradient between the HV and the RA, thereby leading to a systolic predominant forward flow pattern (Fig. 9-17). As the RAP rises, the pressure gradient between the HV and RA drops leading to a diminution in systolic forward flow and an increase in systolic forward flow. A pattern of diastolic predominant forward flow suggests the presence of a high RAP (Fig. 9-17). A characteristic velocity pattern in hepatic venous flow is seen in patients with pulmonary hypertension. There is a prominent atrial flow reversal in the HV caused by increased diastolic pressure and decreased compliance of the RV. There is very little respiratory variation of atrial flow reversal in pulmonary hypertension, unlike the variation seen in restrictive cardiomyopathy or constrictive pericarditis. There is little correlation between RAP and transtricuspid gradient. Therefore, it is important to estimate RAP independent of the peak TR velocity. The echocardiographer should not

therefore assume the RAP is elevated solely because the TR velocity is high.

FIGURE 9-17 The right atrial (RA) pressure should be estimated based on an integrative assessment of the inferior vena cava (IVC) size, change in size with a sniff or inspiration, and the hepatic vein (HV) pulsed-wave (PW) Doppler profile. The HV Doppler profile has systolic (S)-predominant forward flow in the setting of normal or low RA pressure and diastolic (D) predominant when the RA pressure is high.

PA Diastolic Pressure The velocity of PV regurgitation reflects the pressure gradient between the PA and the RV. At end diastole, this velocity will reflect the end-diastolic PA-RV pressure gradient (see Fig. 4-22). As at end diastole, in the absence of TV stenosis, RV pressure should be equal to RAP. Therefore,

where PAEDP is PA end-diastolic pressure and PREDV is pulmonary regurgitation end-diastolic velocity. Because pulmonary regurgitation (PR) velocity usually reflects small pressure differences between the PA and the RV, atrial contraction with increased RV pressure creates a unique “dip” in the velocity curve. Normally, the PR enddiastolic pressure gradient is less than 5 mm Hg. An increase in this pressure gradient (>5 mm Hg) has been found to correlate with systolic dysfunction, diastolic dysfunction, increased brain natriuretic peptide, and decreased functional status (28).

Mean PA Pressure While RV systolic pressure is the most commonly measured and reported PA hemodynamic by echocardiography, the presence of PH is defined based on the mean PA pressure (mPAP), at a value greater than 25 mm Hg. The mean PA pressure can be estimated in a variety of ways by echocardiography.

mPAP by PASP There is a relatively fixed relationship between the PA systolic (PASP) and PA mean pressure across the spectrum of clinical pressures with the mPAP = (0.67 × PASP) + 0.5. If one estimates PASP by echo, then the PA mean pressure can be estimated in turn by the mean PASP equating to 2/3rd the PA systolic pressure. mPAP by Mean TR Gradient Mean PA pressure can also be estimated from the mean pressure gradient between the RA and the RV. This gradient may be measured by tracing the systolic Doppler profile of the tricuspid regurgitant jet. This is likely the most accurate mPAP pressure estimate but is dependent on a clear and complete TR systolic envelope. In this setting, mPAP = TR systolic mean gradient + RA pressure (Fig. 9-18) (29,30). As with the peak TR velocity, it is important that the denser, modal spectral profile is traced avoiding the “fuzz” on the signal (22). mPAP by PASP and PAEDP MPAP can also be obtained as PAEDP + 1/3(PASP − PAEDP). mPAP by Peak PR Velocity In the setting of a complete pulmonary regurgitant profile, the peak early diastolic PR velocity is also useful in estimating mean PA pressure (mPAP; Fig. 9-18) (31,32).

FIGURE 9-18 Mean pulmonary artery pressure (mPAP) may be estimated by the sum

of the mean systolic gradient obtained from the tricuspid regurgitation (TR) profile and the right atrial pressure (RAP) (left panel) or from the sum of the RAP and 4 × (peak PR regurgitant velocity)2 (right panel). A peak PR velocity of 3 m/s equates to an mPAP of 36 mm Hg plus RAP.

mPAP by Acceleration Time The RVOT flow velocity has a characteristic pattern as PA pressure increases (Fig. 9-19). The acceleration phase becomes shorter with increased PA pressure. Several investigators have derived regression equations to estimate MPAP from the RVOT acceleration time (AcT) (33). Mahan’s equation is the simplest and preferred for estimating mPAP:

It should be noted that AcT is dependent on cardiac output and heart rate (34,35). With increased output through the cardiac chambers on the right side (as in atrial septal defect), AcT may be normal even when PA pressure is increased. If the heart rate is slower than 60 beats per minute or more than 100 beats per minute, AcT needs to be corrected for heart rate. This method is less accurate than the other methods discussed above, and we do not recommend that it be used in our practice.

FIGURE 9-19 Right ventricular outflow tract (RVOT) flow velocity recordings by pulsed-wave Doppler echocardiography. The sample volume is placed in the region of the pulmonary valve annulus. Left: Normal flow pattern. Acceleration time (AcT) is the time interval between the beginning of the flow and its peak velocity (between the two vertical arrows). It is 130 ms (normal, ≥120 ms). Right:Flow velocity in pulmonary hypertension. The arrow indicates peak RVOT velocity with a short AcT. AcT is

shortened to 40 milliseconds. Mean pulmonary artery pressure = 79 − (0.45 × 40) = 61 mm Hg, using Mahan’s regression equation.

CAVEATS IN PULMONARY ARTERY PRESSURE CALCULATION The accuracy of the PA pressure estimation is greatly determined by the quality of the echocardiogram. As with all Doppler data, the accuracy is only as good as the quality of the data. Assessment is required from multiple windows to ensure the signals are obtained as close as possible to parallel to flow. Hence, PA pressure estimate is not recommended by TEE as it is unusual to be able to obtain the appropriate windows where one can align the Doppler interrogation parallel to the direction of flow. Either poor alignment or an incomplete Doppler profile will lead to an underestimation of pressure. Alternatively, PA artery pressure may be overestimated if an overgained signal is traced or in the presence of pulmonary valve stenosis. While it is usually appropriate to use the simplified Bernoulli equation, there are times when this becomes invalid such as states of increased blood viscosity or when there is torrential tricuspid valve regurgitation. Accurate assessment of RAP is also key to accurately estimate pulmonary pressure. Finally, it is important to recognize that pulmonary pressure is not a static variable. Patients with implantable PA monitors have taught us that pulmonary pressures vary dramatically during the day, particularly in patients with PH (36). Pulmonary pressures vary with activity levels, various therapeutic interventions, and hypoxia and in patients with left heart disease changes with systemic blood pressure.

RVOT DOPPLER PROFILE While the AcT of the RVOT Doppler profile does not provide an accurate estimate of PA pressure, the pattern of this profile provides helpful insight into the PA hemodynamics. The distinct Doppler pattern with a notch in the systolic profile, often referred to as the “W sign” of pulmonary hypertension, is the Doppler correlate of high RV afterload. This distinct pattern suggests a compromised pulmonary vascular bed with high resistance. The early time to peak of the profile tends to correlate with elevated PA pressure with reflectance waves from the vascular bed impeding systolic forward flow leading to

midsystolic notching (37). The deceleration time is inversely proportional to the elevated PV resistance. As the pulmonary vascular disease advances and the right heart fails, the late systolic flow profile becomes increasing diminutive. These distinct profiles (Fig. 9-20) have been found to associate to outcome in PAH and may be useful in determining the presence of pulmonary vascular disease in patients at risk (37).

FIGURE 9-20 Pulsed-wave Doppler interrogation of the right ventricular outflow tract provides insight into pulmonary artery hemodynamics. Flow through the right ventricular outflow tract in the normal setting has a symmetrical parabolic shape (1). As the pulmonary pressures increase, (2) the profile has a shortening of the time until the peak velocity. With elevated pressures and resistance in the pulmonary vascular bed, the profile takes on the distinct pattern with a systolic notch, often referred to as the “W sign” of pulmonary hypertension (3). As the pulmonary vascular disease advances and the right heart fails, the late systolic flow profile becomes increasingly diminutive (4).

Pulmonary Vascular Resistance PVR is an important hemodynamic variable in the management of patients with severe heart failure or congenital heart disease and in the evaluation of candidates for cardiac transplantation. Traditionally, PVR is obtained by cardiac catheterization, with the use of the following formula:

where PCWP is pulmonary capillary wedge pressure and CO is cardiac output. A few attempts have been made to estimate PVR with Doppler (29,38,39) and color M-mode (40) echocardiography. The simplest Doppler method for estimating PVR is to divide TRV by the RVOT time velocity integral (TVI) and

multiplying the result by 10.

Although the actual regression formula (29) is more complex, this simple method provides a reasonable estimate of PVR. A cutoff value of 2 for 10 (TRV/RVOT TVI) separates a group with PVR greater than 2 Wood units. Shandas and colleagues used color M-mode–derived propagation velocity of the PA flow to estimate PVR (40). The slope of the aliasing line on the color Mmode of the main PA flow decreases as PVR increases. However, we do not advocate that the echo-derived equation for PVR be used as a substitute for the invasive assessment of PVR as it does not have the precision to make important clinical decisions (22,24). However, incorporating echo-PVR into the comprehensive evaluation of the patient with known or suspected pulmonary vascular disease is of merit. Echo-PVR may help explain situations where PA systolic pressure is increased due to high flow (e.g., in the setting of high output heart failure from anemia, obesity, or hyperthyroidism) or in advanced right heart failure or torrential TR when PA systolic pressure falls due to low stroke volume. It is also important to highlight that the echo-PVR equation while correlating with cath-PVR reflects total PVR rather than pulmonary arteriolar resistance as it does not incorporate a measure of pulmonary capillary wedge pressure.

Pulmonary Vascular Capacitance Pulmonary arteriolar capacitance measures the capacity for the pulmonary arteriolar tree to dilate with RV contraction and therefore inversely reflects the dynamic workload of the right heart. PAC can be approximated by dividing the stroke volume by the PA pulse pressure (41). By echo, the PAC is calculated as the SV/4 × (TRvel2 − PRvel2). PAC as measured invasively or noninvasively has been shown to be associated with all-cause mortality in patients with pulmonary vascular disease (41).

DETERMINATION OF TYPE OF PULMONARY HYPERTENSION BY ECHOCARDIOGRAPHY Pulmonary hypertension is classified into five groups based on its underlying

cause (42): Group 1 = pulmonary arterial hypertension, Group 2 = due to left heart diseases (aortic or mitral valve disease as well as HFPEF), Group 3 = due to lung disease and/or hypoxia, Group 4 = due to chronic thromboembolic pulmonary hypertension and other PA obstructions, and Group 5 = due to an unclear and/or multifactorial mechanisms. After echocardiography has established that PA pressure is increased, the potential causes of this increase should be evaluated thoroughly with 2D, Doppler, and color flow imaging. From the perspective of either echocardiography or catheterization, pulmonary hypertensive disorders can be separated as either precapillary or postcapillary. Precapillary PH conditions are those characterized by an elevated PA pressure in the setting of a normal pulmonary venous pressure (e.g., pulmonary arterial hypertension, PH secondary to hypoxic or parenchymal lung disease, chronic thromboembolic PH). This is in contrast to postcapillary (Group 2) conditions related to left-sided abnormalities (e.g., LV systolic or diastolic dysfunction, severe left-sided valve stenosis or regurgitation). Most left-sided abnormalities that may give rise to significant PH are easily identified by transthoracic echocardiography, although distinguishing pulmonary arterial hypertension from patients with heart failure with preserved EF and advanced PH can be challenging. In heart failure with preserved EF, approximately 80% of patients have elevated pulmonary pressures, the majority of whom tend to have modestly elevated pressures that are proportionate to the degree of left atrial hypertension. These patients tend to have a wider PA pulse pressure. However, approximately 20% of patients with heart failure with preserved EF have pulmonary pressures out of proportion to left atrial hypertension, have an elevated PVR at cardiac catheterization, and tend to have enlarged and dysfunctional RVs (43). This is the subgroup that can be quite challenging to characterize by echocardiography as they have hemodynamic features of both precapillary and postcapillary disease. The noninvasive assessment of whether the patient may have PH in the setting of HFpEF or PAH should be an integration of the presence of clinical features such as increased age, systemic hypertension, diabetes, atrial fibrillation, episodes of pulmonary edema, and various echocardiographic findings (Table 9-1). Some have proposed simple clinical and echocardiographic scores to diagnose HFpEF (44) and to identify the mechanism of PH in these patients (45). Scalia and colleagues have proposed a simple echocardiographic parameter, to aid in the differentiation of precapillary from postcapillary pulmonary hypertension. The echocardiographic pulmonary to left atrial ratio (ePLAR) is calculated as the maximum continuous-wave Doppler tricuspid

regurgitant peak velocity (m/s) divided by the E/e′ ratio (46). A normal ePLAR is approximately 0.30. Patients with postcapillary PH tend to have values of 0.25 or lower and those with precapillary PH over 0.40 (46). Finally, it should be recognized that in some series, up to 50% of patients with a pulmonary capillary wedge pressure in excess of 25 mm Hg (i.e., HFpEF) have a normal resting pulmonary capillary wedge pressure, and hence, assessment of LV filling pressures both at rest and with exercise, either by echocardiography or hemodynamic catheterization, should be considered in patients with suspected HFpEF (47–49). TABLE 9-1 Mayo Clinic Pulmonary Hypertension Protocol Echocardiography In addition to the standard transthoracic echocardiogram, the protocol has the following components. Inclusion criteria

Referral for: The evaluation of known or suspected pulmonary hypertension (e.g., scleroderma, liver disease, HHT) Finding of TR velocity ≥ 3.5 in the absence of left-sided disease

CW Doppler through RVOT

Exclude pulmonary stenosis Measurement of end PR (diastolic PA pressure) Measurement of peak PR (mean PA pressure)

PW Doppler of RVOT

Appearance and presence of notching RV outflow tract time velocity integral

CW Doppler of TR

Peak velocity (systolic PA pressure) Mean gradient (mean PA pressure)

Four-chamber view of RV

RA—monoplane Simpson’s TAPSE Tissue Doppler—S′

RV-focused Apical four-chamber view

RV dimensions: base, mid, and length RV area and fractional area change RV global longitudinal strain RV 3D volumes and ejection fraction

Subcostal

IVC 2D and hepatic vein PW Doppler—to assess RA pressure

Agitated saline bubble study performed

At time of first study Q 6 months in patients with advanced liver disease or HHT When hypoxia refractory to supplemental oxygen develops

Pulse oximetry

Performance of echo on usual resting oxygen prescription Oxygen saturation measured and reported

2D, two-dimensional; 3D, three-dimensional; CW, continuous wave; HHT, hereditary hemorrhagic telangiectasia; PA, pulmonary artery; PR, pulmonary regurgitation; PW, pulse wave; RA, right atrium; RV, Right Ventricle; S′, peak systolic tissue Doppler velocity; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.

Mitral Inflow Velocity Pattern in Pulmonary Hypertension Pulmonary pressure usually is increased in patients with increased LV filling pressures. When LV filling pressures are increased, the mitral inflow velocity pattern becomes restrictive (↑E velocity, ↓A velocity, E/A > 2.0, and ↓deceleration time). Therefore, it is probable that pulmonary hypertension is related to a precapillary process if mitral inflow shows a nonrestrictive diastolic filling pattern (50). RV pressure overload may induce LV filling abnormality because of the shift of the ventricular septum. A delayed relaxation pattern is common in patients with advanced precapillary right heart disease, correlates with RV enlargement and dysfunction, and has been shown to predict poor outcome (50). In patients with chronic obstructive pulmonary disease, mitral inflow velocity may demonstrate a respiratory variation similar to the degree of variation seen in constrictive pericarditis; however, the respiratory change in SVC systolic forward flow velocities is 20 cm/s or less in constriction and is much higher or even monophasic with inspiration in chronic obstructive pulmonary disease. In diseases that affect the right heart but spare the left, for example, idiopathic pulmonary arterial hypertension, intrinsic LV myocardial relaxation should be normal, reflected by normal lateral annular e′ velocities. However, as the medial annulus reflects septal relaxation, e′ velocities may be reduced in advanced right heart disease as they are influenced by both RV and LV disease (51).

ASSESSING SEVERITY OF PULMONARY HYPERTENSION BY ECHOCARDIOGRAPHY

All patients with known or suspected pulmonary hypertension should have a comprehensive echocardiogram with assessment of pulmonary pressures and right heart size and function (Table 9-1). The degree of right heart enlargement and dysfunction is a key marker of pulmonary hypertension severity. In patients with advanced pulmonary hypertension, the right heart dilates, the interventricular septum shifts to the left, and the LV tends to be smaller and underfilled (Fig. 9-21). In short axis, the D-shaped LV cavity and enlarged RV cavity are typical findings in PH. A similar appearance is also seen in RV volume overload; however, flattening of the ventricular septum persists during the entire cardiac cycle in RV and PA pressure overload, but it disappears during systole in RV volume overload. A pericardial effusion may be seen, typically reflecting a chronic elevation in central venous pressure (Fig. 9-22) (52). Some have advocated a definition of PH severity based solely on the degree of pressure elevation, for example, mild PH (RV systolic pressure 40–55 mm Hg), moderate (55–70 mm Hg), and severe (RV systolic pressure >70 mm Hg). However, this is not recommended. While the presence of pulmonary hypertension is universally associated with worse prognosis, regardless of type, the degree of pressure elevation in those with PH is poorly associated with outcome (53). To assess the severity of pulmonary hypertensive disorders, the echocardiographer, and clinician, must integrate the degree of pressure elevation with the state of the right heart. As pulmonary hypertensive disorders progress, the pulmonary pressures rise initially but then plateau and ultimately decline. These latter changes relate to a decline in right heart function. Those with decompensated, end-stage right heart failure will have much lower pulmonary pressures than those with compensated right heart function. Hence, the degree of pulmonary pressure elevation, in isolation, does not reflect the severity of disease well. Many echocardiographic variables have been associated with poor outcome in patients with pulmonary hypertension (Table 9-2), and these parameters should be measured and reported in patients referred for echocardiography; however, PA pressures, while important in the assessment of a patient with PH, do not define severity well (11,37,52–54).

ACUTE COR PULMONALE AND PULMONARY EMBOLISM

Transthoracic Echocardiography In patients who develop acute severe cor pulmonale (e.g., secondary to a large pulmonary embolus), the right heart chambers are dilated, and the LV is relatively small and hyperdynamic with the ventricular septum deviated to the left because of increased RV pressure (Fig. 9-23). In this acute setting, the RV is unable to adapt and generate a systolic pressure much higher than 60 mm Hg. The flow pattern through the RVOT typically is early peaking and notched, and the RV often has a characteristic pattern of generalized severe hypokinesis with relative sparing of the RV apex (McConnell’s sign) (55). While initially felt to be specific for the echocardiographic findings in acute pulmonary embolus, McConnell’s sign sign may be seen in the setting of many different etiologies of acute cor pulmonale including sepsis, acute respiratory distress syndrome, and pulmonary hemorrhage. Strain studies have suggested the RV apex is actually also dysfunctional and only appears normal due to a tethering effect from the hyperdynamic LV apex (56).

FIGURE 9-21 A: (Left) Parasternal short-axis view demonstrating the D-shaped left ventricular (LV) cavity and enlarged right ventricular (RV) cavity in pulmonary hypertension. A similar appearance is seen in RV volume overload; however, flattening of the ventricular septum (VS) persists during the entire cardiac cycle in RV and pulmonary artery pressure overload, but it disappears during systole in RV

volume overload. (Right) Corresponding pathology specimen. B: In the normal patient (left), the right ventricle (RV) appears in short axis as a cresentic chamber that wraps anteriorly around the circular left ventricle (LV). In the apical four-chamber view, the RV appears smaller than the LV. In the patient with pulmonary hypertension (right), the RV and right atrium (RA) enlarge with the RV taking on a more oval appearance in short axis and the interventricular septum shifting leftward. LA, left atrium.

FIGURE 9-22 Parasternal long-axis view in a patient with advanced pulmonary hypertension, demonstrating right ventricular (RV) hypertrophy (increased RV wall thickness between arrows), RV enlargement, interventricular septum shifted to the left, a small left ventricle (LV), and a circumferential pericardial effusion (PE).

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Video 9-22

TABLE 9-2 Echocardiographic Factors in the Setting of Pulmonary Hypertension that Favor Pulmonary Arterial Hypertension Versus Those that Favor Pulmonary Hypertension in the Setting of Heart Failure with Preserved Ejection Fraction Echo Variables

PAH

HFpEF-PH

Left atrial size

Normal

Enlarged

LV mass

Normal

Increased

RA/LA size ratio

RA >> LA

LA > RA

Intra-atrial septum

Bows to left

Bows to right

Mitral inflow pattern

Delayed relaxation pattern

Restrictive

Medial E′

Maybe low

Low

Lateral E′

Normal

Low

ePLAR (TRVmax/E:e′)

>0.30

50 mmHg, then no provocation maneuvers need to be performed. If the gradient is 50 mm Hg is not present with Valsalva, then provocative testing such as amyl nitrite or squat-tostand maneuver is pursued. LVOT obstruction in HCM is dynamic and depends on LV loading conditions and contractility, with gradient varying on a minute-tominute basis (58,59).

FIGURE 10-14 Apical long-axis view demonstrating midcavitary obstruction (*) in the setting of thickened left ventricular (LV) walls and papillary muscle hypertrophy.

Mitral Regurgitation Mitral regurgitation frequently accompanies the obstructive form of HCM. Typically, the jet is directed posterolaterally (Fig. 10-18). The presence of a more central or anterior jet should raise suspicions of concomitant organic mitral valve disease (Fig. 10-19), which is present in 10 to 15% of HCM patients. Temporally, mitral regurgitation occurs after the onset of LVOT obstruction: ejection→obstruction→leak. It produces a high-velocity jet away from the apex, which can be confused with the LVOT velocity. Flow duration and Doppler spectral configuration help to differentiate mitral regurgitation from LVOT obstruction. Color flow imaging helps to separate the mitral regurgitation from LVOT flow and to guide the continuous-wave Doppler beam. Color flow imaging is also the best method for assessing the severity of mitral regurgitation. The peak velocity of the mitral regurgitant jet can also be used to determine the magnitude of LVOT obstruction, for example

FIGURE 10-15 Two-dimensional echocardiograms of apical HCM with (right) and without (left) contrast administration. The apical wall thickness is markedly increased (arrows on left), and the apical cavity is nearly obliterated except for a small slit (*) during systole which is better seen with contrast administration (right). LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

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Video 10-15A

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Video 10-15B

FIGURE 10-16 Continuous-wave Doppler spectra obtained from the apex demonstrating dynamic left ventricular (LV) outflow tract obstruction. Note the typical late-peaking configuration resembling a dagger or ski slope (left and right, arrow). The baseline (left) velocity is 2.8 m/s, corresponding to the peak LV outflow tract gradient of 31 mm Hg (=4 × 2.82). With the Valsalva maneuver (right), the velocity increased to 3.5 m/s, corresponding to a gradient of 50 mm Hg.

FIGURE 10-17 Continuous-wave Doppler recording of a patient with HOCM with LVOT velocity 2.5 to 3 m/s during a regular sinus rhythm, increased to 5.5 m/s after a ventricular ectopic beat (arrow).

Diastolic Filling Pattern and Tissue Doppler Imaging The predominant diastolic abnormality in HCM is markedly impaired myocardial relaxation due to the hypertrophied myocardium (60). Some degree of diastolic dysfunction is present in virtually all patients with HCM. However, noninvasive assessment of LV filling pressures in HCM can be challenging. Because the decrease in LV pressure after aortic valve closure is slower, isovolumic relaxation time (IVRT) is prolonged, early rapid filling (E) is reduced, DT is prolonged, and atrial filling (A) is increased as long as left atrial pressure is not elevated. Atrial contraction contributes significantly to LV filling during an early stage of diastolic dysfunction. If atrial contraction is compromised because of tachycardia or atrial fibrillation, cardiac output decreases and pulmonary venous congestion can occur. As the LV becomes less compliant and LA pressure increases, early filling gradually increases and DT decreases; however, the same degree of increase in LA pressure does not produce similar shortening of DT in patients with HCM as it does in those with DCM, because DT is markedly prolonged at baseline. Hence, there is no significant correlation between DT and LV filling pressures in patients with HCM (61). Mitral annulus e’ velocity is also markedly reduced so that E/e’ ratio can be falsely elevated when LV filling pressure is not elevated. On the other hand, LV filling pressure is almost always normal when E/e’ is 7 cm/s). Strain imaging findings are normal (85). Left atrial size is typically normal or minimally dilated. Marked resting SAM should not be present.

Occasionally, it is difficult to differentiate HCM from hypertrophy caused by hypertension. Nunez and colleagues (84) demonstrated that a global function index (GFI) is useful in distinguishing them:

where E is mitral early diastolic flow velocity, e′ is mitral annulus early diastolic velocity, and S′ is mitral annulus systolic velocity. A GFI greater than 1.77 was found to support the diagnosis of HCM.

RESTRICTIVE CARDIOMYOPATHY Primary RCM is characterized by restricted ventricular filling resulting from an idiopathic nonhypertrophied myocardial abnormality (i.e., stiffening fibrosis, decreased compliance, or both) (6). Ventricular systolic function usually is well preserved in the initial stage, but diastolic pressure is elevated, which in turn results in increased atrial pressures and marked biatrial enlargement. Therefore, the characteristic morphologic features of primary RCM on 2D echocardiography include ventricular cavities of normal size; normal wall thicknesses, relatively preserved global systolic function (but this can vary), and biatrial enlargement (Fig. 10-25A). The most common RCM is cardiac amyloidosis (see Chapter 18). The typical hemodynamic feature of RCM is the dip-and-plateau, or “square root sign”, configuration in the ventricular diastolic pressure tracing (Fig. 10-26). This hemodynamic feature produces a shortened DT of early rapid filling (E) on mitral inflow Doppler (Fig. 10-25B). With the increase in LA pressure, the mitral valve opens at a higher pressure, resulting in a decrease in IVRT. High atrial pressure also results in an increased transmitral pressure gradient, increased mitral E velocity, and decreased systolic pulmonary venous flow velocity (Fig. 10-25D). Because of high ventricular pressure at end diastole, atrial contraction does not contribute significantly to ventricular filling,

and the A velocity is usually decreased. As a result, the E/A ratio is markedly increased (>2.0). Because of the increase in atrial pressure, venous flow velocity decreases during systole and increases with diastole. In contrast to constrictive pericarditis, hepatic vein diastolic flow reversals are greater during inspiration (Fig. 10-26E). Myocardial relaxation is universally impaired, so the mitral annulus e′ velocity is usually less than 7 cm/s (when obtained from the septal annulus) (Figure 10-25C) (86).

FIGURE 10-25 A: Apical four-chamber view of a typical case of RCM with low-normal left ventricular (LV) cavity size, normal LV ejection fraction, and marked biatrial enlargement. B: Mitral inflow pulsed-wave Doppler velocity recording shows a restrictive filling pattern with E velocity of 80 cm/s and A velocity of 20 cm/s (E/A = 4) along with a very short deceleration time of 140 ms. C: Mitral annulus tissue velocity recording demonstrating e of 4 cm/s indicating a marked reduction in myocardial relaxation, characteristic of myocardial disease. D: Pulsed-wave Doppler of the pulmonary vein shows diastolic (D) predominance with a short deceleration time (arrow). E: Hepatic vein pulsed-wave Doppler shows a marked diastolic flow reversal (arrow) with inspiration. Forward flow velocity (below the baseline) is also increased with inspiration, which increases venous return. This is in contrast to enhanced diastolic flow reversals with expiration, seen in constrictive pericarditis (Chapter 12). F: Strain imaging from a patient with RCM. Strain decreases at the basal segments first and then progresses to mid and apical segment. LA, left atrium; RA, right atrium;

RV, right ventricle.

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Video 10-25 Typical Doppler features in RCM are as follows: 1. Mitral (M) and tricuspid (T) inflow Increased E velocity: M >1 m/s, T >0.7 m/s Decreased A velocity: M 5 mm) or myxomatous. If a stricter definition of mitral valve prolapse is used, the prevalence (1.7%–2.4%) is not as high as previously reported (61,62). The classic pattern of mitral valve prolapse has been associated with an increased risk of endocarditis, severe mitral valve regurgitation, and mitral valve repair or replacement (61–64). Auscultatory findings are not adequate to identify a high-risk group of patients with mitral valve prolapse. The myxomatous feature of mitral valve prolapse most likely represents a biochemical defect involving connective tissue. According to a review of 833 patients in Olmsted County, Minnesota, who had mitral valve prolapse, they were a generally healthy population with a mean age of 47 years (65). Also, most of them had a normal ejection fraction, and 8% had atrial fibrillation. The 10-year cardiovascular mortality rate was 9% ± 2%; the most

powerful predictor was moderate to severe mitral regurgitation, followed by an LV ejection fraction less than 50%. A recent cardiac magnetic resonance imaging study found focal myocardial fibrosis with late gadolinium enhancement in about half of the mitral valve prolapse study patients (65a). We need more studies to see whether focal myocardial fibrosis has any significant association with arrhythmia or a poor clinical outcome.

FIGURE 13-32 Classification of mitral regurgitation. (Reprinted from El Sabbagh A, Reddy YNV, Nishimura RA. Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions. JACC Cardiovasc Imaging, 2018;11(4):628–643. Copyright © 2018 by the American College of Cardiology Foundation. With permission.)

Mitral valve becomes flail when its leaflet tip point to the LA during systole due to lengthening and/or rupture of the supporting chordae (Fig. 13-33B). It is usually associated with severe MR although nonsignificant MR has been observed in 14 of 706 (2%) patients (66) and MR severity did not progress in all but one. This is the most frequent etiology of MR for mitral valve repair. Although there is still a controversy regarding its management in asymptomatic patients with severe MR due to flail mitral valve, the recent data overwhelmingly support earlier repair robotically or by an open-heart surgery before they develop LV dysfunction or atrial fibrillation (67,68). One of the reasons for an early repair is the ability of transthoracic and TEE to diagnose the condition and monitor the surgical result intraoperatively (Chapter 23). With

increasing transcatheter intervention strategies for mitral valve, echocardiography is an essential tool in the interventional or hybrid suite (Chapter 22).

Functional Mitral Regurgitation Mitral regurgitation caused by regional or global LV remodeling without structural abnormalities of the mitral valve is termed functional mitral regurgitation. It is frequent and causes increasing clinical symptoms in ischemic (type 3B) or dilated cardiomyopathy (type 1). The functional regurgitant jet is usually central in nonischemic cardiomyopathy or dilated mitral annulus. However, its jet can be eccentric in patients with ischemic cardiomyopathy usually with tethering of one leaflet (Fig. 13-33F and G). When mitral valve tenting area comitral leaflet is tethered, the mitral valve is more tented (Fig. 1334), and a tenting area of 6 cm2 or more usually indicates grade 3 or higher mitral regurgitation (69).

FIGURE 13-33 A: Left: Parasternal long-axis view demonstrating posterior mitral valve prolapse (arrow) with the leaflet 5 mm below the annulus (dotted line) Right: Color flow imaging shows eccentric mitral regurgitation toward the aorta. B: A composite of parasternal long-axis (upper left), TEE 3D (upper right), and apical longaxis 2D (lower left) image of flail posterior (P3) mitral leaflet (arrows), and color flow imaging of mitral regurgitation (arrow) with PISA (lower right). C: A composite of parasternal long-axis 2D (upper left), color flow imaging (upper right), short-axis view (lower left), and 3D TEE view (lower right) of a cleft in the anterior mitral leaflet

(arrow) with severe mitral regurgitation. D: (Left) 2-D TEE view of calcific mitral leaflets (arrows) with color flow imaging (right) showing severe regurgitation. E: Perforation of posterior mitral leaflet shown by 2-D (arrow in left) and 3-D (arrow in right) TEE. F. Parasternal long axis view of the same patients as in E showing perforation (arrow in left) with severe eccentric mitral regurgitation (right). G: Apical four-chamber view demonstrating restrictive cardiomyopathy, annulus dilation, and severe mitral regurgitation. H: Transthoracic apical four-chamber view showing tethered posterior mitral leaflet (arrow) and severe functional mitral regurgitation. The patient has inferior wall motion abnormality. I: A systolic frame of transthoracic 3D echocardiography of the mitral valve with a gap (arrows) between anterior and posterior leaflets due to tethered posterior leaflet. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; Ao, aorta.

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Video 13-33A

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Video 13-33B

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Video 13-33C

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Video 13-33D

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Video 13-33E

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Video 13-33F

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Video 13-33G

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Video 13-33H

FIGURE 13-34 A: Diagram of the mitral valve apparatus. B: Tenting area (T) from an apical view, defined as an area with boundaries of the mitral annulus (X – X) and two mitral leaflets. LA, left atrium; LV, left ventricle.

STICH trial demonstrated long-term outcome benefit of performing additional mitral valve procedure at the time of coronary artery bypass surgery in patients with ischemic cardiomyopathy (70). However, there was no significant benefit from mitral valve procedure in patients with moderate degree of MR (71). However, it is difficult to standardize determination of MR severity since there are many parameters to analyze and some of them may provide a discordant result. Moreover, there is a confusion over what is the most objective and quantitative criteria for severe function MR with different recommendations (see below) from the American College of Cardiology and European Society of Cardiology (2,3).

Semiquantitative Assessment of MR Severity Color flow imaging, although qualitative, is the most practical initial method to assess the severity of mitral regurgitation. When the area of the turbulent regurgitant jet is more than 40% of the LA area or reaches the posterior wall of the LA, mitral regurgitation is usually severe (53). The area of the regurgitant jet relative to the size of the LA (Fig. 13-35) is most closely related to the regurgitant severity determined with angiography. Color flow imaging of valvular regurgitation depends on the gain setting, pulsed repetition frequency, field depth, direction of jet, and loading conditions. Adjacent cardiac walls influence the size of the regurgitant color flow if the regurgitant jet is eccentric. A flow jet directed against the atrial wall appears smaller than a free jet of the same regurgitant volume (Coanda effect).

Therefore, the size of the jet seen on color flow imaging should be interpreted in the context of jet geometry and the surrounding solid boundaries (72). Color flow jet area usually overestimates MR severity when it is central\in dilated cardiomyopathy (73) and underestimates it when it is eccentric.

FIGURE 13-35 Diagrams of color flow imaging of mitral regurgitation from apical fourchamber view (upper and lower left) and parasternal long-axis (upper right) and shortaxis (lower right) views. Left atrial area (LAA) and regurgitant jet area (RJA) are measured by planimetry. Ao, aorta; AV, aortic valve; H, height; L, length; LA, left atrium; LV, left ventricle; MV, mitral valve; PA, pulmonary artery; RA, right atrium; RV, right ventricle; TV, tricuspid valve; W, width. (Redrawn from Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation, 1987;75(1):175–183. Used with permission.)

FIGURE 13-36 Mitral inflow (left) and continuous-wave Doppler velocity (right) of severe mitral regurgitation (MR). Mitral inflow deceleration time is 120 milliseconds, and MR peak velocity is 3.5 m/s (equivalent to a transmitral systolic gradient of 49 mm Hg). This was obtained from a patient with cardiogenic shock due to severe MR and severe left ventricular systolic dysfunction. Pulmonary capillary wedge pressure was 54 mm Hg, and systolic blood pressure was 100 mm Hg.

In mitral regurgitation, antegrade flow (mitral inflow) velocity increases with severe regurgitation (E velocity is usually >1.2 m/s in severe MR) (Fig. 13-36), and the continuous-wave Doppler velocity of mitral regurgitation tends to be lower (5 m/s or mitral valve area ≤1 cm2, rapid progression, ventricular dysfunction, or ventricular dilation), valvular intervention is recommended. The cutoff values for LV dilation, LVEF, and RV measurement continue to be revised. The current guideline recommends 50% as the cutoff for aortic regurgitation and aortic stenosis, but the most recent data indicate that the clinical outcome in aortic stenosis patients with LVEF less than 60% is worse compared to the patients with LVEF ≥ 60% (30,31). Whether asymptomatic patients with LVEF less than 60% do better with an earlier surgery will require more clinical investigations or trials. The underlying myocardial fibrosis in patients with valvular heart disease can be better evaluated by cardiac MRI and strain imaging. Many have reported that abnormalities in cardiac MRI and strain imaging are associated with a poor clinical outcome in patients with valvular heart disease, and again, it will require more clinical experience to see whether those newer imaging modalities can improve in deciding optimal timing of valvular intervention in asymptomatic patients. Currently, the timing of surgery is usually determined on the basis of echocardiographic findings at rest and with exercise along with clinical symptoms in most patients.

FIGURE 13-56 Automatic 3D PISA extraction, visualized as green overlay on a 3D color Doppler image (top three reference planes: left, four-chamber view; center, twochamber view; right, short-axis view) and 3D-rendered PISA in the volume-rendered image (bottom left). ERO, Effective regurgitant orifice. (Reprinted from de Agustin JA, Viliani D, Vieira C, et al. Proximal isovelocity surface area by single-beat threedimensional color Doppler echocardiography applied for tricuspid regurgitation quantification. J Am Soc Echocardiogr, 2013;26(9):1063–1072. Copyright © 2013 American Society of Echocardiography. With permission.)

FIGURE 13-57 A: Transthoracic basal short-axis view (left) with color flow imaging demonstrating mild pulmonary regurgitation jet (arrow) and (right) continuous-wave Doppler recording shows characteristic configuration of mild pulmonary regurgitation. The jet occupies a third of the RV outflow tract (RVOT), and there is no diastolic flow reversal in the pulmonary artery (PA). B: (Left) Color flow shows a laminar diastolic flow occupying the entire width of the RVOT along with diastolic flow reversal in the pulmonary artery (arrow) consistent with severe pulmonary regurgitation. (Right) Pulsed-wave Doppler shows a rapid deceleration time (arrow) of pulmonary regurgitation flow characteristic of severe pulmonary regurgitation. C: Continuouswave Doppler across the pulmonic valve demonstrates rapid deceleration (downward arrow) and diastolic forward flow (upward arrow) with premature opening of the pulmonic valve.

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Video 13-57

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CHAPTER

14

Prosthetic Valve Evaluation Lori A. Blauwet, Fletcher A. Miller, and Jae K. Oh

Valve replacement is frequently required for severe valvular heart disease, although valve repair is increasingly performed for a regurgitant lesion. It is estimated that more than 280,000 prosthetic heart valves are implanted worldwide each year. As the world’s population is aging, the incidence of prosthetic heart valve implantation and the prevalence of prosthetic heart valves continue to increase. Assessing heart valve prosthesis function remains challenging, as prosthesis malfunction is unpredictable but not uncommon. Echocardiography has become the primary tool for assessment of patients with prosthetic heart valves, particularly for the detection of complications. Prosthetic valves are broadly classified as either biological or mechanical (Fig. 14-1). A heterograft is a biological prosthesis consisting of either a porcine valve or bovine pericardial tissue attached to a metal frame. Homografts and allografts are human valves. Mechanical valves are constructed from nonbiologic material (e.g., pyrolytic carbon, polymeric silicone substances [silastic], or titanium) in a ball-cage, single leaflet or bileaflet design. Biologic transcatheter valves, the newest class of prosthetic valves, currently attach either bovine pericardial tissue or bovine jugular vein to metal frame. Blood flow characteristics, hemodynamics, durability, and thromboembolic tendency vary depending on the type and size of each prosthesis and, more importantly, on the characteristics of the patient. Because prosthetic valves are inherently stenotic and may produce additional prosthetic sounds caused by ball movement or disk closure, it can be challenging to distinguish between abnormal and normal prosthetic valve sounds by physical examination. The evaluation of prosthetic valves requires a thorough knowledge of the unique design and hemodynamic profile of each type of prosthesis. Assessing prosthetic valve function with two-dimensional (2D) transthoracic echocardiography (TTE) is challenging due to acoustic shadowing, particularly with mechanical prostheses. Spectral Doppler and Doppler color flow imaging are essential for assessment of prosthetic valve function. Transesophageal

echocardiography (TEE) may be necessary if TTE findings suggest abnormal prosthesis function. 3D TEE has been particularly helpful for locating the mitral prosthetic regurgitant region and guiding transcatheter replacement or plugging paravalvular leak.

TWO-DIMENSIONAL ECHOCARDIOGRAPHY Two-dimensional echocardiography can identify gross structural abnormalities of a prosthetic valve, such as dehiscence, vegetation, thrombus, or bioprosthesis degeneration. Echo reflectance of the prosthetic material, attenuation of the ultrasound beam, and multiple ultrasound reverberations from the prosthesis may cause difficulties in image interpretation. Imaging a mechanical prosthesis is generally more challenging than imaging a bioprosthesis due to increased acoustic shadowing. Nevertheless, all prostheses should be assessed with 2D imaging from multiple views with particular attention paid to the motion of the occluders/leaflets; the presence or absence of echo densities attached to the sewing ring, cage, struts, and/or occluders/leaflets; and the integrity of the sewing ring/annular interface. Observing abnormal rocking motion of the prosthesis suggests dehiscence. To identify the structural abnormalities associated with a prosthetic valve, it is important to understand the characteristics of the prosthesis and the surgical technique utilized at implantation.

FIGURE 14-1 Prosthetic valve types with patterns of regurgitation. (Left) Photo of prosthesis (center) Transesophageal echocardiography 2D imaging (right) transesophageal echocardiography Doppler color flow imaging. A: Homograft with trivial regurgitation. Arrow, aortic annulus area. A portion of the coronary artery has a tie around it. B: Stented porcine prosthesis with no prosthetic regurgitation. C: Stentless porcine prosthesis with no prosthetic regurgitation. D: Transcatheter prosthesis with trivial perivalvular regurgitation. E: Caged ball mechanical prosthesis with central jet of closing volume regurgitation. F: Single tilting disc mechanical prosthesis with single central washing jet regurgitation. G: Bileaflet mechanical prosthesis with one central and two lateral washing jets regurgitation.

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DOPPLER ECHOCARDIOGRAPHY Prosthetic valve assessment with color flow, pulsed wave (PW), and continuous wave (CW) Doppler imaging should be performed using similar principles and techniques used for assessment of native valves, including interrogation of the prosthesis from multiple acoustic windows and proper alignment of the Doppler beam with flow direction. Essential Doppler-derived variables that should be obtained during TTE to assess the function of prostheses in the aortic, mitral, tricuspid, and pulmonary valve positions are listed in Table 14-1. One key factor to consider during interrogation of prosthetic valves is that Doppler-derived parameters vary with cycle length. For aortic, mitral, and pulmonary valve prostheses, Doppler measurements from three consecutive cardiac cycles should be averaged if the patient is in sinus rhythm and a

minimum of five consecutive cardiac cycles averaged if the patient is in atrial fibrillation or another irregular rhythm. For patients with tricuspid prostheses, it is important to remember that Doppler-derived hemodynamic parameters vary not only with cycle length but also with respiration. Averaging a minimum of three to five consecutive cardiac cycles or obtaining measurements in midexpiratory apnea is recommended for all patients with tricusid prostheses (1–3). TABLE 14-1 Complete Doppler Assessment of Prosthetic Valves Aortic Valve Prostheses

Mitral Valve Prostheses

Tricuspid Valve Prostheses

Pulmonary Valve Prostheses

Peak velocity

E velocity

E velocity

Peak velocity

Mean gradient

Mean gradient

Mean gradient

Mean gradient

Dimensionless index

TVI ratio

TVI ratio

Peak gradient

AT

PHT

PHT



ET







AT:ET







Effective orifice area

Effective orifice area

Effective orifice area



Indexed effective orifice area

Indexed effective orifice area

Indexed effective orifice area



Regurgitation: presence, location, severity

Regurgitation: presence, location, severity

Regurgitation: presence, location, severity

Regurgitation: presence, location, severity

AT, acceleration time; ET, ejection time; PHT, pressure half-time; TVI ratio, ratio of the time velocity integral of the mitral valve prosthesis to the time velocity integral of the left ventricular outflow tract.

Every prosthetic valve is inherently stenotic in varying degrees compared with the respective native valve; therefore, flow velocities across a normal prosthetic valve are higher than expected and calculated effective orifice area (EOA) is smaller than expected for a normal native valve. Doppler-derived hemodynamic profiles of normally functioning prostheses vary according to prosthesis type, size, location, and cardiac output. Hence, it is important to know the ranges of flow velocities across a particular prosthesis for comparison with measured values. Normal Doppler-derived values for several types of aortic, mitral, tricuspid, and pulmonary prostheses are listed in Tables 14-2 to 14-5 (2–12). Mean gradient should not be the sole parameter considered when assessing prosthetic valves because a dysfunctional prosthesis may not have a high mean

gradient. In low-output states, many of the Doppler-derived hemodynamic parameters may be normal or only mildly abnormal even when a prosthesis is severely dysfunctional. In these cases, a high degree of suspicion and careful evaluation is warranted in order to accurately ascertain whether or not a particular prosthesis is dysfunctional. As a corollary, a high mean gradient does not necessarily indicate prosthetic valve dysfunction. Aortic valve prosthesis peak velocity and mean gradient may be elevated due to pathologic obstruction or regurgitation but may also be elevated due to a high flow state or “functional obstruction,” that is, prosthesispatient mismatch (PPM) or pressure recovery phenomenon. Elevated mitral or tricuspid valve prosthesis and mean gradient may be due to pathological obstruction or regurgitation but may also be due to PPM or a high flow state secondary to tachycardia, anemia, hyperthyroidism, arteriovenous fistula or malformation, or severe renal or hepatic disease. TABLE 14-2 Doppler-Derived Hemodynamic Profiles of Normal Aortic Valve Prostheses Prosthesis Type

Size

Peak Velocity, m/s

Mean Gradient, mm Hg

EOA, cm2

Stented Porcine Prostheses Carpentier-Edwards

19





0.85 ± 0.17



21

2.4 ± 0.5

17 ± 6.2

1.48 ± 0.30



23

2.8 ± 0.4

16 ± 6.4

1.69 ± 0.45



25

2.4 ± 0.5

13 ± 4.4

1.94 ± 0.45



27

2.3 ± 0.4

12 ± 5.6

2.25 ± 0.55



29

2.4 ± 0.4

10 ± 2.9

2.84 ± 0.51

Hancock II

21



15 ± 4.1

1.3 ± 0.4



23



17 ± 8.5

1.3 ± 0.4



25



11 ± 2.8

1.6 ± 0.4



27









29



8 ± 1.7

1.6 ± 0.2

Medtronic Mosaic

21



14 ± 5.0

1.4 ± 04



23



14 ± 4.8

1.5 ± 0.4



25



12 ± 5.1

1.8 ± 0.5



27



10 ± 4.3

1.9 ± 0.1



29



11 ± 4.3

2.1 ± 0.2

Medtronic Freestyle

19



13 ± 3.9



21



9 ± 5.1

1.4 ± 0.3



23



8 ± 4.6

1.7 ± 0.5



25



5.±3.1

2.1 ± 0.5



27



5 ± 3.1

2.5 ± 0.1

Stented Pericardial Prostheses Carpentier-Edwards

19

3.1 ± 0.5

21 ± 5.8

1.25 ± 0.18



21

2.6 ± 0.4

15 ± 4.1

1.65 ± 0.29



23

2.5 ± 0.4

14 ± 5.0

2.02 ± 0.43



25

2.5 ± 0.4

13 ± 3.9

2.33 ± 0.43



27

2.4 ± 0.4

13 ± 3.9

2.68 ± 0.49



29

2.3 ± 0.3

11 ± 2.9

3.24 ± 0.49

Sorin Mitroflow

19



10 ± 3

1.13 ± 0.17



21

2.3

15





23

1.9 ± 0.3

8 ± 3.4





25

2 ± 0.71

11 ± 6.5





27

1.8 ± 0.2

7 ± 1.7



St. Jude Medical Trifecta

19



9

1.58



21



8

1.77



23



7

1.94



25



6

2.14



27



5

2.30



29



4

2.50

Caged-Ball Mechanical Prostheses Starr-Edwards

23



22 ± 9.0

1.1 ± 0.2



24



22 ± 7.5

1.1 ± 0.3



26



20 ± 3.1





27



19 ± 3.7





29



16 ± 5.5



Single Tilting Disc Mechanical Prostheses Bjork-Shiley

19

3.3 ± 0.6

27 ± 7.9

0.94 ± 0.19



21

2.9 ± 0.4

22 ± 3.4

1.1 ± 0.3



23

2.7 ± 0.5

16 ± 5.3

1.3 ± 0.3



25

2.5 ± 0.4

13 ± 5.0

1.5 ± 0.4



27

2.1 ± 0.4

10 ± 2.0

1.6 ± 0.3



29

1.0 ± 0.2

8 ± 4.4



Medtronic-Hall

20



17 ± 5.3

1.2 ± 0.5



21



14 ± 5.9

1.1 ± 0.2



23



14 ± 4.8

1.4 ± 0.4



25



10 ± 4.3

1.5 ± 0.5



27



9 ± 5.6

1.9 ± 0.2

Bileaflet Mechanical Prostheses ATS

19

3.4 ± 0.43

26 ± 7.9

0.96 ± 0.18



21

2.4 ± 0.39

14 ± 3.5

1.58 ± 0.37



23



12 ± 4.0

1.80 ± 0.2



25



11 ± 4.0

2.20 ± 0.4



27



9 ± 2.0

2.50 ± 0.3



29



8 ± 2.0

3.10 ± 0.3

Carbomedics Standard

19

3.1 ± 0.38

19 ± 8.3

1.0 ± 0.3



21

2.6 ± 0.51

13 ± 5.4

1.5 ± 0.4



23

2.4 ± 0.37

11 ± 4.6

1.4 ± 0.3



25

2.0 ± 0.37

9 ± 3.5

1.8 ± 0.4



27

2.2 ± 0.36

8 ± 3.2

2.2 ± 0.2



29

1.9 ± 0.25

6 ± 3.0

3.2 ± 1.6

St. Jude Medical Standard

19

2.9 ± 0.48

25 ± 5.8

1.5 ± 0.2



21

2.6 ± 0.48

15 ± 5.0

1.4 ± 0.4



23

2.6 ± 0.44

13 ± 5.6

1.6 ± 0.4



25

2.4 ± 0.45

11 ± 5.3

1.9 ± 0.5



27

2.2 ± 0.42

8 ± 3.4

2.5 ± 0.4



29

2.0 ± 0.10

7 ± 1.7

2.8 ± 0.5

On-X

19



8 ± 2.9

1.53 ± 0.26



21



8 ± 3.4

2.01 ± 0.48



23



7 ± 3.2

2.31 ± 0.79



25



5 ± 2.8

2.75 ± 0.75



27/29



5 ± 2.8

2.75 ± 0.75

From Rosenhek R, Binder T, Maurer G, et al. Normal values for Doppler echocardiographic assessment of heart valve prostheses. Journal of the American Society of Echocardiography, 2003;16(11):1116–1127; Palatianos GM, Laczkovics AM, Simon P, et al. Multicentered European study on safety and effectiveness of the On-X prosthetic heart valve: Intermediate follow-up. Annals of Thoracic Surgery, 2007;83(1):40–46; Rajani R, Mukherjee D, Chambers JB. Doppler echocardiography in normally functioning replacement aortic valves: a review of 129 studies. Journal of Heart Valve Disease, 2007;16(5):519–535; Bavaria JE, Desai ND, Cheung A, et al. The St Jude Medical Trifecta aortic pericardial valve: results from a global, multicenter, prospective clinical study. Journal of Thoracic and Cardiovascular Surgery, 2014;147(2):590– 597; Heimansohn DA, Robison RJ, Walts P, et al. A single-center experience with the Sorin Mitroflow pericardial aortic valve: hemodynamics up to five years. Journal of Heart Valve Disease, 2014;23(3):338–342.

TABLE 14-3 Doppler-Derived Hemodynamic Profiles of Normal Mitral Valve Prostheses Prosthesis Type

Size

E Velocity, m/s

Mean Gradient, mm Hg

EOA, cm2

Stented Porcine Prostheses Carpentier-Edwards Duraflex

27

2.1 ± 0.3

7 ± 2.1

1.44 ± 0.36

29

2.1 ± 0.4

7 ± 2.1

1.53 ± 0.36



31

2.0 ± 0.3

7 ± 1.9

1.67 ± 0.40



33

2.0 ± 0.4

6 ± 1.7

1.65 ± 0.45



35

2.0 ± 0.4

6 ± 1.7

1.98 ± 0.53

Hancock II

25

1.7 ± 0.3

6 ± 3.2

1.44 ± 0.59



27

2.0 ± 0.3

7 ± 2.6

1.51 ± 0.32



29

1.9 ± 0.2

6 ± 2.1

1.80 ± 0.69



31

1.9 ± 0.6

7 ± 2.2

1.58 ± 0.31

Medtronic Mosaic

25

2.1 ± 0.3

8 ± 1.7

1.42 ± 0.29



27

2.0 ± 0.3

6 ± 1.3

1.62 ± 0.47



29

2.0 ± 0.3

7 ± 2.2

1.83 ± 0.68



31

2.0 ± 0.3

6 ± 1.6

1.70 ± 0.41



33

1.96 ± 0.5

6 ± 1.6

2.71 ± 0.77

Stented Pericardial Prostheses Carpentier-Edwards

25

1.7 ± 0.1

4 ± 1.0

1.75 ± 0.53



27

1.7 ± 0.3

6 ± 1.7

1.88 ± 0.52



29

1.8 ± 0.2

6 ± 1.4

2.02 ± 0.57



31

1.8 ± 0.2

6 ± 1.1

2.09 ± 0.48



33

1.7 ± 0.2

6 ± 1.9

2.24 ± 0.97

Caged-Ball Mechanical Prostheses Starr-Edwards

26



10

1.4



28



7 ± 2.8

1.9 ± 0.57



30

1.7 ± 0.3

7 ± 2.5

1.6 ± 50.4



32

1.7 ± 0.3

5 ± 2.5

1.98 ± 0.4



34



5

2.6

Single Tilting Disc Mechanical Prostheses Bjork-Shiley

25

1.8 ± 0.4

6 ± 2

1.72 ± 0.6



27

1.6 ± 0.5

5 ± 2

1.81 ± 0.54



29

1.4 ± 0.3

3 ± 1.3

2.10 ± 0.43



31

1.4 ± 0.3

2 ± 1.9

2.2 ± 0.3

Bileaflet Mechanical Prostheses Carbomedics Standard

25

1.9 ± 0.2

6 ± 1.8

1.88 ± 0.43



27

1.8 ± 0.3

5 ± 1.7

2.12 ± 0.50



29

1.7 ± 0.3

4 ± 1.4

2.31 ± 0.54



31

1.8 ± 0.3

5 ± 1.7

2.21 ± 0.52



33

1.7 ± 0.3

5 ± 1.6

2.19 ± 0.46

St. Jude Medical Standard

25

1.9 ± 0.3

6 ± 1.6

1.89 ± 0.56



27

1.8 ± 0.3

5 ± 1.6

2.11 ± 0.52



29

1.8 ± 0.3

5 ± 1.7

2.12 ± 0.46



31

1.7 ± 0.3

4 ± 1.3

2.32 ± 0.52



33

1.7 ± 0.3

5 ± 1.5

2.30 ± 0.58

On-X

25



5 ± 2.1

1.9 ± 1.1



27/29



5 ± 1.6

2.2 ± 0.5



31/33



5 ± 2.4

2.5 ± 1.1

From Rosenhek R, Binder T, Maurer G, et al. Normal values for Doppler echocardiographic assessment of heart valve prostheses. Journal of the American Society of Echocardiography, 2003;16(11):1116–1127; Blauwet LA, Malouf JF, Connolly HM, et al. Doppler echocardiography of 240 normal Carpentier-Edwards Duraflex porcine mitral bioprostheses: A comprehensive assessment including time velocity integral ratio and prosthesis performance index. Journal of the American Society of Echocardiography, 2009;22(4):388–393; Blauwet LA, Malouf JF, Connolly HM, et al. Comprehensive echocardiographic assessment of normal mitral Medtronic Hancock II, Medtronic Mosaic, and Carpentier-Edwards Perimount bioprostheses early after implantation. Journal of the American Society of Echocardiography, 2010;23(6):656–666; Blauwet LA, Malouf JF, Connolly HM, et al. Comprehensive hemodynamic assessment of 305 normal CarboMedics mitral valve prostheses based on early postimplantation echocardiographic studies. Journal of the American Society of Echocardiography, 2012;25(2):173–181; Blauwet LA, Malouf JF, Connolly HM, et al. Comprehensive hemodynamic assessment of 368 normal St. Jude Medical mechanical mitral valve prostheses based on early postimplantation echocardiographic studies. Journal of the American Society of Echocardiography, 2013;26(4):381–389.

TABLE 14-4 Doppler-Derived Hemodynamic Profiles of Normal Tricuspid Valve Prostheses Prosthesis Type

E Velocity, m/s

Mean Gradient, mm Hg

EOA, cm2

27

1.5 ± 0.3

5 ± 1.7

1.34 ± 0.22

29

1.7 ± 0.3

6 ± 2.0

1.54 ± 0.38

Size

Stented Porcine Prostheses Carpentier-Edwards Duraflex



31

1.5 ± 0.3

6 ± 1.7

1.57 ± 0.39

33

1.5 ± 0.3

6 ± 2.1

1.69 ± 0.44



35

1.5 ± 0.3

5 ± 1.6

1.63 ± 0.38

Hancock II

31

1.6 ± 0.2

6 ± 1.4

1.40 ± 0.21



33

1.4 ± 0.3

6 ± 3.5

1.40 ± 0.59



35

1.3 ± 0.3

5 ± 0.6

2.11 ± 0.23

Medtronic Mosaic

25

1.6

4

1.37



27

1.6 ± 0.2

6 ± 0.6

1.53 ± 0.16



29

1.5 ± 0.3

6 ± 0.2

1.96 ± 0.39



31

1.5 ± 0.2

5 ± 1.4

1.74 ± 0.52



33

1.4 ± 0.2

4 ± 1.3

2.00 ± 0.53

St. Jude Medical Biocor

29

1.6

6

2.84



31

1.5 ± 0.3

5 ± 1.4

1.67 ± 0.30



33

1.3 ± 0.2

4 ± 1.2

1.92 ± 0.50

Stented Pericardial Prostheses Carpentier-Edwards

29

1.1 ± 0.2

2 ± 1.4

2.16 ± 0.43



31

1.2 ± 0.2

4 ± 1.5

2.12 ± 0.53



33

1.4 ± 0.2

4 ± 1.1

1.93 ± 0.43

Caged-Ball Mechanical Prostheses Starr-Edwards

26



10

1.4



28



7 ± 2.8

1.9 ± 0.57



30

1.7 ± 0.3

7 ± 2.5

1.6 ± 50.4



32

1.7 ± 0.3

5 ± 2.5

1.98 ± 0.4



34



5

2.6

Bileaflet Mechanical Prostheses Carbomedics Standard

31

1.4 ± 0.2

4 ± 1.6

2.01 ± 0.51



33

1.2 ± 0.2

3 ± 1.2

2.33 ± 0.43

St. Jude Medical Standard

27

1.1 ± 0.3

2 ± 1.3

2.54 ± 0.64



29

1.2 ± 0.2

3 ± 1.1

2.20 ± 0.33



31

1.4 ± 0.3

3 ± 1.2

2.49 ± 0.45



33

1.3 ± 0.2

3 ± 1.2

2.46 ± 0.59

From Blauwet LA, Burkhart HM, Dearani JA, et al. Comprehensive echocardiographic assessment of mechanical tricuspid valve prostheses based on early post-implantation echocardiographic studies. Journal of the American Society of Echocardiography, 2011;24(4):414–424; Blauwet LA, Danielson GK, Burkhart HM, et al. Comprehensive echocardiographic assessment of the hemodynamic parameters of 285 tricuspid valve bioprostheses early after implantation. Journal of the American Society of Echocardiography, 2010;23(10):1045–1059, 1059.e1–e2.

TABLE 14-5 Doppler-Derived Hemodynamic Profiles of Normal Pulmonary Valve Prostheses Prosthesis Type

Size

Peak Velocity, m/s

Peak Gradient, Mean Gradient, EOA, cm2 mm Hg mm Hg

Stented Porcine Prostheses 21 2.2 ± 0.7 23 2.5 ± 0.5

20 ± 11.9

11 ± 6.3

2.09 ± 1.11

25 ± 9.1

13 ± 7.9

1.72 ± 0.71



25

2.4 ± 0.4

24 ± 8.6

13 ± 5.0

1.62 ± 0.44



27

2.3 ± 0.5

22 ± 8.6

12 ± 4.7

1.87 ± 0.52



29

2.4 ± 0.4

23 ± 7.1

12 ± 3.6

1.99 ± 0.52



31

2.3 ± 0.4

22 ± 8.2

12 ± 4.7

2.19 ± 0.68

Stented Pericardial Prostheses 21 2.6 ± 0.2 23 2.2 ± 0.3

28 ± 3.4

15 ± 0.6

1.61 ± 0.57

19 ± 5.6

10 ± 2.1

1.70 ± 0.49



25

2.1 ± 0.5

19 ± 9.4

10 ± 5.3

2.25 ± 0.93



27

2.1 ± 0.4

17 ± 5.8

10 ± 3.9

2.37 ± 0.73



29

2.3 ± 0.6

22 ± 9.1

11 ± 4.6

2.76 ± 0.89



31

2.2 ± 0.1

20 ± 2.1

11 ± 0.7



Bileaflet Mechanical Prostheses 21 3.4 23 2.1 ± 0.4

28

24



18 ± 5.8

9 ± 4.2

1.88 ± 0.61



25

2.4 ± 0.6

23 ± 11.4

13 ± 6.7

2.01 ± 0.70



27

2.1 ± 0.5

19 ± 8.3

10 ± 4.9

2.50 ± 0.60

From Unpublished Mayo Clinic data.

TIMING OF ECHOCARDIOGRAPHY AFTER IMPLANTATION Because the hemodynamic profile of a prosthesis depends on numerous factors, it is recommended that a baseline Doppler study be performed in the early postoperative period so that it can be used as a reference for comparison with later studies. According to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines on the management of patients with valvular heart disease, obtaining a baseline TTE is a class I recommendation (Level of Evidence: C) (14). The AHA/ACC guidelines recommend that the initial TTE be

obtained 6 weeks to 3 months after valve implantation. The practice at our institution is to “fingerprint” the prosthesis by performing postoperative TTE on patients who have undergone valve replacement prior to hospital discharge. We have shown that there are no significant differences between Doppler-derived hemodynamic profiles obtained in the early postoperative period and profiles obtained up to 13 months after implantation (11,12), so performing a postoperative TTE at any time between several days to several weeks after surgical implantation when the patient is hemodynamically stable should be acceptable.

OBSTRUCTION Prosthetic valve obstruction may be due to thrombus (Fig. 14-2), pannus (Fig. 14-3), vegetations (Fig. 14-4), calcification (Fig. 14-5), or a combination thereof. Whereas the obstruction of a mitral mechanical prosthesis is caused more frequently by thrombus (Fig. 14-6), the obstruction of an aortic mechanical prosthesis is caused more frequently by pannus formation (Fig. 14-7). When a prosthetic valve becomes obstructed, the prosthetic disk, ball, or leaflet motion decreases. Prosthetic valve leaflet/occluder motion is frequently difficult to visualize with 2D TTE imaging but is generally easily visualized with 2D or 3D TEE imaging (Fig. 14-8). The most accurate method for detecting and quantifying the degree of prosthetic obstruction is Doppler echocardiography (Fig. 14-9). CW Doppler interrogation of the prosthesis must be performed from several acoustic windows to ensure that the maximal jet velocity and mean gradient across the obstructed prosthesis are recorded. From the Doppler velocity tracing, the maximal and mean pressure gradients and the EOA can be calculated with the same formulas and equations described for the native valve (see Chapter 13). It is important to remember, however, that increased peak velocity or mean gradient alone does not always indicate prosthetic obstruction. Peak velocity can be increased without stenosis in a high-output state and in the setting of PPM, tachycardia (mitral and tricuspid prostheses), or severe prosthetic or periprosthetic regurgitation (Fig. 14-10).

FIGURE 14-2 Thrombosed bioprosthesis. Arrows, thrombus.

FIGURE 14-3 Bioprosthesis with pannus. Arrows, pannus.

FIGURE 14-4 Bioprosthetic endocarditis resulting in cusp perforation. Arrow, cusp tear.

In patients with an aortic prosthesis, acceleration time (AT) and the ratio of the AT to the ejection time (AT:ET) are useful to determine whether pathologic obstruction is present (13). AT is expected to be prolonged (>100 milliseconds) and AT:ET should be increased (>0.37) when an aortic prosthesis is obstructed, while both AT and AT:ET remain normal in high flow states (12A) (Fig. 14-11). In patients with a mitral or tricuspid prosthesis, pressure half-time (PHT) is useful for determining whether increased E velocity and mean gradient are due to increased flow or obstruction. PHT is expected to be prolonged when a mitral or tricuspid prosthesis is obstructed (Fig. 14-12).

FIGURE 14-5 Bioprosthesis with calcific degeneration. Arrow, calcification.

FIGURE 14-6 Bileaflet mechanical prosthesis with thrombus.

FIGURE 14-7 Caged ball prosthesis with pannus.

If an aortic prosthesis is obstructed, peak velocity and mean gradient increase unless cardiac output decreases. Increased peak velocity and mean gradient across an prosthesis are also expected with severe prosthetic regurgitation due to increased flow through the prosthesis. As with native aortic valve disease, left ventricular outflow tract (LVOT) velocity is normal to slightly decreased with aortic prosthesis obstruction and increased with aortic prosthetic/periprosthetic regurgitation. The ratio of the LVOT to aortic prosthesis velocities or time velocity integrals (TVIs) is helpful in differentiating increased velocity across an aortic prosthesis. With prosthetic obstruction, the TVI ratio decreases to ≤0.25, while the TVI ratio remains normal (≥0.3) with regurgitation. A high cardiac output state increases velocity across any prosthesis, which can be confirmed by recording increased flow velocities across all cardiac orifices (LVOT, atrioventricular valve, and right ventricular outflow tract). Researchers at the Mayo Clinic have developed algorithms for assessing aortic and mitral valve prosthesis function that can be used to assess bioprosthetic and mechanical prostheses in these positions (15) (Fig. 14-13).

PROSTHESIS-PATIENT MISMATCH Prosthesis-patient mismatch was first described by Rahimtoola (16) as a prosthetic EOA that is smaller than that of a normal native valve. PPM is relatively common and patients are usually asymptomatic. However, a marked increase in the transvalvular gradient occurs in a subset of patients with moderate or more severe aortic PPM, resulting in higher incidence of congestive heart failure (17), reduced regression of LV hypertrophy (18), reduced exercise tolerance (19), reduced survival (17,20–22), and early structural deterioration of aortic bioprostheses (23,24). Aortic PPM is classified as follows: Indexed EOA (cm2/m2)



PPM severity

Normal weight

Obese (body mass index ≥30 mg/kg)

>0.85

>0.70

Insignificant

0.66–0.85

0.60–0.70

Moderate

≤0.65

1.20

Insignificant

0.91–1.20

Moderate

≤0.90

Severe

The following three-step approach is recommended to prevent PPM: 1. Calculate the patient’s body surface area (BSA). 2. Calculate the minimally acceptable EOA of the prosthesis: BSA × 0.85 cm2 (aortic) or BSA × 1.20 cm2 (mitral). 3. Choose and implant a prosthesis with an EOA larger than the EOA calculated in step 2.

CALCULATION OF PROSTHETIC EFFECTIVE ORIFICE AREA The PHT method should not be used to calculate mitral or tricuspid prosthesis EOA because this method has not been validated for prosthetic valves. The constant 220 (see Chapter 13) was derived for stenotic lesions of a rheumatic native mitral valve. The constant 190 was suggested when calculating tricuspid valve stenosis based on the relationship between the constants used in the Gorlin equation when calculating the EOA of the mitral and tricuspid valves invasively and the constant used for Doppler assessment of native mitral valve area. The PHT method tends to overestimate the EOA of a mitral or a tricuspid prosthesis (2,3,9,10). The continuity equation is the preferred method for determining EOA of aortic, mitral, and tricuspid prostheses (1):

where the LVOT TVI is the time velocity integral of the LVOT velocity obtained with PW Doppler and the prosthesis TVI is the time velocity integral of the prosthesis inflow velocity obtained with CW Doppler. When a prosthetic valve is in the aortic position, the LVOT diameter is measured just below the insertion of the prosthetic aortic valve, from the junction between the sewing ring and ventricular septum to the junction between the sewing ring and the base of the anterior mitral leaflet. If these landmarks are unable to be adequately visualized, the prosthesis size (outer diameter of the sewing ring) may be substituted for the measured LVOT diameter.

THROMBOLYTIC THERAPY FOR PROSTHETIC VALVE OBSTRUCTION Thrombus formation is responsible for the majority of prosthetic valve obstruction, with or without pannus formation. Although TEE generally provides excellent visualization of prosthetic valves, multimodality imaging with fluoroscopy, and/or computed tomography (CT) scanning may be more effective for detecting and characterizing mechanical prosthetic valve thrombosis, leaflet

motion, and prosthetic valve function (28). Thrombus size is important for leftside heart prostheses when choosing the optimal treatment strategy. Unless the thrombus is large (>0.8 cm2 in area), the patient has New York Heart Association Class III or IV symptoms, or there is a contraindication, slow-infusion of lowdose fibrinolytic therapy is the recommended treatment for persistent thrombosis after IV heparin therapy for left-sided prosthetic valve thrombosis (28). For right-sided prosthetic thrombosis, fibrinolytic therapy is recommended regardless of thrombus size (Fig. 14-15). Emergent surgery is recommended for patients with NYHA Class III-IV symptoms, or large (or persistent) thrombus burden. Studies using an echocardiogram-guided slow-infusion of low-dose fibrinolytic protocol have shown success rates greater than 90%, with embolic event rates less than 2% and major bleeding rates less than 2% (29,30). The decision of whether to treat with thrombolysis or surgery should be made on the basis of each patient’s clinical condition, functional status, valve location, and comorbid status. The management of patients who have prosthetic valve obstruction can be facilitated if TEE can separate thrombus from pannus formation. Prosthetic valve obstruction due to thrombus can be predicted by inadequate anticoagulation or antiplatelet therapy as well as the location of the mass in relation to the prosthesis. Thrombus tends to form on the downstream side of the prosthesis, while pannus tends to form on the upstream side of the prosthesis.

FIGURE 14-14 A: Parasternal long-axis view of the LVOT (left), pulsed wave Doppler recording of LVOT velocity (center), and continuous wave Doppler recording of aortic

prosthetic valve flow velocity (right). LVOT diameter is small (1.9 cm) due to a small aortic prosthesis, LVOT TVI is 30 cm, and aortic prosthesis TVI is 100 cm with LVOT TVI and AV TVI ratio of greater than 0.3. Arrows on the right demonstrate acceleration time of 90 milliseconds, which is more consistent with prosthesis-patient mismatch. B: Continuous wave Doppler recording from the apex and the right parasternal window from another patient with an obstructed aortic mechanical prosthesis. The peak velocity is higher from the right parasternal (RPS) location with mean gradient of 46 mm Hg, similar to the patient described in (A), but acceleration time is over 150 milliseconds, consistent with obstruction, rather than mismatch.

ANTICOAGULATION AND ANTIPLATELET THERAPY FOR PROSTHETIC VALVES After valve replacement, treatment with low dose aspirin with or without warfarin may reduce thromboembolic events, while potentially increasing bleeding complications. The current recommendations for aspirin and warfarin therapy for patients with prosthetic heart valves are as follows (28): 1. Mechanical (bileaflet or current-generation single tilting disc) aortic prosthesis with no risk factors for thromboembolism: anticoagulation with warfarin to achieve an INR of 2.5 is recommended. 2. Mechanical (bileaflet or current-generation single tilting disc) aortic prosthesis with risk factors for thromboembolism (atrial fibrillation, previous thromboembolism, left ventricular dysfunction, or hypercoagulable conditions) and mechanical ball-in-cage prosthesis: anticoagulation with warfarin to achieve an INR of 3.0 is recommended. 3. Mechanical (all types) mitral prosthesis: anticoagulation with warfarin to achieve an INR of 3.0 is recommended. 4. Mechanical prostheses (all types and all valve positions): aspirin 75 to 100 mg daily is recommended. 5. Bioprosthetic aortic prosthesis or mitral prosthesis: aspirin 75 to 100 mg daily is reasonable. 6. The first 3 months after bioprosthetic mitral valve prosthesis or mitral valve repair: anticoagulation with warfarin to achieve an INR of 2.5 is reasonable. 7. The first 3 months after bioprosthetic aortic prosthesis: anticoagulation with warfarin to achieve an INR of 2.5 may be reasonable. 8. Patients with a mechanical valve prosthesis who have a thromboembolic event despite adequate anticoagulation: increase the INR goal from 2.5 (range, 2.0 to 3.0) to 3.0 (range, 2.5 to 3.5) for patients with an aortic prosthesis or increase

the INR goal from 3.0 (range, 2.5 to 3.5) to 4.0 (range, 3.5 to 4.5) for patients with an mitral prosthesis.

FIGURE 14-15 A: Longitudinal transesophageal view of a St. Jude Medical tricuspid valve prosthesis (arrow). The disks of the prosthesis failed to move because of thrombotic obstruction. Ao, aorta; LA, left atrium; RA, right atrium. B: Continuous wave Doppler echocardiography examination from the apex showed peak velocity across the tricuspid valve prosthesis to be close to 2 m/s, with a slight respiratory variation that is typical for a tricuspid valve prosthesis. The velocity and mean gradient returned to baseline after 2 days of treatment with continuous infusion of streptokinase. After thrombolytic therapy, peak velocity was 1 m/s, with a mean gradient of 4 mm Hg.

Anticoagulant therapy with oral direct thrombin inhibitors or anti-Xa agents is contraindicated in patients with mechanical valve prostheses. The RE-ALIGN (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement) trial was stopped prematurely for excessive thrombotic complications in the Dabigatran arm (31). Due to lack of data on their safety and effectiveness, oral direct thrombin inhibitors or anti-Xa agents are not recommended in patients with bioprosthetic valves who require anticoagulation.

REGURGITATION Regurgitant jets may travel through the prosthesis (transprosthetic regurgitation) or around the sewing ring (periprosthetic regurgitation). Central jets are most often transprosthetic. Jets that originate anteriorly, posteriorly, medially, or laterally may be either transprosthetic or periprosthetic. If the regurgitant color flow jet can be clearly identified outside the ring, then the diagnosis of periprosthetic regurgitation can be made with confidence. On occasion, particularly with tissue prostheses, transprosthetic jets may occur very close to the inner edge of the sewing ring and may be difficult to distinguish from periprosthetic regurgitation. Some transprosthetic jets are normal. For instance, it is relatively common to see a trivial central regurgitant jet with normal tissue prostheses. Mechanical prostheses are designed such that a small amount of transprosthetic regurgitation occurs during normal prosthesis function. Theoretically, these regurgitant jets help to prevent thrombus formation on mechanical prostheses. It is important that physicians interpreting echocardiography studies of prosthetic valves are familiar with the appearance of these jets so that the presence of these normal regurgitant jets does not lead to an erroneous interpretation of pathologic regurgitation (Fig. 14-1). Doppler color flow imaging is the principal technique used to detect prosthetic valve regurgitation. The same criteria used for native valve regurgitation are used for semiquantification of prosthetic valve regurgitation. However, color Doppler imaging of a mitral or tricuspid prosthesis with TTE is frequently unsatisfactory (especially for a mechanical prosthesis) because of the marked attenuation of the ultrasound beam by the prosthesis and reverberation artifact. TEE circumvents these limitations. As in the assessment of native valve regurgitation, an integrated approach is required for the evaluation of transprosthetic and periprosthetic regurgitation, with color Doppler imaging being one of several determinants. Because TTE Doppler color flow imaging has more limitations with prosthetic valves than with native valves, it is essential to obtain complete hemodynamic data with PW and CW Doppler studies before considering TEE. For aortic prosthetic or periprosthetic regurgitation, the following should be determined: vena contract width, intensity of the aortic regurgitant CW Doppler signal, PHT of the regurgitant jet, mitral inflow pattern, diastolic flow reversal in the descending thoracic aorta, effective regurgitant orifice (ERO) area, regurgitant volume, and

regurgitant fraction. The circumferential extent of aortic paravalvular regurgitation is discussed below for transcatheter aortic prosthesis. For mitral prosthetic or periprosthetic regurgitation, the following should be determined: E velocity, PHT, ratio of the mitral prosthesis TVI obtained with CW Doppler to the LVOT TVI (TVI ratio), intensity of the mitral regurgitant CW Doppler signal, ERO area, regurgitant volume, and regurgitant fraction. The continuity and PISA methods described for a native mitral valve regurgitation may be helpful in assessing the severity of prosthetic mitral valve regurgitation (see Chapter 13). Although a regurgitant jet in the LA may not be detected with surface echocardiography, proximal flow can be visualized clearly enough so the PISA method can be used. The following variables indicate chronic severe aortic prosthetic and/or periprosthetic regurgitation: 1. 2. 3. 4. 5. 6. 7.

Vena contracta width ≥6 mm Dense CW aortic regurgitation jet Regurgitant jet PHT less than 200 milliseconds (but can be longer) ERO area ≥0.30 cm2 Regurgitant volume greater than 60 mL Regurgitant fraction ≥50% Prominent holodiastolic flow reversal in the descending thoracic and abdominal aorta 8. Restrictive mitral inflow pattern (in acute and semiacute aortic regurgitation) The following variables indicate chronic severe mitral prosthetic and/or periprosthetic regurgitation: 1. Dense CW mitral regurgitation jet 2. Increased E velocity and TVI ratio with normal PHT (60 mL 5. Regurgitant fraction ≥50% 6. Systolic flow reversal in the pulmonary vein The amount of regurgitant volume can be much smaller for acute or subacute regurgitation than for chronic regurgitation. Good examples are acute regurgitation due to endocarditis, papillary muscle rupture, or periprosthetic lesion after transcatheter valve replacement.

TRANSESOPHAGEAL ECHOCARDIOGRAPHY Prosthetic valve obstruction is usually diagnosed or suspected by detecting increased flow velocity with CW Doppler echocardiography during TTE examination because visualizing decreased motion of the prosthetic valve leaflets/occluders with 2D imaging is usually challenging. The motion of prosthetic valve occluders/leaflets, especially those of mitral and tricuspid prosthetic valves, is seen more clearly with TEE. A TEE view of decreased occluder motion in a patient with obstruction of a mitral bileaflet mechanical prosthesis is shown in Figure 14-17. Occluder motion may be only intermittently abnormal, so prolonged TEE observation is necessary if an intermittent abnormality is suspected clinically. TEE is essential in the evaluation of mitral and tricuspid prosthetic regurgitation and, sometimes, aortic prosthetic regurgitation. The TEE view of the atria is not hindered by the prosthesis, and the origin and extent of mitral or tricuspid prosthetic regurgitation are demonstrated clearly with TEE. When aortic prosthetic regurgitation originates from the posterior aspect of the prosthesis, TEE is also quite helpful, but anteriorly located aortic prosthetic regurgitation may not be well seen, especially in the presence of a mitral prosthesis.

FIGURE 14-16 Continuous wave Doppler recordings (A,B) from a patient with bioprosthetic mitral valve and marked dyspnea. Peak velocity is 3.3 m/s, mean gradient is 16 mm Hg with TVI of 63 cm, and pressure half-time (B) is 62 milliseconds, most consistent with increased flow across the prosthesis. LVOT pulsedwave Doppler recording (C) shows reduced peak velocity (88 cm/s) and TVI of 13 cm.

Therefore, the mitral flow TVI and LVOT TVI ratio is markedly elevated at 4.8, consistent with severe mitral prosthetic regurgitation.

FIGURE 14-17 Transesophageal echocardiography of a bileaflet mechanical prosthesis with an immobile occluder in an elderly patient with sepsis. A: Midesophageal four-chamber zoomed view of the mitral prosthesis shows that the lateral occluder has normal excursion but the medial occluder (arrow) is immobile. B: Doppler color flow imaging shows flow acceleration across the lateral orifice of the prosthesis with no flow through the medial orifice of the prosthesis.

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Video 14-17A

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Video 14-17B TEE is also useful in the evaluation of dehiscence (Fig. 14-18), endocarditis (Fig. 14-19), ring abscess (Fig. 14-20), torn bioprosthetic cusps (Fig. 14-21), and intracardiac (especially atrial) mass or thrombi in the presence of a prosthetic valve (Fig. 14-22). These applications are discussed separately in other chapters (see Chapters 15 and 19).

FIGURE 14-18 Transesophageal echocardiography of a porcine mitral prosthesis with severe dehiscence due to endocarditis. A: Midesophageal three-chamber zoomed view of the prosthesis with color compared imaging shows a large posterolateral gap (arrow) between the mitral prosthesis sewing ring and the annulus with severe periprosthetic regurgitation. B: 3D imaging shows that the area of dehiscence encompasses approximately 25% of the circumference of the sewing ring. C: At the time of operation, several large vegetations attached to the atrial aspect of the bioprosthesis were identified.

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Video 14-18A

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Video 14-18B With the widespread clinical use of TEE, filamentous strands of varying lengths have been seen attached to prosthetic valves (32). These have been observed as early as 2 hours after valve replacement, suggesting that they are composed of fibrin. Although these strands are visible on TEE, even experienced surgeons may not detect them because they are transparent. A pathology study demonstrated that they consist of collagen with fibroblasts (32). The role of these strands in cardioembolic events remains uncertain.

FIGURE 14-19 Transesophageal echocardiography, midesophageal three-chamber zoomed view, shows a mitral bioprosthesis with a large vegetation (arrow) attached to the ventricular aspect of the prosthesis and a small vegetation attached to the atrial aspect of the prosthesis. Blood cultures grew Candida albicans.

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Video 14-19

HEMOLYSIS AFTER MITRAL VALVE REPAIR OR REPLACEMENT Hemolysis is an uncommon but alarming complication of mitral valve

replacement or repair. It is associated with distinct patterns of disturbance of mitral regurgitation flow. The collision of a mitral regurgitation jet against a cardiac structure, with rapid deceleration, is the most common reason for hemolysis (Fig. 14-23). According to a review of 13 consecutive patients with hemolytic anemia after mitral valve repair at our institution, the most commonly observed mechanism of hemolysis involved direct collision of the regurgitant jet with a prosthetic surface, usually the annuloplasty ring (33). Fragmentation of the regurgitant jet by a dehisced annuloplasty ring or rapid acceleration of the jet within a narrow zone of pararing dehiscence was also observed. Largeorifice eccentric regurgitant jets decelerating along the wall of the LA and central free jets were not associated with hemolysis (33). The abnormalities associated with hemolysis were not seen on intraoperative TEE after the initial operation and developed postoperatively. Typical laboratory findings of hemolysis include severe anemia, an increased reticulocyte count, increased lactate dehydrogenase, decreased haptoglobin (38°C) is the most common symptom of IE, reported in about 95% of patients (1), but may be absent in up to 20% of patients who are elderly, are immunocompromised, have CIED infections, or have received previous empiric antibiotic therapy (1,6,7). Constitutional symptoms of infection such as chills, sweats, malaise, myalgias, and arthralgias may be present in 30% to 70% of patients. Symptoms of heart failure are important to recognize, as heart failure is the most frequent complication of IE that also has the greatest impact on prognosis with both medical and surgical management. Heart failure has been reported to complicate the course of 30% to 50% of patients with IE; is the most common indication for surgery in IE, and even with early surgical intervention; and doubles inhospital mortality to approximately 25% (1,8–10). Symptoms of a central neurologic deficit consistent with stroke are present in 10% to 20% of patients and are most commonly cardioembolic in etiology and less often associated with local cerebrovascular complications of IE, such as mycotic aneurysm (1,4,5,8,11). On physical examination, a new heart murmur is detected in about 50% of patients with IE, and increased intensity of a previously heard murmur is noted in 20% (1). Signs of heart failure are often detected early in the course of patients with severe left-sided valvular regurgitation, commonly associated with the finding of a significant new murmur. Evidence of a new neurologic deficit

may be detected in 20% of patients with IE on initial presentation. Signs of peripheral septic embolism, such as the painless Janeway lesions or sequelae of immune complex deposition, such as the painful Osler nodes or Roth spots detected on retinal examination, are distinctly uncommon, being observed in less than 10% of the patients reported in contemporary clinical series of IE (1,5,8,12). TABLE 15-1 Definition of Terms Used in the Proposed Diagnostic Criteria Major criteria Positive blood culture for infective endocarditis Typical microorganisms for infective endocarditis from two separate cultures Viridans streptococci, Streptococcus bovis, HACEK group or Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus or Persistently positive blood culture, defined as microorganism consistent with infective endocarditis from Blood samples drawn more than 12 hours apart or All of three, or majority of four or more, separate blood samples, with the first and last drawn at least 1 hour apart Evidence of endocardial involvement Positive echocardiogram for infective endocarditis: Oscillating intracardiac mass on valve or supporting structures or in the path of regurgitant jets or on iatrogenic devices, in the absence of an alternative anatomical explanation or Abscess or New partial dehiscence of prosthetic valve or New valvular regurgitation (worsening or changing of preexisting murmur not sufficient) Minor criteria Predisposition: predisposing heart condition or intravenous drug use

Fever: ≥38.0°C Vascular phenomena: arterial embolism, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, Janeway lesions Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots Echocardiogram: consistent with infective endocarditis but not meeting major criterion as noted above Microbiologic evidence: positive blood culture but not meeting major criterion as noted above or serologic evidence of active infection with organism consistent with infective endocarditis HACEK, Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella spp., and Kingella kingae.

DIAGNOSIS OF INFECTIVE ENDOCARDITIS The protean clinical presentations of IE encompass a broad range of differential diagnostic possibilities, which would include 1) connective tissue disorders and vasculitides, 2) numerous other systemic infectious diseases, 3) paraneoplastic syndromes, and 4) other cardiovascular disorders such as acute rheumatic fever, left atrial myxoma, antiphospholipid syndrome, and other nonbacterial thrombotic endocarditis (NBTE) syndromes. Two decades ago, Durack and associates (13) proposed the Duke criteria for the diagnosis of IE, which were subsequently modified by Li and associates in 2000 (14) and are presented in Table 15-1. Major clinical criteria for the diagnosis of IE are 1) blood culture positivity for bacteria typically associated with IE, or persistently positive cultures for organisms, which are atypically associated with IE, or definitely positive serology for Coxiella burnetii and 2) echocardiographic evidence of endocardial involvement with the detection of vegetation, significant new valvular regurgitation (particularly with evidence of disruption of the valve structural anatomy), or findings consistent with PVEI, such as an abscess or prosthetic valve dehiscence. Echocardiographic imaging in IE will be presented in detail in the remainder of this chapter. In a review (15) of the contemporary microbiology of IE, viridans streptococci remain the most frequently isolated organism in community-acquired native valve IE, whereas Staphylococcus aureus is the predominant etiology of health care–associated IE, intravenous drug abuse, and early-onset (≤60 days postoperative) prosthetic valve IE. Coagulase-negative staphylococci are the most common organism in intermediate (days 60 to 365 postoperative) onset

prosthetic valve IE and are the infecting agent in 10% to 15% of health care– associated IE but quite uncommonly are the cause of native valvular IE. Enterococcus is a pathogen detected in approximately 10% to 15% of all cases of IE. About 10% to 15% of IE cases are also due to infection with fastidious or atypical organisms such as the HACEK group, Bartonella, Tropheryma whipplei, Legionella, Coxiella burnetii, or fungi. Blood culture positivity may be significantly delayed with these infections, and more rapid detection of such infections is facilitated by polymerase chain reaction (PCR) assays. Blood culture– and PCR-negative IE occurs in 5% to 15% of all cases of IE, with the most common cause being empiric antibiotic therapy administration before evaluation for IE (1,3,15). As noted in Table 15-1, minor clinical criteria include 1) predisposing cardiac conditions or intravenous drug abuse; 2) persistent fever of greater than 38°C without an alternative etiology evident; 3) vascular phenomena such as systemic or pulmonary embolism, mycotic aneurysm, and intracranial or cutaneous hemorrhagic lesions; 4) findings of immunologic phenomena such as Osler nodes, Roth spots, or glomerulonephritis; and 5) blood culture positivity not meeting major criteria or serologic evidence of active infection with an atypical organism consistent with IE. By this diagnostic classification, now recognized as the Modified Duke Criteria, a definite clinical diagnosis of IE is established in the presence of 1) two major criteria, or 2) one major and three minor criteria, or 3) five minor criteria. A possible clinical diagnosis of IE would be suspected in the presence of 1) one major and one minor criterion or 2) three minor criteria. The diagnosis of IE is rejected if clinical evaluation 1) does not meet criteria for possible IE, or 2) there is complete resolution of the suspected IE syndrome or there is no anatomic evidence for IE on a course of antibiotic therapy for ≤4 days, or 3) an alternative diagnosis is confirmed (14). The Modified Duke Criteria have been validated in multiple clinical series with a diagnostic sensitivity of approximately 80%, with specificity and negative predictive value being both greater than 90% (9,16). This approach to the diagnosis of IE remains fully endorsed in current guideline recommendations (3,9,14).

ECHOCARDIOGRAPHIC IMAGING Echocardiography is the established imaging modality of choice for the evaluation of the patient with suspected IE and provides the foundation for a

major Modified Duke Criteria for diagnosis. The echocardiographer must be carefully aligned with the clinical presentation and assessment of the patient before imaging. It should be realized that microbiologic findings may not yet (or ever) be established for the other major Modified Duke Criterion and multiple other minor criteria, particularly classic physical examination findings for IE, are often absent. This not uncommonly confuses the pretest probability of imaging diagnosis of IE by both transthoracic echocardiography (TTE) and even transesophageal echocardiography (TEE). Comprehensive echocardiographic imaging for suspected IE should be guided by index of clinical suspicion while maintaining an objective differential diagnosis of findings that could represent, or mimic, endocarditis.

Vegetation Vegetations are a hallmark finding for IE and, as per originating document of the Duke Criteria (13), can be described as an oscillating intracardiac mass(es), without an alternative anatomic explanation, attached to a valve, valvular support structure, in the endocardial path of a regurgitant jet, or attached to any intracardiac prosthetic device or implanted endocavitary system. Vegetations are typically located on the upstream aspects of the valves, that is, the atrial side of the atrioventricular valves and the ventricular side of the semilunar valves (Figs. 15-1 and 15-2). As IE is predominantly associated with native valvular regurgitant lesions, it has been proposed that upstream vegetation location is due to pathogen deposition into the disrupted valvular endothelium within the lowerpressure eddy zones of the egressing high-velocity regurgitant jet. Vegetations typically have a soft, tissue density echocardiographic texture (particularly early in the course of IE) and are lobulated to amorphous in shape, with a variable degree of motion independent of the valvular structure to which it is attached. Vegetations associated with IE may also occur at any site of endocardial disruption, such as in the trajectory of eccentric regurgitant jets (Fig. 15-3). A differential diagnosis of mobile endocardial echodensities must always be considered. Filamentous linear mobile echodensities usually represent degenerative valvular changes such as Lambl excrescences, endocardial fenestrations, or ruptured chordae; fibrinous valvular strands may be detected on both native and prosthetic valves. Hyper-refractile, discrete, and nodular echodensities are typical of calcified, sclerotic valvular lesions; however, associated acoustic artifacts may give the false impression of mobility of such lesions. Valvular thickening and redundancy due to myxomatous degeneration

may give the appearance of mass lesions but without independently mobile components. Valvular neoplasms, such as papillary fibroelastoma, often have a more circumscribed, shimmering mass appearance (see Chapter 19) compared to vegetations and are more often located on the downstream side of the valve, particularly in the aortic position.

FIGURE 15-1 Parasternal long-axis view TTE imaging during viridans streptococcal IE. Large vegetations (arrows) are attached to the ventricular aspects of the aortic valve, characterizing their typical upstream location. LV, left ventricle; LA, left atrium; Ao, ascending aorta.

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Video 15-1

FIGURE 15-2 Long-axis TEE imaging during coagulase-negative staphylococcal IE complicating hemodialysis catheter infection. A large vegetation (arrows) is attached to the atrial aspect of the anterior mitral valve leaflet (arrowhead). This location was in the upstream trajectory of moderate mitral regurgitation noted to be present before this illness. LV, left ventricle; LA, left atrium; Ao, ascending aorta.

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Video 15-2 Nonbacterial Thrombotic Endocarditis Nonbacterial thrombotic endocarditis (NBTE) is also characterized by valvular vegetations usually localized on the upstream aspects of the affected valve, usually the mitral, less commonly the aortic, and rarely a right-sided valve (17). Typically, the vegetations in NBTE are sessile, are verrucous in appearance, and aggregate along the inflow closing edges of the valve. Although largely immobile, these vegetations are friable with a propensity for embolism in 30% to 50% of patients (17–19). In postmortem series, NBTE is most commonly associated with metastatic malignancies, particularly adenocarcinomas of the lung, pancreas, and gastrointestinal tract, in a condition previously known as marantic endocarditis. Associated with these cancers are elevated levels of circulating cytokines, which mediate endocardial damage and hypercoagulable states that promote thrombotic vegetation deposition (18). In surgical series, NBTE is most commonly associated with an immune-mediated primary antiphospholipid syndrome or a secondary antiphospholipid syndrome associated with a systemic connective tissue disease, which is most often lupus erythematosus (initially referred to as Libman-Sacks endocarditis), and, uncommonly, in rheumatoid arthritis or rheumatic valvular heart disease. In the antiphospholipid syndromes, antibodies to cardiolipin, beta-2 glycoprotein I, and other phospholipids induce immune complex deposition at the disrupted valvular endothelium, with resulting cytokine and adhesion molecule activation promoting laminating fibrinous thrombotic vegetation deposits. In later stages of antiphospholipid disease, leaflet thickening, fibrosis, retraction, and valvular regurgitation occur (17,19) (Fig. 15-4).

Diagnostic Accuracy of TTE and TEE The reported sensitivity of TTE imaging for the diagnosis of native valve IE has ranged from approximately 50% to 85% with a specificity of 80% to 90% but remains highly dependent upon the quality of TTE imaging windows available and the size of the vegetations (3,16,20,21). With prosthetic valve IE, there is a significantly lower frequency of valvular vegetations on the prosthesis itself and higher incidence of periprosthetic infectious complications. These manifestations of IE are much more difficult to delineate by TTE, and the diagnostic sensitivity for this imaging modality is much less, in the range of 40% to at best 60% (3,20,22,23). TEE provides an excellent imaging work-around of the numerous impediments to TTE imaging such as body habitus, postoperative status, severe lung disease, and multiple potential sources of acoustic interference. Given the smaller depth of field of imaging from the TEE transducer, higher-frequency imaging greatly improves spatial resolution, and vegetations of 2 to 3 mm in dimension can be detected. Details regarding vegetation size, burden, mobility, and impact on the functional valvular anatomy are often far better delineated with TEE (Fig. 15-5). Even with the use of contemporary TTE imaging systems, vegetations are detected in less than 50% of patients with both native and prosthetic valve IE when compared to TEE (24) (Figs. 15-5 and 15-6). With native valve IE, the reported sensitivity of TEE for vegetation detection ranges from 90% to 100% and is in the range of 85% to 95% for prosthetic valve IE (3,9,10,20,22,23). The specificity and positive predictive value of TEE for the diagnosis of IE are in the range of 90% (3,20,23). Given the significant limitations of TTE in patients with suspected prosthetic valve IE, TEE is hence the first imaging modality of choice. Three-dimensional (3D) TEE has been reported to add ancillary information regarding extent of vegetations, local valve disruption, and PVEI to the findings on two-dimensional (2D) TEE when compared to the findings on surgical inspection (25,26). In a recent report, it has been suggested that 3D TEE is superior to 2D TEE in the determination of maximal vegetation dimension, a parameter having definite implications in embolic risk assessment (27,27a). The quantitative incremental value of 3D TEE imaging over multiplane 2D TEE imaging for the diagnosis of IE and its complications is still yet to be fully established. Enlarging vegetations noted on serial echocardiographic imaging despite ongoing appropriate antibiotic therapy portend high risk, as this finding is associated with increased risk of complications, primarily embolism, and higher inhospital mortality (28).

FIGURE 15-3 Long-axis TEE imaging during Streptococcus mutans IE. A: There is systolic override of the vegetation encrusted A2-3 portion of the anterior mitral valve leaflet (large arrow) with vegetations present on the atrial aspect of the posterior mitral leaflet and its annular insertion (small arrows). B: An eccentric jet of severe mitral regurgitation (large arrow) is directed against the base of the posterolateral left atrium (small arrows). C: Multiple left atrial endocardial jet lesion vegetations (arrows) are present in the path of the mitral regurgitant jet seen in Panel B. D: Two additional left atrial endocardial jet lesion vegetations (arrows) are present near the orifice of the left atrial appendage. LV, left ventricle; LA, left atrium; LA App, left atrial appendage; MV, mitral valve.

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Video 15-3A

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Video 15-3B

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Video 15-3C

FIGURE 15-4 Transverse four-chamber TEE imaging in the antiphospholipid syndrome. A: Systolic frame. Sessile and verrucous vegetations (arrows) of nonbacterial

thrombotic endocarditis (NBTE) are characteristically located along the atrial aspect closure margins of both mitral leaflets. Incomplete central systolic leaflet coaptation caused severe mitral regurgitation. B: Diastolic frame. The closure margin vegetations (arrows) produce a club-like appearance to the mitral leaflets, associated with restricted diastolic leaflet excursion and functional inflow stenosis. LV, left ventricle; LA, left atrium; RA, right atrium; RV, right ventricle.

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Video 15-4

FIGURE 15-5 A: Parasternal long-axis TTE imaging. Poorly defined mobile echodensities are detected in the left ventricular outflow tract (arrow) and attached to the mitral valve (arrowhead) in the presence of cutaneous abscess, fever, and a stroke. B: Long-axis TEE imaging demonstrates large, highly mobile vegetation (arrows) attached to the ventricular aspect of the noncoronary cusp of the aortic valve (open arrow) with prolapse far into the left ventricular outflow tract. Attached to the P2 portion of the posterior mitral leaflet (asterisk) is another vegetation (arrowheads). LV, left ventricle; LA, left atrium; Ao, ascending aorta; RV, right ventricle.

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Video 15-5A

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Video 15-5B

FIGURE 15-6 A: Apical four-chamber TTE focused imaging of a mitral bioprosthesis (arrowheads) with a mean inflow gradient of 25 mm Hg during chronic fever. Indeterminate echodensities (arrows) are detected within the inflow orifice of the prosthesis. B: Transverse four-chamber TEE imaging focusing on the mitral bioprosthesis (arrowheads), systolic frame. Multiple vegetations are attached to the atrial aspects of the prosthetic leaflets (arrows). C: Focused TEE imaging, diastolic frame. Severe mitral inflow obstruction is caused by the vegetation encrusted leaflets (arrows) of the bioprosthesis (arrowheads). Cultures of the surgically removed bioprosthesis confirmed Hormographiella aspergillus endocarditis. LV, left ventricle; LA, left atrium.

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Video 15-6A

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Video 15-6B

Local Valvular Destruction Severe left-sided valvular regurgitation is the most common cause of heart failure in IE, which is the most powerful independent predictor of both medical and surgical prognosis in IE, with inhospital mortalities in the range of 50% and 25%, respectively (3,10,29). Heart failure is also the most common primary indication for early surgery for IE m(10,20,29). Heart failure is three times more common in native versus prosthetic valve IE, with the incidence being most common in aortic (30%), then mitral (20%), and least common in tricuspid (15 mm) vegetations are an independent predictor of 1-year mortality (11). In high

clinical risk patients, imaging with 3D TEE should be considered for more complete assessment of vegetation size. A recent study has found that 2D TEE measurements may underestimate the maximum vegetation dimension by a mean of approximately 3 mm as well as the total vegetative burden (27) (Fig. 15-15). Embolic risk also increases the more independently mobile the vegetative mass is relative to its attached valvular structure. Highly mobile vegetations that are quite large (>15 mm in dimension) have an embolism rate reported to exceed 80% (39). Severe vegetation mobility is also predictive of new embolic events on antibiotic therapy with an odds ratio of 2.4 (11). Mitral valve location (either native or prosthetic) is also an independent risk factor for embolism, with the native anterior mitral leaflet vegetation location further adding increased embolic potential (20,40,41). Infection with Staphylococcus aureus has been consistently found to be an independent multivariate predictor of embolic risk (particularly for stroke) and, less so, IE associated with Streptococcus bovis and viridans (11,39–41). The presence of PVEI further adds to embolic potential (41). Prompt initiation of appropriate antibiotic therapy is of paramount importance in minimizing embolic events associated with IE. Within 1 week of antibiotic therapy, the embolic event significantly decreases to less than 10%, and the risk of embolic stroke is reduced to approximately 3% (11,39,41). With this documented response to antibiotic therapy, pre-emptive surgical intervention for potentially high embolic risk vegetations has not been previously advised unless there are recurrent embolic events despite ongoing appropriate antibiotic therapy (3,9,16). This position has been challenged by a recent study (42) of patients with left-sided vegetations greater than 10 mm in diameter randomized to conventional management versus early surgery (within 48 hours). On admission, nearly 30% of each group had evidence of cerebral emboli and had no other indications for urgent surgical intervention. In patients randomized to conventional therapy, recurrent cerebral embolic events occurred in 13% with an overall embolic event rate of 21% at 6 weeks compared to a 0% embolic event rate over the same time period for the early surgical patients; the inhospital mortality was 3% for both groups (42).

FIGURE 15-14 Short-axis TEE imaging during Propionibacterium aortic prosthetic IE. A: The mechanical aortic prosthesis (asterisk) is surrounded by extensive PVEI encircling the posterior aortic annulus (arrowheads) with a large vegetative mass extending into the right atrium (open arrows) above the tricuspid valve (arrow). B: A large endocarditic mass has infiltrated the crux of the heart (large white arrow) with extension far into the right atrium (open arrows) adjacent to the tricuspid valve (small white arrow) and also into the left atrium (arrowheads). C: A fistula is present from the basal left ventricle with color Doppler showing shunt flow (large white arrow) entering the right atrium just above the tricuspid valve (small white arrow). LV, left ventricle; LA, left atrium; RV, right ventricle; RA, right atrium; * indicates mechanical aortic prosthesis.

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Video 15-14A

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Video 15-14B

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Video 15-14C Systemic anticoagulation and/or antiplatelet therapy has no proven prophylactic benefit in reducing risk of embolic events in IE and could precipitate hemorrhagic transformation of ischemic embolic infarctions,

particularly in the brain. Hence, such therapy should not be administered unless another compelling indication exists (3). With successful antibiotic therapy, serial echocardiographic imaging may demonstrate a gradual reduction in vegetation size and mobility, with an increase in echodensity (Fig. 15-16). Commonly, an early dramatic reduction in vegetation size is not observed, and the process of vegetation healing and involution may take months to occur.

FIGURE 15-15 Transverse plane TEE imaging during Staphylococcus aureus IE. A: A large vegetation (arrows) is attached to the posterior mitral leaflet (arrowhead) and had the maximal dimensions of 20 mm × 12 mm by 2D TEE imaging. B: Imaging from the left atrial perspective with 3D TEE. The vegetative mass (open arrows) is much larger than appreciated on 2D TEE imaging and encompassed most of the atrial surface of the posterior mitral leaflet (asterisk), with a maximal dimension of 33 mm. LV, left ventricle; LA, left atrium; AV, aortic valve.

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Video 15-15A

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Video 15-15B

Approach to Echocardiographic Imaging Clinical risk stratification of the patient with suspected IE is important in defining pretest probability of detecting IE and prioritizing which echocardiographic imaging modality, that is, TTE versus TEE, to pursue first. Features defining patients at low initial clinical risk and pretest probability for IE would include the following: 1) undifferentiated fever with a broad differential diagnosis, 2) absent or unchanged chronic murmur (especially nonregurgitant in etiology), 3) no physical examination findings to suggest IE, 4) no prosthetic devices (valves, conduits, or patches), 5) no CIED, and 6) no high-risk cardiovascular anatomy, such as complex congenital heart disease (3,16,20). Patients at high initial clinical risk and pretest probability of IE would include those having 1) a significant new murmur, especially of left-sided valvular regurgitation, 2) new heart failure, 3) physical examination findings consistent with IE, 4) a prior history of IE, 5) prosthetic or mechanical devices in the circulation (valves, nonendothelialized conduits or patches, CIED, ventricular assist device), 6) complex congenital heart disease, or 7) Staphylococcus aureus bacteremia. As the number of these risk factors increases in any given patient so also does the morbidity and mortality of the IE syndrome (3,9,16,43). In the presence of Staphylococcus aureus bacteremia, the prevalence of definite native valve IE has been found to be 19%, with the prevalence of prosthetic valve or CIED IE being 38% (44,45). Imaging with TTE has been proposed as the initial imaging study in all patients with suspected IE (3), and this is the general approach in low clinical risk patients. If high-risk findings are detected on TTE, such as large mobile

vegetations, evidence of PVEI, grade III to IV/IV valvular regurgitation, and/or significant new left ventricular dysfunction, TEE should be immediately performed for further evaluation and definition of such findings (16). If highquality TTE imaging is negative for IE, other diagnoses should be investigated. A technically nondiagnostic TTE study or a persistent high clinical index of suspicion for IE would warrant TEE for exclusion of this diagnosis. If the TEE study is negative for IE, a follow-up TEE should be considered within 5 to 7 days if clinical suspicion of IE persists. The diagnosis of IE is highly unlikely with two sequential negative TEE studies, noting a negative predictive value of approximately 98% (16). Given the limited diagnostic sensitivity of TTE for the diagnosis of prosthetic valve and CIED IE, initial imaging with TEE is the approach to optimize expeditious diagnosis with the best diagnostic accuracy. Given the significant prevalence of IE in patients with Staphylococcal aureus bacteremia (44), high frequency of associated PVEI, and the independent impact this organism has on both early medical and surgical mortality, initial imaging with TEE is also very reasonable. Initial TEE evaluation should also be considered in the other high clinical risk patient subsets noted above, especially in the patient with complex congenital heart disease. Supplemental TTE should be pursued if further definition of hemodynamics or ventricular function is required after TEE evaluation. Cardiac CT may also provide important adjunctive imaging information to echocardiography in IE, particularly with delineating the extent of PVEI, great vessel involvement, and postoperative complex congenital heart disease (3,46).

FIGURE 15-16 Longitudinal long-axis TEE imaging during the course of Corynebacterium IE. A: A large, pedunculated, and mobile vegetation (arrows) attached to the posterior mitral valve leaflet was present at the time of initial diagnosis of IE. B: After 5 weeks of antibiotic therapy, repeat TEE shows the vegetation to be consolidated with decreased size and no mobility. There were no interim embolic events. C: Another TEE was performed 7 months later for the evaluation of recurrent fever. The previously seen posterior mitral valve leaflet vegetation is now much smaller with echodense hyper-refractility (arrow), typical of a healed and involuted vegetation. There was no evidence of recurrent IE.

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Video 15-16A

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Video 15-16B

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Video 15-16C Following the diagnosis of IE, follow-up TEE imaging should be performed to evaluate patients with clinical evidence of persistent infection, especially with ongoing bacteremia that fails to clear with appropriate antibiotic therapy, investigating for PVEI. For the same reason, TEE should be pursued for the evaluation of new atrioventricular heart block. New-onset heart failure complicating IE, especially if accompanied by a significantly new or changing heart murmur, should be evaluated by TEE in search of destructive valvular regurgitant lesions or fistulous shunts. A new or recurrent embolic event despite appropriate antibiotic therapy may be indicative of an enlarging vegetative burden and, hence, failure of medical therapy. Identification of these complications of IE is of great importance, as all represent class I indications for early surgical intervention (3,16). Being essential to the initial evaluation and diagnosis of IE and associated complications, TEE also has great utility in the

operating room. Intraoperative TEE has been found to impact both the operative plan prior to cardiopulmonary bypass while prompting additional surgical intervention after the initial procedure and cessation of bypass in about 10% of patients undergoing surgery for IE (47).

REFERENCES 1. Murdoch DR, Corey GR, Hoen B, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century. Archives of Internal Medicine, 2009;169:463–473. 2. Knirsch W, Nadal D. Infective endocarditis in congenital heart disease. European Journal of Pediatrics, 2011;170: 1111–1117. 3. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 2014;63(22): e57– e185. 4. Duval X, Delahaye F, Alla F, et al. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications. Three successive population-based surveys. Journal of the American College of Cardiology, 2012;59:1968–1976. 5. Benito N, Miro J, de Lazzari E, et al. Health care-associated native valve endocarditis: Importance of non-nosocomial acquisition. Annals of Internal Medicine, 2009;150:586–594. 6. Durante-Mangoni E, Bradley S, Selton-Suty C, et al. Current features of infective endocarditis in elderly patients: Results of the International Collaboration on Endocarditis Prospective Cohort Study. Archives of Internal Medicine, 2008;168:2095–2103. 7. Athan E, Chu VH, Tattevin P, et al. Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices. Journal of the American Medical Association, 2012;307: 1727– 1735. 8. Lopez J, Revilla A, Vilacosta I, et al. Age-dependent profile of left-sided infective endocarditis: A three center experience. Circulation, 2010;121:892–897. 9. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). European Heart Journal, 2009;30:2369–2413. 10. Nadji G, Rusinaru D, Remadi JP, et al. Heart failure in left-sided native valve infective endocarditis: Characteristics, prognosis, and results of surgical treatment. European Journal of Heart Failure, 2009;11:668–675 11. Thuny F, Disalvo G, Belliard O, et al. Risk of embolism and death in infective endocarditis: Prognostic value of echocardiography. A prospective multicenter study. Circulation, 2005;112:69–75. 12. Lopez J, Fernandez-Hidalgo N, Revilla A, et al. Internal and external validation of a model to predict adverse outcomes in patients with left-sided infective endocarditis. Heart, 2011;97:1138–1142. 13. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings. Duke endocarditis service. The American Journal of Medicine, 1994;96:200–209. 14. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clinical Infectious Diseases, 2000;30:633–638. 15. Que YA, Moreillon P. Infective endocarditis. Nature Reviews Cardiology, 2011;322–336.

16. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: A statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation, 2005;111:e394–e434. 17. Eiken PW, Edwards WD, Tazelaar HD, et al. Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985–2000. Mayo Clinic Proceedings, 2001;76:1204 18. el-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic endocarditis in cancer patients: Pathogenesis, diagnosis, and treatment. The Oncologist, 2007;12:518. 19. Ruiz-Irastorza G, Crowther M, Branch W, et al. Antiphospholipid syndrome. Lancet, 2010;376:1498– 1508. 20. Habib G, Badano L, Tribouilloy C, et al. Recommendations for the practice of echocardiography in infective endocarditis. European Journal of Echocardiography, 2010;11: 202–219. 21. Bai AD, Steinberg M, Showler A, et al. Diagnostic accuracy of transthoracic echocardiography for infective endocarditis findings using transesophageal echocardiography as the reference standard: a meta-analysis. J Am Soc Echocardiogr 2017;30:639–646. 22. Banchs J, Yusuf SW. Echocardiographic evaluation of cardiac infections. Expert Review of Cardiovascular Therapy, 2012;10:1–4. 23. Graupner C, Vilacosta I, San Roman JA, et al. Periannular extension of infective endocarditis. Journal of the American College of Cardiology, 2002;39:1204–1211. 24. Kini V, Logani S, Ky B, et al. Transthoracic and transesophageal echocardiography for the indication of suspected endocarditis: Vegetations, blood cultures, and imaging. Journal of the American Society of Echocardiography, 2010;23: 396–402. 25. Hansalia S, Biswas M, Dutta R, et al. The value of live/real time three-dimensional transesophageal echocardiography in the assessment of valvular vegetations. Echocardiography, 2009;26:1264–1273. 26. Anwar AM, Nosir YF, Alasnag M, et al. Real time three-dimensional transesophageal echocardiography: A novel approach for the assessment of prosthetic heart valves. Echocardiography, 2014;31(2):188–196. 27. Berdejo J, Shibayama K, Harada K, et al. Evaluation of vegetation size and its relationship with embolism in infective endocarditis: A real-time 3-dimensional transesophageal echocardiography study. Circulation: Cardiovascular Imaging, 2014;7(1):149–154. 27a. Utsunomiya H, Berdejo J, Kobayashi S, Mihara H, Itabashi Y, Shiota T. Evaluation of vegetation size and its relationship with septic pulmonary embolism in tricuspid valve infective endocarditis: a real time 3DTEE study. Echocardiography, 2017;34:549–556. 28. Thuny F, Grisoli D, Collart F, et al. Management of infective endocarditis: Challenges and perspectives. Lancet, 2012; 379:965–975. 29. Kiefer T, Park L, Tribouilloy C, et al. Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure. Journal of the American Medical Association, 2011;306:2239–2247. 30. Tribouilloy C, Rusinaru D, Sorel C, et al. Clinical characteristics and outcome of infective endocarditis in adults with bicuspid aortic valves: A multicentre observational study. Heart, 2010;96:1723–1729. 31. De Castro S, Cartoni D, d’Amati G, et al. Diagnostic accuracy of transthoracic and multiplane transesophageal echocardiography for valvular perforation in acute infective endocarditis: Correlation with anatomic findings. Clinical Infectious Diseases, 2000;30:825–826.

32. Alluri N, Kumar S, Marfatia R, et al. Aortic valve perforation diagnosed with use of 3-dimensional transesophageal echocardiography. Texas Heart Institute Journal, 2012;39: 590–591. 33. Wang A, Athan E, Pappas PA, et al. Contemporary clinical profile and outcome of prosthetic valve endocarditis. Journal of the American Medical Association, 2007;297: 1354–1361. 34. Anguera I, Miro JM, Cabell CH, et al. Clinical characteristics and outcome of aortic endocarditis with periannular abscess in the International Collaboration on Endocarditis Merged Database. The American Journal of Cardiology, 2005;96:976–981. 35. Sudhakar S, Sewani A, Agrawal M, et al. Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (MAIVF): A comprehensive review. Journal of the American Society of Echocardiography, 2010;23:1009–1018. 36. Anguera I, Miro JM, Vilacosta I, et al. Aorto-cavitary fistulous tract formation in infective endocarditis: Clinical and echocardiographic features of 76 cases and risk factors for mortality. European Heart Journal, 2005;26:288–297. 37. Duval X, Iung B, Klein I, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis. Annals of Internal Medicine, 2010;152:497–504. 38. Grabowski M, Hryniewiecki T, Janas J, et al. Clinically overt and silent cerebral embolism in the course of infective endocarditis. Journal of Neurology, 2011;258:1133–1139. 39. Di Salvo G, Habib G, Pergola V, et al. Echocardiography predicts embolic events in infective endocarditis. Journal of the American College of Cardiology, 2001;37:1069–1076. 40. Vilacosta I, Graupner C, San Roman JA, et al. Risk of embolization after institution of antibiotic therapy for infective endocarditis. Journal of the American College of Cardiology, 2002;39:1489–1495. 41. Dickerman SA, Abrutyn E, Barsic B, et al. The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: An analysis from the ICE Prospective Cohort Study (ICE-PCS). American Heart Journal, 2007;154:1086–1094. 42. Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. The New England Journal of Medicine, 2012;366:2466–2473. 43. Young WJ, Jeffery DA, Hua A, et al. Echocardiography in patients with infective endocarditis and the impact of diagnostic delays on clinical outcomes. Am J Cardiol. 2018 May 11. [Epub ahead of print] 44. Rasmussen RV, Host U, Arpi M, et al. Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteremia: The value of screening with echocardiography. European Journal of Echocardiography, 2011;12: 414–420. 45. Longobardo L, Klemm S, Cook M, Ravenna V, et al. Risk assessment for infective endocarditis in Staphylococcus aureus bacteremia patients: when is transesophageal echocardiography needed? Eur Heart J Acute Cardiovasc Care, 2017 Oct. 46. Feuchtner GM, Stolzmann P, Dichtl W, et al. Multislice computed tomography in infective endocarditis. Journal of the American College of Cardiology, 2009;53:436–444. 47. Shapira Y, Weisenberg DE, Vaturi M, et al. The impact of intraoperative transesophageal echocardiography in infective endocarditis. The Israel Medical Association Journal, 2007;9:299–302.

CHAPTER

16

Stress Echocardiography Robert B. McCully, Patricia A. Pellikka, and Jae K. Oh

HISTORICAL PERSPECTIVE The observation that myocardial ischemia produced by coronary artery occlusion rapidly results in regional myocardial dysfunction, along with the development of M-mode and two-dimensional echocardiographic technologies, provided the impetus for development of the field of stress echocardiography. The feasibility of acquiring and recording two-dimensional ultrasonic images of human subjects’ hearts before, during, and after exercise was first reported by Wann et al. in 1979 (1). Review of videotaped images allowed for the sequential assessment of left ventricular systolic function before and after stress testing. The introduction in the mid-1980s of wide-angle scanners with higher resolution, and of digital acquisition systems, provided further incentive for progress. These technologies allowed for the acquisition and subsequent editing of high-resolution images of the heart during a single cardiac cycle, which were then played back as continuous loops. The side-by-side presentation of the baseline and stress echocardiographic images simplified test interpretation by making possible a direct comparison of regional and global left ventricular systolic function before and with exercise or pharmacologically induced stress, utilizing multiple acoustic windows in a more user-friendly manner (2). In the more than three decades that have followed, the clinical use and impact of stress echocardiography have grown substantially. The diagnostic and prognostic value of stress echocardiography has been confirmed by multiple studies involving thousands of patients. Guidelines and expert consensus statements that summarize the body of literature that underpins the clinical utility and role of stress echocardiography have been published on behalf of the American Society of Echocardiography (3) and the European Association of Cardiovascular Imaging (4).

APPLICATIONS The versatility of stress echocardiography is unparalleled. The ability of the sonographer or echocardiologist to acquire two-dimensional, color flow, and pulsed-wave (PW) or continuous-wave (CW) Doppler data allows for full flexibility when certain clinical questions need to be answered. As a result, the clinical applications are numerous (Fig. 16-1). Stress echocardiography has a proven and established role not only in the assessment of patients with suspected or known coronary artery disease but also in the evaluation of those who have diastolic dysfunction or structural and valvular heart disease.

INDICATION The efficient and appropriate utilization of stress imaging tests such as stress echocardiography, nuclear myocardial perfusion imaging, and cardiac magnetic resonance has been increasingly emphasized in recent years. Updates of clinical practice guidelines and appropriate use criteria documents have clarified aspects of, and indications for, stress test ordering (5,6). In many situations, a treadmill exercise ECG without imaging will suffice as the initial stress test for diagnosis. For patients who have chest discomfort, dyspnea, or other symptoms that are suggestive of coronary artery disease, stress testing with imaging is indicated for initial diagnosis or for risk assessment if the ECG is uninterpretable or if patients are unable to exercise. If patients are able to exercise, exercise testing with echocardiography or nuclear myocardial perfusion imaging is reasonable and appropriate if their pretest likelihood of coronary artery disease is intermediate to high. In general, stress imaging is rarely appropriate in patients who are asymptomatic. Exceptions may be patients who are at high risk of having a coronary artery disease event or those who have a high coronary calcium Agatston score. For patients who have valvular heart disease, stress echocardiography is indicated if there is a discrepancy between the patient’s resting hemodynamic abnormalities and his or her symptomatic status (7).

FIGURE 16-1 Clinical applications of stress echocardiography. (CAD, coronary artery disease; CW, continuous wave; HCM, hypertrophic cardiomyopathy; LV, left ventricle; LVOT, left ventricular outflow tract; MR, mitral regurgitation; PW, pulsed wave; RV, right ventricular; TR, tricuspid regurgitation; 2D, twodimensional.)

MAYO CLINIC EXPERIENCE Stress echocardiography was introduced into clinical practice at Mayo Clinic at the end of 1989. From that time onwards, there was steady growth in the number of stress echocardiograms performed annually, reaching a peak in the year 2005, when approximately 8,500 studies were performed. Since then, there has been a gradual decline in the annual number of studies performed, with a plateau of approximately 6,500 studies per year being reached recently. This trend reflects the changes in clinical practice that have been brought about by closer adherence to established practice guidelines and the utilization of appropriate use criteria by referring physicians. During the year 2017, which was the 28th year of stress echocardiography at Mayo Clinic, the 150,000th stress echocardiogram was performed. During the first decade of clinical use of stress echocardiography, the ratio of exercise to dobutamine stress echocardiograms performed was 2:1; during the second decade, the ratio was 1.5:1; and currently, the ratio is 1.2:1.

THE STRESS ECHO TEAM The team responsible for performing stress echocardiograms is composed of an ECG technician, a specially trained cardiovascular registered nurse, and a sonographer. The ECG technician rooms the patient, hooks up the ECG leads to the patient, monitors the ECG before and during the stress echocardiogram and in the recovery period, and assists the patient at the end of the test before dismissal. The registered nurse reviews the patient’s medical record prior to stress testing, making sure that there are no clinical contraindications to stress testing. The stress echocardiogram, whether exercise or dobutamine stress, is conducted and supervised by the registered nurse. This supervisory role includes monitoring the patient’s symptoms and blood pressure during the stress test and deciding when to terminate the test. Alternatively, an exercise specialist supervises the exercise echocardiograms. These personnel also apply and monitor finger oximetry during the stress test if patients are being evaluated for dyspnea. The sonographer acquires echocardiographic images at baseline and with stress. A staff echocardiologist is in attendance in close proximity to the stress echocardiogram room and can be called into the room immediately if any questions or issues arise. The echocardiologist’s other major role is to interpret the stress echocardiographic images and generate a stress echocardiogram report.

SAFETY The safety of performing stress echocardiography has been well documented in several studies. An audit of more than 15,000 stress echocardiograms performed at Mayo Clinic over a 2-year period and directly supervised by registered nurses showed that complications are uncommon (8). Complications occurred more frequently with dobutamine stress echocardiography (0.7%) compared to exercise echocardiography (0.09%). The frequency of potentially lifethreatening complications was 0.4 per 1,000 patients. No patient had cardiac rupture or died.

IMAGE ACQUISITION The standard two-dimensional echocardiographic images acquired at baseline are the parasternal long-axis view, the parasternal short-axis view at

midventricular level, and the apical four-chamber and two-chamber views. These four views are utilized when comparing the digitized images side by side with those obtained with stress. Additionally, other images are routinely acquired and recorded. These include the apical long-axis and the apical short-axis views. The cardiac valves are routinely evaluated at baseline in multiple views with twodimensional and color flow imaging. The aortic root and ascending aorta are also imaged. Left ventricular and left atrial sizes are measured, the latter with a volumetric measurement indexed to body surface area. A limited Doppler examination is performed to screen patients for left ventricular diastolic dysfunction and pulmonary hypertension. These data include pulsed-wave Doppler of the mitral inflow (E and A), tissue Doppler imaging of the medial mitral annulus (e′), E/e′ ratio, and CW Doppler to measure the peak tricuspid regurgitant velocity for calculation of the right ventricular systolic pressure with the simplified Bernoulli equation and an assumed right atrial pressure. In our experience, abnormal findings on the baseline images can lead to cancellation of the stress echocardiogram 1% to 2% of the time. The presence of unexpected abnormalities such as a sizeable pericardial effusion, severe pulmonary hypertension, aortic root or ascending aorta pathology, severe aortic or mitral valve disease, severe right ventricular dysfunction, or severe regional or overall left ventricular systolic dysfunction can lead to a change in the referring health care provider’s plan of investigation. The standard images are acquired immediately after exercise in the case of treadmill exercise testing and at different levels of stress during dobutamine or supine bike stress echocardiography. Commercially available microbubbles are used in approximately 50% of our stress echocardiograms for left ventricular opacification to enhance endocardial border definition (see Chapter 6). The quality of images of the left ventricle can be transiently affected in the parasternal view by the bolus of microbubbles in the right ventricle that cause image attenuation in the far field. In this situation, acquiring the first set of images from the apical window may be necessary, that is, apical four-chamber, apical long-axis, apical two-chamber, and apical short-axis views. Sometimes, when the quality of the apical images is poor and that of the parasternal images good, all images can be acquired from the left parasternal window (parasternal long axis and parasternal short axis at three levels: base, midventricle, and apex). Rarely, when imaging windows are limited, all views can be acquired from the subcostal window (subcostal four-chamber and subcostal short axis views at three levels: base, midventricle, and apex). A limited Doppler examination to

assess pulmonary pressures and diastolic function is also performed after acquisition of the two-dimensional images. Baseline and stress echocardiographic images have, until recently, also been routinely recorded on videotapes. These recorded images are an essential and indispensable component of stress echocardiographic acquisition and interpretation; two-dimensional images of multiple cardiac cycles can be reviewed in addition to the single cardiac cycle images that are reviewed on the side-by-side digitized images (9). Also, being able to review videotaped images in real time has allowed for identification of the ischemic threshold when a dobutamine stress echocardiogram is positive for ischemia. Recently, we replaced our aging videotape recording and playback equipment with digital video recorders. These instruments record high-definition video images, which are then sent electronically to an institutional server for archiving and linked to the stress echocardiogram desktop review stations. These digital video recordings average 5 minutes in duration for exercise echocardiography and 10 minutes for dobutamine stress echocardiography.

IMAGE INTERPRETATION The visual assessment of left ventricular regional wall motion and thickening and overall systolic function remains the cornerstone of stress echocardiographic interpretation. This interpretive skill is one that requires extensive training and ongoing experience. It can be mastered by the learner who is methodical and thorough. One-on-one review of studies with expert readers constitutes the best training and can result in improvement of reading skills after interpretation of as few as 100 stress echocardiograms (10). Readers can usually maintain their skill level if they review 100 or more studies each year. One of the more straightforward aspects of stress echocardiographic interpretation is the side-by-side comparison of left ventricular end-systolic size at baseline and with stress. Normally, the left ventricular end-systolic volume decreases with exercise or dobutamine stress (Fig. 16-2).

FIGURE 16-2 Digital quad view of normal exercise echocardiography demonstrating (A) end-systolic parasternal long- and short-axis view at rest (left) and immediately after exercise (right), (B) apical four (top)- and two (bottom)-chamber view at rest (left) and after exercise (right). Left ventricle is shown on the left side of the apical fourchamber images. LV cavity becomes smaller with exercise and wall motion is normal.

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Video 16-2A

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Video 16-2B

An abnormal response is defined as an increase or no appreciable change in the left ventricular end-systolic volume (Fig. 16-3). The left ventricular ejection fraction at baseline and with stress can be assessed visually or quantitated with various methods. Normally, the left ventricular ejection fraction increases with exercise or dobutamine stress.

FIGURE 16-3 A: Still frame of end-systolic parasternal long-axis (PLX) and short-axis (PSX) views of an exercise echocardiogram that is positive for stress-induced myocardial ischemia. The anteroseptum and anterior wall become severely hypokinetic (arrows) with exercise. B: Still frame of end-systolic apical views of positive exercise echocardiogram. The apical septum and anteroapex become akinetic to dyskinetic (arrows). (2 ch, two-chamber view; 4 ch, four-chamber view; LV, left ventricle; RV, right ventricle.)

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Video 16-3A

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Video 16-3B Left ventricular regional function is assessed using a 16-segment model recommended by the American Society of Echocardiography. The left ventricle is divided into six basal and six midventricular segments (anterior, anteroseptum, inferoseptum, inferior, inferolateral, and anterolateral), and four apical segments (anterior, septal, inferior, and lateral). A visual examination of the motion and thickening of each segment is performed. All segments should ideally be evaluated in more than one view. Because inward motion can be due to translational change or the pull of an adjacent segment, assessment of systolic thickening is most reliable. At our institution, the criterion for an abnormal test result is the presence of one abnormal segment. Other institutions may require two abnormal segments to call a test abnormal. Semiquantitative scoring is routinely performed. Segmental systolic thickening is normal (score 1) if thickening is greater than 30% to 40%. A segment is hypokinetic (score 2) if there is reduced thickening (10%–30%) and severely hypokinetic if there is minimal thickening (200/110 mm Hg) is a relative contraindication to exercise testing. Exercise testing imposes higher physiologic stress on the patient than does pharmacologic stress testing and provides complementary prognostic information such as the patient’s hemodynamic response and exercise capacity. Symptom-limited exercise testing should be performed. The test should be terminated when the patient develops symptoms or signs of marked fatigue or symptoms or signs of myocardial ischemia. A commonly used aid is the 6- to 20grade Borg scale of perceived exertion. When the patient reaches 17 to 18 on this scale, that is, when his or her perceived exertional workload is “very hard,” the test is stopped. Otherwise, absolute indications for terminating the exercise test are electrocardiographic ST elevation in leads that do not have Q waves, moderate to severe angina, central nervous system symptoms such as dizziness or ataxia, signs of poor perfusion such as cyanosis or pallor, a drop in systolic blood pressure of more than 10 mm Hg below the baseline blood pressure if accompanied by other evidence of ischemia, sustained ventricular arrhythmias, or the patient’s desire to stop (11). Achieving a certain heart rate, such as 85% of the age-predicted maximal heart rate, should not be a reason for test termination.

FIGURE 16-6 Graphic illustration of the extent and severity of regional wall motion abnormalities at rest and peak stress. A 71-year-old man with a history of declining exercise capacity and exertional dyspnea exercised for 5.5 minutes on the Bruce protocol, stopping because of dyspnea and fatigue. His heart rate increased from 62 to 137 bpm and his blood pressure from 128/78 to 166/88 mm Hg. The exercise ECG showed 2 mm of horizontal ST depression in the inferolateral leads. The left ventricular ejection fraction decreased from 60% to 30%, and the left ventricular endsystolic size increased in response to exercise. The stress echocardiographic findings were consistent with multivessel coronary artery disease with evidence of a prior inferior infarct and extensive anterior and lateral ischemia (13 ischemic segments, wall motion score index 2.63). Coronary arteriography revealed severe multivessel coronary artery disease (80% left main, 70% proximal left anterior descending, 80% proximal circumflex, 70% first obtuse marginal, and 50% proximal right coronary stenoses, and a totally occluded distal right coronary artery). (LV, left ventricle; RV, right ventricle; LVOT, left ventricular outflow tract; MVO, mitral valve orifice.)

FIGURE 16-7 Side-by-side comparison of apical four (top) and long-axis (bottom) view at rest (left) and immediately after exercise (right) demonstrating a larger LV with global but more anterior septal wall motion abnormality in a patient with LBBB. A subsequent coronary angiography showed normal epicardial coronary arteries.

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Video 16-7A

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Video 16-7B The most commonly used exercise protocols in our laboratory are treadmillbased ramp protocols. The Bruce protocol is used more than 95% of the time. Elderly and deconditioned patients may not be able to exercise at the level required by the Bruce protocol. In this setting, a protocol that has more modest increases in workload from one stage to another, the Naughton protocol, is used. Bruce Protocol (3-minute Stages) Stage

Speed (mph)

Incline (%)

METs

I

1.7

10

5

II

2.5

12

7

III

3.4

14

10

IV

4.2

16

13

V

5.0

18

16

VI

5.5

20

19

VII

6.0

22

22

Speed (mph)

Incline (%)

METs

I

1.0

0

1

II

2.0

0

2

III

2.0

3.5

3

IV

2.0

7

4

V

2.0

10.5

5

VI

2.0

14

6

VII

2.0

17.5

7

Naughton Protocol (2-minute Stages) Stage

After the exercise test is stopped, the patient is quickly helped off the treadmill and lies down in the left lateral decubitus position on the examination table. There is no cooldown walking period. During this immediate postexercise period, and preferably within the first minute, the sonographer acquires twodimensional echocardiographic images of the heart, focusing on the left ventricle. Depending on the imaging characteristics of each patient, the acoustic window of first choice will vary and could be either the left parasternal or the apical window. The patient will be asked to briefly hold the breath while images are being acquired. An in-house treadmill protocol, specifically designed so that the workload achieved by the patient is approximately 1 MET for every minute of exercise completed, is used at Mayo Clinic when oxygen consumption (VO2) testing is added to the exercise echocardiogram. Information obtained from this combined echocardiographic and cardiopulmonary exercise test can provide the referring clinician with useful data and insights regarding the etiology of some patients’ symptoms. Mayo Protocol—1 MET/min (2-minute Stages) Stage

Speed (mph)

Incline (%)

METs

I

2.0

0

2

II

2.0

7

4

III

2.0

14

6

IV

3.0

12.5

8

V

3.0

17.5

10

VI

3.4

18

12

VII

3.8

20

14

For patients who are familiar with bicycling, and who prefer to exercise in this manner, two types of stationary bicycles, an upright cycle and a semirecumbent cycle, are available for use in our stress laboratory. Patients can exercise on either of these stationary bicycles and perform lower-intensity exercise (Protocol I) or higher-intensity exercise (Protocol II). The upright cycle and the higherintensity protocol are ideal for younger subjects who will be in a typical cyclist’s crouch while exercising. The semirecumbent cycle offers patients a more comfortable seated ride and is preferred by older and deconditioned patients. Upright or Semirecumbent Cycle Protocols (2-minute Stages)

Protocol I Stage

Protocol II

Watts

Stage

Watts

I

12

I

25

II

25

II

50

III

50

III

100

IV

75

IV

150

V

100

V

200

VI

125

VI

250

VII

150

VII

300

When the exercise test is stopped, the patient is helped off the cycle and placed in the left lateral decubitus position on the examination table so that the sonographer can perform immediate postexercise echocardiographic imaging. At some institutions, echocardiographic imaging is also performed at peak exercise. This is more challenging from a technical standpoint. Some recumbent cycles can be tilted toward the left so that the patient exercises in a left-tilted recumbent position. This facilitates imaging at peak exercise. We have not adopted this approach; our preference is for patients to exercise in as unencumbered a manner as possible.

DOBUTAMINE STRESS ECHOCARDIOGRAPHY The pharmacologic agent dobutamine is widely used for stress testing when patients are unable to exercise because of debilitating medical conditions such as peripheral vascular disease, severe chronic lung disease, or certain orthopedic

conditions. Dobutamine is a synthetic catecholamine that increases myocardial oxygen consumption through mostly inotropic and chronotropic effects. Its predominant mechanism of action is agonism of cardiac beta-1 adrenergic receptors. It has weaker effects on the peripheral vasculature from opposing effects of beta-2 adrenergic and alpha-1 adrenergic receptor agonism. Thus, at low doses, myocardial contractility increases. At higher doses, heart rate increases and eventually systemic vasodilation occurs. The blood pressure response is variable, but typically, there is a slight increase in systolic blood pressure and a decrease in diastolic blood pressure during dobutamine stress (12). Atropine is a parasympatholytic agent that exerts its effects by competitive antagonism of cardiac muscarinic acetylcholine receptors. This counters the decrease in heart rate that is mediated by vagal tone. Atropine is administered to patients undergoing dobutamine stress testing if they do not reach their target heart rate, which is defined as 85% of age-predicted maximal heart rate. The age-predicted maximal heart rate is calculated by subtracting the patient’s age from 220. Contraindications to dobutamine/atropine stress echocardiography are similar to those for exercise, as well as untreated narrow angle glaucoma and urinary retention. After fasting for 3 hours and undergoing screening by the supervising nurse, the patient is placed in the left lateral decubitus position on the examination table. A peripheral intravenous catheter is placed, usually in the left antecubital fossa. Systolic and diastolic blood pressure measurements are recorded at baseline and every 3 minutes during the test, near or at peak stress, and in the recovery period. Continuous ECG monitoring is performed by the ECG technician. Dobutamine is administered by an infusion pump run by the supervising nurse, starting at a dose of 5 μg/kg/min. The dobutamine dose is increased every 3 minutes. Intravenous atropine is administered to further increase the heart rate if necessary; in our experience, it is required 60% of the time. Atropine is administered in 0.25 mg bolus increments every 1 minute to a maximal cumulative dose of 2 mg and initially given at the end of the 20 μg/kg/min stage if the heart rate is less than 90 beats per minute (bpm), at the end of the 30 μg/kg/min stage if the heart rate is less than 70% of the age-predicted maximum, or at the end of the 40 μg/kg/min stage if the heart rate is less than 85% of the age-predicted maximum.

Dobutamine Stress Echo Protocol (3-minute Stages) Stage

Dobutamine Dose (μg/kg/min)

Atropine (mg)

I

5



II

10



III

20



IV

30

0.25

V

40

q 1 min

Echocardiographic images are acquired and recorded by the sonographer at baseline and during each stage of the study. The images are digitized for side-byside comparison at baseline, low dose (10 μg/kg/min), prepeak (when the heart rate is ~10 beats from the target heart rate or just prior to atropine administration), and at peak stress. Images acquired at all stages and in the recovery period are recorded on digital video (Fig. 16-8A and B). The development of intracavitary or left ventricular outflow tract (LVOT) obstruction with the administration of dobutamine is not uncommon, and can occur in the presence or absence of basal septal hypertrophy. We recommend that CW Doppler data be acquired across the LVOT at peak dobutamine dose if patients develop hyperdynamic left ventricular systolic function, systolic anterior motion of the mitral leaflets, or hypotension. The use of microbubbles for left ventricular opacification precludes visual assessment of the mitral valve apparatus. Test endpoints are the attainment of target heart rate, intolerable symptoms, significant arrhythmias, ischemic wall motion abnormalities of at least moderate degree (Fig. 16-8C), severe hypertension (blood pressure >250/115 mm Hg), and severe hypotension (systolic blood pressure 182 mm Hg) had obstructive CAD (defined as ≥50% stenosis). The positive predictive value of DSE was similar for patients with a hypertensive response and normal blood pressure responses (69% and 73%, respectively, p = 0.3). The likelihood of finding severe CAD (defined as ≥70% stenosis) was lower in patients who had a hypertensive response compared to those who had normal blood pressure responses (54% and 65%, respectively, p = 0.005). (CAD, coronary artery disease; DSE, dobutamine stress echocardiography; SBP, systolic blood pressure.)

To distinguish between infarcted and viable myocardium, two-dimensional echocardiography may be helpful. If segmental wall thickness is less than 6 mm, it is very likely that the segment is nonviable and infarcted, especially if its echodensity is increased. Wall thickness of 6 mm or greater may or may not indicate myocardial viability. It has been shown in animals that beta-adrenergic stimulation improves

contractility of chronically ischemic or postischemic myocardium, but not of infarcted myocardium. Low to intermediate doses of dobutamine (5–20 μg/kg/min) induce contractility of viable heart muscle, be it stunned or hibernating myocardium (23). Dobutamine-responsive wall thickening predicts improvement in regional left ventricular wall thickening after coronary revascularization. A biphasic response is the best predictor of recovery of regional left ventricular systolic function after revascularization (Fig. 16-11). When performing a dobutamine viability study in our laboratory, intermediate stages are added and the duration of each stage is increased to 5 minutes. Sublingual nitroglycerin is no longer administered routinely at the beginning of the viability study. Images are acquired at baseline and at the end of each stage. On occasion, when specifically requested, a viability/ischemia study is performed, and higher doses of dobutamine and atropine are administered. The presence of myocardial viability of LV in patients with ischemic cardiomyopathy was defined as positive dobutamine augmentation of myocardial contractility in at least five segments with no significant resting contractility (24). In a substudy of the STICH trial, patients with coronary artery disease and left ventricular dysfunction who underwent dobutamine echocardiography were defined as having myocardial viability if 5 or more dysfunctional segments at rest manifested contractile reserve during dobutamine administration. There was a significant univariate association between myocardial viability, as assessed by dobutamine echocardiography or single photon emission computed tomography, and 5-year outcomes. The presence of myocardial viability, however, did not increase the likelihood that patients would benefit from coronary artery bypass surgery as compared to medical therapy (24). Recently, 10-year survival data from the STICH trial showed improved survival after coronary artery bypass surgery compared to medical therapy (J. Panza et al., unpublished data). Thus, there may be renewed interest in obtaining myocardial viability data on patients who have ischemic cardiomyopathy.

FIGURE 16-11 Schematic of myocardial response to low and higher doses of dobutamine in three clinical situations. Top. If the akinetic myocardium is infarcted/scarred (xx) with no myocardial viability, there is no systolic thickening at rest or with low or higher doses of dobutamine. Middle. If the akinetic myocardium is viable and there is no high-grade stenosis of the coronary artery supplying the myocardium, there is a sustained improvement in systolic thickening with low- and higher-dose dobutamine (stunned). Bottom. If the akinetic myocardium is viable and there is a high-grade stenosis of the coronary artery supplying the myocardium, myocardial contractility and systolic thickening improve with low-dose dobutamine but worsen with higher-dose dobutamine (hibernating). This is the classic biphasic response.

Dobutamine Echo Viability Protocol (5- minute Stages) Stage

Dobutamine Dose (μg/kg/min)

I

5

II

7.5

III

10

IV

15

V

20

DIASTOLIC STRESS ECHOCARDIOGRAPHY Although exertional dyspnea may be an angina equivalent and indicative of coronary artery disease (25), it can of course be nonischemic in origin and due to left ventricular diastolic dysfunction, valvular heart disease, pulmonary hypertension, pulmonary disease, or deconditioning. Stress echocardiography is

uniquely positioned to characterize several different cardiovascular causes of dyspnea. In addition to evaluating for coronary artery disease, we routinely screen patients referred to the stress echocardiography laboratory for valvular heart disease, pulmonary hypertension, and diastolic dysfunction, as described earlier. In patients who undergo exercise echocardiography, Doppler assessment of pulmonary and left ventricular filling pressures is also routinely performed in the early postexercise recovery period (Fig. 16-12). The rationale for doing this is that patients who have exertional dyspnea due to diastolic dysfunction may have normal left ventricular filling pressures at rest that only increase with exercise, leading to breathlessness (26) (see Chapter 8). Immediately after acquiring the two-dimensional images for regional wall motion and overall left ventricular systolic function assessment, the sonographer acquires the CW Doppler signal of the tricuspid regurgitation jet to measure peak velocity and calculate right ventricular systolic pressure. As the heart rate slows, and when the mitral inflow PW Doppler signal is no longer fused, the E wave and medial mitral annular e′ velocities are measured for calculation of the E/e′ ratio. Normally, the mitral E and mitral annular e′ velocities increase proportionately with exercise. As a result, E/e′ does not change and remains less than 8. In patients with abnormal relaxation, the increase in e′ velocity with exercise is less than that of the E velocity, leading to an increase in E/e′ (27,28). Hemodynamic studies of simultaneously measured left ventricular filling pressures using cardiac catheterization and Doppler echocardiography at rest and with exercise show satisfactory correlation between invasively measured left ventricular filling pressure and Doppler-derived E/e′ (29–31). E/e′ can therefore be used as a noninvasive means of estimating left ventricular diastolic pressure during exercise as well as at rest. A postexercise E/e′ greater than 13 is indicative of elevated left ventricular diastolic pressure (29,31). Patients without ischemia on exercise echocardiography who have Doppler-derived evidence of diastolic dysfunction at rest are more likely to have impaired exercise capacity and less favorable outcomes than those who have normal diastolic function (32,33). It has also been shown that exercise E/e′ is an independent and incremental predictor of cardiovascular outcomes (34). The specificity of an elevated E/e’ is improved by the concomitant finding of an elevated peak tricuspid regurgitant velocity. E/e’ can be falsely elevated in patients who have mitral annular calcification, left bundle branch block, or a paced rhythm.

FIGURE 16-12 Components of a contemporary exercise echocardiogram at Mayo Clinic. (DT, deceleration time; EF, ejection fraction; E and A, early (E) and late (A) diastolic mitral inflow velocities by pulsed-wave Doppler; e′, mitral annular early diastolic tissue Doppler velocity; LA, left atrium; RWMA, regional wall motion abnormalities; TR Vmax, tricuspid regurgitation peak velocity.)

Although the assessment of diastolic function is most commonly performed at the time of treadmill exercise echocardiography at our institution, a dedicated diastolic stress echocardiogram can be performed in selected patients using a supine bike exercise protocol where the above-described Doppler data are acquired at different stages of exercise. Right ventricular or pulmonary artery systolic pressure normally increases by approximately 8 to 10 mm Hg with exercise. The upper normal (i.e., 95th percentile) values for right ventricular systolic pressure after treadmill exercise are age-dependent and range from 50 to 55 mm Hg (Fig. 16-13) (35). The development of exercise-induced pulmonary hypertension is often seen in association with elevated left ventricular filling pressures but can also occur in isolation when there is pulmonary or pulmonary vascular disease. Normative values for right ventricular systolic pressure with exercise appear to be lower when a supine bike protocol is used and are in the range of 40 to 45 mm Hg.

HEMODYNAMIC SUPINE BIKE FOR VALVULAR

HEART DISEASES Stress echocardiography is frequently used to evaluate patients who have valvular heart disease in order to clarify the relationship between their symptoms and the hemodynamic severity of the valve lesion (36). This often aids in clinical decision-making. For example, a patient with exertional dyspnea who has moderate mitral stenosis on transthoracic echocardiography may have another cause for his or her symptoms such as left ventricular diastolic dysfunction, pulmonary disease, or deconditioning (see Chapter 13). In this situation, exercise testing with Doppler hemodynamics can be helpful for excluding mitral stenosis that is hemodynamically severe during exercise. Exercise testing using a supine bike is preferred in this situation so that Doppler data can be acquired at baseline and at different stages of exercise.

FIGURE 16-13 Normative values of right ventricular systolic pressure at rest and immediately after treadmill exercise, stratified by age. The peak velocity of the tricuspid regurgitation signal, acquired with continuous-wave Doppler before and immediately after treadmill exercise, was used to calculate the right ventricular systolic pressure (RVSP) in 469 subjects without known cardiopulmonary disease. The exercise protocol used was the Bruce protocol. The simplified Bernoulli equation (4v2) was used. Assumed right atrial pressure is 5 mm Hg. (Adapted from Kane GC et al. Impact of age on pulmonary artery systolic pressures at rest and with exercise. Echo Research and Practice, 2016;3:53–61, with permission.)

Dobutamine Echo Viability Protocol (5- minute Stages) Stage

Watts

I

25

II

50

III

75

IV

100

V

125

VI

150

VII

175

The Doppler data acquired by the sonographer include CW Doppler of the mitral inflow and tricuspid regurgitation jet, for measurement of the transmitral mean diastolic pressure gradient and tricuspid regurgitation peak velocity at rest and with exercise (Fig. 16-14). An increase in the mean mitral gradient to 15 mm Hg or more indicates that the mitral stenosis is hemodynamically significant and that the patient will likely benefit from an intervention such as percutaneous mitral balloon valvuloplasty or mitral valve replacement. Another supportive finding is that of exercise-induced right ventricular systolic pressure of 60 mm Hg or greater. Supine bike exercise echocardiography has been used to assess change in the severity of degenerative mitral regurgitation (37). Magne et al. found that the severity of degenerative mitral regurgitation increases with exercise in one-third of patients. Patients with a marked increase in regurgitant volume with exercise had lower symptom-free survival compared to those with decreased or unchanged mitral regurgitant volume (37). Exercise echocardiography in valvular heart diseases is also discussed in Chapter 13.

HYPERTROPHIC CARDIOMYOPATHY Although just over 1/3 of patients with hypertrophic cardiomyopathy have systolic anterior motion–related LVOT obstruction at rest, another 1/3 will have provocable obstruction, defined as a peak gradient of 50 mm Hg or greater (38). Interventions that are commonly used in the echocardiography laboratory to provoke LVOT obstruction include the Valsalva maneuver, amyl nitrite inhalation, and exercise testing. The last two are more likely to induce LVOT obstruction. If no significant obstruction is induced by the Valsalva maneuver or amyl nitrite inhalation, it is still worthwhile exercising the patient. We favor

upright treadmill exercise and immediate postexercise imaging with the patient positioned in the left lateral decubitus position. Continuous-wave Doppler, twodimensional, and color flow imaging is performed before and immediately after exercise to assess the peak LVOT velocity and gradient and the severity of any systolic anterior motion–related mitral regurgitation. Continuous-wave Doppler data of the mitral regurgitant jet are also acquired to prevent confusion with interpretation of the Doppler signal that might occur if there is contamination of the LVOT Doppler signal by mitral regurgitation (Fig. 16-15). Symptomatic patients who have inducible LVOT obstruction may require additional medical therapy. If symptoms remain refractory to medical therapy, ventricular septal reduction therapy with surgical myectomy or percutaneous septal ablation may be necessary (39). Dobutamine is not recommended as a stressor because it can induce LVOT obstruction in patients who do not have hypertrophic cardiomyopathy. Other findings on exercise echocardiography, including new regional wall motion abnormalities, are of prognostic value and may have a role in stratifying the cardiovascular risk of these patients (40).

FIGURE 16-14 Doppler-derived hemodynamics of mitral stenosis before and during supine bike exercise. A 47-year-old woman with mild exertional dyspnea had a transmitral mean diastolic gradient of 10 mm Hg at rest (heart rate 80 bpm). She exercised for 7 minutes on a supine bike protocol, stopping because of dyspnea. Continuous-wave Doppler data were acquired at 3 stages of exercise: transmitral mean gradient (A), tricuspid regurgitation (TR) peak velocity, and right ventricular (RV) systolic pressure (B). The diagnosis of hemodynamically severe mitral stenosis was confirmed. There was also severe exercise-induced pulmonary hypertension. The patient underwent percutaneous mitral balloon valvotomy with subsequent resolution of her symptoms. Assumed right atrial pressure is 5 mm Hg.

DOBUTAMINE ECHO FOR LOW-FLOW, LOWGRADIENT AORTIC STENOSIS

Some patients with calcific aortic stenosis have left ventricular systolic dysfunction (ejection fraction 6 cm ascending aorta and >7 cm descending thoracic aorta), traumatic aneurysm, and associated coronary and carotid artery disease. Rupture risk is a function of aneurysm size at recognition (0% for aneurysms 4 mm thick, mobile lesions, ulceration) in descending aorta has the strongest association with the presence of coronary artery disease (15). Antiplatelet agents, statin therapy, and aggressive modification of other cardiovascular risk factors are warranted in patients with aortic atherosclerosis. ACE inhibitors also reduce the risk of ischemic cardiovascular events in patients with aortic atherosclerosis. Warfarin may be beneficial for reducing subsequent embolic events in patients with mobile lesions, but it may also exacerbate embolism in some patients; further randomized trials are required. The treatment of choice in symptomatic patients is to identify the source of embolism and to

exclude it from the circulation with either surgical resection or placement of an endovascular graft.

ACUTE AORTIC SYNDROMES Acute aortic syndrome refers to a group of clinical syndromes including acute aortic dissection (AAD) and other variant forms of classic aortic dissection, notably aortic IMH, and PAU. Imaging findings, rather than clinical features, are critical in the differential diagnosis of acute aortic syndrome (16), and, therefore, careful interpretation of imaging results is necessary to provide an accurate diagnosis and improve clinical decision-making and patient outcomes.

AORTIC DISSECTION The most common predisposing factors for AAD are advanced age, male gender, hypertension, Marfan syndrome, and congenital abnormalities of the aortic valve (bicuspid or unicuspid valve). When AAD complicates pregnancy, it usually occurs in the third trimester. Iatrogenic aortic dissection, as a result of cardiac surgery or invasive angiographic procedures, can also occur. AAD involving the ascending aorta is designated as type A (proximal, type I, type II), and dissection confined to the descending thoracic aorta is designated as type B (distal, type III). The sudden onset of severe pain (often migratory) in the anterior chest, back, or abdomen is the most suggestive clinical finding in AAD (sensitivity [90%]; specificity [84%]). Additional findings include hypertension (36% type A, 70% type B), an aortic diastolic murmur (28%), pulse deficits or blood pressure differential (30% type A, 21% type B), and neurologic changes (17%) (17). Syncope in association with AAD occurs when there is rupture into the pericardial space, producing cardiac tamponade. Congestive heart failure is due most commonly to severe aortic regurgitation. Acute myocardial infarction (most commonly inferior infarction due to right coronary artery ostial dissection) and pericarditis are additional cardiac presentations.

FIGURE 20-7 A: Multiplane transesophageal echocardiogram (0-degrees imaging plane) exhibits variable degrees of immobile atherosclerotic disease (arrows) diffusely involving the descending thoracic aorta. B: Multiplane transesophageal echocardiogram (99-degrees imaging plane) reveals severe immobile atherosclerosis and a long, highly mobile thrombus in the distal transverse aortic arch. C: Real-time three-dimensional transesophageal echocardiogram demonstrates severe immobile atherosclerotic disease (*) as well as two mobile atherosclerotic lesions involving the proximal descending thoracic aorta.

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Video 20-7A

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Video 20-7B

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Video 20-7C Bedside calculation of the aortic dissection detection risk score can estimate the pretest probability of disease, allows for rapid identification of high-risk patients, and facilitates prompt evaluation and treatment (18). Routine blood tests are nonspecific in the diagnosis of AAD, although, in a large cohort of patients with suspected aortic dissection, the presence of an ADD risk score 0 or ≤1 combined with a negative D-dimer (5 mm) in the absence of detectable blood flow (Fig. 20-15) (30). With expansion, the hematoma may encroach on the aortic lumen and, if intimal calcium is present, displace it centrally. In clinical practice, multidetector CT is the best diagnostic modality, since it can image the entire aorta and branch vessels. The classification schemes and management of IMH are currently similar to AAD— operation for type A IMH and medical treatment for type B IMH.

FIGURE 20-15 A: Transverse transesophageal view of the descending thoracic aorta (Ao) showing an intramural hematoma in a patient with hypertension and severe back pain. The soft tissue mass with a smooth surface appears different from aortic debris. During the next 6 months, the intramural hematoma disappeared while the patient was taking antihypertensive medications, including a β-blocker. B: Long-axis transesophageal view showing intramural hematoma (arrows) in the ascending aorta (Ao). LA, left atrium.

INCOMPLETE AORTIC RUPTURE Incomplete aortic rupture (IAR) most often occurs in the region of the aortic isthmus (located between the left subclavian artery and the first intercostal arteries) in patients who sustain high-energy blunt chest trauma involving rapid deceleration, such as in a motor vehicle collision. IAR should be suspected when there is evidence of trauma to the chest wall, decreased or absent leg pulses, and left-sided hemothorax or widening of the superior mediastinum on chest radiography. Patients usually are hypertensive on initial presentation. Although the diagnosis of IAR can be confirmed with TEE, CT, MRI, or aortography, contrast-enhanced CT and TEE are currently the predominant imaging modalities. Characteristic TEE findings include disruption of the aortic wall and the presence of a thick and irregular intraluminal flap traversing the lumen of the aorta in the transverse plane, in the region of the aortic isthmus (25 to 35 cm from the incisors, immediately distal to the origin of the left subclavian artery) (Figs. 20-16 and 20-17). In the longitudinal view, the intraluminal flap is nearly perpendicular to the aortic wall, since traumatic lesions are usually confined to a

few centimeters. Color Doppler echocardiography demonstrates similar blood flow velocities on both sides of the lesion. An abnormal aortic contour is also commonly seen due to the acute formation of a localized false aneurysm (pseudoaneurysm).

FIGURE 20-16 Transesophageal view of a ruptured (arrows) descending aorta (Ao) that resulted in a pseudoaneurysm (PsA) with thrombus (T). This image is from a patient who was in a motor vehicle accident 3 years before this study was performed.

TEE has high sensitivity (91%–100%) and specificity (98%–100%) and can be performed in hemodynamically unstable patients in the emergency department or the operating room, requires no contrast, and provides additional information on cardiac and valvular function, as well as pericardial effusion (30). TEE is operator dependent and is also limited by loss of sensitivity as the interposition of the air-filled trachea between the aorta and esophagus creates a blind spot, precluding adequate evaluation of the distal ascending aorta and proximal arch. In addition, TEE should not be performed in patients with unstable cervical spine injuries or esophageal injuries. TEE compares favorably to angiography or CT scan in the majority of cases and can identify some intimal tears not seen on corresponding angiography. TTE cannot reliably exclude the diagnosis of IAR and, therefore, should not be used for this indication.

FIGURE 20-17 A: Multiplane transesophageal echocardiogram in the transverse (0 degree) imaging plane demonstrates a thick and intraluminal flap (arrow) traversing

the lumen of the aorta in the region of the aortic isthmus, immediately distal to the origin of the left subclavian artery in a patient with incomplete aortic rupture following a motor vehicle accident. B: In the longitudinal plane, the intraluminal flap (arrow) is nearly perpendicular to the aortic wall, a characteristic feature of incomplete aortic rupture.

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Video 20-17A

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Video 20-17B No single imaging test can identify all cases of IAR; therefore, more than one imaging test may be required to establish the diagnosis. Computed tomography and TEE are the major diagnostic modalities currently used to evaluate traumatic aortic injury. Given the high sensitivity and specificity of CT for thoracic aortic injury and the wide availability of CT in the emergency setting, it is the diagnostic test of choice for hemodynamically stable patients. TEE is primarily indicated in the assessment of hemodynamically unstable patients and in those patients with equivocal CT findings. Treatment of IAR is an emergent surgical repair in patients who are suitable

surgical candidates (31). At initial presentation, 40% to 50% of the patients are unstable, and there are no clinical or imaging criteria that accurately predict future complete rupture. Therefore, even if a patient presents with a chronic incomplete rupture, surgery is indicated. Furthermore, most of the patients are young, and the risk of elective surgical repair is low, with an otherwise good prognosis for long-term survival if aortic repair is successful. Thoracic endovascular aortic repair can be performed with acceptable results in a highrisk population (32).

AORTITIS Aortitis is a pathologic term for the presence of inflammatory changes of the aortic wall. Aortic wall inflammation may be of infectious etiology but is more common of noninfectious origin. Infectious aortitis is usually the result of septic embolism that may result in mycotic aneurysm formation, but bacteremia and spread of contiguous infection, as well as chronic syphilis, can also occur. Inflammatory disorders that are associated with the development of aortitis include giant cell arteritis, Takayasu arteritis, rheumatoid arthritis, ankylosing spondylitis, granulomatosis with polyangiitis, reactive arthritis, and Behçet disease. Multimodality imaging of aortitis is useful to identify acute and chronic mural changes due to inflammation, edema, and fibrosis, as well as detection of an aneurysm, stenosis or occlusion (33). PET is the most sensitive test for early vessel inflammation; however, CT or MR imaging is required for anatomic localization. CT provides excellent anatomical characterization of structural aortic changes but is limited in its assessment of early disease activity. MR provides characterization of both early inflammatory vessel changes and late structural changes, as well as dedicated cardiac and valvular assessment. Echocardiography can provide both anatomical and physiologic information regarding aortic and valvular abnormalities. Although not primarily utilized in the diagnosis of aortitis, TTE and TEE can provide useful information. Echocardiography is accurate in identifying complications of aortitis such as aortic dilatation, aortic aneurysm, and aortic valve insufficiency, as well as secondary myocardial dysfunction. Other suggestive features of aortitis on TEE include a diffuse and homogeneous increase in aortic wall thickness (Fig. 20-18). In chronic aortitis, thoracic aortic stenosis and aneurysm formation may occur. Ankylosing spondylitis most

frequently affects the aortic root and results in dilatation, wall thickening, and nodularities of the aortic cusps. Syphilis most frequently affects the aortic root resulting in aneurysmal dilatation.

FIGURE 20-18 Transesophageal images from a 61-year-old man with giant cell arteritis who presented with fever of unknown origin, erythrocyte sedimentation rate of 102 mm/1h, and jaw claudication. Descending thoracic aorta (Ao) (A) and arch (Arch) (B) views showed increased thickness of the intima (arrows) due to aortitis, which has an appearance similar to that of intramural hematoma.

AORTIC TUMOR AND MASS Aortic sarcomas are rare and aggressive tumors with a propensity for arterial embolization, disseminated metastases, and rapid clinical deterioration. Clinically, most of these patients present with symptoms such as abdominal pain, unrelenting hypertension, lower extremity claudication, or symptoms of distal embolization. MRI, CT, and positron emission tomography are the preferred noninvasive tests for diagnosis (34). The diagnosis of aortic sarcoma with echocardiography (TTE/TEE) is difficult. TEE findings in aortic sarcoma include an inhomogeneous and echo-dense mass with an outer membrane, unlike a thrombus, suggestive of a primary aortic tumor (Fig. 20-19).

FIGURE 20-19 In a patient with mesenteric ischemia, transthoracic echocardiography (subcostal view) in the longitudinal plane demonstrated a broad-based mass (arrows) with a smaller mobile component attached to the wall of the proximal abdominal aorta. Subsequent surgical pathology demonstrated the mass to be grade 4 epithelioid angiosarcoma with associated organizing thrombus.

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Video 20-19 Prognosis is poor overall, but long-term survivors have been reported in the setting of aggressive management. Due to the paucity of cases worldwide, knowledge of the diagnosis and management of aortic sarcoma is limited. Paragangliomas are neuroendocrine tumors that can be either benign or

malignant and can be hormonally active or inactive. Approximately 2% of paragangliomas are found in the mediastinum, where they most commonly present as an anterior or posterior mediastinal mass, less commonly as a middle mediastinal mass (35). Paragangliomas do not occur commonly in the chest, but when they do, the hormonally inactive tumors are more frequent in the pericardium, while hormonally active tumors (pheochromocytomas) more frequently arise elsewhere in the thorax. Characteristic features of paraganglioma on echocardiography include a well marginated and round or ovoid-shaped mass of variable diameter, with homogeneous and moderate echogenicity (36) (Fig. 20-18). Paraganglioma can compress or invade the adjacent aorta and influence hemodynamics. Complete resection of tumor is usually possible. As is true of all pheochromocytoma resections, preoperative and intraoperative adrenergic blockade must be employed. We have also seen a large sessile or mobile mass in the aorta that turned out to be a thrombus (Fig. 20-20) and also in another case was associated with malignancy and infection (Fig. 20-21). Their initial presentation was an embolic event to various organs. There have been reports of resolving thrombotic mass in the aorta with anticoagulation, but it is often difficult to distinguish thrombus from other etiologies. Unless contraindicated, it may be clinically reasonable to try anticoagulation for 4 to 6 weeks and reassess before consideration of surgical removal (Fig. 20-22).

FIGURE 20-20 Intraoperative multiplane transesophageal echocardiogram in a patient with posterior mediastinal paraganglioma reveals a large, well-circumscribed inhomogeneous mass (*) adjacent to the distal descending thoracic aorta.

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Video 20-20

FIGURE 20-21 A: Suprasternal notch view of the ascending and transverse aorta showing a large sessile mass (*) in a young woman with multiple embolic events. The mass disappeared on 2 days of intravenous anticoagulation, but the mass returned with another embolic event. The patient was taken to the operating room for a surgical removal. B: Intraoperative transesophageal echocardiography shows a mass (*) with mobile component (2D left and 3D right). Pathology demonstrated thrombus. Comprehensive evaluation showed no coagulopathy or malignancy.

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Video 20-21A

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Video 20-21B

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Video 20-21C

FIGURE 20-22 This transesophageal echocardiogram (2D top, 3D bottom) of the descending thoracic aorta was obtained from an 82-year-old man with fever, night sweats, and weight loss as well as multiple painful toes. There was mobile mass (arrows and asterisk), which was not present on a TEE 2 days prior that was performed for evaluation of endocarditis. He was also found to have epithelioid hemangioendothelioma with lytic lesions in the spine.

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Video 20-22A

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Video 20-22B

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Video 20-22C

COARCTATION OF THE AORTA Acquired coarctation of the aorta may occur in the setting of prior aortic surgery, blunt thoracic aortic injuries, aortic tumor, bulky atherosclerotic lesions (coral reef aorta), and chronic Takayasu disease (37). Characteristic TTE findings include narrowing of the descending thoracic aorta and an increase in Doppler velocity across the narrowing and diastolic forward flow in the proximal abdominal aorta. TEE is usually required to visualize the obstructing lesion. Congenital coarctation of the aorta is covered in Chapter 21.

REFERENCES 1. Goldstein SA, Evangelista A, Abbara S, et al. Multimodality imaging of diseases of the thoracic aorta in adults: From the American Society of Echocardiography and the European Association of

Cardiovascular Imaging: Endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance. Journal of the American Society of Echocardiography, 2015;28(2): 119–182. 2. Amsallem M, Ou P, Milleron O, et al. Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography. International Journal of Cardiology, 2015;184:22–27. 3. Vriz O, Aboyans V, D’Andrea A, et al. Normal values of aortic root dimensions in healthy adults. The American Journal of Cardiology, 2014;114(6):921–927. 4. Campens L, Demulier L, De Groote K, et al. Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories. The American Journal of Cardiology, 2014;114(6): 914–920. 5. Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. The Annals of Thoracic Surgery, 2002;74(5): S1877–S1880. 6. Ghulam Ali S, Fusini L, Dalla Cia A, et al. Technological advancements in echocardiographic assessment of thoracic aortic dilatation: Head to head comparison among multidetector computed tomography, 2-dimensional, and 3-dimensional echocardiography measurements. J Thorac Imaging, 2018; 33(4):232–239. 7. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography. A report of the American College of Cardiology Foundation appropriate use criteria task force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance American College of Chest Physicians. Journal of the American Society of Echocardiography, 2011;24(3): 229– 267. 8. Hiratzka L, Creager M, Isselbacher E, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves: A statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 2016;133(7):680–686. 9. Hiratzka LF, Creager MA, Isselbacher EM, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves: A statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 2016;67(6):724–731. 10. Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA, 2011;306(10):1104–1112. 11. Weinreich M, Yu PJ, Trost B. Sinus of valsalva aneurysms: Review of the literature and an update on management. Clinical Cardiology, 2015;38(3):185–189. 12. Bird A-N, Davis AM. Screening for abdominal aortic aneurysm. JAMA, 2015;313(11):1156–1157. 13. Parkinson F, Ferguson S, Lewis P, et al. Rupture rates of untreated large abdominal aortic aneurysms in patients unfit for elective repair. Journal of Vascular Surgery, 2015;61(6):1606–1612. 14. Aboyans V, Bataille V, Bliscaux P, et al. Effectiveness of screening for abdominal aortic aneurysm during echocardiography. The American Journal of Cardiology, 2014;114(7):1100–1104. 15. Gu X, He Y, Li Z, et al. Relation between the incidence, location, and extent of thoracic aortic atherosclerosis detected by transesophageal echocardiography and the extent of coronary artery disease by angiography. The American Journal of Cardiology, 2011;107(2):175–178. 16. Acute aortic syndromes: diagnosis and management, an update. Eur Heart J, 2018;33(9):739–749.

17. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA, 2000;283(7):897–903. 18. Rogers AM, Hermann LK, Booher AM, et al. Sensitivity of the aortic dissection detection risk score, a novel guideline-based tool for identification of acute aortic dissection at initial presentation results from the International Registry of Acute Aortic Dissection. Circulation, 2011;123(20):2213–2218. 19. Nazerian P, Morello F, Vanni S, et al. Combined use of aortic dissection detection risk score and Ddimer in the diagnostic workup of suspected acute aortic dissection. International Journal of Cardiology, 2014;175(1):78–82. 20. Bossone E, Suzuki T, Eagle K, et al. Diagnosis of acute aortic syndromes: Imaging and beyond. Herz, 2013;38(3):269–276. 21. Cecconi M, Chirillo F, Costantini C, et al. The role of transthoracic echocardiography in the diagnosis and management of acute type A aortic syndrome. American Heart Journal, 2012;163(1):112–118. 22. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation, 2010;121:1544–1579. 23. Booher AM, Isselbacher EM, Nienaber CA, et al. The IRAD classification system for characterizing survival after aortic dissection. The American Journal of Medicine, 2013;126(8): 730.e19–730.e24. 24. Bossone E, Gorla R, LaBounty TM, et al. Presenting systolic blood pressure and outcomes in patients with acute aortic dissection. J Am Coll Cardiol, 2018;71(13):1432–1440. 25. Disabella E, Grasso M, Gambarin FI, et al. Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2). Heart, 2011;97(4): 321–326. 26. Lansman SL, Saunders PC, Malekan R, et al. Acute aortic syndrome. The Journal of Thoracic and Cardiovascular Surgery, 2010;140(6):S92–S97. 27. Cheng D, Martin J, Shennib H, et al. Endovascular aortic repair versus open surgical repair for descending thoracic aortic disease: A systematic review and meta-analysis of comparative studies. Journal of the American College of Cardiology, 2010;55(10):986–1001. 28. Slavich M, Bertoglio L, Fisicaro A, et al. The role of contrast enhanced transesophageal echocardiography in the diagnosis and in the morphological and functional characterization of acute aortic syndromes. The International Journal of Cardiovascular Imaging, 2014;30(1):31–38. 29. Uchida K, Imoto K, Karube N, et al. Intramural haematoma should be referred to as thrombosed-type aortic dissection. European Journal of Cardio-Thoracic Surgery, 2013;44(2): 366–369. 30. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. European Heart Journal, 2014;35(41):2873–2926. 31. Spencer SM, Safcsak K, Smith CP, et al. Nonoperative management rather than endovascular repair may be safe for grade II blunt traumatic aortic injuries: An 11-year retrospective analysis. J Trauma Acute Care Surg, 2018;84(1):133–138. 32. Patel HJ, Williams DM, Drews JD, et al. A 20-year experience with thoracic endovascular aortic repair. Annals of Surgery, 2014;260(4):691–696. 33. Hartlage GR, Palios J, Barron BJ, et al. Multimodality imaging of aortitis. JACC. Cardiovascular Imaging, 2014;7(6):605–619.

34. Rusthoven CG, Liu AK, Bui MM, et al. Sarcomas of the aorta: a systematic review and pooled analysis of published reports. Annals of Vascular Surgery, 2014;28(2):515–525. 35. Wald O, Shapira OM, Murar A, et al. Paraganglioma of the mediastinum: Challenges in diagnosis and surgical management. Journal of Cardiothoracic Surgery, 2010;5:19. 36. Li L, Zhu W, Fang L, et al. Transthoracic echocardiographic features of cardiac pheochromocytoma: A singleinstitution experience. Echocardiography, 2012;29(2):153–157. 37. Palcau L, Gouicem D, Cameliere L, et al. Calcified obstructive disease of the aortic arch. Interactive Cardiovascular and Thoracic Surgery, 2014;18(5):683–684.

CHAPTER

21

Congenital Heart Disease Patrick O’Leary, Naser Ammash, and Frank Cetta

Congenital heart disease (CHD) is one of the most common birth defects, involving approximately 1% of live births. CHD can often be life threatening and at times necessitate intervention in infancy and early childhood. The success of these interventions is dependent on clear anatomic and functional understanding of the anomalies. Echocardiography has become the primary tool used to evaluate these hearts. Due to progressive improvements in medical care, diagnostic imaging, surgical/interventional techniques, and critical care for CHD, it is estimated that over 90% of infants with CHD will survive to reach adulthood. As a result, the number of adults with CHD now exceeds the number of children with CHD in the United States. Current estimates suggest that the growth rate for the U.S. adult “CHD population” is approximately 5%/year. Patients with CHD represent a heterogeneous group including simple defects (atrial septal defects, ventricular septal defects [VSDs], coarctation of the aorta) and complex malformations such as Ebstein anomaly, tetralogy of Fallot (TOF), transposition of the great arteries, and functionally univentricular hearts. It is commonly recognized that repairs of CHD are not “curative.” As a result, many residua and complications after repair of CHD continue to require evaluation and potentially reintervention in adulthood. These issues and the expanding population of adults with CHD emphasize the need for both “pediatric” and “adult” cardiac sonographers to understand these malformations. Echocardiographic imaging in those with CHD can be challenging for those who do not perform these examinations frequently due both to the broad spectrum of malformations and patient to patient variability. This chapter will first describe an approach to imaging CHD patients that can be applied by/to all and will conclude with sections illustrating the varied presentations and echocardiographic features of common forms of CHD both before and after repair.

SEGMENTAL APPROACH TO CONGENITAL HEART DEFECTS A systematic method for echocardiographically evaluating CHDs is required to understand the anatomic and the resultant pathophysiologic disturbances seen in these patients. The first step in any analysis of the cardiovascular system is to determine the position and orientation of the cardiac structures within the thorax relative both to adjacent CV structures and also to the surrounding organ systems, primarily the lungs and abdominal viscera. Once this information is outlined, the cardiovascular system can be divided into segments for more detailed analysis. Typically, the cardiovascular system thought to be composed of four major segments and the three connections between these segments (Fig. 21-1). The segments are the great veins, the atria, the ventricles, and the great arteries. The connections consist of the venous connections to the atria (venoatrial), the atrioventricular (AV) connection (primarily the AV valves; mitral and tricuspid, or common, and the ventriculoarterial [VA] connection, namely, the semilunar valves [aortic and pulmonary or truncal]). The echocardiographic examination must not only assess the position and size of each segmental component but one must also define the functional status and state of septation (separation of the right-sided from the left-sided circulatory structures) of all structures within a segment. For example, a complete evaluation of the ventricular segment includes descriptions of the positions of the two ventricular chambers (both in space and relative to the other ventricle); the size of the chambers; assessments of contractility, relaxation, and wall thickness; and an anatomic description of the ventricular septum (usually focusing on its relation to the outflow tracts and the presence or absence of VSDs). Similarly, an examination of a connection should include descriptions of the position, anatomy, “appropriateness” of the connection (e.g., pulmonary veins “appropriately” connect to the left atrium [LA], not to the superior vena cava [SVC]), and the functional status of the connection (e.g., to what degree is there stenosis or regurgitation?). By following this type of systematic approach, even the most complex malformations can be described accurately and completely (1–6).

FIGURE 21-1 Segmental approach to CHD. A diagrammatic representation of the four major cardiovascular segments and the three connections between these segments.

IMAGE ORIENTATION IN CONGENITAL HEART DEFECTS CHDs involve structural and positional abnormalities that can be complex and do not necessarily follow expected norms. Therefore, congenital echocardiographic examinations tend to orient images using the congenital (anatomic) conventions described below (7). These conventions dictate that the image should be oriented based on the major axes of the body and in the same way for every exam, independent of the imaging technique used (transthoracic echocardiography [TTE], transesophageal echocardiography [TEE] (8), or intracardiac echocardiography). Horizontal views, such as parasternal short-axis scans, are displayed with anterior structures toward the top of the image and leftsided structures to the viewer’s right. Sagittal views, such as a parasternal longaxis scan, are displayed with anterior structures toward the top of the image and superior structures to the viewer’s right. Coronal views, such as the apical fourchamber scan, are displayed with superior structures at the top of the image and left-sided structures to the viewer’s right (American Society of Echocardiography option one; (9)). These imaging conventions provide a consistent and unambiguous display of the anatomy, with the viewer “looking” at the heart as from apex to base (horizontal plane), from anterior to posterior (coronal plane), or from left to right (sagittal plane), even when the cardiac structures are markedly displaced.

CLINICAL PRESENTATIONS OF CONGENITAL HEART DEFECTS Prenatal and Neonatal The prenatal presentation of CHD is most often the result of an abnormal cardiac appearance discovered during a screening obstetric ultrasound examination and less frequently due to heart failure or an abnormal rhythm (10,11). These fetal patients often have complex anatomic malformations involving the AV valves (AV canal defects, Ebstein anomaly) or abnormalities that create disproportion between the size of the right-sided and left-sided cardiac structures (functionally univentricular hearts, critical outlet stenoses, or atresia of a connection). These complex lesions dominate the prenatal presentation of CHD because screening obstetric examinations depend primarily on appearance of the four-chamber view of the heart (normal or abnormal) to predict the presence of CHD. However, many important malformations do not alter the four-chamber view (particularly before the 16th week of gestation when most of these scans are performed). Consequently, lesions such as transposition of the great arteries, with normal four-chamber appearances, are underrepresented in reports of prenatal CHD. When scans of the great arteries are included in obstetric screening studies, the detection rates for important neonatal cardiac defects increase significantly (12). Neonatal presentations of CHD can be quite variable, ranging from a prominent heart murmur in a healthy baby to the cyanotic newborn in shock due to a ductal-dependent malformation. For these patients, TTE is the cornerstone for diagnosis and evaluation. Most neonates with symptomatic CHD will have either a critical obstructive lesion or a complex malformation that results in cyanosis. These babies often require urgent intervention. However, in cases where pulmonary vascular resistance remains high after birth, selected defects that usually are considered to have primarily left-to-right shunt physiology (e.g., complete AV septal defects) can demonstrate transient but significant cyanosis. As pulmonary resistance decreases and pulmonary flow increases, the shunts reverse and the patient may display the pulmonary overcirculation expected from their anatomic defect. Only direct cardiac imaging, usually with TTE, can distinguish the cyanotic newborn in need of urgent intervention from those that will improve without such treatment. The role of TEE in neonatal cardiology is primarily for intraoperative evaluation during the surgical repairs performed in

these young patients.

Pediatric and Adult Presentations of Congenital Heart Disease Infants, children, and adolescents with CHD may present with heart murmurs, heart failure, cyanosis, or failure to thrive or may remain asymptomatic for many years (if they have “balanced” circulations). Although adults with CHD can have similar presentations, older CHD patients tend to manifest more exercise intolerance, dyspnea on exertion, lower extremity edema, stroke, and atrial arrhythmias than do pediatric patients. These presenting symptoms and signs are mostly nonspecific and should lead to a generalized CV evaluation. However, certain constellations of problems can at times point one toward more specific anatomic or hemodynamic problem. For example, progressive cyanosis usually results from decreasing pulmonary blood flow suggesting either a progression in pulmonary stenosis or gradually increasing pulmonary arterial pressure/resistance when there is a coexisting intracardiac shunt (ASD or VSD). Alternatively, differential cyanosis of the lower extremities (blue feet/pink hands), in an adult, should strongly suggest the presence a patent ductus arteriosus complicated by Eisenmenger syndrome. Multimodality imaging techniques provide important information to supplement TTE in many clinical scenarios. TEE, cardiac computed tomography (CT), and magnetic resonance imaging (MRI) are all extremely useful adjuncts to TTE, especially in the larger or postoperative patient. Cardiac CT and MRI are of particular benefit when evaluating the adult with abnormalities of the great veins or the thoracic aorta. The remainder of this chapter will discuss the spectrum of CHD from the perspective of cardiac imaging, primarily focusing on TTE, but with supplemental information relative to other imaging modalities where they are most useful.

MALFORMATIONS ASSOCIATED WITH SHUNT PHYSIOLOGY Atrial Septal Defects Atrial septal defects (ASD) are one of the most common forms of CHD. They

can present in either childhood or in adult life. Typically, an ASD results in a left-to-right shunt crossing the atrial septum from the LA to the RA. The volume of that shunt flow is proportional to the size of the ASD, but right ventricular (RV) compliance, RV outflow stenosis, and/or pulmonary arterial (PA) resistance can also influence the volume of shunt flow and right heart enlargement. Atrial septal defects can be seen in isolation or can be encountered in association with other defects. Associated defects range from “simple” (partial anomalous pulmonary venous connections [PAPVCs], VSD, or pulmonary stenosis [PS]) to more complex forms of CHD, such as TOF, functionally single ventricle physiology or Ebstein malformation. TTE and TEE play very important roles in the diagnosis and assessment of patients with ASD, both before and after surgical or percutaneous closure (13). Since ASDs are rarely perfect circles, it is very important to image the atrial septum from multiple echocardiographic planes. This will ensure that the position and maximal dimensions of a defect are demonstrated and will allow for definition of all of the tissue rims surrounding the circumference of the defect. Understanding the tissue rims surrounding the defect is critical to selecting an appropriate intervention (surgical vs. device closure). The examiner must also remember that multiple ASDs can be present in the same patient. In addition to the anatomy of the ASD, the exam should assess the degree of shunting/right heart enlargement, the presence/absence of RV outflow stenosis, the presence and severity of pulmonary hypertension (if any), the amount of tricuspid regurgitation, and other associated CHD, most commonly PAPVC. Secundum ASDs are the most common of these defects, accounting for 60% to 75% of all ASDs. Secundum defects are deficiencies in the central, thin segment of the atrial septum and can be circular, oblong, or elliptical in shape (Figs. 21-2 and 21-3). In patients who have poor acoustic windows, the cause of right atrial (RA) or right ventricular (RV) enlargement may not be immediately evident during TTE examination. In these situations, TEE is very helpful. Not only can the atrial septum and ASD be defined in great detail (Fig. 21-4), but other causes of RV enlargement can also be excluded, such as PAPVC. In appropriately selected cases, transcatheter closure of secundum ASD can be accomplished with good results. Consequently, this approach has been the treatment of choice in many centers. It should be noted that percutaneous closures are only appropriate for secundum defects, as all other forms of ASD lack the circumferential tissue rims to support currently available devices. Echocardiography has an important role in preintervention patient selection and

in guiding ASD device placement in the catheterization laboratory. Before catheter closure of secundum ASD, it is important to exclude/define additional abnormalities that would require surgical rather than device therapy, such as PAPVC and tricuspid regurgitation. In addition, the size of the ASD must be defined, and the amount of atrial septal tissue present along the four primary rims (superior, apical, anterior, and posterior) of the defect should be quantified. In general, a minimum of 5 mm of tissue “rim” is needed to adequately secure a closure device (Fig. 21-5). TEE allows excellent visualization of not only the tissue rims but also the structures adjacent to the defect and a better appreciation of defect shape (particularly with three-dimensional imaging) (Figs 21-6 and 217). During device deployment, TEE or intracardiac echocardiography are used to guide delivery and placement of the occluder. TEE images of successfully deployed occlusion devices are shown in Figure 21-8.

FIGURE 21-2 Secundum ASD. A: Parasternal short-axis image showing right ventricular (RV) dilatation from a secundum atrial septal defect (ASD). B: Apical fourchamber view shows dilatation of the right atrium (RA) and RV in the same patient. There appears to be a dropout in the echo return from the atrial septum in B. Although this patient did have an ASD, the apical four-chamber image is not a reliable

view for detecting or quantifying the size of a secundum ASD because the scan plane is parallel with the thinnest portion of the septum in this view; therefore, the apparent dropout is often an artifact. C: A subcostal four-chamber view showing the dropout in the atrial septum as well as right ventricular enlargement. D: Parasternal short-axis view demonstrating the ASD with a defect dimension of 2.3 cm (measurement markers). A, anterior; L, left; LA, left atrium; LV, left ventricle; S, superior.

FIGURE 21-3 Secundum ASD. Typical anatomy of a moderate secundum ASD from subcostal window. A: Subcostal sagittal plane image (bicaval view) showing the central gap in the septum typical of a secundum defect (arrows). Asterisk, superior vena cava; LA, left atrium; P, posterior; RA, right atrium; S, superior. B: Color Doppler map showing the shunt flow crossing from LA to RA (arrow). To obtain the bicaval (sagittal) view (A), the scan plane was rotated clockwise approximately 90 degrees from the subcostal four-chamber (coronal) plane in (B).

FIGURE 21-4 Secundum ASD. A: Two-dimensional transesophageal echocardiographic (TEE) longitudinal plane view of the atrial septum demonstrating a moderate secundum ASD. B: Color flow Doppler image shows the left-to-right shunt.

TEE should be strongly considered in cases in which the clinical suspicion of an ASD is high on the basis of either physical examination findings or the presence of unexplained right ventricular and right atrial (RA) dilatation on surface images. In older patients, TEE can also be used to better define the edges, or rims, of the defect in an attempt to determine the suitability for a catheter-based device closure. A, anterior; LA, left atrium; S, superior.

FIGURE 21-5 Secundum ASD (assessing tissue “rims”). The tissue rims, which are outlined by the arrows, are demonstrated in the three major plains; base to apex (panels A and B), superior/inferior (Panel C), and anterior/posterior (panel D). The rims shown in (panels A and C) should be adequate to secure a device (>5 mm). However, the basal/posterior rim in (panels B and D) was less than 3 mm in length and was not likely to adequately secure a closure device. The small anterior (retroaortic) rim in this example (panel D) presents less of a problem for device stability. However, the small posterobasal rim argued strongly for surgical referral. The asterisk in panel B indicates the center of the ASD, while the asterisk in panel C shows the postion of the superior vena cava. A, anterior; Ao, aorta; L, left; LA, left atrium; LV, left ventricle; P, posterior; RA, right atrium; RV, right ventricle; S, superior.

Primum ASDs represent approximately 15% of all ASDs and are one form of a group of malformations characterized by arrested endocardial cushion development. These defects will be discussed and illustrated more completely in

the section of the chapter outlining all forms of endocardial cushion-related anomalies (atrioventricular septal defects).

FIGURE 21-6 Secundum ASD. This series of figures and videos represent a

combination images from a transthoracic examination (upper panels) and subsequent transesophageal echocardiography (middle and lower panels). The two upper still images in the figure are taken from a subcostal transducer position and demonstrate the atrial septum, with two dimensional the dropout suggesting a defect and color flow confirming the presence of a shunt. TEE imaging improves definition of the ASD and its associated left-to-right shunt has seen in the middle panels of the figure. The lower panel is three-dimensional representations of the atrial septum obtained by transesophageal imaging. One can see that the defect itself (indicated by the asterisk) is relatively smooth and circular in nature with significant rims of tissue surrounding and separating it from adjacent cardiovascular structures. A, anterior; Ao and AOV, aortic valve; IAS, interatrial septum; L, left; LA, left atrium; P, posterior; RA, right atrium; S, superior.

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Video 21-6A

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Video 21-6B

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Video 21-6C

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Video 21-6D

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Video 21-6E

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Video 21-6F

FIGURE 21-7 Secundum ASD. These images were taken from a transesophageal echocardiogram performed in a patient with a large secundum atrial septal defect. The still image on the left of figure shows what appears to be a centrally positioned atrial septal defect (asterisk) of nearly 2 cm in diameter. However, with threedimensional imaging (right hand panel), it became clear that the defect is larger in an anterior to posterior dimension than was appreciated in the four-chamber plane to the left. In addition, there was a secondary orifice shown by the red arrow. The accompanying video actually reveals that the two defects are confluent making device closure significantly more complicated. This case highlights how three-dimensional imaging can improve the understanding of ASD “shape,” potentially influencing treatment strategies. L, left; LA, left atrium; RA, right atrium; S, superior.

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Video 21-7

FIGURE 21-8 ASD occluder. Transesophageal echocardiographic appearance of ASD occlusion device. A: Longitudinal (bicaval) view of an Amplatzer Atrial Septal Occluder shortly after placement within a secundum ASD. Both disks are fully deployed on the appropriate sides of the septum. The hub used to connect the device to the delivery wire is on the right atrial surface (arrow in A and B). B: Horizontal (short-axis) image of a similar Amplatzer Atrial Septal Occluder after device deployment. Echocardiographic evaluation after the occlusion device has been placed requires imaging in all planes with color flow Doppler to exclude residual shunt. Twodimensional imaging needs to ensure there is no thrombus formation or interference with surrounding cardiovascular structures. Ao, aorta; LA, left atrium; RA, right atrium; SVC, superior vena cava.

Sinus venosus atrial septal defects represent less than 5% of ASDs and occur (most commonly) in the superior and posterior aspect of the atrial septum, near the SVC to RA junction (Fig. 21-9). As a result, these defects lie in a more horizontal plane than secundum and primum defects (Fig. 21-10). The deficiency of tissue usually includes the wall separating the vena cavae from the pulmonary veins, leading to the nearly universal association of PAPVC with this malformation (Figs. 21-11 and 21-12). Occasionally, the venosus septal

deficiency can extend posteriorly and inferiorly toward the IVC. In rare cases, the defect may only involve the inferior portion of the septum

FIGURE 21-9 Sinus venosus ASD. Subcostal views showing a sinus venosus ASD (asterisk). A: Biatrial view (coronal plane), similar to a four-chamber plane but focused on the atria. The typical sinus venosus ASD (asterisk) is positioned superiorly and posteriorly near the superior vena cava (SVC) orifice (arrow). In this plane (shown in A and B), the SVC often seems to be related to both atria. However, it is normally connected to the right atrium (RA), as shown in (B) and (C). Note the proximity of the SVC and RA junction with the defect. The anomalous right pulmonary veins are not seen on these images and are often best demonstrated from the right or high left parasternal windows. When the pulmonary veins are not evident with surface imaging, transesophageal echocardiography (TEE) provides excellent definition of the right pulmonary venous connections. C: Color flow map showing the large left-to-right shunt associated with the defect. Note that standard subcostal four-chamber imaging may not detect a sinus venosus defect. If right-sided volume overload is present and the atrial septum appears intact, the transducer should be tilted superiorly and rotated clockwise to visualize the septum near the SVC and RA junction (sagittal view). In many older children and adults, this area cannot be visualized adequately during a transthoracic examination. TEE can provide excellent delineation of the venosus septum and right pulmonary veins in these cases. IVC, inferior vena cava; LV, left ventricle; P, posterior; PA, pulmonary artery; RPA, right pulmonary artery; RV, right ventricle; S, superior.

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Video 21-9A

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Video 21-9B The most common PAPVCs seen in sinus venosus ASD involve the right upper or middle veins (or both), connecting to either the SVC or RA. In those with inferior extension of a venosus ASD, the right lower vein may also connect anomalously, usually to the RA. In older patients, TEE is often required to confidently visualize these posteriorly positioned abnormalities. A comprehensive echocardiographic study in a patient with an ASD requires not only imaging the defect and its associated rims but also evaluating right heart enlargement and RV and pulmonary artery pressure. The hemodynamic assessment is based on Doppler quantification of the tricuspid and pulmonary regurgitation velocities. Attention to septal flattening and RV wall thickness is also helpful. Diastolic flattening is indicative of RV volume overload, while systolic flattening is associated with increased systolic pressure. The latter should prompt a search for other causes of pulmonary or RV hypertension. Pulmonary hypertension due to an isolated ASD is unusual, while RV outflow obstructions are not uncommon. It is not typically necessary to quantify shunt volume with Doppler measurements using the continuity equation. In fact, such assessments are often inaccurate because of the number of component measurements involved in the calculation of multiple stroke volumes and the variation in right heart stroke volume associated with the respiratory cycle. The two-dimensional (2D) finding of moderate RV enlargement is a clinically sufficient reason to recommend ASD closure, even in the asymptomatic patients. This is especially true when there is documentation of progression in the degree of RV enlargement over time.

FIGURE 21-10 Sinus venosus ASD. These subcostal “bicaval” views are oblique sagittal images of the upper atrial septum. The two-dimensional image on the left revealed that the communication between the right and left circulations exists above the limbus of the true atrial septum, at the junction of the SVC and right atrium (*). Color flow Doppler seen in the right hand panel confirms the presence of a significant shunt flow at this level. A, anterior; L, liver; LA, left atrium; RA, right atrium; S, superior.

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Video 21-10A

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Video 21-10B An unroofed coronary sinus is often referred to as a “coronary sinus ASD.” However, although there is a left-to-right atrial shunt in most of these cases, the defect is not within the atrial septum. Instead, the anterior wall of the coronary sinus is incomplete (Fig. 21-13), allowing shunt flow from the LA through the coronary sinus to the right heart. Coronary sinus defects present clinically in ways similar to ASDs (enlarged heart by chest x-ray, or murmur) but also may show exertional cyanosis. This is related to the frequent association of a persistent left SVC with this defect. When a left SVC connects to an unroofed coronary sinus, an obligate bidirectional shunt is created (LSVC to left heart and LA to right heart) with the incompletely formed coronary sinus as the “crossroads.” Exertion will augment the amount of right-to-left shunt resulting in cyanosis.

Atrioventricular Septal Defects—Complete and Partial Forms Atrioventricular septal defects (AVSD) are also known as atrioventricular (AV) canal defects and occur because of deficient development of the AV septum from the embryonic endocardial cushions (Fig. 21-14). The complete form of AVSD results from the failure of separation of the embryonic common AV valve into right and left components. Rather the embryonic cushions develop into a common AV valve and the AV septum never forms. Therefore, a complete AVSD consists of a common (single) AV valve and large communications between both the ventricles (inlet VSD) and atria (primum ASD) (Fig. 21-15). The physiologic consequences of this malformation include a large left-to-right shunt (with biventricular volume overload), pulmonary hypertension (due to the

large VSD), and variable degrees of common AV valve dysfunction (most often regurgitation). Complete AVSDs, when left unrepaired, result in pulmonary hypertension and Eisenmenger syndrome, usually within the first few years of life. Partial AVSD represents a less severe form of AVSD, in that at least one component of the complete defect is absent. In the most common form of partial AVSD, the AV valves connect directly to the crest of the muscular ventricular septum, eliminating the VSD. In this chapter, we will limit the discussion only to this type of partial AVSD; the combination of a primum ASD and a “cleft” anterior leaflet of the left AV (or mitral) valve (Fig. 21-16). This malformation has no offset between the septal insertions of the AV valves, allowing rapid and accurate recognition (Fig. 21-16). Since these defects lack the inlet VSD found in complete AVSD, they have physiology more similar to that of an isolated ASD, in the absence of significant AV valve regurgitation. The common AV valve seen in the complete AVSD is divided into a right and left component by attachment to the muscular ventricular septum. However, the AV septum itself is still absent in these patients, creating an unusual anatomy of the internal cardiac crux in these patients. The absence of AV septum eliminates the normal apical displacement of the right AV (tricuspid) valve. Therefore, in partial AVSD, both the right-and-left AV valves attach to the muscular septum at the same level (no septal offset). Figure 21-17 shows not only this level attachment of the septal leaflets but also how insertion of the AV valve onto the septum eliminates the VSD in partial AVSD (panel B).

FIGURE 21-11 Sinus venosus ASD (transesophageal imaging). These two images were taken from a moderately “high” esophageal position in both coronal (panels A and B) and horizontal (panels C and D) orientations. They highlight the unique anatomy of this defect. Panels A and B demonstrate anatomy analogous to that seen in the subcostal coronal images in Figure 21-7. Unlike secundum and primum defects, the tissue deficiency in a sinus venosus ASD exists just inferior to the superior vena cava (SVC)/right atrial (RA) junction and lies in a right/left (horizontal) plane (lower panels). Panels A and C show the two-dimensional anatomy with the defect highlighted by the asterisk. The color images show the left-to-right shunt (blue jet) crossing in a directly anterior orientation from the left to the right atrium. A, anterior; L, left; LA, left atrium; RA, right atrium; RMPV, right middle pulmonary vein orifice; RPA, right pulmonary artery.

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Video 21-11A

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Video 21-11B The left-to-right atrial shunt in a partial AV septal defect results primarily in enlargement of the right heart. The size of the left ventricle (LV) is usually normal, unless there is coexisting significant regurgitation of the left AV valve (mitral). The left AV valve is abnormal in all patients who have partial AVSD, although it can function normally in many children and some adults. These valves have a three component structure rather than the typical bileaflet morphology (Fig. 21-17C and D). The valve apparatus is also rotated counterclockwise relative to the normal mitral valve. As a result, the anterior leaflet(s) of the valve lie parallel to the ventricular septum in systole, while the mural leaflet is positioned more laterally than the typical posterior mitral leaflet. The anterior leaflet in partial AVSD is divided into two sections by a “cleft,” sometimes referred to as an additional commissure or zone of apposition. This “cleft” is oriented (points) toward the midportion of the ventricular septum in diastole and can be incompletely supported, leading to regurgitation. If

unrepaired, these clefts will be associated with progressive regurgitation in most. A small number of patients may also develop left AV valve stenosis in association with this lesion. These patients often have only one left AV valve papillary muscle (parachute deformity). Unrepaired partial AVSD can present in adulthood, either with signs/symptoms similar to an isolated ASD or a combination of ASD and mitral regurgitation.

FIGURE 21-12 Anomalous right upper pulmonary vein in sinus venosus ASD. Anomalous right upper pulmonary vein in sinus venosus atrial septal defect—TEE. This high esophageal horizontal plane image shows the right upper pulmonary vein (RUPV) connected to the side of the right-sided superior vena cava (SVC). The orifice/entrance of the RUPV creates an incomplete lateral wall of the SVC, which has been referred to as the “broken ring” sign. A, anterior; L, left; RPA, right pulmonary artery (dilated due to the left-to-right shunt present in this case).

Surgical repair of these defects is required to avoid the late complications of pulmonary hypertension (in the complete form) and volume overload (in partial AVSD). Complete AV septal defects are repaired in the first 6 months of life by patch closure of both the VSD and the ASD. The common valve is separated into right and left components by resuspending the central segments of the valve to the patches. In a partial AV septal defect, only an atrial patch is required (Fig. 21-18). However, simultaneous closure/repair of the cleft in the anterior leaflet of the left AV valve will decrease the likelihood of late regurgitation (14). One of the most frustrating and sometimes confusing aspects of congenital

cardiology is the tendency for more than one nomenclature to be applied to the same malformation. Some of the more common synonyms for AV septal defects are listed in Table 21-1.

FIGURE 21-13 Coronary sinus “atrial septal defect” (unroofed coronary sinus). These parasternal long-axis images show the anatomic defect seen in a teenage male with unroofed coronary sinus. Unlike other ASD, the tissue deficiency does not exist in the atrial septum, instead the anterior wall of the coronary sinus (CS) is partially or totally absent allowing a communication with the left atrial (LA) cavity. The left-to-right “shunt” is comprised of blood flow from the LA into the CS and then entering the right atrium (RA) through the ostium of the CS adjacent to the tricuspid annulus and the internal cardiac crux. The arrows in the left panel show multiple gaps in the anterior wall of this CS and the arrow in the right panel highlights the “shunt” (blue jet) exiting the LA and entering the CS. A, anterior; Ao, aorta; LV, left ventricle; RVOT, right ventricular outflow tract.

Ventricular Septal Defects Ventricular septal defects (VSDs) are the most common form of CHD (excluding bicuspid aortic valve) and can be present in up to 25% of all patients with CHD. Clinical impact of a VSD is usually related to its size. Patients with small, isolated defects may be completely asymptomatic and only be recognized by the presence of a loud systolic murmur. Moderate VSDs can result in left heart enlargement secondary to left-to-right shunt flow. Large VSDs will be associated with equalization of right and left heart pressures and shunt volume will be dependent on the status of the RV outflow tract (RVOT) and pulmonary arteries. In the absence of RVOT obstruction and with normal pulmonary arterial resistance, there will be a large left-to-right shunt with volume overload of the PA, LA, and LV. When unrepaired, such large VSDs will lead to irreversible

pulmonary vascular obstructive disease, associated with irreversible pulmonary hypertension and Eisenmenger syndrome. Coexisting right ventricular out flow obstruction or pulmonary stenosis may protect the patient from these complications by reducing PA pressure and flow, but RV pressures will still equal those in the LV.

FIGURE 21-14 Atrioventricular septal defect. Diagram of the internal cardiac crux showing the attachment of the AV valves to the cardiac septum in the normal heart, partial AV septal defect (partial AVC [AV canal]), and the complete form of the defect (complete AVC). In the normal heart, the anterior mitral and septal tricuspid valve leaflets attach to both the atrial and ventricular septum. The tricuspid septal leaflet inserts just apical to the anterior mitral leaflet. In partial AVC, the septal leaflets of neither valve connect to the atrial septum, creating the primum atrial septal defect. However, they are attached to the ventricular septum, either directly or by imperforate chordae. This attachment eliminates the potential ventricular septal defect. In complete AVC, the leaflets of the common AV valve have no attachment to the atrial septum, and their chordae do not cover the inlet ventricular septal defect, creating septal defects on both sides of the valve.

There are 4 major classes of VSD: membranous, muscular, inlet (AVSD), and subarterial. The most common defect seen in the adult is the membranous VSD. Membranous defects are found at the base of the septum in its thinnest segment, wedged between the aortic valve and the tricuspid valve. The membranous VSD can easily be appreciated in the short-axis view (Figs. 21-19 and 21-20). Due to the proximity of the membranous septum to the aortic and tricuspid valves, defects in this area can lead to regurgitation of either valve. Muscular VSDs are more common in children and are located away from the

level of the cardiac valves within the trabecular (muscular) portions of the ventricular septum (Fig. 21-21). These defects are surrounded by a complete muscular rim and have a tendency to decrease in size (often closing completely) over time. As a result of the complete rim of muscle that surrounds these defects, they are not associated with progressive valve dysfunction. Most muscular VSDs are small and close spontaneously in early childhood, but large defects can cause significant left-to-right shunts and result in pulmonary hypertension. As with any septal defect, single or multiple VSDs may occur in the same patient. Isolated inlet VSDs of the AV canal type are an uncommon “partial” form of AV septal defect. In these cases, there is a large-inlet VSD, no atrial level communication (since the abnormal AV valve has fused to the atrial septum), and abnormal AV valves with no septal offset. The AV valve will have a similar morphology to that seen in primum ASD, with a “cleft” anterior leaflet of the left-sided AV valve. These patients require surgical repair early in life similar to those with the complete form of AVSD. Subarterial VSDs are often also referred to as supracristal VSDs. These are the least common type of VSD seen in patients of European extraction. Subarterial VSD is more common in patients of Asian descent. These defects involve the outlet septum immediately adjacent to both the aortic and pulmonary annulus and result in insufficient muscular support to both valves. These defects do not close spontaneously and are associated with distortion of the aortic valve and sinuses (Fig. 21-22). The prolapsing right aortic cusp reduces the effective the size of the interventricular communication and the resultant left-to-right shunt at the expense of potentially progressive aortic regurgitation.

FIGURE 21-15 Atrioventricular septal defect (complete). Apical four-chamber images in systole (A) and diastole (B) showing a complete atrioventricular canal defect with large primum atrial septal defect (asterisk), large-inlet ventricular septal defect (arrow), and common atrioventricular valve. Note that this valve is indeed a common valve that opens (B) as a single unit with only lateral, and no central, hinge points visible in this four-chamber plane. Also note the right atrial (RA) and biventricular enlargement. This patient also had a small secundum atrial septal defect. L, left; LA, left atrium; LV, left ventricle; RV, right ventricle; S, superior.

FIGURE 21-16 Partial atrioventricular septal defects. A: Four-chamber anatomic specimen of a large primum atrial septal defect (ASD) (arrow) showing severe right atrial (RA) and right ventricular (RV) dilatation. The connection of both atrioventricular (AV) valves to the septum occurs at the same level. B: The corresponding apical fourchamber diastolic image showing severe RA and RV dilatation due to a large primum ASD (arrow). LA, left atrium; LV, left ventricle. C: Color flow Doppler scan from the apex shows a large left-to-right shunt crossing the primum ASD in diastole (red flow jet). D: Systolic color flow Doppler scan shows moderate right-and-left AV valve regurgitation. The video is a color Doppler example of these flow patterns. L, left; S, superior.

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Video 21-16A

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Video 21-16B

FIGURE 21-17 Partial atrioventricular (AV) septal defect. AV valve anatomy. A: Systolic apical four-chamber image showing that both right-and-left AV valves insert onto the crest of the ventricular septum at the same level. L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior. B: The corresponding diastolic frame showing a large primum atrial septal defect. Systolic frames often understate the size of the interatrial communication. There is marked RA and RV enlargement in this case. C and D: Parasternal short-axis scans focused at the valve leaflet level of the LV inflow tract. The two-dimensional scan (C) showing the cleft in the anterior leaflet of the left AV or mitral valve (asterisk). In essence, the anterior leaflet consists of two separate components that move independently. This creates the appearance of a diastolic gap in the leaflet seen in this frame. The color flow Doppler scan (D) shows that the cleft is the source of mitral regurgitation in this patient. A, anterior.

FIGURE 21-18 Postoperative partial atrioventricular (AV) septal defect. A: Fourchamber anatomic specimen of a partial AV septal defect after patch closure of a primum atrial septal defect and repair of a left AV valve cleft. The patch (arrows in A and B) is attached to the right side of the atrial septum and the right AV valve to avoid damage to the conduction tissue and left AV valve. B: The corresponding apical fourchamber echocardiographic image. Note that the right heart is no longer enlarged. L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior.

Imaging notes: Echocardiography is a very sensitive tool for detecting VSDs and assessing their associated hemodynamic burdens and complications. The changes associated with significant VSDs include volume overload of the left ventricle and atrium, pulmonary hypertension, aortic regurgitation, and/or midcavitary RV obstructing muscle bundles (double chambered right ventricle). However, diagnosis of a VSD should primarily be based on two-dimensional inspection of the ventricular septum. Ventricular septum itself is a complex structure that does not lie in a single imaging plane. Slow two-dimensional and color flow sweeps of the septum are required to fully exclude VSD. Sweeps directed from apex to base in parasternal views or anterior to posterior in apical views allow for inspection of the entire septum for defects. A VSD should be suspected when there is two-dimensional “drop out” noted in the usually smooth left ventricular surface of the septum. Changes in the highly trabeculated RV septal surface are less reliable indicators of VSD. When a VSD is suspected, its location should be confirmed by color or spectral Doppler techniques that demonstrate flow between the two ventricle (crossing the septal plane). Small VSDs may not be evident to 2D examinations alone. However, if RV pressure is less than LV pressure, these small defects will generate a high-velocity flow jet crossing the septum that is easily seen with color flow imaging.

TABLE 21-1 Nomenclature of Atrioventricular Septal Defects Synonyms Endocardial cushion defects Atrioventricular septal defects Atrioventricular canal defects Common anatomic variations Complete atrioventricular septal defect Common atrioventricular valve + large primum atrial septal defect + large-inlet ventricular septal defect Partial atrioventricular septal defect This name can be applied to any malformation that includes some, but not all, the components of a complete atrioventricular septal defect Most frequent form: primum atrial septal defect + cleft anterior leaflet of mitral valve

Patients with a complex CHD (such as TOF or double-outlet RV) often have a special type of VSD. These are usually large defects located adjacent to the semilunar valves and are referred to as outlet, malalignment, or conoventricular VSDs. The main body of the ventricular septum and the subarterial (infundibular) septum are oriented in different planes. Therefore, they do not “meet,” resulting in the typical overriding of one semilunar valve, as seen in Fig. 21-23. These defects never close spontaneously and are frequently associated with stenosis or hypoplasia of one ventricular outflow tract, as in TOF, pulmonary valve atresia with VSD, or truncus arteriosus. Aortic regurgitation is also a common late complication of this type of VSD.

Anomalous Pulmonary Venous Connections An anomalous pulmonary venous connection (APVC) exists when some or all the pulmonary veins do not connect directly with the LA. The connection is described as partial APVC (PAPVC) if only some veins connect anomalously or as a total APVC (TAPVC) when all the veins connect anomalously. The anomalous veins may connect to a variety of nonleft atrial chambers or veins. The SVC and innominate vein are the most common sites of abnormal connection, but the azygos vein, coronary sinus, right atrium, and IVC may also receive anomalous pulmonary venous connections in some cases.

FIGURE 21-19 Membranous ventricular septal defect (VSD). A: Parasternal shortaxis scan of a large membranous VSD (arrow). Note the proximity of the defect to the tricuspid and aortic valve leaflets. A, anterior; Ao, aorta; L, left; LA, left atrium; PA, pulmonary artery; RA, right atrium; RV, right ventricle. B: Color flow Doppler scan of a large left-to-right shunt crossing the VSD (arrow). In the parasternal short-axis projection, the aortic valve should be inspected carefully for aortic leaflet prolapse into the VSD. The severity of aortic regurgitation, if present, should be assessed. A slow systematic sweep from the cardiac base to the apex should be performed with color flow Doppler imaging to rule out other small muscular defects. Membranous defects are best viewed in parasternal short-axis and anterior-angulated subcostal coronal views (the five-chamber view).

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Video 21-19A

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Video 21-19B TAPVC usually presents in early childhood. Those with obstructive (stenotic) connections present as critically ill neonates with respiratory distress and pulmonary edema. The physiologic features in these cases are similar to that of very severe mitral valve stenosis. Unobstructed connections behave like a large atrial level shunt, and patients present with murmurs or heart failure, most often within the first year of life. TAPVCs are usually classified by the position of the anomalous connection relative to the heart. A supracardiac connection occurs when the common pulmonary vein connects to the superior systemic venous circulation (innominate vein, azygos vein, or SVC) (Fig. 21-24). The connection between the pulmonary venous confluence and the systemic venous circulation is usually described as a vertical vein or a vertical draining vein. This connection may be obstructed when the left vertical vein travels in between the left pulmonary artery and left mainstem bronchus and is compressed by these structures. This has been called a vascular vise. TAPVC with a cardiac connection occurs when the common pulmonary vein connects directly to a cardiac chamber or to the coronary sinus. These connections are almost never stenotic. In contrast, infracardiac connections are almost always obstructive. The common pulmonary vein connects to a descending draining vein that crosses the diaphragm and connects to the hepatic circulation via the ductus venosus. These connections are always obstructive at or below the level of the diaphragm. Mixed connections do not have a common venous confluence. In these cases, the individual pulmonary veins connect to different sites in the systemic venous circuit. The connections occur in various combinations of the three types listed above. The echocardiographic examination must identify each individual pulmonary venous connection because of these mixed connections. The five

major pulmonary venous segments are the right upper, middle, and lower lobes and the left upper and lower lobes. PAPVC can coexist with an ASD (Figs. 21-25 to 21-27) or it can occur in isolation (Fig. 21-24). Most patients with a PAPVC have an anomalous connection involving only one of the two lungs. Right-sided APVCs are more common (80%) than are APVC involving the left veins. Patients with PAPVC often present in adulthood with symptoms and findings similar to those of an isolated ASD. Obstructive connections are rare in PAPVC. Common patterns of PAPVCs include the following: 1. Right upper and middle pulmonary veins to the SVC or RA (or both) can be seen in association with sinus venosus ASD and less often with secundum ASD. Right-sided PAPVC to azygos vein has also been reported. 2. Right lower pulmonary vein to the inferior vena cava (IVC) is most frequently encountered in Scimitar syndrome. These patients will also have hypoplasia of the right lung and typically have an intact atrial septum. Some patients also have an incomplete connection of the lower lobe bronchus to the central airway and an anomalous arterial supply to this area (bronchopulmonary sequestration). 3. Isolated left pulmonary veins to a left-sided vertical vein (a remnant of the embryonic left anterior cardinal vein. The vertical vein connects the anomalous pulmonary veins to the innominate vein and the shunt flow reaches the right heart via the SVC (Fig. 21-28). Alternatively, one or both of the left pulmonary veins may connect directly to the coronary sinus.

FIGURE 21-20 Restrictive membranous VSD. These images were taken in similar orientations to those seen in Figure 21-19. However, this defect is restrictive, being closed by adherence of the septal tricuspid apparatus to the ventricular septal myocardium. Only a small communication between the ventricles remains (asterisk). The shunt flow through the VSD occurs at high velocity as seen in the continuous wave Doppler tracing in the lower panel. A, anterior; Ao, aorta; L, left; LA, left atrium; RA, right atrium; RV, right ventricle.

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Video 21-20A

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Video 21-20B

FIGURE 21-21 Muscular ventricular septal defect (VSD). Parasternal long- (A) and short-axis (B) images with a color flow Doppler jet showing a small anterior muscular VSD (arrows in A and B) with a small left-to-right shunt. LA, left atrium; LV, left ventricle; RV, right ventricle. C: Continuous wave Doppler signal showing the VSD velocity profile for this defect. Maximum velocity is high (~5 m/s), consistent with a restrictive VSD and normal RV systolic pressure. There is a low-velocity diastolic leftto-right flow signal, confirming that RV diastolic pressures are also low.

FIGURE 21-22 Supracristal ventricular septal defect (VSD). Diastolic two-dimensional (A) and systolic color flow (B) parasternal long-axis images of a supracristal VSD with small left-to-right shunt.A: Prolapse of the right aortic leaflet and sinus through the VSD (arrow). A, anterior; Ao, aorta; LA, left atrium; LVOT, left ventricular outflow tract; S, superior. Because of the distortion of the right sinus of Valsalva, this defect is sometimes confused with aneurysm and rupture of the right sinus of Valsalva. To distinguish the two abnormalities, it helps to know that the shunt passes below the

aortic leaflet and flow is confined to systole in supracristal VSDs. The shunt seen in a ruptured sinus passes through the wall of the aorta (not always adjacent to the septum) and is almost always continuous with a high-velocity diastolic component (due to the aortic origin of the jet).

Imaging Notes—Both TTE and TEE can be used to detect APVC and assess the hemodynamic impact of the anomaly. APVC should be suspected when unexplained RV enlargement is noted on echocardiography or when the normal connections of the pulmonary veins cannot be established to the LA. In addition, PAPVC should be excluded in all patients with secundum ASD since coexisting APVC impacts treatment. Adequate imaging of the pulmonary venous connections needs to be obtained from multiple imaging planes. In infants and children, suprasternal coronal plane scans with posterior angulation demonstrate the “crab” view, with connections of four pulmonary veins to the body of the LA (or to the venous confluence in TAPVC). However, the potential for multiple connections coexisting in the same patient makes a diligent search for pulmonary veins, using all available planes, mandatory in these cases.

FIGURE 21-23 Outlet ventricular septal defect (VSD) in tetralogy of Fallot. A: Parasternal long-axis view of a large subaortic VSD (asterisk) with aortic override. B: Subcostal sagittal view of another perspective on the aorta’s overriding relation with the VSD (asterisk). Ao, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle.

In the normal heart, apical four-chamber views show the connections of the right and left lower pulmonary veins to the posterior and inferior LA. Subcostal four-chamber and sagittal scans allow visualization of the connection of the right upper pulmonary vein to the LA. Subcostal scans can also detect the superiorly positioned sinus venosus ASD. The left upper pulmonary vein is often best seen in parasternal short-axis or suprasternal scans described above. In patients with

enlargement of the right heart, scans from the right parasternal area often provide clear images of the atrial septum and pulmonary veins. If all the pulmonary venous connections to the LA are not visualized confidently, an exhaustive search must be made to exclude possible anomalous connections. This is often one of the most challenging tasks in congenital echocardiography. TEE is helpful in identifying the right pulmonary veins, even when they are anomalous. TEE should be used in mature patients with unexplained RV enlargement in order to exclude PAPVC. An anomalous connection of the pulmonary vein to a vertical vein is often best demonstrated in TTE scans from the suprasternal notch or the left supraclavicular space. Anomalous left veins can be missed by TEE because of acoustical interference from the left bronchial tree. When TTE scans are suggestive, but not diagnostic of an anomalous left pulmonary venous connection, MRI or CT are often the most effective noninvasive methods available for demonstrating the anatomy.

Anomalous Systemic Veins The persistent left SVC is the most common anomalous systemic venous connection. In fact, it is encountered often enough to be considered a normal variant. This vessel always connects to the coronary sinus because both are remnants of the embryonic left horn of the sinus venosus. The echocardiographic hallmark of a typical isolated persistent left SVC is unexplained enlargement of the coronary sinus (Fig. 21-29) with normal RV size. The dilated coronary sinus seen in a parasternal long-axis image is often the first clue to the presence of a left SVC. However, when the coronary sinus is dilated in this manner (especially when the RV is enlarged), the examiner must confirm more directly the presence of a left SVC and the absence of other causes (Figs. 21-30 and 21-31). Enlargement of the coronary sinus can be caused by any of the following conditions: 1) Persistent LSVC, 2) an anomalous connection of the left pulmonary veins to the coronary sinus, 3) coronary artery fistulae to the coronary sinus, 4) coronary sinus ASD or unroofed coronary sinus, 5) cardiac conditions that produce markedly increased RA pressure (e.g., pulmonary artery hypertension or tricuspid regurgitation), or 6) obstruction/stenosis of the coronary sinus junction with the RA.

FIGURE 21-24 Total anomalous pulmonary venous connection. Echocardiographic findings typical of total anomalous pulmonary venous connection, supracardiac type. A: Four-chamber view of the two-chambered left atrial (LA) appearance with the more posterior chamber is actually the confluence of the anomalous pulmonary veins (PVC). It is completely separated from the true LA. B and C: Supracardiac images. Note the suprasternal “crab” view of the venous confluence (PVC). Four pulmonary veins connect with this common confluence. C: Color flow image shows aliased flow traveling through a superiorly oriented vein that drains this confluence, a vertical vein (arrow). In this case, the vertical vein was connected to the innominate vein and the pulmonary venous return was then directed to the right atrium via the superior vena cava. Ao, aorta; LA, left atrium; LV, left ventricle; MPA, main pulmonary artery; PA, pulmonary artery; PVC, pulmonary venous confluence; RA, right atrium; RV, right ventricle.

Patent Ductus Arteriosus A patent ductus arteriosus (PDA) is an essential component of normal fetal cardiac anatomy and physiology. It is an arterial communication between the upper descending aorta and the distal main pulmonary artery, near the origin of

the left pulmonary artery. A PDA is present in all normal newborns and usually closes spontaneously within 72 hours after birth.

FIGURE 21-25 Partial anomalous pulmonary venous connection to the right atrium (RA) with an atrial septal defect. Transthoracic four-chamber view of a 36-year-old man with new onset of exercise intolerance. The RA and right ventricle (RV) are dilated, but no clear cause was delineated by transthoracic scans. LA, left atrium; LV, left ventricle.

Most persistent PDAs are small causing a small left-to-right shunt, no hemodynamic burden, but increased risk for endarteritis. Small and moderate PDAs are associated with a continuous, left-to-right shunt with volume overload of the pulmonary arteries, left atrium, and left ventricle proportional to the size of the PDA. Large PDAs, when left untreated, can lead to pulmonary hypertension and Eisenmenger syndrome (see VSD section). Echocardiography is an excellent tool used to visualize the PDA and to assess its hemodynamic significance (including the size of the left atrium and ventricle as well as the

degree of pulmonary hypertension). Figure 21-32 is a high left parasternal long-axis scan of the main pulmonary artery and the adjacent structures. This view is referred to as the “ductal” view, and is one of the most useful images used to assess the PDA. This view is parallel to the long axis of the main pulmonary artery and the PDA as it travels from the upper descending aorta to the main pulmonary artery. The ductal view usually is one of the best positions for Doppler interrogation of PDA flow. The ductal view is obtained by imaging one interspace higher than the standard parasternal short axis, with slight leftward and anterior angulation of the scan plane (toward the left shoulder) and counterclockwise rotation of the transducer from a typical short-axis position. The suprasternal and parasternal short-axis views (at the level of the pulmonary artery bifurcation) can also be helpful in imaging a PDA (Fig. 21-33). When imaging a large PDA, care must be taken to avoid misinterpreting the large duct as the aortic arch. Identification of the brachiocephalic vessels should help avoid this pitfall.

FIGURE 21-26 Partial anomalous pulmonary venous connection to the right atrium (RA) with an atrial septal defect. A and B: Transesophageal echocardiograms of the same patient as in Figure 21-18. These four-chamber images show a large posterior atrial septal defect (arrows). The eustachian valve (asterisks), which should not be mistaken for the septum. LA, left atrium; LV, left ventricle; RV, right ventricle.

FIGURE 21-27 Partial anomalous pulmonary venous connection to the right atrium (RA) with an atrial septal defect. A–F: Transesophageal echocardiographic images from the same patient as in Figures 21-18 and 21-19. A and B: Short-axis images of the atrial septal defect (arrows) with (B) and without (A) color flow Doppler. Not only is there a large posterior atrial septal defect, but there is also a separate patent foramen ovale. LA, left atrium; RV, right ventricle; RA, right atrium. C and D: The anomalous connection of the right middle (RMPV) and right lower (inferior) (RLPV) pulmonary veins. These veins connect directly with the posterolateral border of RA, just above the inferior vena caval (IVC) orifice. E: Bicaval (sagittal) view shows nearly complete absence of the atrial septum in this plane. F: Short-axis (horizontal) image of the superior vena cava (SVC) just above the SVC and RA junction. The right upper (superior) pulmonary vein (RUPV) is also connected anomalously and can be seen at the lateral surface of the SVC. The image of the RUPV entering the SVC at this level is often described as a teardrop or broken ring. This case illustrates how anomalous

pulmonary venous connections can occur at multiple, different sites in the same patient and emphasizes the need to identify each pulmonary vein individually in cases of unexplained right heart enlargement. RA, right atrium.

FIGURE 21-28 Partial anomalous pulmonary venous connection. A–C: The anatomy of an isolated partial anomalous pulmonary venous connection involving the left superior pulmonary vein only. A: There is enlargement of the right atrium (RA) and right ventricle (RV) with no definitive ASD. However, the left atrium (LA) appears relatively normal and several pulmonary veins were observed connecting to it in a normal manner. LV, left ventricle. B and C: Suprasternal scans showed a dilated innominate vein (Inn V) with an abnormal vein (the left superior pulmonary vein in this case) connecting to ventricle vein (V.V.). C: Color flow imaging confirmed a venous flow pattern with a superiorly directed flow consistent with a partial anomalous pulmonary venous connection via a left-sided vertical vein and differentiating this vein from a persistent left superior vena cava (SVC) (in which flow would be directed inferiorly). Ao, aorta.

OBSTRUCTION TO BLOOD FLOW Coarctation of the Aorta Coarctation of the aorta (CoA) is an arterial stenosis of the upper descending aorta, typically located beyond the origin of the left subclavian artery from the aortic arch. This narrowing can be seen in the region just opposite the origin (or remnant) of the ductus arteriosus and has been referred to as juxtaductal

coarctation (Fig. 21-34). CoA can present at any age and should be excluded in all patients referred for evaluation of hypertension. It can be an isolated defect or seen in association with VSD, bicuspid aortic valve, aortic aneurysms, or additional left-sided obstructive lesions such as mitral stenosis and subaortic stenosis in Shone syndrome. The physiology of the coarctation varies depending on the age at presentation, the severity and location of the stenosis, and the presence of associated lesions. Clinical presentation can range from severe heart failure and shock in a young infant to asymptomatic systemic hypertension with diminished femoral pulses or a murmur in an older child or young adult. Coarctation of the aorta causes upper extremity hypertension with reduced lower extremities pulse and pressure that should be readily noted on routine physical examination.

FIGURE 21-29 Coronary sinus enlargement due to left SVC. Parasternal long-axis image showing the typical appearance of an enlarged coronary sinus (CS). This is often the first clue to the presence of a left superior vena cava. However, when the CS is dilated in this manner, the presence of a left superior vena cava must be confirmed more directly as the only cause of the enlargement (Figs. 21-23 and 2124). Other potential causes of dilated CS include anomalous connection of the left

pulmonary veins to the CS or coronary artery fistulae draining into CS or increased right atrial pressure due to right ventricular dysfunction or tricuspid regurgitation. Ao, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle.

Clinical and Imaging Notes In young patients, a large PDA can provide an alternative source of flow and pressure for the descending aorta. In these cases, it may difficult to exclude a hemodynamically significant coarctation by palpation of femoral pulses. Echocardiographically, a Doppler examination for coarctation is useless in the presence of a large PDA with right-to-left systolic flow. Instead, one must rely on anatomic (2D) demonstration of the narrowed aortic lumen beyond the origin of the left subclavian artery. After the PDA closes, the echocardiographic and clinical examination findings are interpreted more easily. However, a neonatal patient with a ductal-dependent coarctation may become clinically unstable at this time because of inadequate perfusion of the descending aorta. Coarctation is best imaged with high left parasternal views, with lateral angulation of the scan toward the left shoulder (the so-called ductal-coarctation view) (Figs. 21-34 and 21-35). The suprasternal notch views are used for Doppler interrogation (Figs. 21-34), but they often do not display the anatomy of the coarctation well (the plane of ultrasound is parallel with the aortic wall). These views give a sense of tapering of the distal transverse arch with flow acceleration, but usually cannot visualize the aorta beyond the coarctation, making it difficult to know whether the impression of narrowing is real or artifactual.

FIGURE 21-30 Left superior vena cava. A and B: An isolated left superior vena cava (LSCV) and its relation to other cardiovascular structures as it passes through the left hemithorax. A: Parasagittal scan oriented along the long axis of the persistent LSVC

(asterisk). Note that the LSVC passes posterior to the left atrial appendage and body of the left atrium (LA) before entering the coronary sinus (CS) and is anterior to the left pulmonary artery (LPA). At this level, the pulmonary veins are posterior to the LSVC and inferior to the LPA. B: Parasternal short-axis image at the level of the pulmonary artery (PA) bifurcation demonstrating the LSVC as a circular vessel (asterisk), anterior to the LPA. The pulmonary veins will always follow an initial course that is posterior to the LPA. This anatomic feature allows reliable distinction between an isolated LSVC to the CS and a partial anomalous pulmonary venous connection to the CS. Also, an isolated LSVC will not result in any right ventricular or atrial enlargement. In the setting of an enlarged right heart, an isolated LSVC can be differentiated from one that receives an anomalous pulmonary venous connection by directly identifying each pulmonary vein and its specific connection. Ao, aorta.

FIGURE 21-31 Left superior vena cava. A: Transesophageal echocardiogram (shortaxis image) of a persistent left superior vena cava (LSVC). In this plane, the LSVC is seen in cross-section, cradled between the left atrial appendage (LAA) and left upper (superior) pulmonary vein (LUPV). B: Color Doppler profile of LSVC (asterisk) that is distinct from the LAA, and (in the absence of an atrial septal defect) spectral Doppler will show a venous profile different from that seen in the adjacent LUPV. Ao, aorta; LA, left atrium; RVO, right ventricular outflow.

FIGURE 21-32 Patent ductus arteriosus. A small patent ductus arteriosus (PDA) with normal pulmonary artery pressure. A and B: High parasternal scans (ductal view) of a small PDA (arrow) with (B) and without (A) color flow. This PDA had a small left-toright shunt. A, anterior; Ao, aorta; PA, pulmonary artery; S, superior. C: Continuous wave Doppler interrogation of the ductal flow showing the characteristic continuous left-to-right shunt pattern seen in PDA. The high systolic and diastolic velocities are suggestive of normal pulmonary artery pressures. (Maximum systolic velocity, 4.7 m/s [aorta-to-pulmonary artery systolic gradient, 88 mm Hg]; end-diastolic velocity, 3.4 m/s [aorta-to-pulmonary artery diastolic gradient, 46 mm Hg]).

FIGURE 21-33 Patent ductus arteriosus. A and B: A small patent ductus arteriosus

(PDA) in the standard parasternal short-axis view. The parasternal short-axis image at the level of the pulmonary artery (PA) bifurcation shows a small PDA (arrow in B) with a small left-to-right shunt. Note the position of the upper descending aorta (Ao on the right in A). When the PDA is present, the main PA appears to have three branches, the right PA, left PA, and the PDA. The PDA is the most leftward and superior of the three. In the newborn, all three vessels must be specifically identified. A neonatal PDA is often as large as the left PA and continuous flow may not be present because PA resistance is still increased. A, anterior; L, left.

FIGURE 21-34 A: Anatomic specimen of severe juxtaductal coarctation of the aorta (arrow). Note that the distance between the origins of the left common carotid and left subclavian arteries is increased (double-headed arrow). The ductus arteriosus (asterisk) and main pulmonary artery are included in the specimen. The coarctation site is immediately adjacent to the connection of the ductus to the aorta. B and C: Echocardiographic images from an infant with severe, discrete coarctation of the aorta. In the two-dimensional image (B) of the coarctation (arrow) in the ductalcoarctation view, note the deformation of the posterior aortic wall associated with the coarctation. LA, left atrium; PA, pulmonary artery; RA, right atrium. C: Color flow image shows flow acceleration and aliasing at the site of coarctation. D: Continuous wave Doppler signal from the coarctation showing the continuous sawtooth pattern seen in severe obstruction. The peak velocity was 3.5 m/s, consistent with a maximum instantaneous gradient of 49 mm Hg. The holodiastolic forward flow is due to the severe nature of the vascular stenosis (proximal pressure is greater than the

distal pressure at all times during the cardiac cycle). If the velocity in the aorta proximal to the coarctation is elevated, then the gradient across the coarctation needs to be corrected to account for the proximal velocity in the expanded Bernoulli equation: [4(v22 − v12)] = corrected maximum instantaneous gradient, where v2 = maximum coarctation velocity and v1 = velocity in the transverse arch, proximal to the obstruction.

FIGURE 21-35 Coarctation of the aorta. A and B: Sagittal plane, suprasternal images showing a severe short-segment coarctation (arrow). The obstruction begins at a point just distal to the left subclavian artery and is usually positioned at the origin of the ductal artery. In this view, the right pulmonary artery can be visualized posterior to the ascending aorta. Note that the distal descending aorta and precise anatomy of the coarctation can be difficult to assess in two-dimensional scans from this position (that path of the sound beam is nearly parallel with the vessel walls). Ao, aorta; LA, left atrium; RA, right atrium. B: Color flow aliasing occurs at and through the length of the narrowed segment, consistent with the stenosis caused by the decrease in luminal diameter. This Doppler finding allows for easier identification of the obstruction in this plane, because the two-dimensional anatomy can be obscured by interference from the surrounding lungs.

The stenotic segment can be discrete or segmental and long. Therefore, before an intervention is planned, the examination must define not only the degree of stenosis but also the length of the vessel involved. The entire aortic arch must be imaged, particularly the region of the origin of the left subclavian artery. Transverse arch hypoplasia is common in coarctation, especially in young children. In these cases, the distance between the origin of the left common carotid artery and left subclavian artery may be increased. In a young child with a PDA, the superior edge of the ductus may simulate an anterior shelf of tissue in the descending aorta. This should not be mistaken for a coarctation, which should also display deformity of the posterior aortic wall.

Doppler Evaluation of Coarctation of the Aorta Doppler evaluation of coarctation is essential because 2D scans of the area in older patients are difficult to obtain. Color flow aliasing is present at and beyond the narrowed segment (Figs. 21-34 to 21-36). Systolic velocity in the descending aorta is increased. The frequent association of transverse arch hypoplasia with coarctation often increases proximal velocities as well. Therefore in coarctation, the systolic pressure gradient should be calculated only with the expanded Bernoulli equation [4(v22 − v12)] to account for the more proximal stenosis (when present). In severe coarctations, there is a gradient between both the systolic and diastolic pressures on either side of the stenosis. This results in a classic sawtooth pattern with continuous flow on continuous wave Doppler interrogation (Figs. 21-34 and 21-36). The systolic velocity is always the most prominent, with continuation of lower velocity flow throughout diastole because of a persistent pressure gradient. This sawtooth pattern with increased systolic velocity and mean gradient can be provoked with exercise in patient with suspected CoA. Images of the upper thoracic descending aorta are often difficult to obtain; therefore, alternatives to direct echocardiographic imaging of the coarctation are frequently helpful in assessing the severity of obstruction. Subcostal imaging should be performed to assess the pulsatility of and Doppler flow in the lower descending thoracic or upper abdominal aorta. Brisk systolic upstrokes are present in patients without proximal obstruction, whereas diminished systolic velocity, delayed more gradual upstrokes, and diastolic flow continuation are characteristic of severe thoracic coarctation (15) (Fig. 21-37). In many older patients, echocardiography alone may not provide enough data to manage the patient confidently. In these cases, CTA or MRI usually provide excellent anatomic evaluation of the aorta, and it can also define the presence and importance of any associated ascending thoracic aneurysm and any arterial collateral circulation that may have developed (Fig. 21-38).

FIGURE 21-36 Coarctation of the aorta in the adult. Images of the upper descending aorta are often challenging in the mature patient. In this case, the area of coarctation is not completely defined in the upper panels or in the video. There is an “impression” of narrowing (black arrows), but the continuation of the aortic lumen is not visible. Color Doppler seen in the video also suggests narrowing, but does not penetrate beyond the level of the left pulmonary artery. The continuous wave Doppler signal (lower left panel) from the upper descending aorta is consistent with severe obstruction. There is not only a high systolic flow velocity (4 m/s), but there is also a significant diastolic gradient maintained, creating the typical saw-toothed pattern associated with severe coarctation. An internal low-velocity envelope representing transverse aortic arch flow can also be seen. Pulsed-wave Doppler interrogation of the abdominal aorta (lower right panel) shows delayed upstroke and continuous forward flow confirming the severity of the coarctation. Ao, aortic arch; Abd. Ao, abdominal aorta; CWD, continuous wave Doppler; dAo, descending aorta; InVn, innominate vein; P, posterior; PA, pulmonary artery; PWD, pulsed-wave Doppler; S, superior.

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Video 21-36A

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Video 21-36B

Ventricular Outflow Tract Obstruction Obstruction to or stenosis of a ventricular outflow tract is a common component of many complex congenital cardiac malformations. However, the most common forms of outflow obstruction are isolated aortic valve and pulmonary valve stenosis (Figs. 21-39 to 21-41). The examination of a congenitally stenotic aortic valve or pulmonary valve is similar to that described in Chapter 12 (Valvular Heart Diseases). Therefore, this chapter discusses only how pediatric or congenital stenosis differs from that of acquired stenosis. The most common mechanism for congenital semilunar valve stenosis is fusion of one or more commissures, with or without thickening of the valve leaflets (Fig. 21-39). Two-dimensional scans show reduced leaflet mobility, which creates the classic domed systolic appearance associated with congenital aortic valve stenosis and pulmonary valve stenosis (Figs. 21-40 and 21-41).

When viewed in a short-axis format, the systolic opening of the valves has an oval shape instead of a triangular cross section. Both pulmonary and aortic valve stenoses induce compensatory hypertrophy of the associated ventricle. The degree of hypertrophy is usually proportional to the degree of stenosis. Quantitative echocardiographic evaluation of outflow stenosis depends heavily on Doppler techniques. For pediatric patients, calculated valve areas are less useful than for adults (16,17). This is because of the larger degree of error introduced into the continuity equation by the small annulus diameters in children. As a result, the primary Doppler variables used to assess the severity of outflow obstructions are mean systolic Doppler gradients (18–21). In the presence of low cardiac output or a large ductus arteriosus, Doppler gradients are decreased or eliminated. In these cases, outflow stenosis must be graded by relying exclusively on anatomic findings (reduced leaflet motion, degree of valve thickening, and ventricular hypertrophy).

FIGURE 21-37 Coarctation of the aorta. Doppler assessment of abdominal aortic flow in coarctation of the aorta. A: Pulsed-wave Doppler interrogation of normal abdominal aortic flow imaged from a subcostal longitudinal plane. Note the brisk upstroke (short time to peak velocity) and rapid down stroke as well as the early diastolic reversal of flow (arrows) and lack of notable forward flow in diastole. These features are associated with a patent aortic (or ductal) arch. B: Pulsed-wave Doppler signal recorded from the abdominal aorta of a patient with severe coarctation of the aorta. Note the delayed upstroke or prolonged time to peak velocity (relative to the QRS on the ECG), reduced pulsatility (difference between the maximal and minimal velocities), and the continuation of forward flow throughout diastole. Abdominal aortic pulse delay can be quantified with pulsed-wave Doppler echocardiography by measuring the time to peak velocity in the abdominal aorta and comparing it with the same value measured from flow at the aortic annulus. This value should be indexed to the heart rate by dividing the absolute value by the square root of the RR interval. In the absence of a patent ductus arteriosus and an early diastolic reversed flow, a corrected pulse delay value less than 2.8 is suggestive of severe coarctation (12). Abdominal pulsation can also be assessed by calculating the pulsatility index. The difference between the maximal and minimal velocities is divided by the mean velocity

of the flow signal to derive this index. A value less than 2 is also suggestive of severe coarctation, but the predictive value of this index is not as robust as that of the corrected pulse delay.

Subaortic stenosis most commonly presents as a fibrous, often circumferential membrane/ridge or a tunnel-like fibromuscular band causing fixed LVOT obstruction. The latter is often associated with aortic annular hypoplasia. Subaortic stenosis can be seen as an isolated defect or in association with VSD, CoA, and other left-sided obstructive lesions in “Shone syndrome.” Subaortic stenosis is a progressive lesion that leads to left ventricular hypertrophy and aortic regurgitation either caused by direct fibrous attachments into the aortic valve or as a result of “jet lesions.” Although there is some overlap between this defect and hypertrophic obstructive cardiomyopathy, the latter causes a dynamic and not a fixed LVOT obstruction on echocardiography. Subaortic stenosis can be subdivided into three groups on the basis of the underlying anatomic and physiologic features: discrete, tunnel, and dynamic. Echocardiography provides a comprehensive assessment for the level and type of subaortic stenosis, its hemodynamic significance and potential late complications such as left ventricular hypertrophy, and aortic regurgitation which have significant implications as to the timing of surgical intervention. Discrete subaortic stenosis is usually the result of a circumferential fibromuscular ridge that involves not only the ventricular septum but also the outflow surface of the anterior mitral leaflet (Fig. 21-42). In contrast, tunnel subaortic obstructions involve diffuse hypoplasia of the LV outflow tract (LVOT) and are associated with pronounced septal thickening and variable amounts of aortic annular hypoplasia. Both discrete subaortic stenosis and tunnel subaortic stenosis produce fixed obstructions to LV ejection, with the largest pressure differences occurring in early systole. On the other hand, hypertrophic obstructive cardiomyopathy produces dynamic gradients. The narrowing of the outflow progressively worsens during ejection, creating the largest gradients in late systole. The late peaking nature of these obstructions makes their Doppler evaluation unique among LV outflow stenoses in that the maximal instantaneous Doppler gradient is usually the variable associated most closely with the pressure difference between the LV and the aorta (22).

FIGURE 21-38 Coarctation of the aorta. A: Gadolinium-enhanced magnetic resonance angiogram of severe coarctation in an adult. The discrete narrowing in the upper descending aorta (arrow) is easily appreciated, as is the length of the stenotic segment. In addition, multiple collateral arteries (intercostal and internal mammary arteries) are seen; they provide an alternative path for arterial flow from the ascending to the descending aorta. B: Three-dimensional magnetic resonance reconstruction of an aorta with a coarctation treated with an intra-arterial stent (arrow).

FIGURE 21-39 Pulmonary valve stenosis. Anatomic specimens from patients with severe pulmonary valve stenosis showing various valve morphologies. A: Markedly dysplastic valve with virtually no commissures. B: Unicommissural valve with marked thickening of the leaflets. C: Bicuspid valve with commissural fusion and thin leaflets. D: Trileaflet, dysplastic valve with prominent thickening of the leaflets.

FIGURE 21-40 Pulmonary valve stenosis in a 1-year-old child. A: Parasternal longaxis anatomy of the right ventricular (RV) outflow tract, pulmonary valve, and main pulmonary artery (PA). The valve annulus is normal, but the leaflets are thickened and have decreased systolic excursion, often described as “doming” (arrow). B: Doppler flow turbulence (aliasing) begins at the valve level (upper right). C–E: Images from the subcostal window. C: Sagittal plane two-dimensional anatomy of the stenotic valve (arrow) and right ventricle (RV). The RV and lateral ventricle (LV) walls have a similar thickness (RV hypertrophy), and the interventricular septum shows a left and posterior systolic flattening, which is due to increased RV systolic pressure. D: Color flow Doppler mapping shows there is no subvalvular component to the stenosis. Optimal alignment of the Doppler beam with the stenotic jet could be obtained only from this position. E: Subcostal Doppler flow signal. The maximum velocity was 4.7 m/s (predicting a maximum instantaneous gradient of 84 mm Hg and a mean gradient of 49 mm Hg).

Supravalvular aortic stenosis (SVAS) is a rare lesion causing focal or diffuse narrowing at and above the sinotubular junction. It can be sporadic or familial or seen in association with Williams syndrome (60%). Most cases of SVAS are localized to the proximal ascending aorta, but diffuse hypoplasia of both the ascending and descending aorta can be encountered. The latter require multimodality imaging to truly appreciate the full extent of the pathology. Patients may present with murmurs, dyspnea, fatigue, or syncope caused by severe left ventricular outflow obstruction. Chest pain, due to ostial stenosis or aortic valve cusps adhesion to sinotubular junction, has been reported. Aortic

regurgitation can result from adhesions of the aortic cusps to the sinotubular junction but is rarely significant. Echocardiography should define not only the proximal narrowing due to SVAS but also the involvement of the aortic valve, distal ascending aorta, and arch vessels. Mean systolic Doppler gradients provide noninvasive assessment of SVAS severity. The latter has significant therapeutic implications especially in the asymptomatic patients.

FIGURE 21-41 Severe pulmonary valve stenosis. A: Parasternal image with a leftward and 45-degree clockwise rotation from a standard long-axis projection. This image provides an elongated view of the right ventricular (RV) outflow tract, pulmonary valve (arrow), and main pulmonary artery (MPA). From this position, leaflet excursion and thickness and annular diameter can be determined. B: Systolic apical four-chamber view shows severe RV hypertrophy, with the leftward shift of both the interventricular and atrial septa from increased RV and right atrial (RA) pressure. L, left; LA, left atrium; LV, left ventricle; S, superior. C: Continuous wave Doppler signal across the pulmonary valve (Vmax, 4.7 m/s), predicting a maximum instantaneous gradient (PGRAD) of 88 mm Hg and a mean gradient (MnGRAD) of 60 mm Hg. D: The tricuspid regurgitation (TR) signal shows a peak velocity of 5.6 m/s, predicting an RV systolic pressure greater than 125 mm Hg. VTI (= TVI), time velocity integral.

CORONARY ARTERY FISTULAE Coronary artery fistulae (Fig. 21-43), although rare, are the second most cause of congenital continuous murmurs, after the PDA. Approximately two-third of these fistulae originates from the right coronary artery. When the fistulae are moderate or large, the resultant continuous left-to-right shunt causes enlargement of the affected coronary artery and the receiving chambers typically the right

atrium, coronary sinus, or right ventricle. Left ventricular enlargement is seen only in those with the largest shunts. Patients can be asymptomatic presenting only with a murmur or can have chest pain due to “coronary steal” or dyspnea and fatigue due to volume overload. Echocardiography, computer tomography, and coronary angiography play complimentary roles in the assessment and treatment of coronary artery fistulae. Anomalous origin of the left main coronary artery from the main pulmonary artery, or ALCAPA, typically presents with severe left ventricular dysfunction and heart failure in infancy. However, if there are adequate collateral communications between the right and left coronary circulations, then these patients may survive undetected into adulthood. In these cases, the physiologic manifestations of ALCAPA are similar to those of a large coronary to pulmonary arterial fistula (Fig. 21-44). The unique feature seen in ALCAPA but not other fistulae are the large intramyocardial collateral channels that can be demonstrated by low Nyquist limit color Doppler scans (Fig. 21-44, lower right).

COMPLEX CONGENITAL CARDIAC MALFORMATIONS Ebstein Anomaly Ebstein anomaly of the tricuspid valve is a rare condition caused by abnormal development of the RV myocardium. Therefore, the pathology in Ebstein anomaly (EA) involves not only the tricuspid valve (TV) but also the ventricular muscle itself. The anatomic and physiologic manifestations of these abnormalities include displacement and tethering of the TV leaflets, tricuspid regurgitation, myocardial dysfunction (RV more often than LV), and arrhythmias (atrial > ventricular) (see Figs. 21-45 to 21-53). This disorder has a very broad spectrum and can present at any time of life. The fetus and neonate will have the most severe anatomic and physiologic abnormalities. While those that present in adulthood often manifest progressive myocardial dysfunction and atrial arrhythmias.

FIGURE 21-42 Discrete subaortic stenosis. A: Parasternal long-axis systolic frame shows a circumferential fibrous membrane (asterisk) narrowing the left ventricular (LV) outflow tract. The membrane is immediately below the aortic valve annulus and attaches to the septum and anterior leaflet of the mitral valve. B: Continuous wave Doppler echocardiogram showing a moderate outflow gradient (mean gradient, 34 mm Hg). (A and B: Transthoracic echocardiograms.) Note: These obstructive membranes or ridges are often associated with hypertrophy of the basal ventricular septum. As a result, septal myectomy and myotomy in addition to resection of the membrane are often required to eliminate the obstruction. Aortic valve regurgitation can occur in these patients because of either the turbulent outflow jet or the direct distortion of the valve (when the membrane attaches to the valve leaflets). C and D: Longitudinal plane transesophageal echocardiographic demonstration of a discrete, obstructive subaortic membrane. In patients with limited transthoracic windows, TEE provides excellent visualization of this area. These TEE images show a discrete, circumferential subaortic membrane (arrow in C) that causes severe outflow obstruction. The obstruction begins at the ridge, below the valve annulus, as shown in the color flow image (D). When the basal ventricular septum is thickened or posteriorly displaced, the “length” of the obstructive zone can increase. In these cases, a tunnel of obstruction is created. Thus, the length of the obstructive subaortic zone should be quantified to facilitate surgical planning. Note that many patients with subaortic stenosis also have abnormal aortic valves. It usually is not possible to differentiate subvalvular obstruction from the valvular stenosis by Doppler hemodynamics. Therefore, one must rely on two-dimensional images (degree of

annular or LV outflow tract hypoplasia, presence of leaflet thickening, degree of leaflet excursion) to determine whether intervention is required for one or both lesions. A, anterior; Ao, aorta; LA, left atrium; RV, right ventricle; S, superior.

FIGURE 21-43 Right coronary artery (RCA) to superior vena cava (SVC) fistula. The upper panels are two-dimensional parasternal long- and short-axis images showing a dilated, proximal RCA (asterisk) in a patient with an RCA to SVC fistula. The color Doppler image (lower left panel) shows the distal fistula connecting to the SVC (arrow). The image on the lower right is a three-dimensional magnetic resonance reconstruction of the aortic root (Ao), proximal coronary arteries, the fistula (arrows), and the SVC.

During cardiac development, the tricuspid valve leaflets are derived from the embryonic RV walls. In Ebstein anomaly, the leaflets fail to separate completely (delaminate) from the underlying myocardium. The septal and posterior leaflets are affected more severely than the anterior leaflet, which is usually larger than normal. The large anterior leaflet has been described as sail-like when it is freely mobile. The failure of tricuspid leaflet delamination leads to displacement of the

functional valve orifice and the leaflet hinge points as well as tethering of the tricuspid valve leaflets (Fig. 21-45). These abnormalities lead to tricuspid regurgitation, myocardial dysfunction (RV followed by LV), and arrhythmias (atrial more than ventricular). Most patients with Ebstein anomaly also have an interatrial communication (secundum ASD or patent foramen ovale). Pulmonary stenosis or RVOT obstruction is noted in 15%. The most reliable echocardiographic marker associated with Ebstein anomaly is excess apical displacement of the septal insertion of the tricuspid valve (Figs. 21-46 to 21-49) relative to the MV anterior leaflet’s septal insertion. In the normal heart, the septal insertion of the tricuspid valve (as seen in the apical four-chamber view) occurs at a point slightly apical to the septal insertion of the anterior mitral leaflet. The linear distance between these two points can be measured and divided by the patient’s body surface area to obtain a displacement index. Shiina and colleagues (23) and Gussenhoven and coworkers (24) found that a displacement index greater 8 mm/m2 is invariably associated with Ebstein anomaly. This displacement index combined with the characteristic tethering of the septal and posterior leaflets and shifted the position of the functional TV orifice (into the RV cavity toward the RVOT) differentiate Ebstein anomaly from other TV abnormalities that may mimic it including tricuspid valve dysplasia. The role of echocardiography in Ebstein malformation is to confirm the diagnosis, assess the severity of tricuspid valve distortion/dysfunction (see Fig. 21-48), to define the degree of right ventricular enlargement and dysfunction, as well as to exclude other associated defects. Lastly, one needs to use this information to determine the likelihood and feasibility of valve repair.

FIGURE 21-44 Anomalous origin of the left coronary artery from the pulmonary artery or ALCAPA. The video and the two upper panels demonstrate the long axis of the main pulmonary artery (MPA) from the parasternal perspective. The left main coronary artery (LCA: asterisk, left panel; and black arrow, right panel) arises from the inferior surface of the MPA. Color Doppler shows a diastolic jet coursing from the coronary ostium into the MPA. This flow is a left-to-right shunt and produces “steal” from the myocardium. The panel on the lower left and video are parasternal short-axis images demonstrating a dilated proximal right coronary artery (#), which is the source of the shunt flow exiting the anomalous left coronary artery. The color Doppler images on the lower right and in the video show abnormal intramyocardial flow traveling from the posterior descending coronary, through the septum toward the anomalous connection of the LCA. A, anterior; Ao, aorta; L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.

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Video 21-44D Historically, repair of Ebstein anomaly relied on the anterior leaflet contacting the interventricular septum in systole to form a functional monocusp valve. More recently, Di Silva reported excellent results with the cone procedure whereby the anterior and posterior tricuspid valve leaflets are mobilized from their anomalous attachments in the right ventricle, and the free edge of this complex is rotated clockwise to be sutured to the septal border of the anterior leaflet, thus creating a cone the vertex of which remains fixed at the right ventricular apex and the base of which is sutured to the true tricuspid valve annulus level. Echocardiography and especially the four-chamber view obtained on TTE identifies certain features that are important when the cone repair is being considered such as the presence and mobility of the septal and anterior leaflets; the presence of inferior leaflet can also be determined (Fig. 21-47). This view readily identifies the points of attachment(s) between the leaflet(s) and the underlying myocardium (between the annulus and apex) and provides the road map to the extent of the surgical delamination process that will be required. The presence of mobile septal leaflet tissue has become a more important finding in predicting feasibility of a typical cone reconstruction, as this tissue serves to anchor the final suture line of the “cone.” This tissue can be seen in Figures 21-47 and 21-49 but is absent in the example seen in Figure 21-50.

FIGURE 21-45 Ebstein anomaly. A: Four-chamber view of an anatomic specimen showing a severe form of Ebstein anomaly. No functional valve tissue is present within the anatomic inflow tract. The mobile segments of the valve are displaced anteriorly and apically and are out of the plane of the image. The right heart is globally enlarged and the vestiges of the anterior tricuspid valve (TV) leaflet are attached at multiple points (arrows) to the walls of the right ventricle. The area between the anatomic TV annulus and the coaptation point of the functional TV leaflets is the atrialized portion of the right ventricle (aRV). The anatomic annulus (asterisk) is adjacent to the right atrioventricular groove. B: Apical four-chamber echocardiographic view showing features of severe Ebstein anomaly, with displacement and tethering of the septal (arrow) and anterior TV leaflets. The septal insertion of the TV is closer to the apex (farther from the atrioventricular groove) than normal. The right ventricular (RV) free wall is thin, demonstrating that both the valve and myocardium are abnormal in these patients. Although the anterior leaflet is more developed in this case than in the anatomic specimen (A), there are two areas of direct papillary muscle insertion that impair leaflet mobility (asterisk). This type of papillary muscle attachment reduces the likelihood of successful valve repair in this patient. LA, left atrium; LV, left ventricle; RA, right atrium.

In the most advanced cases of Ebstein anomaly, virtually no mobile tricuspid valve tissue is present (Fig. 21-50). These patients often have the most severely dysfunctional myocardium and the most deformed valves. The functional severity of the anomaly also displays a broad spectrum, even when delaminated tissue is present within the inflow tract of the right ventricle (Fig. 21-51). The severity of myocardial dysfunction combines with leaflet tethering to influence the degree of regurgitation and symptomology present and both require definition during the exam. Surgical repair using the “cone” reconstruction (25) of the tricuspid apparatus not only reduces the amount of regurgitation and RV volume load but also

relocates the annular hinge points “back” to a more anatomic position near the atrioventricular groove (Fig. 21-52). The functional valve orifice is made entirely of mobile leaflet tissue (Fig. 21-53), instead of relying on septal myocardium to function as a part of the valve, as was the case in most monocusp/monoleaflet repairs.

FIGURE 21-46 Displacement index in Ebstein anomaly. The septal insertion of the tricuspid valve is always slightly apical to that of the mitral valve. A: This relation in the normal heart. B: Excessive apical displacement seen in Ebstein anomaly. Arrows, the mitral and tricuspid septal insertions. The linear distance between these two points is divided by the patient’s body surface area to obtain the displacement index. AML, anterior mitral leaflet; L, left; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior; STL, septal tricuspid leaflet.

FIGURE 21-47 Ebstein anomaly with a repairable tricuspid valve. Apical four-chamber images from middiastole (A), midsystole (B), and end systole (C). Successful creation of a monocusp repair depends on the mobility of the anterior leaflet (arrow). In the patient here, the anterior leaflet is freely mobile, including its leading edge, and no muscular insertions limit or distort the motion of the valve. The regurgitant jet originated only from the gap in coaptation between the anterior leaflet and the remnant of the septal leaflet. The leading edge of the valve reaches a point close

enough to the septum that, given the degree of annular dilatation, annuloplasty can “advance” it to a point where it will coapt with the septum. The evaluation of leaflet mobility must be made by imaging the valve within the anatomic inflow tract. To be certain that the imaging plane is sufficiently posterior, the mitral valve annulus and leaflets should also be visible in the frame. The outflow tracts should not be visible at all. Many Ebstein valves have mobile segments anterior to this true inlet plane. Unless the inlet portion of the anterior leaflet is free, these valves do not create adequate valves after repair, partly because the annuloplasty does not affect the motion of the outlet portion of the valve and the amount of right ventricular (RV) myocardium distal to these severely displaced valves is often only a small portion of the RV (frequently only the infundibulum). L, left; LV, left ventricle; RA, right atrium; S, superior.

FIGURE 21-48 Ebstein anomaly. Poor candidate for valve repair in Ebstein anomaly. Although the anterior leaflet has some mobility, there is a direct muscular insertion of a free wall papillary muscle into the anterior leaflet (arrow in A). This will limit the motion of the leaflet. More importantly, the anterior leaflet has multiple fenestrations, causing at least three separate jets of tricuspid regurgitation (arrows in B). The multiple points of regurgitation and limited systolic mobility made this patient a poor candidate for repair. L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior.

FIGURE 21-49 Ebstein anomaly. A and B: Apical four-chamber images of a patient with Ebstein anomaly whose valve is likely repairable. The anterior leaflet is freely mobile (A), and color flow mapping (B) shows only a single central jet of tricuspid regurgitation. The severity of the enlargement of the right heart makes the displacement of the tricuspid valve seem less prominent, but the displacement index in this case was 20 mm/m2. The patient subsequently had successful valve repair, with only mildresidual tricuspid regurgitation. L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior.

Tetralogy of Fallot Tetralogy of Fallot is most common cyanotic CHD: occurring in 4% to 9% of series with congenital defects. Tetralogy is an outflow malformation that that results from anterior malalignment of the infundibular portion of the interventricular septum. This septal malposition leads to the four characteristics of this malformation including 1) a large outlet VSD, 2) override of the aortic annulus across the VSD, 3) subpulmonary/pulmonary valve stenosis, and 4) right ventricular hypertrophy (26) (Fig. 21-54). Common associated abnormalities seen in association with Tetralogy include ASD, right-sided aortic arch, and anomalous left anterior descending coronary artery arising from the right coronary artery. Patients with TOF are now rarely treated with palliative procedures, such as the Blalock-Taussig shunt. Instead, primary definitive repair is preferred and most repairs are completed within the first year of life. Definitive repair includes patch closure of the VSD, resection of obstructive subpulmonary muscle, further enlargement of the subpulmonary outflow tract (usually with a transannular patch), and relief of pulmonary valve stenosis. Despite the preference for early repair, one may still encounter unoperated or palliated patients with TOF in adulthood. These patients will be anatomically similar to the infant but bear the additional burden of lifelong RV hypertension

and hypertrophy and greater risk for RV dysfunction and arrhythmia.

FIGURE 21-50 Ebstein anomaly. Apical four-chamber image of one of the most advanced forms of Ebstein anomaly. The right heart is markedly dilated (annulus diameter, 50 mm). Right ventricular function was severely depressed. There is no evidence of any mobile valve tissue in the inflow tract. The anterior leaflet is attached completely to the free wall, beginning just 2 cm below the anatomic annulus (arrow). No septal leaflet tissue is seen. The native valve tissue was displaced to the entrance of the right ventricular outflow tract (the infundibular orifice). This valve was not suitable for repair.. aRV, atrialized portion of the right ventricle; L, left; LA, left atrium; LV, left ventricle; RA, right atrium; S, superior.

Although long-term survival following either palliation or repair of TOF is achieved in most patients, significant residua and sequelae are not uncommon. Many children require a transannular enlargement of their stenotic RVOT in order to relieve the severe obstruction often seen in tetralogy. This approach results in universal “free” (severe) pulmonary regurgitation. As a result, these patients deserve/require lifelong surveillance of their RV size and performance. Many will develop progressive RV enlargement with varying degrees of dysfunction that can result in dyspnea, heart failure, arrhythmias, sudden death. The most common indications for late reoperation are pulmonary regurgitation

followed by residual stenosis (Fig. 21-55). Chronic severe pulmonary regurgitation in repaired TOF causes RV volume overload, leading to tricuspid annular dilatation, tricuspid regurgitation, progressive RV dysfunction, LV dysfunction, and ventricular arrhythmias.

FIGURE 21-51 Functional spectrum of Ebstein anomaly. These two cases both show significant right heart enlargement secondary to Ebstein anomaly. The still figures are both systolic frames and show a complete lack of tricuspid coaptation in the right panel. The videos show that despite the presence of tissue within the inlet from both the anterior and septal components of the valve, the degree of tethering and myocardial dysfunction can alter the functional impact greatly. The patient depicted on the left panel had moderate regurgitation and no symptoms. While the patient depicted in the right panel had torrential regurgitation and was not able to exercise. L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior.

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Video 21-51A

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Video 21-51B A comprehensive transthoracic echocardiogram is the single most important examination needed during the initial and follow-up evaluation of patients with repaired TOF. It should include the assessment of residual RV outflow obstruction, pulmonary regurgitation, aortic regurgitation, tricuspid regurgitation, RV/pulmonary hypertension, RV size and function, LV size, and systolic/diastolic function as well as exclusion of residual VSD and ASD. Free pulmonary regurgitation can be challenging to detect, as the flows are laminar (low velocity). Common echocardiographic signs of severe pulmonary regurgitation include pulsation of and diastolic flow reversal in the pulmonary artery branches. Continuous wave Doppler interrogation of the RV outflow tract demonstrating an abbreviated diastolic flow signal that lasts less than 75% of diastole is also consistent with severe PR and rapid equilibration of MPA and RV diastolic pressures.

FIGURE 21-52 “Cone” repair for Ebstein anomaly. All four images and videos are apical four-chamber views of a heart with Ebstein anomaly. The two upper panels are from a preoperative scan and demonstrate marked displacement of the functional valve orifice (upper left, white arrow) and severe regurgitation (broad color jet shown by the asterisk in the upper right panel). The lower panels show how the cone reconstruction shifts the functional orifice back to the anatomic right atrioventricular groove or “true annulus” (white arrow, lower left) and significantly reduces the amount of tricuspid regurgitation (lower right, asterisk). L, left; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, superior.

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Video 21-52A

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Video 21-52B

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Video 21-52C

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Video 21-52D Magnetic resonance imaging has emerged as a very important complimentary tool used in the assessment of patients with Tetralogy and pulmonary regurgitation. Quantitative determinations of right ventricular size and function now play a significant role in determining the timing of reoperation for severe pulmonary regurgitation. Multiple series have shown that relief of PR when the indexed diastolic RV volume is less than 170 mL/m2 and the systolic volume is less than 85 mL/m2 results in a favorable reduction/normalization of RV volume postoperatively (references). If operation is delayed until the RV is larger than this, the likelihood of reverse RV remodeling is reduced. Typically, RV ejection fraction remains unchanged after pulmonary valve replacement. Therefore, referral for intervention should generally be made while RV systolic performance is normal or mildly reduced at most. MRI provides a reproducible assessment of both RV volume and ejection fraction, that when coupled with clinical, exercise and echocardiographic data form the basis for determining when to proceed with valve replacement.

FIGURE 21-53 Ebstein anomaly (cone repair). “En face” view of tricuspid valve after cone repair. This series of magnified short-axis images and videos were focused on the orifice of the reconstructed tricuspid valve after a cone repair for Ebstein anomaly.

The center panel highlights the fact that the reconstructed valve does not include the septal myocardium as a portion of the functional orifice (arrow). The color Doppler images (diastolic to the left) show the flow crossing the reconstruction. There is no turbulence (undisturbed “red” inflow) in diastole and only a small regurgitant jet in systole (right panel). LV, left ventricle; RV, right ventricle.

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Video 21-53A

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Video 21-53B

FIGURE 21-54 Tetralogy of Fallot. A: Typical parasternal long-axis appearance of the ventricular septal defect and aortic override in tetralogy of Fallot. The aortic valve is located centrally over the muscular interventricular septum (50% override). In this plane, the ventricular septal defect (asterisk) is between the septum and valve. This long-axis image is typical of both the major defects involving conotruncal malformations: tetralogy of Fallot and truncus arteriosus. The connection of the pulmonary arteries distinguishes the two lesions. In tetralogy of Fallot, the right ventricular outflow tract and pulmonary valve are stenotic but connect to the right ventricle (RV). In truncus arteriosus, the overriding semilunar valve is the only outlet for both ventricles, and the pulmonary arteries arise as branches from the proximal truncal artery (usually just beyond the sinotubular junction). B: The biphasic Doppler pattern is characteristic of dynamic obstruction. Panels C and D show the subpulmonary stenosis caused by the anteriorly deviated outlet septum (arrows). Ao, aorta; LA, left atrium; LV, left ventricle; RA, right atrium.

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Video 21-54A

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Video 21-54B

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Video 21-54C

FIGURE 21-55 Tetralogy of Fallot (postoperative). Echocardiographic findings in a patient after repair of tetralogy of Fallot with a transannular right ventricular outflow tract patch. A: Parasternal long-axis image. The ventricular septal defect (VSD) patch has created complete continuity between the left ventricle (LV) and aorta (Ao). The patch attaches to the muscular septum apically and to the infundibular septum superiorly. This not only closes the communication between the LV and right ventricle (RV) but also eliminates the aortic override. B: Apical four-chamber view shows an enlarged, but not hypertrophied, RV. The left atrium (LA) and right atrium (RA) are not dilated, suggesting that filling pressures and tricuspid valve function remain relatively normal in this patient. C–E: Parasternal short-axis images at the base of the heart. C: Two-dimensional scan shows the VSD patch (asterisk) and enlarged RV outflow tract. The transannular patch has dilated over time (stretched by the repetitive jet of regurgitation). As a result, the RV outflow tract has the appearance of a moderate aneurysm. D: Most of the pulmonary valve was removed at the time of repair, leaving only a remnant of one leaflet attached to the medial annulus (across from the arrow marking the lateral edge of the native annulus). E: Diastolic color flow image of the same area. Severe (free) pulmonary regurgitation is confirmed by the broad color flow jet (arrow).

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Video 21-55A

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Video 21-55B

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Video 21-55C

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Video 21-55D

Complete Transposition of the Great Arteries Transposition of the great arteries (d-TGA) is the most common cyanotic CHD diagnosed in the newborn. It is characterized by incorrect connection of the ventricles to the arteries (ventriculoarterial discordance). During embryonic development, the primitive truncus arteriosus undergoes abnormal septation resulting in the aortic valve and aorta connecting with the right ventricle, whereas the pulmonary valve and pulmonary artery arise from the left ventricle (Figs. 21-56 and 21-57). The unbranched segments of the great arteries in TGA will exit their ventricles and travel in a parallel relationship (Fig. 21-52), in contrast to the usual perpendicular arrangement of the ascending aorta and MPA. In order for the infant to survive at birth, an intracardiac shunt, in form of PFO, ASD, PDA or VSD, is necessary to allow the mixing of the systemic and pulmonary venous blood. If such mixing is not present or very small, an urgent percutaneous atrial septostomy is performed before definitive repair.

FIGURE 21-56 Complete transposition of the great arteries. A: Anatomic specimen showing the anatomy typical of complete transposition of the great arteries. The great arteries originate from an inappropriate ventricle: the aorta (A) from the right ventricle (RV) and the pulmonary artery (P) from the left ventricle (LV). The arteries follow a parallel course, and the aorta and aortic valve are positioned to the right and anterior of the pulmonary artery and valve. This heart also has several small midmuscular

ventricular septal defects. B–E: Echocardiographic images from a neonate with complete transposition of the great arteries before surgical treatment with an arterial switch operation. B: Parasternal short-axis image at the base showing the classic arrangement of the semilunar valves in this defect. The aortic valve is anterior and to the right of the pulmonary valve. C: Parasternal long-axis image showing the parallel relation of the great arteries. The pulmonary artery (PA) courses posteriorly after exiting the LV. Both semilunar valves can be seen in long axis in this plane, which never occurs when the great arteries are normally positioned. Note, slight modifications of the imaging plane in this area will show the origin and initial branching pattern of the coronary arteries from the aortic sinuses, which is an important part of the initial evaluation of a neonate who has complete transposition of the great arteries as coronary arterial transfer is the component of the arterial switch operation that is associated with the greatest difficulty and risk. D: This subcostal image confirms that the right-sided great artery is the aorta (Ao) (vertical course with no proximal branches). E: Subcostal four-chamber image with angulation posterior to the aorta. It demonstrates that the posterior great artery (connected to LV) bifurcates into a right-and-left pulmonary artery, confirming the presence of ventriculoarterial discordance. A, Ao, aorta; LA, left atrium; LV, left ventricle; P, PA, pulmonary artery; RA, right atrium; RV, right ventricle.

FIGURE 21-57 Complete transposition of the great arteries (d-TGA). These subcostal, coronal plane images demonstrate the discordant (abnormal) connection of the ventricles to the great arteries that defines this defect. The left-sided image shows the right ventricle (RV) with its outflow tract leading to the anterior aorta (Ao), note the left coronary origin (black arrow). The right panel was obtained with posterior angulation of the imaging plane and demonstrates the left ventricle (LV), its outflow tract and connection to the main pulmonary artery (PA). The PA is “shorter” than one would expect an aorta to be and has a bifurcation (asterisk), confirming the discordant nature of this connection. L, left; RAA, right atrial appendage; RA, right atrium; S, superior.

Preoperative evaluation of dTGA requires recognition of the discordant ventricular to arterial connection (27) (Figs. 21-57 and 21-58). ASD and PDA

are understandably common in patients with dTGA. VSD and pulmonary stenosis also coexist with transposition frequently, and their presence can significantly alter the surgical approach to the patient. In terms of the arterial switch operation, definition of the coronary arterial anatomy is of central importance. The most frequent coronary anomaly encounter is origin of the circumflex coronary artery as a branch of the right coronary artery. This can be recognized by detecting a coronary vessel travelling from right to left posterior to the pulmonary root/LVOT. Most coronary artery anomalies have been successfully transferred during arterial switch procedures. However, coronary arteries with an intramural segment, similar to those seen in anomalous origin of a coronary artery from the contralateral sinus of Valsalva required special techniques and their preoperative recognition is critical to surgical planning and outcome. Arterial Switch Operations Since the mid 1980s most babies born with dTGA have been treated with an “arterial switch” operation. This approach establishes correct (concordant) connections between the ventricles and great arteries but requires transfer of the coronary arteries from the vessel connected to the RV to the arterial root connected to the LV. The pulmonary arterial confluence and distal main pulmonary artery are moved into a unique position; anterior to the native aorta (Fig. 21-59). Those who have been treated with an arterial switch operation, tend to maintain normal ventricular and AV valve performance. Neoaortic root enlargement is common, can be progressive, and may lead to aortic regurgitation in some. The anterior translocation of the pulmonary arterial confluence may result in distortion/stenosis of the pulmonary arteries (Fig. 21-59). Less frequently, pulmonary regurgitation or coronary arterial abnormalities can be encountered. Atrial Switch Operations Prior to the advent of the arterial switch operation, the surgical approach to dTGA focused on redirecting the venous flows to the inappropriate ventricle, using atrial switch operations such as Mustard or Senning operations. These procedures were examples of two “wrongs” making a “right.” Oxygenated blood from the pulmonary veins was directed to the tricuspid valve and right ventricle, which led to the discordantly connected aorta. These atrial baffle procedures also shifted desaturated blood from the SVC and IVC to the mitral valve and left

ventricle leading to the pulmonary artery (Fig. 21-60). Following the atrial switch procedure, the tricuspid valve and right ventricle remain connected to the aorta and therefore under systemic pressure. As a result, they are more prone to develop regurgitation and dysfunction over time. Although some degree of RV failure is present in most adults after a Mustard or Senning operation, the clinical course for these patients is quite variable. Other common late postoperative problems seen with atrial switch operations include obstruction of one or more venous pathways.

FIGURE 21-58 Complete transposition of the great arteries (d-TGA); sagittal images. These subcostal, sagittal plane images also demonstrate the discordant (abnormal) connection of the right and left ventricles to the great arteries. However, one can also appreciate the parallel ascending course taken by the aorta (Ao) and pulmonary artery (PA) in these patients. These images allow visualization of the patent ductus or PDA (asterisk in both panels) connecting the two circulations and allowing for desaturated blood from the aorta to reach the PA (red color flow on the right, asterisk). LA, left atrium; LV, left ventricle; RV, right ventricle.

FIGURE 21-59 Arterial switch operation with LeCompte maneuver. This most often includes translocation of the pulmonary arterial confluence to an anterior position (in front of the ascending aorta. This unique spatial arrangement is demonstrated by the two images in the figure. The diagram, on the left, shows a frontal projection of the anatomy after arterial switch (note how the PA confluence overlies the ascending aorta). The horizontally oriented echocardiographic image (right panel) demonstrates how the pulmonary confluence (PA) is anterior to the body of the ascending aorta (Ao). The branch pulmonary arteries are “pulled” forward in the procedure described by LeCompte, often resulting in mild narrowing of the lumen. The aliased color flow seen in the branch PAs (asterisks) is due to the mild gradient caused by this narrowing. A, anterior; L, left.

FIGURE 21-60 Senning operation for complete transposition of the great arteries. A: Anatomic specimen showing the apical four-chamber anatomy. The pulmonary venous pathway (PV) is widely patent. The pulmonary venous flow sweeps through

the baffle from the posterior and leftward pulmonary veins to the anterior and rightward tricuspid valve. The area of “atrium” just above the mitral valve annulus (arrow) is the confluence of the systemic venous pathways (inferior and superior venae cavae). The actual superior vena cava pathway is anterior to this plane and not visible. The dark circle at the inferior aspect of the confluence leads to the inferior vena cava. B and C: Apical four-chamber echocardiographic images from a 16-yearold patient. The plane is comparable to that in (A). B: Two-dimensional image showing a dilated right atrium and right ventricle (RV) (with RV hypertrophy). The pulmonary veins (PV) have been baffled to the tricuspid valve, and this pathway appears widely patent. C: Color flow Doppler imaging is useful to confirm laminar flow through the reconstruction and to detect stenoses or residual shunts. In this case, flow from the pulmonary veins to the RV is unobstructed and no residual shunts are seen. D–F: The anatomy of an atrial switch operation for complete transposition of the great arteries in a 30-year-old man. The apical four-chamber views usually are the most informative initial scans (D and E) for evaluation of the venous reconstructions after either a Mustard or Senning operation. The pulmonary vein pathway (PV in D) is usually visualized in the same plane as the internal cardiac crux and atrioventricular valves (as in D). Flow travels horizontally from the left-sided pulmonary veins to the RV inlet. In this view, the narrowest point in the pathway is often centered over (or just to the right of) the plane of the interventricular septum. After the pulmonary vein pathway has been identified, posterior angulation of the scan plane will demonstrate the inferior vena caval (IVC) portion of the reconstruction (E). The pathway from the IVC to the mitral valve also has a primarily horizontal course. The superior vena caval pathway is not usually visible from the apex. This pathway follows a more superior to inferior and leftward course, nearly parallel with the posterior wall of the ascending aorta. In young patients, a combination of parasternal long-axis (angled toward the patient’s right, as in F; asterisk, superior vena cava pathway), right parasternal sagittal, and suprasternal coronal views is necessary to visualize completely this part of the repair. In many mature patients, the superior vena caval pathway is not visible on any surface scans, and transesophageal echocardiography is required to assess this pathway. A, anterior; IVC, inferior vena cava; L, left; LA, left atrium; LV, left ventricle; PV, pulmonary vein S, superior; SV, superior vena cava.

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Video 21-60A

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Video 21-60B

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Video 21-60C

FIGURE 21-61 Pulse-wave Doppler flow patterns in the superior vena cava. The two pulse-wave Doppler tracings in this figure were both obtained (in different patients) from the suprasternal transducer position with the sample volume in the midsuperior vena cava (SVC). The upper panel shows a normal flow pattern, with phasic changes in velocity that reflect cardiac cycle. Augmentation of forward flow occurs with atrial relaxation (S, systole) and atrioventricular valve opening (D, diastole). The arrows indicate flow reversal due to atrial contraction. These phasic changes are blunted in the setting of SVC stenosis, as can be seen in the lower panel, which was obtained in a patient who had undergone Mustard operation and had moderate stenosis in the SVC pathway. Note that the velocity profile never “returns” to the baseline, only showing augmentation with tricuspid valve opening in early diastole. In severe stenosis, the flow profile may become completely flat, augmenting only due to the respiratory cycle (inspiratory increase in velocity).

Pulmonary venous obstruction is not common, but is more frequent after the Senning operation than the Mustard procedure. However, systemic venous compromise is often seen in patients after the Mustard operation, especially involving the SVC pathway. Therefore, the exam of these patients should include assessment of the inferior and SVC flow from the subcostal and suprasternal windows. The SVC baffle can be difficult to define by TTE, but is best seen from the

parasternal long axis and short axis views with the imaging plane angled to the patient’s right. Pulsed Doppler analysis of superior vena caval flow can provide clues to the downstream status of the pathway (Fig. 21-61). Often, the SVC pathway cannot be visualized from surface scans and TEE is required to define the status of the baffle when clinical concerns or SVC Doppler analysis suggest obstruction. The pulmonary venous “baffle” begins at the normal anatomic connection of the pulmonary veins to the native LA. Flow is directed toward the right lateral wall of the native RA by the surgical baffle and then apically to the TV. These features can be appreciated from the apical window, particularly in the fourchamber plane (Fig. 21-60). Residual shunts will have flow directed toward the systemic venous atrium, often seen just proximal to the MV annulus. More posterior angulations of the scan plan from plane of the AV valves will demonstrate the IVC baffle, directing flow from the IVC/native RA junction toward the MV. This pathway follows a primarily horizontal course across the most inferior aspect of the atria. Both arterial and atrial with operations in d-TGA have been associated with good early success, and one will encounter patients with both procedures in 21st century echocardiographic laboratories. Confident echocardiographic assessment of repaired d-TGA requires sonographers to be familiar with the congenital anatomy and different surgical repairs that could have been performed. The availability of the surgical records detailing the kind of repair done is very helpful in guiding the examination.

Congenitally Corrected Transposition of the Great Arteries Congenitally corrected transposition of the great arteries (ccTGA, L-TGA) can be a confusing malformation. This is due in part to the complex anatomy but also from the varied nomenclature (L-TGA, congenitally corrected TGA, ventricular inversion, etc.). The malformation results from abnormal ventricular looping during embryogenesis and leads to “ventricular inversion” in which the systemic and pulmonary venous returns are routed to the appropriate great arteries (pulmonary artery and aorta) but through the “wrong ventricle.” The morphologically right ventricle and its tricuspid valve are on the left side of the heart, and the pulmonary veins, left atrium, and aorta are associated/connected to it (Fig. 21-62). In contrast, the morphologically left ventricle and its mitral valve are on the right side of the heart and is connected to the vena cava, right atrium, and pulmonary artery. Therefore, with this condition is characterized by both

atrioventricular and ventriculoarterial discordances (Fig. 21-62). Unlike complete transposition (dTGA), patients with ccTGA are usually not cyanotic. The most common associated defect is VSD. Other common associations include pulmonary stenosis, dextrocardia, and dysplasia of the systemic (left-sided) tricuspid valve. The systemic AV dysplasia is manifest by tethering of the leaflets to the RV myocardium and bears similarities to Ebstein malformation, although valve repair has not generally been successful in ccTGA patients. The abnormal atrioventricular connection also results in abnormal development of the conduction system and a greater frequency of complete atrioventricular block than in most CHD. Significant AV block can occur in ccTGA patients at any age. Patients with ccTGA and other coexisting cardiovascular abnormalities will usually present in early infancy or childhood. In the absence of other abnormalities, they may survive into adulthood prior to clinical presentation. Signs leading to late presentation may be related to an abnormal ECG, a heart murmur from systemic (tricuspid) valve regurgitation, complete heart block, cardiac arrhythmias, or exercise intolerance/heart failure due to progressive systemic ventricular (morphologically RV) dysfunction and/or tricuspid regurgitation. Although, ccTGA has characteristic electrocardiographic and chest x-ray findings, echocardiography has the primary role in its diagnosis and clinical follow-up. In those with normally positioned hearts (in the left chest), the classic echocardiographic finding associated with ccTGA is appreciated in the apical 4 chamber view. The discordant AV connection results in a reversal of the typical septal insertions of the atrioventricular valves. The left-sided AV valve is tricuspid in morphology, connecting the LA to the systemic RV. As a result, its left-sided septal insertion lies apical to that of the right-sided (morphologically mitral) AV valve. This finding alone, in a biventricular heart, is diagnostic of AV discordance. In classic cc TGA, there is an intact ventricular septum and discordant connection between the ventricles and the great arteries. This results in malposition of the arterial roots. The aortic valve is found anterior and to the left of the pulmonary valve and arising from a complete muscular infundibulum from the left-sided morphologically RV. This creates a distinct muscular discontinuity between the left AV valve and the aortic annulus. This can be seen in parasternal long- and short-axis views, demonstrating the discontinuity between the left-sided tricuspid valve and the anteriorly placed aortic valve (Fig. 21-63). Early identification of ccTGA with proper assessment of the severity of tricuspid regurgitation and morphologic systemic right ventricular dysfunction,

and associated anomalies, has significant prognostic and therapeutic implications. This is particularly true relating to conventional surgical replacement of the systemic AV valve. Those with significant regurgitation and reduced morphologically RV ejection fraction have increased risk of mortality and ongoing ventricular failure when valve replacement is performed. It is thought that valve replacement should be reserved for those with morphologically right ventricular ejection fractions greater than 40% to 45%. If the ejection fraction is below that level, then transplantation may offer a better long-term result.

Univentricular Atrioventricular Connections Some of the most complex congenital cardiac malformations involve univentricular AV connections (Fig. 21-64). These hearts can also be thought of as functionally single ventricles (univentricular hearts). The terms single ventricle and univentricular are misnomers because all human hearts will have components of both an RV and LV. What distinguishes these patients from those with biventricular hearts is one of two anatomic variables. Either one of the ventricles is too small to be used as a circulatory pump or coexisting lesions make it impossible to divide the two circulations surgically (such as major straddling of an AV valve). Three of the common forms of univentricular AV connection are shown in Figure 21-64.

FIGURE 21-62 Congenitally corrected transposition of the great arteries. A: A “fourchamber view” of a normal heart. B: Same view as in A, but the heart is from a patient with congenitally corrected transposition of the great arteries. This specimen shows the unique septal insertions of the two atrioventricular valves encountered with a discordant atrioventricular (AV) connection. The septal leaflet of the morphologic tricuspid valve always inserts onto the ventricular septum at a point closer to the cardiac apex than does the anterior leaflet of the morphologic mitral valve. The left AV valve has a septal insertion that is apical in relation to the insertion of the right AV valve, confirming that it is anatomically a tricuspid valve (arrow). Because the AV valves develop from their ventricles, the morphologic right ventricle (mRV) is always connected to a morphologic tricuspid valve and vice versa. Thus, images of only the septal AV valve insertions allow for confident echocardiographic identification of not only the type of AV valve present but also the morphology of the underlying ventricle. This relation is easily demonstrated in apical four-chamber echocardiographic images of the internal cardiac crux. C: Two-dimensional systolic apical four-chamber image from an adult with congenitally corrected transposition of the great arteries. Note the anatomy of the internal cardiac crux (arrow). The septal insertion of the left AV valve

is slightly apical to that of the right AV valve (arrow). This relation is one of the anatomic hallmarks of congenitally corrected transposition of the great arteries. It is the most reliable echocardiographic finding for identifying the morphology of the ventricle associated with the AV valve and discordant AV connections. In this case, the moderator band (asterisk) can also be seen within the left-sided ventricle, further confirming its status as a morphologically “right” ventricle (mRV). D: A systolic color flow image of the left AV valve of the same patient demonstrating severe left AV valve regurgitation. Note that this patient also had an implantable cardiac defibrillator; the leads are visible in the right atrium (RA) (C) and the right-sided morphologic LV (mLV). L, left; LA, left atrium; LV, left ventricle; RV, right ventricle; S, superior.

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Video 21-62

FIGURE 21-63 Congenitally corrected transposition of the great arteries (ccTGA): discontinuity between the aorta and the left atrioventricular valve (AVV). These twodimensional images were taken from an examination of an adult with ccTGA. The apical four-chamber image (left panel) shows anatomy similar to that demonstrated in Figure 21-56, although the left AVV is thicker and shows more apical displacement than the preceding example. The right panel is a “parasternal short-axis” image of the relationships between the left AVV, subaortic outflow tract, and aortic valve. The aortic

valve is positioned to the left, “on top of” a long segment of subaortic conus muscle, the outflow tract of the left-sided, morphologically right ventricle. As a result, there is significant muscular separation or discontinuity between the anterior leaflet of the left AVV (arrow) and the aortic valve leaflets (asterisk). A, anterior; L, left; LA, left atrium; mLV, morphologically left ventricle; mRV, morphologically right ventricle; RA, right atrium; S, superior.

A consequence of the inability to create a biventricular circulation is that treatment strategies must focus on a method that preserves the “usable” ventricle in connection with the aorta. The ultimate goal is to redirect systemic venous flows to the pulmonary arteries (allowing for gas exchange) without overloading the ventricle. The standard strategy that has been used to achieve this is known as the Fontan operation, and this cannot be performed in the newborn, since pulmonary vascular resistance remains too high to allow a venous source of flow at that time. Therefore, a variety of initial palliative procedures may be needed early in life to stabilize the patient. Then, after pulmonary artery resistance has matured (decreased), the patient can be considered for connection of the SVC (the so-called Glenn procedure) and IVC (Fontan completion) to the pulmonary arteries. These procedures can occur simultaneously, but better results have been achieved with a staged approach in which the SVC to PA connection is made between 3 and 6 months of age and the Fontan completion delayed until the patient is older (2–4 years). Fontan completion (and/or Glenn procedures) can be performed later in life, but the goal of the overall strategy is to eliminate/reduce cyanosis and to reduce the workload placed on the functionally single ventricle as early in life as is possible and safe. Patients will have increased systemic venous pressures after Fontan completion since the venous and pulmonary arterial pressure will be equal. Factors that are associated with a better outcome after Fontan completion include normal ventricular systolic and diastolic performance; large, low resistance pulmonary arteries; lack of significant valvular regurgitation, and outflow obstructions (subaortic stenosis, coarctation, etc.). Even in patients with the lowest risk profile, late complications are common due in part to the inherently abnormal nature of the ventricle. In addition to coexisting arterial issues, complications seen after Fontan include ventricular dysfunction/failure, atrial arrhythmias, and protein losing enteropathy (thought to be in part related to increase systemic venous pressure). The most common form of univentricular AV connection is that of hypoplastic left syndrome (Fig. 21-64 panel C). The degree of underdevelopment (hypoplasia) of the left ventricle and its associated valves is variable, but results in a systemic circulation supported entirely by the right heart. In addition to the

single ventricular physiology, the aorta and the arch are hypoplastic as well, making a complex neonatal arch reconstruction obligatory. This procedure is known as the Norwood operation and involves coarctation repair, surgical connection of the ascending aorta and main pulmonary artery, enlargement of the aortic arch, provision of pulmonary arterial blood flow with a shunt (either from the RV or the aorta), and creation of a large ASD to allow pulmonary venous flow free access to the TV and RV. Results with this strategy have improved and early cohorts treated in this way are now young adults. Tricuspid atresia (Fig. 21-64 panel A) and double-inlet left ventricle (Fig. 2164 panel B) are the next most frequently encountered forms of functionally univentricular heart. Other, more complex, malformations also exist in which there is only one functional ventricle. These cases often have a single, common atrioventricular valve and multiple systemic and pulmonary venous anomalies.

FIGURE 21-64 Univentricular AV connections (functional single ventricle physiology). A–C: Echocardiographic images of three common types of univentricular atrioventricular (AV) connection. These hearts are often classified as functional single ventricles. A: Double-inlet AV connection. Although this connection can be seen with either a dominant left ventricle (LV) or right ventricle morphology, double inlet to an LV is by far the more common. In this case, the left atrium (LA), right atrium (RA), and AV valves are committed to a ventricle that has distinct papillary muscles and relatively fine trabeculations, LV morphology. The right ventricular remnant is anterior to the plane of imaging and gives rise to one of the great arteries. This remnant usually consists of only the infundibulum and is always too small to act as an independent pump in a patient with double-inlet LV. B and C: Single-inlet connections. This is usually associated with atresia (absence) of one of the AV valves. The most common examples of this connection are hypoplastic left heart syndrome and tricuspid atresia. B: An example of tricuspid valve atresia. The apical “floor” of the RA (arrow) shows no evidence of a valve and there is no right ventricular inlet. The only outlet from the RA is across the atrial septum. Similar to double-inlet LV, the right ventricular remnant is anterior and usually gives rise to one of the great arteries. The size of this remnant is more variable in tricuspid atresia than in double-inlet LV and is related to the size of the ventricular septal defect connecting it to the LV cavity and the adequacy of the arterial outlet. C: A subcostal “four”-chamber view from a neonate with hypoplastic left

heart syndrome. The LV is extremely diminutive in this case (asterisk), where both the mitral and aortic valves were atretic. The LA is moderately hypoplastic and the right heart chambers are enlarged. The ascending aorta is always small in these patients and there is always a coexisting coarctation. All these patients require a patent ductus arteriosus to provide blood flow to the systemic circulation. RV, right ventricle.

In tricuspid atresia (Fig. 21-64 panel A), the right AV connection is absent leaving only an ASD as an exit from the right atrium. Systemic venous blood crosses the defect, mixing with pulmonary venous flow to enter the functionally single LV. Most often, the ventricular to arterial connection is normal (concordant) with the aorta arising from the “single” LV and the pulmonary artery arising from a remnant of the RV (its outflow tract). Flow from the LV is ejected both to the aorta and across a VSD to the PA. Variable degrees of pulmonary/subpulmonary stenosis may be seen in these patients, but aortic obstructions (sub-AS or coarctation) are rare. A more complex form of tricuspid atresia involves a discordant ventricular to arterial connection or transposed great arteries. In these cases, the aorta originates from the RV remnant and obstruction to aortic flow (both subaortic stenosis and coarctation) are more common. Double-inlet left ventricle (DILV, Fig. 21-64 panel B) is characterized by connection of both atria via an AV valve to the same, morphologically left, ventricular chamber. There will also be a remnant of the right ventricle present, similar to tricuspid atresia, giving rise to one of the great arteries. Patients with DILV may have normally related great arteries (concordant connection) but will have discordantly connected (transposed) great arteries more frequently than is seen in tricuspid atresia. The variable nature of the VA connection results in a broad spectrum of clinical presentations, from marked cyanosis (severe PS) to hypotensive shock (severe sub-AS or coarctation to pulmonary overcirculation and heart failure (no outflow obstruction of any kind). Although most functionally single ventricle patients have been treated with some form of surgical palliation, survival into adulthood without intervention has been reported. These adult survivors are cyanosed and typically fall into two major categories: 1) those with pulmonary or subpulmonary stenosis (associated with loud systolic murmur) and low pulmonary artery pressure and 2) those with unobstructed pulmonary blood flow and secondary irreversible pulmonary hypertension (physiology similar to the Eisenmenger VSD).

REFERENCES

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patients with pulmonary stenosis by quantitative two-dimensional echocardiographic Doppler studies. Circulation, 1983;67:866–871. 20. Silvilairat S, Cabalka AK, Cetta F, et al. Echocardiographic assessment of isolated pulmonary valve stenosis: Which outpatient Doppler gradient has the most clinical validity? Journal of the American Society of Echocardiography, 2005;18:1137–1142. 21. Silvilairat S, Cabalka AK, Cetta F, et al. Outpatient echocardiographic assessment of complex pulmonary outflow stenosis: Doppler mean gradient is superior to the maximum instantaneous gradient. Journal of the American Society of Echocardiography, 2005;18:1143–1148. 22. Sasson Z, Yock PG, Hatle LK, et al. Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy. Journal of the American College of Cardiology, 1988;11:752–756. 23. Shiina A, Seward JB, Edwards WD, et al. Two-dimensional echocardiographic spectrum of Ebstein’s anomaly: Detailed anatomic assessment. Journal of the American College of Cardiology, 1984;3:356– 370 24. Gussenhoven EJ, Stewart PA, Becker AE, et al. “Offsetting” of the septal tricuspid leaflet in normal hearts and in hearts with Ebstein’s anomaly: Anatomic and echographic correlation. American Journal of Cardiology, 1984;54:172–176. 25. Dearani JA, Mora BN, Nelson TJ, et al. (2015) Ebstein anomaly review: what’s now, what’s next? Expert Review of Cardiovascular Therapy, 2015;13:1101–1109. 26. Valente AM, Cook S, Festa P, et al. Multimodality imaging guidelines for patients with repaired tetralogy of fallot: A report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance and the Society for Pediatric Radiology. Journal of the American Society of Echocardiography, 2014;27:111–141. 27. Cohen MS, Eidem BW, Cetta F, et al. Multimodality imaging guidelines of patients with transposition of the great arteries: A report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography. Journal of the American Society of Echocardiography, 2016;29:571–621.

CHAPTER

22

Interventional Echocardiography Jeremy J. Thaden, Brandon M. Wiley, Peter M. Pollak, and Charanjit S. Rihal

INTERVENTIONAL ECHOCARDIOGRAPHY AND STRUCTURAL HEART DISEASE The frequency and complexity of catheter-based interventions for structural heart disease have grown exponentially in recent years. Interventional echocardiography is a relatively new field that has grown in parallel to the recent increase in transcatheter structural heart procedures. Transcatheter procedures are performed percutaneously, and as a result, the proceduralists do not have the benefit of directly visualizing the cardiac anatomy and therefore rely on cardiac imaging to safely complete these complex interventions. Echocardiography has emerged as an indispensable tool to plan and guide catheter-based interventional procedures in the cardiac catheterization laboratory and hybrid operating room. To be most effective, the echocardiographer should have an intimate working knowledge of the unique features of the various transcatheter procedures and delivery systems in use. Although transthoracic echocardiography (TTE) is used to guide some procedures, more complex catheter-based interventions in structural heart disease rely on 2-D and 3-D transesophageal echocardiography (TEE).

Interventional Echocardiography: Basic Principles To varying degrees, based on the procedure being performed, interventional echocardiographers are charged with preprocedural planning, live procedural guidance, and postprocedural assessment. The imager must be well versed on the technical aspects of the procedure being performed in order to anticipate potential complications and to optimize patient safety and procedural efficacy. To do this effectively requires constant and unambiguous communication between the echocardiographer and the proceduralist. Because interventional

cardiologists are generally more familiar with fluoroscopic imaging planes and echocardiographers utilize 2-dimensional (2D) and three-dimensional (3D) anatomical image display, it can be helpful to communicate with reference to anatomic landmarks that are mutually visible in both imaging modalities when possible. As the complexity of transcatheter procedures increases and there is increased reliance on echocardiographic guidance, effective communication can be more challenging but remains a critical component for procedural success. Interventional echocardiography introduces a number of challenges that are somewhat unique compared with routine echocardiographic imaging. Many procedures require the imager to locate and follow devices and/or catheters in 3D space while they cross various tissue planes in a dynamic heart that changes position with the respiratory and cardiac cycles. Visualizing the tips of these various catheters and devices to ensure safe passage can be challenging. Frequently, intracardiac devices also cause acoustic shadowing, which inhibits adequate visualization of normal cardiac structures. These devices may also distort normal cardiac anatomy, which can complicate the assessment of the procedural result itself. As an example, transcatheter mitral valve repair (TMVR) with the MitraClip device involves implantation of a clip to oppose the anterior and posterior leaflets at the site of regurgitation. The clip often fragments regurgitant jets, resulting in multiple jets, which are often eccentric and difficult to grade. A multiparametric approach to grading is recommended in such situations, but additional research is needed to determine the best method of assessment. Interventional echocardiography relies on TTE and/or TEE imaging using a combination of 2D, 3D, color Doppler, and spectral Doppler imaging. The advantage of 2D imaging is its ability to see cardiac tissues in high spatial and temporal resolution. As a result, 2D imaging is well suited when attempting to grasp the mitral leaflets during a MitraClip procedure, which is a step that requires high spatial and temporal resolution imaging. 3D imaging, by contrast, lacks the spatial and temporal resolution of 2D imaging but has the ability to display complex spatial relationships such as the relationship of catheters to surrounding cardiac tissues. 3D echocardiography can also be used to perform a variety of quantitative measurements, which can be used for preprocedural planning, device size selection, or in some cases postprocedural assessment. Color Doppler is most useful as a screening tool to evaluate for residual blood flow through regurgitant lesions or between cardiac chambers. Spectral Doppler is frequently utilized to assess the hemodynamic significance of regurgitant or

stenotic lesions. Commonly performed procedures in current clinical practice include transcatheter aortic valve replacement (TAVR), valve-in-valve (ViV) therapy for dysfunctional bioprosthetic valves, TMVR, percutaneous closure of prosthetic valve paravalvular regurgitation (PVR), left atrial appendage (LAA) occlusion, and many others (Table 22-1). At the time of this writing, a number of studies are also actively evaluating new devices aimed at TMVR/replacement and tricuspid valve repair. For the purposes of this chapter, we will focus on important echocardiographic imaging considerations for the following commonly performed interventional procedures: TAVR for aortic stenosis, transseptal puncture, percutaneous ViV therapy for dysfunctional bioprosthetic valves, TMVR, percutaneous closure of PVR, and LAA occlusion. We will also briefly review the current transcatheter mitral valve landscape and discuss general considerations and several devices currently undergoing clinical trials. TABLE 22-1 Transcatheter or Percutaneous Structural Heart Procedures Structural Procedures Transseptal catheterization Balloon or blade atrial septostomy Percutaneous balloon mitral valvuloplasty Transcatheter closure of ASD, VSD, and PFO Alcohol septal ablation in HOCM Transcatheter mitral valve repair (TMVR) Transcatheter mitral valve replacementa Transcatheter tricuspid valve repaira Percutaneous closure of prosthetic paravalvular regurgitation Transcatheter valve-in-valve implants Percutaneous left ventricular assist device placement Transcatheter aortic valve replacement Percutaneous left atrial appendage occlusion Transcatheter closure of intracardiac fistulas Transcatheter closure of aortic root or intracardiac pseudoaneurysms Right ventricular biopsy Placement of aortic endograft Multiple devices currently under investigation.

a

Radiation Safety Another unique challenge in interventional echocardiography, compared with conventional echocardiography, is that of radiation safety. Structural heart interventions are performed in a cardiac catheterization lab or a hybrid operating room where fluoroscopy is frequently used during the procedure. Fundamental knowledge of radiation safety is vital to maintaining a safe working environment. Radiation exposure can be minimized by reducing the time of exposure, increasing the distance from the fluoroscopic c-arm, and by adding radiation shielding. Radiation strength and exposure risk drop exponentially with distance according to the inverse square law. As such, by moving twice the distance from the x-ray source, the radiation is reduced to a fourth, and moving that distance again reduces it to a sixteenth. Stepping away from the radiation source has a powerful effect on reducing radiation exposure. Shielding refers to the use of “lead” and lead substitutes to block radiation from reaching radiation-sensitive tissue. Every interventional echocardiographer should use a lead or lead-equivalent apron and lead glass protective eyewear. Because the echocardiographer may frequently turn his or her back to the radiation source while obtaining images, we have found garments that wrap completely to be safest. Standing or hanging lead shields may also be systematically incorporated into the room setup for structural interventions to create a safe “radiation shadow” for the imager to stand behind decreasing overall radiation exposure. Finally, it is recommended that all members of the team who will be working regularly in a radiation environment undergo radiation safety training and wear a personalized radiation dosimeter to track their exposure level. Structural intervention procedures can involve substantial time and radiation exposure. Proper planning, communication, and understanding of radiation safety can minimize the occupational exposure for all involved.

TRANSCATHETER AORTIC VALVE REPLACEMENT Large epidemiological studies estimate the prevalence of moderate or severe aortic stenosis to be 2.8% to 4.6% in those aged 75 years or older (1). The prognosis of symptomatic severe aortic stenosis is poor, and even in

asymptomatic patients, there is a high rate of progression to symptomatic stenosis. Historically, surgical valve replacement via sternotomy was the only option for symptomatic patients. However, with the success of several pivotal clinical trials, TAVR has evolved into an effective therapy for a select group of patients. Current indications for TAVR are in those with severe, symptomatic native aortic stenosis at intermediate or greater risk of surgical mortality (2–7) or in those with a severely dysfunctional aortic bioprosthetic valve at high risk to undergo reoperation (8,9). Currently, the commercially available TAVR platforms in the United States are delivered using either balloon-expandable or self-expanding transcatheter heart valves (THVs) (Fig. 22-1). The Sapien XT and Sapien 3 (Edwards Lifesciences, Irvine, CA) are balloon-expandable THVs. The CoreValve Evolut (Medtronic, Minneapolis, MN) is a self-expanding THV. The Evolut platform is partially retrievable, which provides the option to reposition the valve during the deployment procedure if necessary. Both valves have a skirt mounted to the stent frame that improves apposition to the aortic annulus and reduces PVR and have been approved for use in native aortic stenosis and degenerative aortic bioprosthetic valves. The CoreValve Evolut has a longer profile than the Sapien 3, and its leaflets sit supra-annular after implantation. THV options are growing as multiple additional platforms are awaiting approval in the United States including the Lotus (Boston Scientific, Marlborough, MA), Portico (Abbott, Chicago, IL), and Centera 3 (Edwards Lifesciences, Irvine, CA).

FIGURE 22-1 Transcatheter heart valves (THVs). A: Evolut™ PRO Valve is a selfexpanding THV. (Reproduced with permission of Medtronic, Inc. Copyright ©2018 Medtronic.) B: Sapien 3 is a balloon-expanding THV. (Courtesy of Edwards Lifesciences LLC, Irvine, CA. Edwards, Edwards Lifesciences, Edwards SAPIEN, SAPIEN, SAPIEN XT and SAPIEN 3 are trademarks of Edwards Lifesciences

Corporation.)

Preprocedure Echocardiographic Evaluation Echocardiography provides “real-time” evaluation of cardiac anatomy and physiology during the TAVR procedure, which is critical to ensure proper THV implantation and rapid diagnosis of potential complications. Echocardiographic guidance of TAVR begins with a comprehensive preprocedural baseline echocardiogram to help with procedural planning and to assess for potential risk factors for complications. The checklist presented in Figure 22-2 provides a thorough guide for the preprocedural evaluation.

FIGURE 22-2 Preprocedure checklist prior to transcatheter aortic valve replacement.

The echocardiographic imaging modality chosen (TTE vs. TEE) varies according to institution and remains a controversial topic. Many institutions are moving away from general anesthesia and instead utilizing a “minimalist approach” for TAVR with monitored anesthesia care (MAC) and TTE guidance in an effort to reduce cost and procedural times (10,11). TTE guidance is reasonable in uncomplicated cases using percutaneous femoral access when adequate thoracic acoustic windows are present (12). However, compared with TTE, 2D and 3D TEE offers better assessment of aortic annular dimensions as well as improved imaging resolution with the ability to evaluate cardiac anatomy in multiple imaging planes while limiting contact with the surgical sterile field. TEE is the preferred modality for cases with complex cardiac anatomy or highrisk features including severe calcification of the “implantation zone,” a low coronary ostium, subaortic septal hypertrophy, severe atherosclerosis of the aorta, or severe left ventricular systolic dysfunction. Additionally, TEE may be preferred in patients with renal dysfunction in order to potentially reduce the amount of contrast exposure. The preprocedural TTE in the catheterization laboratory can alert the interventional echocardiographer to the presence of poor transthoracic acoustic windows or high-risk anatomic features that would require a change to TEE. Additionally, the interventional team should be prepared to switch to TEE guidance during the procedure in the setting of unforeseen hemodynamic perturbations, inability to accuracy define THV function or if there is concern for PVR that is not well visualized by TTE. Aortic Root Anatomy Assessment The aortic root contains the “implantation zone” for the THV and incorporates multiple important structures: the aortic annulus, aortic valve commissures and leaflets, sinuses of Valsalva, coronary ostia, sinotubular junction, and ascending aorta. A comprehensive evaluation of the aortic root is important to determine appropriate THV size and to assess for potential obstacles to successful deployment. The native aortic valve should be assessed for number and size of leaflets. Although TAVR therapy has been successful for congenital bicuspid valve stenosis, the outcomes have not been as favorable as for tricuspid valves and the indication remains off-label (13). Functional bicuspid valves are not a contraindication to TAVR, but the presence of severe ectopic calcification can increase the risk for PVR. Excessive calcification of the aortic root, annulus, and

aortomitral curtain (intertrigonal area) increases the risk of postprocedure aortic injury (annular rupture, aortic dissection, or intramural hematoma) and PVR. Assessment for potential coronary artery obstruction is an important periprocedural consideration. The most common cause of obstruction is occlusion of the left main coronary ostium by the native leaflets. Risk factors for coronary artery obstruction include the use of balloon-expandable THV, female sex, coronary ostia height ≤10 to 11 mm from the annulus, sinus of Valsalva diameter