Heart Valve Disease: State of the Art [1st ed. 2020] 978-3-030-23103-3, 978-3-030-23104-0

Table of contents :
Front Matter ....Pages i-x
Introduction to Valve Heart Disease (Jose Zamorano, Álvaro Marco del Castillo)....Pages 1-8
Evaluation of Patients with Heart Valve Disease (Jose Zamorano, Ciro Santoro, Álvaro Marco del Castillo)....Pages 9-19
Aortic Stenosis (Marie-Annick Clavel, Nancy Côté, Philippe Pibarot)....Pages 21-46
Aortic Regurgitation (Covadonga Fernández-Golfín)....Pages 47-64
Aortic Valve Intraoperative Echocardiography (Covadonga Fernández-Golfín)....Pages 65-75
Mitral Stenosis (Luc Pierard)....Pages 77-88
Mitral Regurgitation (Madalina Garbi, Julien Magne, Francesco Maisano, Martin Swaans, Raluca Dulgheru, Patrizio Lancellotti)....Pages 89-109
Mitral Valve Intraoperative Echocardiography (Alessandra Carvelli, Covadonga Fernández-Golfín)....Pages 111-126
Tricuspid Valve Disease (Rebecca T. Hahn)....Pages 127-145
Pulmonic Valve Diseases (Bogdan A. Popescu, Maria-Magdalena Gurzun, Andreea C. Popescu)....Pages 147-161
Acute Rheumatic Fever and Rheumatic Heart Disease (G. Itzikowitz, E. A. Prendergast, B. D. Prendergast, L. Zühlke)....Pages 163-175
Infective Endocarditis (Gilbert Habib, Maria Abellas-Sequeiros)....Pages 177-192
Multiple Valve Disease (Philippe Unger, Mauro Pepi)....Pages 193-205
Prosthetic Heart Valves (John Chambers)....Pages 207-230
Valvular Heart Failure (Madalina Garbi)....Pages 231-243
Antithrombotic Therapy in Valvular Heart Disease (Steven Droogmans, Simon Vanhentenrijk, Bernard Cosyns)....Pages 245-256
Heart Valve Diseases in Pregnancy (Denisa Muraru, Elena Surkova)....Pages 257-269
Back Matter ....Pages 271-279

Citation preview

Heart Valve Disease State of the Art Jose Zamorano Patrizio Lancellotti Luc Pierard Philippe Pibarot Editors

123

Heart Valve Disease

Jose Zamorano Patrizio Lancellotti Luc Pierard  •  Philippe Pibarot Editors

Heart Valve Disease State of the Art

Editors Jose Zamorano Hospital Universitario Ramón y Cajal Madrid Spain Luc Pierard University of Liège Liège Belgium

Patrizio Lancellotti Cardiology University Hospital Sart Tilman Cardiology Liège Belgium Philippe Pibarot Institut Universitaire de Cardiologie et de Pneumologie de Québec Quebec Heart & Lung Institute Québec Canada

ISBN 978-3-030-23103-3    ISBN 978-3-030-23104-0 (eBook) https://doi.org/10.1007/978-3-030-23104-0 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

Valvular heart disease has been one of the most prominent areas of interest in cardiology in the recent years. The development of new diagnostic methods and therapeutic strategies has been a focus in the main cardiology meetings and journals in the last decade. In addition, the relationship of valve disease with other concomitant pathologies such as heart failure often leads to complex decision-making. In this book, we have tried to summarize the state of the art in valvular heart disease from pathophysiology to diagnosis and treatment. In the different chapters included in this book, top experts in the field have described complex disease entities and challenges in a concise and practical manner. This book is also densely illustrated with figures and tables that help to describe each clinical scenario and latest guidelines have been incorporated in each chapter to enhance clinical decision-making. We do believe that the book is proving cutting edge information on valvular heart diseases in Europe and worldwide and we hope this document will help you in your daily practice. The Council on Valvular Heart Disease of the ESC has recommended this book as the pivotal one for understanding and treating valvular heart diseases. Please do not hesitate to share with us your comments and feedback and to tell us how we can improve in future editions. Madrid, Spain Liège, Belgium  Liège, Belgium  Québec, Canada 

Jose Zamorano Patrizio Lancellotti Luc Pierard Philippe Pibarot

v

Acknowledgements

The editors would like to acknowledge Dr. Alvaro Marco, MD, for his editorial assistance throughout the preparation of this book. Dr. Marco provided enormous help in coordinating all chapters and in review of both the manuscript and the final version of the book. Madrid, Spain Québec, Canada  Liège, Belgium  Liège, Belgium 

Jose Zamorano Philippe Pibarot Patrizio Lancellotti Luc Pierard

vii

Contents

1 Introduction to Valve Heart Disease����������������������������������������������   1 Jose Zamorano and Álvaro Marco del Castillo 2 Evaluation of Patients with Heart Valve Disease��������������������������   9 Jose Zamorano, Ciro Santoro, and Álvaro Marco del Castillo 3 Aortic Stenosis����������������������������������������������������������������������������������  21 Marie-Annick Clavel, Nancy Côté, and Philippe Pibarot 4 Aortic Regurgitation������������������������������������������������������������������������  47 Covadonga Fernández-Golfín 5 Aortic Valve Intraoperative Echocardiography����������������������������  65 Covadonga Fernández-Golfín 6 Mitral Stenosis����������������������������������������������������������������������������������  77 Luc Pierard 7 Mitral Regurgitation������������������������������������������������������������������������  89 Madalina Garbi, Julien Magne, Francesco Maisano, Martin Swaans, Raluca Dulgheru, and Patrizio Lancellotti 8 Mitral Valve Intraoperative Echocardiography���������������������������� 111 Alessandra Carvelli and Covadonga Fernández-Golfín 9 Tricuspid Valve Disease ������������������������������������������������������������������ 127 Rebecca T. Hahn 10 Pulmonic Valve Diseases������������������������������������������������������������������ 147 Bogdan A. Popescu, Maria-Magdalena Gurzun, and Andreea C. Popescu 11 Acute Rheumatic Fever and Rheumatic Heart Disease��������������� 163 G. Itzikowitz, E. A. Prendergast, B. D. Prendergast, and L. Zühlke 12 Infective Endocarditis���������������������������������������������������������������������� 177 Gilbert Habib and Maria Abellas-Sequeiros 13 Multiple Valve Disease �������������������������������������������������������������������� 193 Philippe Unger and Mauro Pepi

ix

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14 Prosthetic Heart Valves�������������������������������������������������������������������� 207 John Chambers 15 Valvular Heart Failure�������������������������������������������������������������������� 231 Madalina Garbi 16 Antithrombotic Therapy in Valvular Heart Disease�������������������� 245 Steven Droogmans, Simon Vanhentenrijk, and Bernard Cosyns 17 Heart Valve Diseases in Pregnancy������������������������������������������������ 257 Denisa Muraru and Elena Surkova Index���������������������������������������������������������������������������������������������������������� 271

Contents

1

Introduction to Valve Heart Disease Jose Zamorano and Álvaro Marco del Castillo

Etiology of Valve Heart Disease

Rheumatic Fever

The etiology of valve heart diseases has slightly changed during the last half of the twentieth century, as rheumatic fever’s incidence has declined in developed countries [1]. However, it is still the most common cause of valve disease in the young and in developing countries including Africa, Middle East, Indochina, South America and some parts of Australia. The decline in the prevalence of rheumatic fever is related to sociosanitary evolution, which has led to an improvement in living conditions and in the access to health care. It is also due to the improvement of life expectancy that valve diseases tend to be much more prevalent in the elderly [2]: an U.S. registry showed how global prevalence is around 2.5%; however, the prevalence amongst patients older than 75 years increased to 13%. Between elderly patients, the most common diseases are calcific aortic stenosis, aortic regurgitation due to aortic root dilation and secondary mitral regurgitation. Nevertheless, an unknown but probably significant percentage of patients with valve disease remains undiagnosed [3].

Rheumatic fever is the consequence of an impaired immune response against group A beta-­ hemolytic Streptococcus (also known as Streptococcus Pyogenes). After the initial infection, which usually takes place during childhood [4], patients can develop acute rheumatic fever after the first 3 weeks post infection. Albeit it is uncommon after a first pharyngitis episode, up to 75% develop rheumatic fever is recurrent episodes occur. Approximately, around 50% of patients with acute rheumatic fever suffer from heart involvement materialized as valve endocardial inflammation [5–7], and, again, the incidence increases with recurrent episodes [8]. Although the initial damage can cause severe valve lesions, rheumatic valve disease is more often based on cumulative damage due to either recurrent episodes of acute rheumatic fever or chronic degeneration cause by an impaired valve function. The mechanism of the immune response relies on molecular mimicries between several streptococcal and human proteins. Although the exact pathophysiology remains obscure, some advances have been made in this field. The abnormal immune response is based on the streptococcal strain, the presence of genetic susceptibility and an aberrant host-bacteria interaction. Some bacterial strains are more likely to cause disease than others [9]. S. Pyogenes is adhered to

J. Zamorano (*) · Á. M. del Castillo Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain e-mail: [email protected]

© Springer Nature Switzerland AG 2020 J. Zamorano et al. (eds.), Heart Valve Disease, https://doi.org/10.1007/978-3-030-23104-0_1

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throat epithelial cells thanks to a variety of surface proteins: M, T and R. One of the proposed molecular mimicry associations is the one between streptococcal protein M and several cardiac proteins (myosin, tropomyosin, laminin, vimentin), and it is hypothesized that protein M from several serotypes is keener to the disease, probably because of a higher proximity to human proteins [10, 11]. In addition, some complex carbohydrate structures present in both streptococcus and valve tissue have been implicated in molecular mimicry mechanisms. In 1889, it was noted that the probability of an acute rheumatic fever episode is significantly higher in patients with familiar history of rheumatic fever [12]. Although no single HLA haplotype has been consistently linked to the development of rheumatic fever, it is generally accepted that HLA class II molecules seem to be more closely associated with an increased risk of the disease [13]. Also, some genetically determined immune markers alter the risk of acute infection and chronic rheumatic disease, such as Mannose-binding lectin (MBL) [14]. Nevertheless, the exact mechanism is unknown. Although improved living conditions, universalization of medical care and increase in the use of penicillin have substantially changed the epidemiology of rheumatic fever [15], it still prevails in developing nations and indigenous populations. However, the real prevalence is difficult to estimate, as almost all the information comes from passive survey systems, and a underreporting of acute and chronic cases is still an unaddressed issue [16]. The global incidence of acute rheumatic fever per year in children (5–14 years) is somewhere around 300,000–350,000 cases, taking into account significant regional deviations [1, 9, 15, 17]. Modifiable factors are related to socioeconomic situations: poverty, overcrowding, malnutrition and employment [6]. The yearly incidence of an acute episode ranges from 5 per 100,000 population in richer communities up to more than 350 per 100,000 population in indigenous Australian communities [18, 19]. Approximately 200,000–250,000 deaths per year are caused by rheumatic fever, and is the major cause of car-

J. Zamorano and Á. M. del Castillo

diovascular death in developing countries in children and young adults [15]. By using Jones diagnostic criteria, 15–19 million people worldwide have rheumatic heart disease [15]. However, global distribution is markedly unequal, being sub-Saharan countries and indigenous communities in Australia those with the highest numbers. Those regions reach 8 per 1000 population cases, whether the estimate prevalence in developed countries is below 0.3 per 1000 population [1]. However, if echocardiography rather than clinical criteria is used as screening tool, prevalence increases significantly [3].

Calcific Valve Disease This term gathers all those valve diseases caused by calcific degeneration of either the leaflets or the annulus, being aortic stenosis (AS) the main entity of this group. Mitral annulus calcification is also a frequent condition, but rarely causes enough valve dysfunction as to require surgery or specific therapeutics. The incidence of AS is markedly related to age, as valve degeneration is part of the normal process of ageing. However, the whole degenerative course is definitely not a passive one [20], as it involves active calcification, atherosclerotic lipid deposition, angiogenesis and an impaired local immune response. It has come to light that the real prevalence of AS is higher than what was previously known [21]. Amongst a 30,000-people sample composed of patients who underwent a transthoracic echocardiography examination, 7.2% had any grade of AS. Even so, 2.8% had severe AS. This data is, to best of the knowledge of the authors, the largest registry ever carried out at the time of the writing of this book, and is in contrast with previous registries [2, 22] in which AS prevalence was found to be lower. As AS is markedly related to age, probably the increase in life expectancy is accountable for the rise in this disease’s prevalence. Aortic sclerosis (ASc), which is the first stage of aortic degeneration, is a highly frequent entity.

1  Introduction to Valve Heart Disease

Defined as valve thickening and calcification in the absence of significant transvalvular gradient (peak velocity 5.5 m/s). Ao Aortic, AVA Aortic valve area, AVAi AVA indexed for body surface area, AVC aortic valve calcification, LVET left ventricular ejection time, LVOT left ventricular outflow tract, LVOTd LVOT diameter, MG mean gradient, Q mean flow rate (SV/LV ejection time), SV stroke volume, SVi SV indexed for body surface area, Vpeak peak aortic jet velocity, VTI velocity-time integral

M.-A. Clavel et al.

28 Moderate Aortic Valve Stenosis

e

f

g

h

i

Fig. 3.5 (continued)

3  Aortic Stenosis

29 Severe Aortic Value Stenosis

j

k

m

l

n

Fig. 3.5 (continued)

is important to assess the extent of anatomical and functional cardiac damage associated with AS in order to enhance risk stratification and better determine the optimal timing for valve intervention. The grading of AS severity and staging of cardiac damage are primarily based on Doppler-echocardiography but other imaging modalities such as multi-detector computed tomography (MDCT) and cardiac magnetic resonance (CMR) may provide important complementary information.

Grading AS Severity The identification of the different grades of severity of AS are based on the assessment the anatomic (aortic valve leaflet morphology and

mobility) and hemodynamic (peak velocity, mean gradient, AVA etc.) severity of AS (Figs. 3.4, 3.5, and 3.6 and Tables 3.1 and 3.2).

 t Risk for AS (Grade 0 or Stage A) A Subjects with aortic sclerosis as well as those with a bicuspid valve irrespective of the presence or absence of sclerosis are at risk of developing AS (Grade 0 or Stage A in American Guidelines) (Fig. 3.5 and Tables 3.1 and 3.2). The identification of bicuspid valve (Fig. 3.1) is generally done by echocardiography but may require other ­imaging modalities such as CMR or MDCT if the valve is calcified. Aortic valve sclerosis is defined at echocardiography by focal areas of valve calcification and thickening with normal leaflet mobility and normal valvular hemodynamics (Fig. 3.5). Although

M.-A. Clavel et al.

30 “Classical” Low-Flow, Low-Gradient Aortic Stenosis

a

b

Rest Echocardiography

c

Fig. 3.6  Illustrative examples of low-gradient aortic stenosis. Panel a–f: “Classical” Low-Flow, Low-Gradient Aortic Stenosis with reduced LV ejection fraction; (a) 2D echocardiographic parasternal long-axis zoomed view of the LVOT and aortic valve; (b) parasternal short-axis zoomed view of the aortic valve; (c) rest LVOT velocity obtained by pulsed-wave Doppler, (d) rest peak aortic velocity measured by continuous-wave Doppler; (e) peak dobutamine stress LVOT velocity, and (f) peak dobutamine stress peak aortic velocity and equation for the calculation of the projected AVA. Note that projected AVA is below 1 cm2, thus is accordance with a severe AS despite that MG did not reach 40 mmHg under dobutamine. This is probably due to the fact that at peak stress, flow rate is still not normal. Panel g–k: “Paradoxical” Low-Flow, Low-Gradient Aortic Stenosis with preserved LV ejection fraction; (g) 2D echocardiographic parasternal long-axis zoomed view of the LVOT and aortic valve; (h) parasternal short-axis zoomed view of the aortic valve, (i) LVOT

d

velocity obtained by pulsed-wave Doppler, (j) peak aortic velocity measured by continuous-wave Doppler, and (k) Multidetector computed tomography of the aortic valve. Note that despite the preserved LVEF, the SVi is reduced at 31.8  mL and the flow rate is severely reduced (190 mL/s). Interestingly, the aortic valve calcification is consistent with a severe AS in this woman (AVC >1200  AU). Panel l–p: Normal-Flow, Low-Gradient Aortic Stenosis; (l) 2D echocardiographic parasternal long-axis zoomed view of the LVOT and aortic valve; (m) parasternal short-axis zoomed view of the aortic valve; (n) LVOT velocity obtained by pulsed-­ wave Doppler, (o) peak aortic velocity measured by continuous-wave Doppler, and (p) Multidetector computed tomography of the aortic valve. This man, with normal LVEF and normal flow, presented with low gradient despite a severe aortic valve calcification (AVC >2000  AU). The low gradient could be associated with increased blood pressure or decreased arterial compliance. Abbreviations as in Fig. 3.5

3  Aortic Stenosis

31

e

f

Peak Dobutamine Stress Echocardiography

Projected AVA = AVARest +

Projected AVA = 0.78 +

AVAPeak – AVARest QPeak – QRest

0.94 – 0.78 230 – 154

h

i

j

Fig. 3.6 (continued)

2

* (250 – 154) = 0.98 cm

"paradoxical"LOW-Flow, Low-Gradient Aortic Stenosis

g

X (250 – QRest)

M.-A. Clavel et al.

32 Normal-Flow, Low-Gradient Aortic Stenosis

k

l

n

m

p

o

Fig. 3.6 (continued)

3  Aortic Stenosis

33

AORTIC STENOSIS WITH DISCORDANT GRADING AT ECHOCARDIOGRAPHY Low gradient (MG< 40mmHg) and Low velocity (Vpeak< 4m/s) and Small Aortic Valve Area 2 and/or Indexed AVA £ 0.6 cm2/m2 — 0.5 cm2/m2 in obese patients) (AVAS£1 cm - Multi-window (especially right parasternal) CW Interrogation - Measurement of LVOTd in off-axis parasternal view, visualizing right coronary leaflet and commissure between left and non-coronary leaflets, at the level of leaflet insertion. - Corroborate LVOT stroke volume by other methods: Simpson, 3D echo

Rule Out measurement errors

Confirm AS Severity LVEF  140 mL) Systolic sphericity index > 0.7

Annular dilatation Mild/moderate Mild/moderate Moderate

Repair feasible Feasible Feasible Difficult

Extensive (anulus + leaflet) No

Severe

Unlikely

No/mild

Unlikely

Localized

Moderate

Difficult

Extensive (anulus + leaflet)

Moderate/ severe

Unlikely

Calcification No/localized No/localized Localized (anulus)

in advance so the case can be carefully evaluated and discussed with the surgeon and degree and location of MR can be better assessed under normal hemodynamic conditions. It is well known that under general anaesthesia, many patients demonstrate marked reductions in the severity of regurgitation that may pose some limitations in the evaluation of the case. It is very important to define the defect and regurgitant jet [6] that is going to be repaired, specially in complex cases, where additional jets not amenable to repair may be present after surgery that may limit the postoperative evaluation of not addressed before. It is

113

8  Mitral Valve Intraoperative Echocardiography

also important to identify anatomical parameters that may be associated with complications during surgery so we can anticipate to them in patient’s hemodynamic management in the first minutes after pumb exit. This way and as summarized in Table  8.3, a complete evaluation of the MV is recommended with evaluation of prolapse and/or flail site [7] (anterior or posterior, and the scallop affected) with the identification of the cordial break and the presence of abnormal mitral leaflet coaptation. Multiple 2D views are needed and if possible real time 3D echo images with an “en face” view of the MV allows the best delineation of the defect in one single acquisition (Fig. 8.2). Along with anatomical defect, MR jet should be identified, also with multiple 2D views but also with real time 3D colour images that shows in the surgical view the site of the regurgitant jet. Both anterior and posterior leaflet should be measured

in the mid esophageous long axis view as well as the mitral annulus (MA) in 2D but preferable in 3D images. Evaluation of left ventricular outflow

Fig. 8.2  TEE 3D image of the mitral valve, en face view (surgical view) showing P2 mitral valve flail with chordae rupture (arrow)

Table 8.3  Preoperative evaluation of the MR mechanism Identification of prolapse or flail

Measures

Echo modality 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image 2D echo or real time 3D-image

Acquisition protocol Transducer angle: 0°–10° level: mid-high-esophageal

Structures imagen Mitral valve (A1-P1)

Transducer angle: 0°–10° level: mid-esophageal

Mitral valve (A2-P2)

Transducer angle: 0°–10° level: mid-low esophageal

Mitral valve (A3-P3)

Transducer angle: 50°–70° level: mid-esophageal

Mitral valve (P3-A3A2A1-P1)

Transducer angle: 80°–100° level: mid-esophageal

Mitral valve (P3-A3A2A1)

Transducer angle: 120°–140° level: mid-esophageal

Mitral valve (P2-A2)

Transducer angle: 0°–20° level: transgastric (advance + Anteflex)

Mitral valve (Sax)

Transducer angle: 120°–140° mid-­ esophageal for the minor axis; 50°–70° bi-commissural midesophageal view for the major axis. Transducer angle: 0°–10° level: mid-high-esophageal

Mitral annulus

Transducer angle: 90° level: transgastric (advance + Anteflex)

Anterior and posterior leaflet: length, thickness, calcification and mobility, coaptation line Subvalvular apparatus: chordae tendineae and papillary muscles

114 Table 8.4  Echocardiografic predicitors of postoperative SAM (late systole in the mid esophageal long-axis view Posterior leaflet lenght of more than 1.5 cm Anterior leaflet lenght of more than 2.0 cm Posterior leaflet relative to anterior leaflet lenght (AL/PL) less than 2.5 cm C-sept distance (shortest distance between the coaptation point and the anterior septal wall) of less than 2.5 cm Aorto-mitral angle less than 120° Septal thickness greater than 1.5 cm LV end-diastolic (LVEDD) less than 45 mm

tract (LVOT) anatomy, including the thickness of the upper interventricular septum and the distance to the anterior leaflet is important to define probability of SAM after repair (Table  8.4). Finally LV and RV systolic function should be addressed to optimize fluid and vasoactive agents administration.

Echocardiographic Assessment After Repair Before we start to evaluate repair results, first thing to do is to assure a correct hemodynamic situation in terms of blood pressure [6], fluid status and heart rate. The closer to real life parameters the better, so we can be sure that residual MR assessed intraop is going to be very close toe the one assessed afterwards when the patients is discharge. Once the hemodynamic situation is optimized the anatomical results should be address. Different parameters have been described and the anatomical appearances of the MV will doffer according to the surgical technique. However, probably the most reliable parameters that is associated with good term results in terms of freedom of significant MR is the coaptation depth. Coaptation depth greater than 8 mm are considered excellent results, between 4 and 8  mm requires individualized decision and residual MR evaluation, and below 4  mm requires re-repair or MV prostheses implantation. Along with anatomical evaluation in the different planes using 2D echocardiography and 3D real time echo, hemodynamic assessment is performed. Mean

A. Carvelli and C. Fernández-Golfín

mitral gradient should be evaluated to rule out significant stenosis. Mean gradients below 4 are acceptable but those above 8 mm should be taken care of. MR severity evaluation is difficult, since the anatomy of the valve has changes and we may face with different regurgitant jets with different origins and directions. In general non or trace MR with regurgitant area below 2  cm2, with small vena contracta that remain close to mitral ring area acceptable. Larger jets, going into the LA, with large colour Doppler areas and vena contract requires reintervention. In cases of significant residual MR a careful evaluation of the anatomy is needed to identify its mechanism and guide re-repair. Also SAM should be ruled out is significant eccentric MR is seen after repair. Careful evaluation of LV segmental contractility needs to be performed to rule out complications.

Mitral Valve Replacement After mitral valve replacement, it is important to determine normal opening of bileaflet disks or valvular leaflets with a biological prosthetic valve and measure transvalvular gradients. Using multiple echocardiographic sections it is also important look for paravalvular mitral regurgitation. A turbulent paravalvular jet, even if small, should not be ignored, because it may exhibit progression and cause clinically important hemolysis.

 ercutaneous MV Repair P (MitraClip System) In the guidance of the Mitraclip procedure, echocardiography [8] is superior compared with fluoroscopy. Essential steps of the procedure are guided by TEE, which is a must for the implant. TEE is also of critical importance in the pre procedural evaluation of the patient, since specific anatomic requirements are needed to proceed with the intervention. Table  8.5 shows basic anatomical requirements to define candidate suitability.

8  Mitral Valve Intraoperative Echocardiography

Guiding the Procedure MitraClip implantation is performed through a venous femoral access trough a transseptal puncture with well-defined steps where TEE guidance is essential [9, 10]: 1. Transseptal puncture: The optimal transseptal puncture site, located superiorly and posteriorly in the interatrial septum, is determined by 2D TEE imaging planes: short-axis view (30° to 45°) for

Table 8.5  Morphological suitability criteria for Mitraclip (EVEREST) Optimal morphology Central A2/P2 No calcification

MVA >4 cm2 Posterior leaflet >10 mm Tenting height 2 mm Normal leaflets and mobility Flail gap 1.5  cm2 are acceptable. When MR reduction is not sufficient after Mitra-Clip placement, additional clips may be implanted, where fluoroscopy is particularly helpful (Fig. 8.12). TEE can also identify complications of the intervention: chordae tendineae entrapment by the clip, partial clip detachment and pericardial effusion that should be evaluated pre and post procedural.

 ercutaneous Mitral Balloon P Valvuloplasty Percutaneous valvuloplasty has gained increasing space among the therapeutic choices of mitral stenosis. In selected patients, without favourable clinical and anatomical characteristics, according to ESC Guidelines [1], is considered the procedure with the best cost/benefit ratio. The procedure is performed in most centres under fluoroscopy guidance and only in selected cases IOE is needed. However, both TTE and TEE plays an important role in ruling our left atrial appendage thrombus before the procedure and to define candidate’s suitability. Evaluation of suitability for PMBV is based on echocardiography. Primarily it is important to exclude contra-indications for percutaneous mitral commissurotomy and calculate the Wilkins score to predict PMBV success: a score of 2 constitutes the most important reason to not perform PMBV and is associated with worse long term outcomes after

A. Carvelli and C. Fernández-Golfín

120 Fig. 8.12  Mitral valve 3D image, en face view showing final result after two clip implantation in A2-P2

Table 8.6  Wilkins score Grade Mobility 1 Highly mobile valve with only leaflet tips restricted 2 Leaflet midlle and base portions have normal mobility 3 Valve continues to move forward in diastole, mainly from the base 4 No or minimal forward movement of the leaflets in diastole

Thickness Leaflet near normal in thickness (4–5 mm)

Calcification A single area of increased echo brightness Scattered areas of Midleaflet normal, considerable thickening brightness confined to leaflet margins of margins (5–8 mm) Brightness extending Thickening extending through the entire leaflet into the mid portions of the leaflets (5–8 mm) Considerable thickening Extensive brightness throughout much of of all leaflet tissure the leaflet tissue (>8–10 mm)

PMBV. The absence of commissural fusion also identifies a subgroup of patients with limited benefit of the technique. A prediction score that includes echocardiographic factors such as a small MV area (0.75  cm2 was the most sensitive cutoff (Sens. 85.2%, Spec. 82.1%). This higher cutoff has also been shown by Chen et al., with severe TR by 2D criteria associated with a 3D VCA of >0.6 ± 0.4 cm2 and non-severe TR by 2D methods with a 3D VCA of ≤0.3 ± 0.1 cm2. However, receiver-operator curve demonstrated that a 3D VCA of 0.36  cm2 was the best cutoff value for severe TR, with sensitivity of 89% and specificity of 84% in predicting severe TR defined by 2D echocardiographic integrative criteria. Few studies have used quantitation of TR by relative stroke volumes [103, 112, 113]. In these studies, a single plane tricuspid annular diameter was measured from the 4-chamber view and the tricuspid annular area calculated using a circular formula to calculate the tricuspid annular area. The sample volume for measuring the velocity-­ time-­integral was placed at the tips of the leaflets, unlike the recommended position of the sample volume for mitral quantitation, which is at the level of annulus. Despite these limitations, there was a high correlation with catheterization-­ derived data. The Percutaneous Tricuspid Valve Annuloplasty System (PTVAS) for Symptomatic

R. T. Hahn

Chronic Functional Tricuspid Regurgitation (SCOUT) trial (ClinicalTrials.gov Identifier: NCT02574650) was the first early feasibility trial of a transcatheter device to use comprehensive quantitative analysis to determine severity of TR, including PISA and quantitation of TR by relative stroke volumes [114]. The method for assessing diastolic stroke volume included a measurement of the tricuspid annular area using orthogonal plane annular diameters (inflow and 4-chamber views) in early diastole (1 frame after initial valve opening), using an ellipse formula. If a simultaneous biplane image of the annulus was obtained, the orthogonal diameters were obtained from that image. Importantly, this study was one of the first to show that the EROA by PISA significantly underestimated the quantitative Doppler method by 40–50%. Three-dimensional methods may again help improve the accuracy of quantitative Doppler methods [115]. Using either 3D planimetered diastolic annular area, or 2 orthogonal diastolic annular diameters and a pulsed sample volume at the annulus to measure the velocity time integral, a diastolic stroke volume can be measured. Subtracting the forward stroke volume (either from the left ventricular outflow tract or right ventricular outflow tract) results in the regurgitant volume. Dahou et al. recently evaluated multiple quantitative parameters for assessing TR: PISA, Doppler volumetric methods, and 3D VCA measurement [116]. A strong correlation between Doppler volumetric methods and 3D VCA measurement was found whereas the correlation was modest between those measures and the PISA method. The EROA cutoffs for severe TR were: 0.34 cm2 for the PISA method, 0.65 cm2 for the Doppler method and 0.60  cm2 for the 3D VCA method. Finally, the current grading scheme for tricuspid regurgitation fails to capture the severity of regurgitation in patients currently presenting for treatment in early feasibility trials of transcatheter devices [101, 115]. Although the European echocardiographic guidelines suggests that a grade of “massive” exists beyond “severe”, a new proposal to formally extend the severity grades to “massive” and “torrential” has been suggested

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Table 9.3  Proposed expansion of the grading of tricuspid regurgitationi severity (after Hahn RT and Zamorano JL. The need for a new tricuspid regurgitation grading scheme. Eur Heart J Cardiovasc Imaging. 2017;18:1342–3) Variable

Mild

Moderate

Severe

Massive

Torrential

VC (biplane)

1.0  cm2 predicts >mild TR [124, 125]. Tenting volume and the septal leaflet tethering angle are also echocardiographic predictors of TR severity [126]. In a retrospective study of patients with severe MR and normal EF, 56% had ≥2+ TR and 24% had grade 3 or 4+ TR. After adjusting for group differences (except for atrial fibrillation), grade ≥ 2+ TR was associated with a higher mortality (relative risk 1.4, 95% confidence interval 1.1–1.8, p  =  0.02) which improved with mitral valve surgery [127]. Significant tricuspid annular dilatation may be a better predictor of severe late TR after MV surgery [30, 128, 129] and has been used as an indication for TV surgery in the setting of less than severe TR.  Significant annular dilatation is defined by a diastolic diameter  ≥40  mm or >21  mm/m2 in the four-chamber transthoracic view [30] or > 70 mm on intraoperative inspection [129]. Tenting areas and volumes also correlate with TR severity and with outcomes following surgical repair [125, 126, 130, 131]. In addition to annular dimensions, if the TV tethering distance is >0.76 cm [130] or tethering area >1.63 cm2 [132] the use of adjunctive surgical techniques to tricuspid annuloplasty or TV replacement should be considered. Tricuspid regurgitant severity can be associated with a number of 3D echo measurements such as: annular area, non-planarity, right ventricular diastolic area, anteroposterior diameter, and left ventricular ejection fraction [31]. Recurrent tricuspid regurgitation following surgical repair warrants continued follow-up for these patients. Although outcomes following TV

surgery are generally good short-term mortality may be lower for repair procedures compared to valve replacement [133, 134]. High TR recurrence in the repair group (up to 45%) versus the replacement group has been reported in multiple studies. [133, 135–138] The recurrence rate varies according to the type of repair performed, with higher recurrences for suture annuloplasty particularly the De Vega repair. Despite this recurrence of TR, re-operation which may be necessary in up to 11% of patients is a relatively late occurrence. Reported freedom from TV re-­operation 10 years after TV surgery is between 79 and 87% with no significant difference between the repair and replacement groups [133, 134]. Right ventricular dilatation with associated displacement of the papillary muscles may predict TR severity and outcomes [139–141]. RV end-systolic area ≥20.0 cm2 predicts worse eventfree survival [140]. End-systolic RV eccentricity index defined from short-axis views as the long axis (largest lateral distance) divided by short axis (septo-free wall distance at the mid-­septum) is a predictor of >mild TR [140]. RV sphericity index, calculated as the RV area divided by RV long-axis dimension (apical view) predicts the tethering height: the greater the sphericity index, the larger the TR regurgitant orifice. In vitro studies suggest that papillary muscle displacement of individual papillary muscles or all papillary muscles may result in malcoaptation of the leaflet with more severe regurgitation seen with the latter abnormality [77]. Thus causes of right ventricular dilatation such as ischemia or infarction [142, 143], volume overload from significant pulmonic regurgitation [144], chronic pulmonary disease [145] or pulmonary thromboembolism [146] may all result in tethering, malcoaptation and significant tricuspid regurgitation.

Conclusion Interest in the tricuspid valve has increased in the setting of evidence that functional tricuspid regurgitation impacts morbidity and mortality. The complex anatomy and function of this valve can be imaged using multiple echo-

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cardiographic outcomes after percutaneous mitral valve repair with the MitraClip System: 30-day and 12-month follow-up from the GRASP Registry. Eur Heart J Cardiovasc Imaging. 2014;15:1246–55. 9. Lindman BR, Maniar HS, Jaber WA, Lerakis S, Mack MJ, Suri RM, Thourani VH, Babaliaros V, Kereiakes DJ, Whisenant B, Miller DC, Tuzcu EM, Svensson Disclosures Dr. Hahn is the Principle Investigator LG, Xu K, Doshi D, Leon MB, Zajarias A.  Effect SCOUT Trial for which she receives no compensation; of tricuspid regurgitation and the right heart on surshe is a speaker for Abbott Vascular, GE Medical and St. vival after transcatheter aortic valve replacement: Jude Medical. insights from the placement of aortic transcatheter valves II inoperable cohort. Circ Cardiovasc Interv. 2015;8:e002073. 10. Di Mauro M, Bivona A, Iaco AL, Contini M, References Gagliardi M, Varone E, Gallina S, Calafiore AM. Mitral valve surgery for functional mitral regur 1. Nath J, Foster E, Heidenreich PA. Impact of tricusgitation: prognostic role of tricuspid regurgitation. pid regurgitation on long-term survival. J Am Coll Eur J Cardiothorac Surg. 2009;35:635–9. discussion Cardiol. 2004;43:405–9. 639-40. 2. Lee JW, Song JM, Park JP, Kang DH, Song 11. Henein MY, O'Sullivan CA, Li W, Sheppard M, JK. Long-term prognosis of isolated significant triHo Y, Pepper J, Gibson DG.  Evidence for rheucuspid regurgitation. Circ J. 2010;74:375–80. matic valve disease in patients with severe tricuspid 3. Neuhold S, Huelsmann M, Pernicka E, Graf A, regurgitation long after mitral valve surgery: the Bonderman D, Adlbrecht C, Binder T, Maurer G, role of 3D echo reconstruction. J Heart Valve Dis. Pacher R, Mascherbauer J. Impact of tricuspid regur2003;12:566–72. gitation on survival in patients with chronic heart 12. Nishimura RA, Otto CM, Bonow RO, Carabello failure: unexpected findings of a long-term observaBA, Erwin JP III, Fleisher LA, Jneid H, Mack MJ, tional study. Eur Heart J. 2013;34:844–52. McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM III, 4. Calafiore AM, Gallina S, Iaco AL, Contini M, Bivona Thompson A. 2017 AHA/ACC focused update of A, Gagliardi M, Bosco P, Di Mauro M. Mitral valve the 2014 AHA/ACC guideline for the management surgery for functional mitral regurgitation: should of patients with valvular heart disease: a report of moderate-or-more tricuspid regurgitation be treated? the American College of Cardiology/American a propensity score analysis. Ann Thorac Surg. Heart Association Task Force on Clinical Practice 2009;87:698–703. Guidelines. J Am Coll Cardiol. 2017;70:252–89. 5. Mascherbauer J, Kammerlander AA, Marzluf BA, 13. Baumgartner H, Falk V, Bax JJ, De Bonis M, et al. Graf A, Kocher A, Bonderman D. Prognostic impact 2017 ESC/EACTS guidelines for the management of of tricuspid regurgitation in patients undergoing valvular heart disease: the task force for the manaortic valve surgery for aortic stenosis. PLoS One. agement of valvular heart disease of the European 2015;10:e0136024. Society of Cardiology (ESC) and the European 6. Dahou A, Magne J, Clavel MA, Capoulade R, Association for Cardio-Thoracic Surgery (EACTS). Bartko PE, Bergler-Klein J, Senechal M, Mundigler Eur Heart J. 2017;38(36):2739–91. G, Burwash I, Ribeiro HB, O’Connor K, Mathieu P, 14. Xanthos T, Dalivigkas I, Ekmektzoglou Baumgartner H, Dumesnil JG, Rosenhek R, Larose KA. Anatomic variations of the cardiac valves and E, Rodes-Cabau J, Pibarot P.  Tricuspid regurgitapapillary muscles of the right heart. Ital J Anat tion is associated with increased risk of mortalEmbryol. 2011;116:111–26. ity in patients with low-flow low-gradient aortic 15. Martinez RM, O’Leary PW, Anderson RH. Anatomy stenosis and reduced ejection fraction: results of and echocardiography of the normal and abnorthe Multicenter TOPAS Study (true or pseudo-­ mal tricuspid valve. Cardiol Young. 2006;16(Suppl severe aortic stenosis). JACC Cardiovasc Interv. 3):4–11. 2015;8:588–96. 16. Fawzy H, Fukamachi K, Mazer CD, Harrington 7. Varadarajan P, Pai RG.  Prognostic implications of A, Latter D, Bonneau D, Errett L.  Complete maptricuspid regurgitation in patients with severe aortic ping of the tricuspid valve apparatus using three-­ regurgitation: results from a cohort of 756 patients. dimensional sonomicrometry. J Thorac Cardiovasc Interact Cardiovasc Thorac Surg. 2012;14:580–4. Surg. 2011;141:1037–43. 8. Ohno Y, Attizzani GF, Capodanno D, Cannata S, 17. Hahn RT.  State-of-the-art review of echocardioDipasqua F, Imme S, Barbanti M, Ministeri M, graphic imaging in the evaluation and treatment of Caggegi A, Pistritto AM, Chiaranda M, Ronsivalle G, functional tricuspid regurgitation. Circ Cardiovasc Giaquinta S, Farruggio S, Mangiafico S, Scandura S, Imaging. 2016;9:e005332. Tamburino C, Capranzano P, Grasso C. Association 18. Rodés-Cabau J, Hahn RT, Latib A, Laule M, Lauten of tricuspid regurgitation with clinical and echoA, Maisano F, Schofer J, Campelo-Parada F, Puri

cardiographic modalities. In addition, intraprocedural imaging for transcatheter solutions for functional tricuspid regurgitation relies on echocardiography.

140 R, Vahanian A.  Transcatheter therapies for treating tricuspid regurgitation. J Am Coll Cardiol. 2016;67:1829–45. 19. Taramasso M, Pozzoli A, Basso C, Thiene G, Denti P, Kuwata S, Nietlispach F, Alfieri O, Hahn RT, Nickenig G, Schofer J, Leon MB, Reisman M, Maisano F.  Compare and contrast tricuspid and mitral valve anatomy: interventional perspectives for transcatheter tricuspid valve therapies. EuroIntervention. 2018;13(16):1889–98. 20. Fukuda S, Saracino G, Matsumura Y, Daimon M, Tran H, Greenberg NL, Hozumi T, Yoshikawa J, Thomas JD, Shiota T. Three-dimensional geometry of the tricuspid annulus in healthy subjects and in patients with functional tricuspid regurgitation: a real-time, 3-dimensional echocardiographic study. Circulation. 2006;114:I492–8. 21. Antunes MJ, Barlow JB.  Management of tricuspid valve regurgitation. Heart. 2007;93:271–6. 22. Shah PM, Raney AA. Tricuspid valve disease. Curr Probl Cardiol. 2008;33:47–84. 23. Kostucki W, Vandenbossche JL, Friart A, Englert M. Pulsed Doppler regurgitant flow patterns of normal valves. Am J Cardiol. 1986;58:309–13. 24. Anwar AM, Geleijnse ML, Soliman OI, McGhie JS, Frowijn R, Nemes A, van den Bosch AE, Galema TW, Ten Cate FJ.  Assessment of normal tricuspid valve anatomy in adults by real-time three-­ dimensional echocardiography. Int J Cardiovasc Imaging. 2007;23:717–24. 25. Tretter JT, Sarwark AE, Anderson RH, Spicer DE.  Assessment of the anatomical variation to be found in the normal tricuspid valve. Clin Anat. 2016;29:399–407. 26. Karas S Jr, Elkins RC.  Mechanism of function of the mitral valve leaflets, chordae tendineae and left ventricular papillary muscles in dogs. Circ Res. 1970;26:689–96. 27. Silver MD, Lam JH, Ranganathan N, Wigle ED.  Morphology of the human tricuspid valve. Circulation. 1971;43:333–48. 28. Lim KO.  Mechanical properties and ultrastructure of normal human tricuspid valve chordae tendineae. Jpn J Physiol. 1980;30:455–64. 29. Messer S, Moseley E, Marinescu M, Freeman C, Goddard M, Nair S. Histologic analysis of the right atrioventricular junction in the adult human heart. J Heart Valve Dis. 2012;21:368–73. 30. Dreyfus GD, Corbi PJ, Chan KM, Bahrami T.  Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair? Ann Thorac Surg. 2005;79:127–32. 31. Ton-Nu TT, Levine RA, Handschumacher MD, Dorer DJ, Yosefy C, Fan D, Hua L, Jiang L, Hung J.  Geometric determinants of functional tricuspid regurgitation: insights from 3-dimensional echocardiography. Circulation. 2006;114:143–9. 32. Dreyfus J, Durand-Viel G, Raffoul R, Alkhoder S, Hvass U, Radu C, Al-Attar N, Ghodbhane W, Attias D, Nataf P, Vahanian A, Messika-Zeitoun

R. T. Hahn D.  Comparison of 2-dimensional, 3-dimensional, and surgical measurements of the tricuspid annulus size: clinical implications. Circ Cardiovasc Imaging. 2015;8:e003241. 33. Mahmood F, Kim H, Chaudary B, Bergman R, Matyal R, Gerstle J, Gorman JH III, Gorman RC, Khabbaz KR. Tricuspid annular geometry: a three-­ dimensional transesophageal echocardiographic study. J Cardiothorac Vasc Anesth. 2013;27:639–46. 34. Yiwu L, Yingchun C, Jianqun Z, Bin Y, Ping B. Exact quantitative selective annuloplasty of the tricuspid valve. J Thorac Cardiovasc Surg. 2001;122:611–4. 35. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB.  Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685–713. quiz 786-8. 36. Mahlon MA, Yoon HC. CT angiography of the superior vena cava: normative values and implications for central venous catheter position. J Vasc Interv Radiol. 2007;18:1106–10. 37. Sonavane SK, Milner DM, Singh SP, Abdel Aal AK, Shahir KS, Chaturvedi A.  Comprehensive imaging review of the superior vena cava. Radiographics. 2015;35:1873–92. 38. Lin FY, Devereux RB, Roman MJ, Meng J, Jow VM, Simprini L, Jacobs A, Weinsaft JW, Shaw LJ, Berman DS, Callister TQ, Min JK. The right sided great vessels by cardiac multidetector computed tomography: normative reference values among healthy adults free of cardiopulmonary disease, hypertension, and obesity. Acad Radiol. 2009;16:981–7. 39. Chandraratna PN, Lopez JM, Fernandez JJ, Cohen LS.  Echocardiographic detection of tricuspid valve prolapse. Circulation. 1975;51:823–6. 40. Rippe JM, Angoff G, Sloss LJ, Wynne J, Alpert JS.  Multiple floppy valves: an echocardiographic syndrome. Am J Med. 1979;66:817–24. 41. Schlamowitz RA, Gross S, Keating E, Pitt W, Mazur J.  Tricuspid valve prolapse: a common occurrence in the click-murmur syndrome. J Clin Ultrasound. 1982;10:435–9. 42. Emine BS, Murat A, Mehmet B, Mustafa K, Gokturk I. Flail mitral and tricuspid valves due to myxomatous disease. Eur J Echocardiogr. 2008;9:304–5. 43. van Son JA, Danielson GK, Schaff HV, Miller FA Jr. Traumatic tricuspid valve insufficiency. Experience in thirteen patients. J Thorac Cardiovasc Surg. 1994;108:893–8. 44. Choi JS, Kim EJ.  Simultaneous rupture of the mitral and tricuspid valves with left ventricular rupture caused by blunt trauma. Ann Thorac Surg. 2008;86:1371–3. 45. Reddy VK, Nanda S, Bandarupalli N, Pothineni KR, Nanda NC.  Traumatic tricuspid papillary

9  Tricuspid Valve Disease muscle and chordae rupture: emerging role of three-­ dimensional echocardiography. Echocardiography. 2008;25:653–7. 46. Braverman AC, Coplen SE, Mudge GH, Lee RT. Ruptured chordae tendineae of the tricuspid valve as a complication of endomyocardial biopsy in heart transplant patients. Am J Cardiol. 1990;66:111–3. 47. Mielniczuk L, Haddad H, Davies RA, Veinot JP.  Tricuspid valve chordal tissue in endomyocardial biopsy specimens of patients with significant tricuspid regurgitation. J Heart Lung Transplant. 2005;24:1586–90. 48. Sloan KP, Bruce CJ, Oh JK, Rihal CS. Complications of echocardiography-guided endomyocardial biopsy. J Am Soc Echocardiogr. 2009;22:324 e1–4. 49. Christogiannis Z, Korantzopoulos P, Pappas K, Pitsis A. Flail septal leaflet of the tricuspid valve due to rupture of chordae tendineae ten years after pacemaker implantation. Int J Cardiol. 2014;176(2):e41–6. 50. Waller BF, Howard J, Fess S. Pathology of tricuspid valve stenosis and pure tricuspid regurgitation—Part I. Clin Cardiol. 1995;18:97–102. 51. Waller BF, Howard J, Fess S. Pathology of tricuspid valve stenosis and pure tricuspid regurgitation—Part II. Clin Cardiol. 1995;18:167–74. 52. Sultan FA, Moustafa SE, Tajik J, Warsame T, Emani U, Alharthi M, Mookadam F.  Rheumatic tricuspid valve disease: an evidence-based systematic overview. J Heart Valve Dis. 2010;19:374–82. 53. Daniels SJ, Mintz GS, Kotler MN.  Rheumatic tricuspid valve disease: two-dimensional echocardiographic, hemodynamic, and angiographic correlations. Am J Cardiol. 1983;51:492–6. 54. Kerut KD, Kerut EK.  Echo diagnosis of rheumatic tricuspid valve disease. Echocardiography. 2014;31(5):680–1. 55. Osler W.  The Gulstonian lectures, on malignant endocarditis. Br Med J. 1885;1:577–9. 56. Chan P, Ogilby JD, Segal B. Tricuspid valve endocarditis. Am Heart J. 1989;117:1140–6. 57. Robbins MJ, Frater RW, Soeiro R, Frishman WH, Strom JA.  Influence of vegetation size on clinical outcome of right-sided infective endocarditis. Am J Med. 1986;80:165–71. 58. Chambers HF, Korzeniowski OM, Sande MA.  Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine (Baltimore). 1983;62:170–7. 59. Robbins MJ, Soeiro R, Frishman WH, Strom JA.  Right-sided valvular endocarditis: etiology, diagnosis, and an approach to therapy. Am Heart J. 1986;111:128–35. 60. Frontera JA, Gradon JD. Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis. Clin Infect Dis. 2000;30:374–9. 61. Howard RJ, Drobac M, Rider WD, Keane TJ, Finlayson J, Silver MD, Wigle ED, Rakowski H.  Carcinoid heart disease: diagnosis by two-­ dimensional echocardiography. Circulation. 1982;66:1059–65.

141 62. Bhattacharyya S, Toumpanakis C, Burke M, Taylor AM, Caplin ME, Davar J.  Features of carcinoid heart disease identified by 2- and 3-dimensional echocardiography and cardiac MRI. Circ Cardiovasc Imaging. 2010;3:103–11. 63. Moerman VM, Dewilde D, Hermans K.  Carcinoid heart disease: typical findings on echocardiography and cardiac magnetic resonance. Acta Cardiol. 2012;67:245–8. 64. Lin G, Nishimura RA, Connolly HM, Dearani JA, Sundt TM III, Hayes DL. Severe symptomatic tricuspid valve regurgitation due to permanent pacemaker or implantable cardioverter-defibrillator leads. J Am Coll Cardiol. 2005;45:1672–5. 65. Kim JB, Spevack DM, Tunick PA, Bullinga JR, Kronzon I, Chinitz LA, Reynolds HR. The effect of transvenous pacemaker and implantable cardioverter defibrillator lead placement on tricuspid valve function: an observational study. J Am Soc Echocardiogr. 2008;21:284–7. 66. Mediratta A, Addetia K, Yamat M, Moss JD, Nayak HM, Burke MC, Weinert L, Maffessanti F, Jeevanandam V, Mor-Avi V, Lang RM. 3D echocardiographic location of implantable device leads and mechanism of associated tricuspid regurgitation. J Am Coll Cardiol Img. 2014;7:337–47. 67. Miglioranza MH, Becker D, Jimenez-Nacher JJ, Moya JL, Golfin CF, Zamorano JL.  A new view of an unusual pacemaker complication: role of three-dimensional transthoracic echocardiography. Echocardiography. 2013;30:E164–6. 68. Addetia K, Maffessanti F, Mediratta A, Yamat M, Weinert L, Moss JD, Nayak HM, Burke MC, Patel AR, Kruse E, Jeevanandam V, Mor-Avi V, Lang RM. Impact of implantable transvenous device lead location on severity of tricuspid regurgitation. J Am Soc Echocardiogr. 2014;27(11):1164–75. 69. Hoke U, Auger D, Thijssen J, Wolterbeek R, van der Velde ET, Holman ER, Schalij MJ, Bax JJ, Delgado V, Marsan NA.  Significant lead-induced tricuspid regurgitation is associated with poor prognosis at long-term follow-up. Heart. 2014;100:960–8. 70. Franceschi F, Thuny F, Giorgi R, Sanaa I, Peyrouse E, Assouan X, Prévôt S, Bastard E, Habib G, Deharo J-C.  Incidence, risk factors, and outcome of traumatic tricuspid regurgitation after percutaneous ventricular lead removal. J Am Coll Cardiol. 2009;53:2168–74. 71. Booker OJ, Nanda NC.  Echocardiographic assessment of Ebstein’s anomaly. Echocardiography. 2015;32(Suppl 2):S177–88. 72. Patel V, Nanda NC, Rajdev S, Mehmood F, Velayudhan D, Vengala S, Copeland RB, Madadi P.  Live/real time three-dimensional transthoracic echocardiographic assessment of Ebstein’s anomaly. Echocardiography. 2005;22:847–54. 73. Misra KP, Hildner FJ, Cohen LS, Narula OS, Samet P. Aneurysm of the membranous ventricular septum. A mechanism for spontaneous closure of ventricular septal defect. N Engl J Med. 1970;283:58–61.

142 74. Nugent EW, Freedom RM, Rowe RD, Wagner HR, Rees JK.  Aneurysm of the membraous septum in ventricular septal defect. Circulation. 1977;56:I82–4. 75. Beerman LB, Park SC, Fischer DR, Fricker FJ, Mathews RA, Neches WH, Lenox CC, Zuberbuhler JR.  Ventricular septal defect associated with aneurysm of the membranous septum. J Am Coll Cardiol. 1985;5:118–23. 76. Shankarappa RK, Papaiah S, Karur S, Math RS, Nanjappa MC.  Giant right atrium due to congenital dysplastic tricuspid valve in an elderly female patient. Echocardiography. 2013;30:E128–31. 77. Spinner EM, Shannon P, Buice D, Jimenez JH, Veledar E, Del Nido PJ, Adams DH, Yoganathan AP.  In vitro characterization of the mechanisms responsible for functional tricuspid regurgitation. Circulation. 2011;124:920–9. 78. Spinner EM, Buice D, Yap CH, Yoganathan AP. The effects of a three-dimensional, saddle-shaped annulus on anterior and posterior leaflet stretch and regurgitation of the tricuspid valve. Ann Biomed Eng. 2012;40:996–1005. 79. Dell’Italia LJ. Anatomy and physiology of the right ventricle. Cardiol Clin. 2012;30:167–87. 80. Ryo K, Goda A, Onishi T, Delgado-Montero A, Tayal B, Champion HC, Simon MA, Mathier MA, Gladwin MT, Gorcsan J III. Characterization of right ventricular remodeling in pulmonary hypertension associated with patient outcomes by 3-­dimensional wall motion tracking echocardiography. Circ Cardiovasc Imaging. 2015;8:e003176. 81. Palau-Caballero G, Walmsley J, Van Empel V, Lumens J, Delhaas T. Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model. Am J Physiol Heart Circ Physiol. 2017;312:H691–h700. 82. Fredriksson AG, Svalbring E, Eriksson J et  al. 4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease. Journal of Magnetic Resonance Imaging: JMRI 2016;43:558–65. 83. MacNee W.  Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part One. Am J Respir Crit Care Med. 1994;150:833–52. 84. Bartelds B, Borgdorff MA, Smit-van Oosten A, Takens J, Boersma B, Nederhoff MG, Elzenga NJ, Gilst WH, De Windt LJ, Berger RMF.  Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load. Eur J Heart Fail. 2011;13:1275–82. 85. Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, Naeije R, Newman J, Oudiz RJ, Provencher S, Torbicki A, Voelkel NF, Hassoun PM.  Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62:D22–33. 86. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer

R. T. Hahn KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39 e14. 87. Naeije R, Brimioulle S, Dewachter L. Biomechanics of the right ventricle in health and disease (2013 Grover Conference series). Pulm Circ. 2014;4:395–406. 88. Guazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, Shah SJ.  RV contractile function and its coupling to pulmonary circulation in heart failure with preserved ejection fraction: stratification of clinical phenotypes and outcomes. JACC Cardiovasc Imaging. 2017;10(10 Pt B):1211–21. 89. Guazzi M, Bandera F, Pelissero G, Castelvecchio S, Menicanti L, Ghio S, Temporelli PL, Arena R.  Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis. Am J Physiol Heart Circ Physiol. 2013;305:H1373–81. 90. Nochioka K, Querejeta Roca G, Claggett B, et  al. Right ventricular function, right ventricular–pulmonary artery coupling, and heart failure risk in 4 us communities: The atherosclerosis risk in communities (aric) study. JAMA Cardiol. 2018;3(10):939–48. 91. Aubert R, Venner C, Huttin O, Haine D, Filippetti L, Guillaumot A, Mandry D, Marie PY, Juilliere Y, Chabot F, Chaouat A, Selton-Suty C.  Three-­ dimensional echocardiography for the assessment of right ventriculo-arterial coupling. J Am Soc Echocardiogr. 2018;31:905–15. 92. Iacoviello M, Monitillo F, Citarelli G, Leone M, Grande D, Antoncecchi V, Rizzo C, Terlizzese P, Romito R, Caldarola P, Ciccone MM.  Right ventriculo-­ arterial coupling assessed by two-­ dimensional strain: a new parameter of right ventricular function independently associated with prognosis in chronic heart failure patients. Int J Cardiol. 2017;241:318–21. 93. Singh JP, Evans JC, Levy D, Larson MG, Freed LA, Fuller DL, Lehman B, Benjamin EJ. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). Am J Cardiol. 1999;83:897–902. 94. Utsunomiya H, Itabashi Y, Mihara H, Berdejo J, Kobayashi S, Siegel RJ, Shiota T.  Functional tricuspid regurgitation caused by chronic atrial fibrillation: a real-time 3-Dimensional Transesophageal Echocardiography Study. Circ Cardiovasc Imaging. 2017;10:e004897. 95. Topilsky Y, Khanna A, Le Tourneau T, Park S, Michelena H, Suri R, Mahoney DW, Enriquez-­ Sarano M. Clinical context and mechanism of functional tricuspid regurgitation in patients with and without pulmonary hypertension. Circ Cardiovasc Imaging. 2012;5:314–23.

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143

tive comparison with 2-dimensional methods. J Am 96. Topilsky Y, Nkomo VT, Vatury O, Michelena HI, Soc Echocardiogr. 2007;20:1050–7. Letourneau T, Suri RM, Pislaru S, Park S, Mahoney DW, Biner S, Enriquez-Sarano M. Clinical outcome 107. de Agustin JA, Viliani D, Vieira C, Islas F, Marcos-­ Alberca P, Gomez de Diego JJ, Nunez-Gil IJ, Almeria of isolated tricuspid regurgitation. JACC Cardiovasc C, Rodrigo JL, Luaces M, Garcia-Fernandez MA, Imaging. 2014;7:1185–94. Macaya C, Perez de Isla L.  Proximal isovelocity 97. Mutlak D, Lessick J, Reisner SA, Aronson D, surface area by single-beat three-dimensional color Dabbah S, Agmon Y. Echocardiography-based specDoppler echocardiography applied for tricuspid trum of severe tricuspid regurgitation: the frequency regurgitation quantification. J Am Soc Echocardiogr. of apparently idiopathic tricuspid regurgitation. J 2013;26:1063–72. Am Soc Echocardiogr. 2007;20:405–8. 98. Najib MQ, Vinales KL, Vittala SS, Challa S, Lee 108. Velayudhan DE, Brown TM, Nanda NC, Patel V, Miller AP, Mehmood F, Rajdev S, Fang L, Frans HR, Chaliki HP.  Predictors for the development EE, Vengala S, Madadi P, Yelamanchili P, Baysan of severe tricuspid regurgitation with anatomically O. Quantification of tricuspid regurgitation by normal valve in patients with atrial fibrillation. live three-dimensional transthoracic echocardioEchocardiography. 2012;29:140–6. graphic measurements of vena contracta area. 99. Mascherbauer J, Kammerlander AA, Zotter-­ Echocardiography. 2006;23:793–800. Tufaro C, Aschauer S, Duca F, Dalos D, Winkler 109. Chen TE, Kwon SH, Enriquez-Sarano M, Wong S, Schneider M, Bergler-Klein J, Bonderman D. BF, Mankad SV.  Three-dimensional color Doppler Presence of isolated tricuspid regurgitation should echocardiographic quantification of tricuspid regurprompt the suspicion of heart failure with preserved gitation orifice area: comparison with conventional ejection fraction. PLoS One. 2017;12:e0171542. two-dimensional measures. J Am Soc Echocardiogr. 100. Zoghbi WA, Adams D, Bonow RO, Enriquez-­ 2013;26:1143–52. Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan 110. Chopra HK, Nanda NC, Fan P, Kapur KK, Goyal R, Daruwalla D, Pacifico A.  Can two-dimensional S, Thavendiranathan P, Thomas JD, Weissman echocardiography and Doppler color flow mapping NJ.  Recommendations for noninvasive evaluation identify the need for tricuspid valve repair? J Am of native valvular regurgitation: a report from the Coll Cardiol. 1989;14:1266–74. American Society of Echocardiography developed in collaboration with the Society for Cardiovascular 111. Gonzalez-Vilchez F, Zarauza J, Vazquez de Prada JA, Martin Duran R, Ruano J, Delgado C, Figueroa Magnetic Resonance. J Am Soc Echocardiogr. A. Assessment of tricuspid regurgitation by Doppler 2017;30:303–71. color flow imaging: angiographic correlation. Int J 101. Lancellotti P, Moura L, Pierard LA, Agricola E, Cardiol. 1994;44:275–83. Popescu BA, Tribouilloy C, Hagendorff A, Monin 112. Loeber CP, Goldberg SJ, Allen HD.  Doppler JL, Badano L, Zamorano JL. European Association echocardiographic comparison of flows distal of Echocardiography recommendations for the to the four cardiac valves. J Am Coll Cardiol. assessment of valvular regurgitation. Part 2: mitral 1984;4:268–72. and tricuspid regurgitation (native valve disease). 113. Meijboom EJ, Horowitz S, Valdes-Cruz LM, Sahn Eur J Echocardiogr. 2010;11:307–32. DJ, Larson DF, Oliveira Lima C.  A Doppler echo 102. Thomas JD, Liu CM, Flachskampf FA, O'Shea JP, cardiographic method for calculating volume flow Davidoff R, Weyman AE. Quantification of jet flow across the tricuspid valve: correlative laboratory and by momentum analysis. An in  vitro color Doppler clinical studies. Circulation. 1985;71:551–6. flow study. Circulation. 1990;81:247–59. 103. Rivera JM, Mele D, Vandervoort PM, Morris E, 114. Hahn RT, Meduri CU, Davidson CJ, Lim S, Nazif TM, Ricciardi MJ, Rajagopal V, Ailawadi G, Vannan Weyman AE, Thomas JD.  Effective regurgitant MA, Thomas JD, Fowler D, Rich S, Martin R, Ong orifice area in tricuspid regurgitation: clinical G, Groothuis A, Kodali S.  Early feasibility study implementation and follow-up study. Am Heart J. of a transcatheter tricuspid valve annuloplasty: 1994;128:927–33. SCOUT trial 30-day results. J Am Coll Cardiol. 104. Francis DP, Willson K, Ceri Davies L, Florea VG, 2017;69:1795–806. Coats AJ, Gibson DG. True shape and area of proximal isovelocity surface area (PISA) when flow con- 115. Hahn RT, Zamorano JL.  The need for a new tricuspid regurgitation grading scheme. Eur Heart J vergence is hemispherical in valvular regurgitation. Cardiovasc Imaging. 2017;18:1342–3. Int J Cardiol. 2000;73:237–42. 105. Rodriguez L, Anconina J, Flachskampf FA, Weyman 116. van Rosendael PJ, Delgado V, Bax JJ. The tricuspid valve and the right heart: anatomical, pathologiAE, Levine RA, Thomas JD. Impact of finite orifice cal and imaging specifications. EuroIntervention. size on proximal flow convergence. Implications 2015;11(Suppl W):W123–7. for Doppler quantification of valvular regurgitation. 117. van Rosendael PJ, Joyce E, Katsanos S, Debonnaire Circ Res. 1992;70:923–30. P, Kamperidis V, van der Kley F, Schalij MJ, Bax 106. Sugeng L, Weinert L, Lang RM.  Real-time JJ, Ajmone Marsan N, Delgado V.  Tricuspid valve 3-­dimensional color Doppler flow of mitral and triremodelling in functional tricuspid regurgitation: cuspid regurgitation: feasibility and initial quantita-

144 multidetector row computed tomography insights. Eur Heart J Cardiovasc Imaging. 2016;17:96–105. 118. van Rosendael PJ, Kamperidis V, Kong WK, van Rosendael AR, van der Kley F, Ajmone Marsan N, Delgado V, Bax JJ. Computed tomography for planning transcatheter tricuspid valve therapy. Eur Heart J. 2017;38:665–74. 119. Kabasawa M, Kohno H, Ishizaka T, Ishida K, Funabashi N, Kataoka A, Matsumiya G. Assessment of functional tricuspid regurgitation using 320-detector-row multislice computed tomography: risk factor analysis for recurrent regurgitation after tricuspid annuloplasty. J Thorac Cardiovasc Surg. 2014;147:312–20. 120. Aquaro GD, Barison A, Todiere G, Festa P, Ait-­ Ali L, Lombardi M, Di Bella G.  Cardiac magnetic resonance ‘virtual catheterization’ for the quantification of valvular regurgitations and cardiac shunt. J Cardiovasc Med (Hagerstown). 2015;16:663–70. 121. Klein AL, Burstow DJ, Tajik AJ, Zachariah PK, Taliercio CP, Taylor CL, Bailey KR, Seward JB. Age-related prevalence of valvular regurgitation in normal subjects: a comprehensive color flow examination of 118 volunteers. J Am Soc Echocardiogr. 1990;3:54–63. 122. Medvedofsky D, Jimenez JL, Addetia K, Singh A, Lang RM, Mor-Avi V, Patel AR.  Multi-parametric quantification of tricuspid regurgitation using cardiovascular magnetic resonance: a comparison to echocardiography. Eur J Radiol. 2017;86:213–20. 123. Fukuda S, Gillinov AM, Song JM, Daimon M, Kongsaerepong V, Thomas JD, Shiota T. Echocardiographic insights into atrial and ventricular mechanisms of functional tricuspid regurgitation. Am Heart J. 2006;152:1208–14. 124. Kim H-K, Kim Y-J, Park J-S, Kim KH, Kim K-B, Ahn H, Sohn D-W, Oh B-H, Park Y-B, Choi Y-S.  Determinants of the severity of functional tricuspid regurgitation. Am J Cardiol. 2006;98:236–42. 125. Sagie A, Schwammenthal E, Padial LR, Vazquez de Prada JA, Weyman AE, Levine RA.  Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol. 1994;24:446–53. 126. Park YH, Song JM, Lee EY, Kim YJ, Kang DH, Song JK.  Geometric and hemodynamic determinants of functional tricuspid regurgitation: a realtime three-­dimensional echocardiography study. Int J Cardiol. 2008;124:160–5. 127. Varadarajan P, Pai RG.  Tricuspid regurgitation in patients with severe mitral regurgitation and normal left ventricular ejection fraction: risk factors and prognostic implications in a cohort of 895 patients. J Heart Valve Dis. 2010;19:412–9. 128. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Lung B, Lancellotti P, Pierard L, Price S, Schafers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL,

R. T. Hahn Zembala M, Bax JJ, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Von Segesser L, Badano LP, Bunc M, Claeys MJ, Drinkovic N, Filippatos G, Habib G, Kappetein AP, Kassab R, Lip GY, Moat N, Nickenig G, Otto CM, Pepper J, Piazza N, Pieper PG, Rosenhek R, Shuka N, Schwammenthal E, Schwitter J, Mas PT, Trindade PT, Walther T.  Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2012;42:S1–44. 129. Van de Veire NR, Braun J, Delgado V, Versteegh MI, Dion RA, Klautz RJ, Bax JJ. Tricuspid annuloplasty prevents right ventricular dilatation and progression of tricuspid regurgitation in patients with tricuspid annular dilatation undergoing mitral valve repair. J Thorac Cardiovasc Surg. 2011;141:1431–9. 130. Fukuda S, Song JM, Gillinov AM, McCarthy PM, Daimon M, Kongsaerepong V, Thomas JD, Shiota T.  Tricuspid valve tethering predicts residual tricuspid regurgitation after tricuspid annuloplasty. Circulation. 2005;111:975–9. 131. Sukmawan R, Watanabe N, Ogasawara Y, Yamaura Y, Yamamoto K, Wada N, Kume T, Okura H, Yoshida K.  Geometric changes of tricuspid valve tenting in tricuspid regurgitation secondary to pulmonary hypertension quantified by novel system with transthoracic real-time 3-dimensional echocardiography. J Am Soc Echocardiogr. 2007;20:470–6. 132. Raja SG, Dreyfus GD.  Basis for intervention on functional tricuspid regurgitation. Semin Thorac Cardiovasc Surg. 2010;22:79–83. 133. Singh SK, Tang GH, Maganti MD, Armstrong S, Williams WG, David TE, Borger MA.  Midterm outcomes of tricuspid valve repair versus replacement for organic tricuspid disease. Ann Thorac Surg. 2006;82:1735–41. discussion 1741. 134. Guenther T, Noebauer C, Mazzitelli D, Busch R, Tassani-Prell P, Lange R.  Tricuspid valve surgery: a thirty-year assessment of early and late outcome. Eur J Cardiothorac Surg. 2008;34:402–9. discussion 409. 135. Chidambaram M, Abdulali SA, Baliga BG, Ionescu MI. Long-term results of DeVega tricuspid annuloplasty. Ann Thorac Surg. 1987;43:185–8. 136. Yada I, Tani K, Shimono T, Shikano K, Okabe M, Kusagawa M.  Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method. J Cardiovasc Surg (Torino). 1990;31:771–7. 137. Konishi Y, Tatsuta N, Minami K, Matsuda K, Yamazato A, Chiba Y, Nishiwaki N, Shimada I, Nakayama S, Fujita S, et  al. Comparative study of Kay-Boyd’s, DeVega’s and Carpentier’s annuloplasty

9  Tricuspid Valve Disease in the management of functional tricuspid regurgitation. Jpn Circ J. 1983;47:1167–72. 138. Scully HE, Armstrong CS. Tricuspid valve replacement. Fifteen years of experience with mechanical prostheses and bioprostheses. J Thorac Cardiovasc Surg. 1995;109:1035–41. 139. Kim JB, Jung SH, Choo SJ, Chung CH, Lee JW. Clinical and echocardiographic outcomes after surgery for severe isolated tricuspid regurgitation. J Thorac Cardiovasc Surg. 2013;146:278–84. 140. Kim YJ, Kwon DA, Kim HK, Park JS, Hahn S, Kim KH, Kim KB, Sohn DW, Ahn H, Oh BH, Park YB. Determinants of surgical outcome in patients with isolated tricuspid regurgitation. Circulation. 2009;120:1672–8. 141. Staab ME, Nishimura RA, Dearani JA.  Isolated tricuspid valve surgery for severe tricuspid regurgitation following prior left heart valve surgery: analysis of outcome in 34 patients. J Heart Valve Dis. 1999;8:567–74. 142. RG MA Jr, Friesinger GC, Sinclair-Smith BC. Tricuspid regurgitation following inferior myocardial infarction. Arch Intern Med. 1976;136:95–9.

145 143. Silverman BD, Carabajal NR, Chorches MA, Taranto AI.  Tricuspid regurgitation and acute myocardial infarction. Arch Intern Med. 1982;142:1394–5. 144. Cheng JW, Russell H, Stewart RD, Thomas J, Backer CL, Mavroudis C. The role of tricuspid valve surgery in the late management of tetralogy of fallot: collective review. World J Pediatr Congenit Heart Surg. 2012;3:492–8. 145. Schoos MM, Dalsgaard M, Kjaergaard J, Moesby D, Jensen SG, Steffensen I, Iversen KK. Echocardiographic predictors of exercise capacity and mortality in chronic obstructive pulmonary disease. BMC Cardiovasc Disord. 2013;13:84. 146. Menzel T, Wagner S, Kramm T, Mohr-Kahaly S, Mayer E, Braeuninger S, Meyer J. Pathophysiology of impaired right and left ventricular function in chronic embolic pulmonary hypertension: changes after pulmonary thromboendarterectomy. Chest. 2000;118:897–903. 147. Badano LP, Muraru D, Enriquez-Sarano M. Assessment of functional tricuspid regurgitation. Eur Heart J. 2013;34:1875–85.

Pulmonic Valve Diseases

10

Bogdan A. Popescu, Maria-Magdalena Gurzun, and Andreea C. Popescu

Introduction The pulmonary valve was neglected for a long time, being the least studied cardiac valve [1]. With the new developments of modern imaging modalities (e.g. 3D echocardiography, cardiac magnetic resonance imaging, CMR) and novel treatment possibilities (e.g. percutaneous pulmonary valve implantation) the interest regarding the pulmonary valve has increased. During the last years a large number of studies tried to answer the question of when and how should pulmonary valve disease be treated.

Pulmonary Valve Anatomy and Pathology The pulmonary valve (or the pulmonic valve, valva trunci pulmonaris) is the valve of the heart that separates the right ventricle (RV) from the pulmonary artery [2]. It is located anterolateral to

B. A. Popescu (*) · M.-M. Gurzun University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania Emergency Institute of Cardiovascular Diseases “Prof. Dr. C. C. Iliescu”, Bucharest, Romania A. C. Popescu University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania Emergency University Hospital “Elias”, Bucharest, Romania

the aortic valve and the plane of pulmonary valve and the plane of aortic valve respect the flow direction, forming an angle of 30°. The pulmonary valve is separated from the tricuspid valve by the RV outflow tract (infundibulum). The complex of the pulmonary valve (PV) is formed by PV leaflets and commissures, the interleaflet triangles, the ventriculo-arterial junction between infundibular RV, pulmonary artery wall, and pulmonary artery sinuses. The leaflets are attached to the wall in a semilunar shape being in continuity partially with the infundibular musculature and partially with the arterial wall. The leaflets’ insertion form an annular ring. The pulmonic ring is not a well-defined fibrous structure, being more a conventional junction between the RV infundibulum and the fibroelastic pulmonary artery walls. The pulmonary artery sinuses lie between the semilunar line of leaflets’ attachment and the sino-tubular junction [3]. Normally, the PV is formed by three semilunar cusps: anterior, left and right. The cusps are named according to their position in the foetus heart, before the heart undergoes rotation. Every leaflet is formed by four zones: the hinge to the pulmonary wall, the belly, the coaptation zone, and the lunnulae (Fig. 10.1). The PV leaflets are thinner than the aortic valve leaflets [4], but the histological differences between the two structures are minimal [5], the PV being used as a substitute for the aortic valve in the Ross procedure [6]. The PV leaflets are formed by multiple layers: ventricu-

© Springer Nature Switzerland AG 2020 J. Zamorano et al. (eds.), Heart Valve Disease, https://doi.org/10.1007/978-3-030-23104-0_10

147

148

Fig. 10.1  Macroscopic anatomy of the pulmonary valve that is composed by three leaflets: anterior, right and left

lar ­ endothelium, lamina ventricularis (tightly arranged reticular fibres), lamina radialis (radial collagenous and elastic fibres), lamina spongiosa (loosely arranged reticular fibres), lamina fibrosa (circular collagen fibres), lamina arterialis, and arterial endothelium. The commissures are mainly formed by fibres from lamina fibrosa which connect the leaflets with the annulus. The annulus is composed by tight collagenous tissue [7]. The PV function (opening in systole and closing in diastole) is based on pressure gradient variation across the valve. Diseases of the PV are generally congenital, although valve function can be affected in some acquired conditions as well. Congenital PV disease includes pulmonary stenosis (inadequate PV opening during systole), or pulmonary regurgitation (inadequate PV closure during diastole determining retrograde flow from the pulmonary artery to the RV). These may be associated with other congenital structural abnormalities of the heart. The association with other cardiac defects is almost always present in patients with pulmonary regurgitation (e.g. absent pulmonary valve syndrome in tetralogy of Fallot), while pulmonary stenosis may be isolated.

B. A. Popescu et al.

Congenital pulmonary stenosis has a prevalence of 8–12% of all congenital heart disease. The stenotic PV may have different pathologic appearance: dome shaped, dysplastic (thickened valvular leaflets associated with hypoplasia of the annular ring), bicuspid/multicuspid. Pulmonary valve stenosis is the most frequent cardiac anomaly in Noonan syndrome, 50% of patients having pulmonary stenosis [8]. The acquired conditions generally determine pulmonary regurgitation by intrinsic primary valvular lesions (e.g. infective endocarditis, cardinoid syndrome, rheumatic fever), or secondary to annular dilatation (e.g. pulmonary hypertension). Some authors have proposed the classification of pulmonary regurgitation (PR) as high pressure or low-pressure PR, depending on pulmonary artery pressure [9]. The involvement of the PV in infective endocarditis is rare and may be encountered in intravenous drug users or in patients with large intracardiac shunts [10]. In rheumatic valve disease the PV is the least commonly affected valve. Pulmonary regurgitation is a common complication after pulmonic stenosis or tetralogy of Fallot treatment [11]. Pulmonary regurgitation is more frequent after surgical valvuloplasty in pulmonary stenosis than after balloon valvuloplasty, and 70% of patients treated for pulmonary stenosis have pulmonary regurgitation [12]. In surgical repair of Fallot tetralogy transannular patching and RV infundibulectomy increase the risk of postoperative severe pulmonary regurgitation and RV dysfunction. In fact, limited RV outflow patching and preservation of the PV are preferred [13–15].

 linical Presentation and Natural C History of Pulmonary Valve Disease Patients with mild pulmonary valve stenosis are generally asymptomatic and the stenosis is not progressive in unoperated adults. Although patients with moderate pulmonary valve stenosis are usually asymptomatic too, stenosis severity may progress during adulthood due to calcifica-

10  Pulmonic Valve Diseases

tions at valvular level or due to RV hypertrophy at the subvalvular level. Patients with severe pulmonary stenosis are symptomatic by exer­ tional dyspnea and fatigue [16]. Dizziness or palpitation related to cardiac arrhythmias and chest pain related to RV ischemia can also be present in patients with severe pulmonary stenosis. Sudden cardiac death can occur in severe pulmonary stenosis. Most of the patients with severe pulmonary stenosis require intervention (60% in the first 10 years after diagnosis) [17]. In patients with pulmonary stenosis the auscultation can reveal: a normal first heart sound, a systolic ejection click determined by doming leaflets, a systolic ejection murmur and a split-­ second heart sound due to the pulmonary component. The ejection click is generally absent in dysplastic valves and the intensity of the ejection murmur is generally proportional to stenosis severity. RV failure signs are generally rare and late in pulmonary stenosis patient’s evolution. In pulmonary regurgitation signs and symptoms generally appear when PR is severe and RV changes occur. These include exertional dyspnoea, arrhythmias [18]. Ventricular arrhythmias and syncope may also occur in patients with dilated and dysfunctional RV. In patients with pulmonary regurgitation the auscultation can reveal: early diastolic pulmonary murmur that increases during inspiration, systolic ejectional murmur and third heart sound due to volume overload. Right ventricular failure signs can be associated with severe pulmonary regurgitation. The prognosis of patients with pulmonary regurgitation depends on aetiology: in secondary pulmonary regurgitation the prognosis is given by pulmonary hypertension, while in primary pulmonary regurgitation the prognosis is related to initial severity, progression of the disease and RV ability to adapt. In mild and moderate pulmonary regurgitation, the prognosis is excellent, while in severe primary pulmonary regurgitation the prognosis is related mainly to RV dilatation and dysfunction [13, 14]. Sudden cardiac death can occur in severe pulmonary regurgitation [19].

149

Imaging of the Pulmonary Valve Echocardiography remains the most commonly used imaging modality for assessing the PV in clinical practice. Echocardiography offers the possibility to assess valve morphology (cusp number: bicuspid, tricuspid or quadricuspid valve; or structure: hypoplasia, dysplasia, absence of pulmonary valve), valve motion (e.g. doming, restricted opening, prolapse, incomplete closure), and the impact of PV disease on RV structure and function. The recommended transthoracic echocardiography (TTE) 2D sections for PV assessment are: modified parasternal view for RV outflow tract visualisation, short axis view at the level of great vessels, subcostal short axis view at the level of great vessels (Fig. 10.2). Generally, two pulmonary valve cusps are simultaneously visualised. The short axis view of pulmonary valve with the visualisation of all three cusps is rare and possible mainly when there is right heart dilatation. Three-dimensional echocardiography offers the possibility for en-face PV visualisation [20]. Although transoesophageal echocardiography is not a main indication for PV examination (being far from probe), the method may be very useful, especially in patients with very poor TTE acoustic window. The PV can be assessed from mid-oesophageal short axis view, inflowoutflow view, and transgastric RV outflow view (Fig.  10.2). In patients with pulmonary valve stenosis the valve has important morphological changes: the leaflets are thickened with systolic doming or the leaflets are dysplastic. The evaluation of pulmonary stenosis severity by echocardiography (Fig.  10.3) is based on peak velocity and peak gradient across the valve [21] (Table  10.1). The post-stenotic dilatation of the pulmonary artery is not directly related to pulmonary stenosis severity and the presence of pulmonary truck dilatation is not anusual finding in dysplastic pulmonary stenosis. The presence of structural remodeling (RV hypertrophy, possible RV and right atrium dilatation) suggests severe pulmonary stenosis [22].

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150

a1

b1

b2

b3

b4

a2

a3

Fig. 10.2  Pulmonary valve visualization by transthoracic and transesophageal echocardiography. By transthoracic echocardiography the pulmonary valve can be visualized in parasternal modified long axis view for right ventricle (a1), parasternal short axis view at the level of great vessels (a2) and subcostal short axis view (a3). By transesophageal echocardiography the pulmonary valve can be visualized in upper esophageal views: short axis view of

the ascending aorta (b1) or short axis view at the arch (b2); in mid-esophageal short axis view of the aortic valve (b3) or ‘inflow-outflow’ view, and in the transgastric right ventricle outflow view (from transgastric mid-papillary view the probe is rotated to the right for short axis of the right ventricle and the multiplane is advanced to 120°). In all the echo images presented the pulmonary valve is marked with an asterisk

In patients with pulmonary regurgitation the valve anatomy can in itself suggest the presence of pulmonary regurgitation (e.g. distorted or absent leaflets, annular dilation), but colour flow Doppler has the central role for diagnosis and grading severity (Table 10.2; Fig.  10.3) [23, 24]. A mild degree of pulmonary regurgitation is a normal finding in the general population. The presence of structural and/or hemodynamic consequences (e.g. paradoxical septal motion due to volume overload or RV enlargement) are also indirect signs of severe valvular regurgitation [22]. Cardiac CT angiography is a useful imaging modality for characterisation of valve anatomy and mobility. Cardiac CT offers the advantage of an accurate pulmonary root, pulmonary arteries and RV outflow tract assess-

ment [25]. For optimal visualisation of the pulmonary valve and the RV a specific gated/ triggered protocol needs to be used: modification of the contrast material administration (split bolus injection [26]), homogeneous enhancement of the right heart cavities to an optimal level of 400–450 HU. In pulmonary valve stenosis cardiac CT angiography allows the characterisation of modified valve anatomy (cusp number, thickness, calcifications) [27] and decreased valve mobility (by cine images). Enlargement of the pulmonary arteries and RV hypertrophy are suggestive of significant pulmonary valve stenosis [28]. Moreover, cardiac CT has a specific role for percutaneous pulmonary valve implantation. Cardiac MR is a very valuable imaging modality for analysing PV function and the

151

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a

b

c

d

Fig. 10.3  Pulmonary valve disease assessment by echocardiography. In pulmonary stenosis the valve cusps are thickened with restricted opening (a, transgastric right ventricle outflow view) and the velocity and gradient across the valve are increased (b). The peak velocity of 4.93  m/s and the peak gradient of 97  mmHg suggest severe pulmonary valve stenosis. In pulmonary regurgitation the valve cusps are often morphologically abnormal (c, modified parasternal long axis view, 2D and color Doppler examination). The pulmonic annulus can be

dilated. The regurgitant jet visualized by color Doppler examination is broad at the origin, covering more than 50% of the right ventricle outflow tract, suggestive of severe pulmonary regurgitation. The continuous Doppler examination of the same patient (d) shows dense signal of pulmonary regurgitation with a steep deceleration due to rapid equalization of pressures in the pulmonary artery and the right ventricle, also indicative of severe pulmonary regurgitation

Table 10.1  Pulmonary stenosis severity assessment by echocardiography [14, 16]

inlet-outlet (two-chamber) views of the RV and sagittal oblique views of the RV outflow tract. An ECG-triggered, double inversion-recovery fast (segmented or single-shot) spin-echo sequence with blood suppression or gadolinium MR angiography are helpful for PV and pulmonary arteries characterisation. Flow volume may also be measured: for pulmonary valve stenosis peak velocities are encoded at the level of narrowing, while for pulmonary valve regurgitation the flow volume is encoded just below the valve level [25] (Fig. 10.4).

Pulmonary stenosis severity Mild Moderate severe Peak velocity (m/s) 4 Peak gradient (mmHg) 64

impact of PV disease on RV dimensions/mass and function. The balanced steady-state free precession (SSFP) cine images offer pulmonary valve and right ventricle visualisation. In addition to the short axis and four chamber views, some modified views should be used: long-axis

B. A. Popescu et al.

152 Table 10.2  Pulmonary regurgitation severity assessment by echocardiography [19, 20] Mild

Moderate

Severe

Qualitative Pulmonic valve morphology

Normal

Abnormal

Colour flow PR jet width (d in diastole immediately below the pulmonic valve in shor axis or subcostal view)

Small, usually 50–65% of right ventricle outflow tract Absent Present Dense/variable Dense/steep deceleration, early termination of diastolic flow Intermediate Greatly increased

a

b

c

d

e

f

Fig. 10.4  Cardiac Magnetic Resonance assessment of pulmonary valve disease. The direct sign of pulmonary stenosis is the restricted opening of the pulmonary valve (cine sequences) with the possibility to measure pulmonary valve area by planimetry (a). The indirect sign for pulmonary stenosis is dilatation and hypertrophy of the right ventricle (b), and the poststenotic dilatation of the pulmonary artery (c). The presence of pulmonary regurgi-

tation may be noticed on cine sequences by regurgitant jet visualization (d) but the pulmonary regurgitation estimation is performed by flow measurements (e). The regurgitant fraction of 42% suggests severe pulmonary regurgitation. Cardiac MR is very useful for right ventricle volume and function measurements (f), the dilated right ventricle suggesting the need for intervention in this case. Courtesy of Dr Ana Daraban

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153

Fig. 10.5  CMR images in a patient with a history of repaired Tetralogy of Fallot in childhood and severe pulmonary valve regurgitation. A broad regurgitant jet can be visualized across de pulmonary valve in a cine CMR still frame (upper left; white arrows); flow CMR through plane measurements in the pulmonary artery (upper mid; red ROI) show an important retrograde flow (upper right, white stripes) of 90 mL/cardiac cycle resulting in a calcu-

lated regurgitation fraction of 50%. Still cine CMR frames in short axis at end-diastole (lower left) and end-systole (lower mid) show a dilated RV with preserved systolic function and akinetic RVOT (arrow head) after reconstruction. In the lower right, a 3D rendering of the LV and RV volumetric analysis (of the short-axis cine’s) is displayed. Measured RV-EDV was 200 mL/m2 compared to LV-EDV only 85 mL/m2. Courtesy of Dr Anca Florian

In patients with pulmonary stenosis CMR allows the assessment of valve morphology and stenosis severity by direct visualisation and planimetry of the valve orifice (by cine image through the leaflet tips), or by peak velocity measurement [29]. In patients with pulmonary regurgitation CMR allows the assessment of valve anatomy and regurgitation severity [30]. The pulmonary regurgitant jet is generally poorly visualized due to low pressures in the right heart. The regurgitant fraction assessment may be performed by measuring right and left ventricular stroke volumes or by through-plane phase contrast velocity mapping [29]. Cardiac MR is the imaging gold standard for quantification of RV volumes and function [31, 32] (Figs. 10.5 and 10.6) (Table 10.3).

Treatment of Pulmonary Valve Disease As for any other valve disease, there is no effective medical treatment for PV disease itself. The only effective treatment of PV disease is valve intervention. Intervention for pulmonary valve stenosis is recommended by ESC guidelines in all patients with severe pulmonary stenosis (peak gradient more than 64  mmHg) regardless of symptoms (class I) and in patients with less than severe pulmonary stenosis (peak gradient less than 64 mmHg) who have pulmonary stenosis-related symptoms, decreased RV function, significant arrhythmias or intracardiac shunt due to inter-­atrial or interventricular septal defect (class IIa) [16].

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154

Fig. 10.6  CMR images in a patient with a history of correction of a complex congenital heart defect, including RVOT reconstruction with implantation of a pulmonary valve homograft and reconstruction of the left and right pulmonary arteries. A narrow distal RVOT is seen (upper left, still cine frame; upper right, reconstruction of the 3D contrast angiography, arrow) together with a stenotic pulmonary valve (upper mid, arrows). Additionally, a stenosis of the origin of left pulmonary artery is noticed (upper

right, arrow head). Flow CMR through plane measurements in the pulmonary artery (lower left; red ROI) show an important forward flow acceleration (lower mid) with a max. Instantaneous velocity of 3.7  m/s. The RV is not dilated, mildly hypertrophied and displays focal enhancement of the inferior RV insertion as a sign of pressure overload (lower right, LGE CMR image in short-axis). Courtesy of Dr Anca Florian

Table 10.3  Imaging modalities in pulmonary valve disease diagnosis

2D echocardiography 3D echocardiography MDCT CMR

Valve Valve morphology mobility ++ +++

Pulmonary stenosis quantification +++

Pulmonary regurgitation quantification +++

Pulmonary annulus ++

RV dimension +

RV function +

+++

+

++

++

++

+++

++

+ ++

+ +

++ ++++

+ ++++

++++ +++

+++ ++++

++ ++++

Balloon valvotomy is preferred in valvular pulmonary stenosis with non-dysplastic leaflets. Surgical valve replacement should be considered in patients in whom balloon valvotomy is ineffective and they are symptomatic with severe pulmonary stenosis or asymptomatic with gradients across the PV more than 80 mmHg. Surgical

treatment is also the method of choice in patients with associated lesions (severe pulmonary regurgitation, severe tricuspid valve disease) [16]. Although significant pulmonary regurgitation after repair for Fallot tetralogy is well tolerated for years, chronic pulmonary regurgitation requires correction according to ESC guidelines

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155

a1

b1

a2

b2

a3

b3

Fig. 10.7  Evaluation of a patient with percutaneous pulmonary valve implantation. Before the procedure transthoracic echocardiography showed on color Doppler examination a broad jet of pulmonary regurgitation (a1). The shape and density of the continuous-wave Doppler diastolic signal supports the diagnosis of severe pulmonary regurgitation (a2). The cardiac MR exam showed

dilated and dysfunctional right ventricle (a3). After valve implantation the pulmonary regurgitation jet is no longer visible on color Doppler (b1) or on continuous-wave Doppler examination (b2), the right ventricle volumes significantly decrease, and right ventricular function improves. (b3). Courtesy of Dr Ana Daraban

in symptomatic patients with severe pulmonary regurgitation and RV systolic pressure more than 60 mmHg (class I), in asymptomatic patients with severe pulmonary and RV dilatation or RV systolic dysfunction (class IIa), with sustained atrial/ ventricular arrhythmias (class IIa) or with progressive tricuspid regurgitation (class IIa) [16]. The optimal timing for pulmonary regurgitation correction is still debatable and lon-

gitudinal follow-up data seems to be more important than isolated stand-alone measurements. The surgical risk is higher in patients with RV dysfunction at the time of intervention [33] and the RV recovery is incomplete after the intervention [34]. Right ventricular size and function are improved when timely pulmonary valve replacement is performed (Fig. 10.7) [35].

156

The cut-off value for RV size proposed for indication of intervention is an RV end-diastolic volume of 160  mL/m2 measured by CMR [36]. On the other hand, the lifespan of biological PV prosthesis is between 15–30  years and young adults will need redo surgery if the intervention is performed too early. Therefore, the balance between these two factors should be considered for the optimal timing of intervention. The newest proposed indications for PV replacement in patients with repaired Fallot tetralogy and pulmonary regurgitation recommend intervention for asymptomatic patients with more than two, or symptomatic patients with at least one of the following criteria: RV enddiastolic volume index more than 150  mL/m2, RV end-systolic volume index more than 80 mL/ m2, RV ejection fraction less than 47%, left ventricle ejection fraction less than 55%, large RV outflow tract aneurysm, QRS complex larger than 160 ms, sustained RV tachyarrhythmias [37–41]. When indicated, correction for pulmonary valve disease may be performed by surgical replacement or by interventional treatment (balloon valvuloplasty for pulmonary stenosis and percutaneous pulmonary valve implantation). For surgical replacement bioprosthetic valves are preferred over mechanical prostheses due to high rate of complications for the latter ones [42]. The main problem with bioprosthetic valves is the limited lifespan and need for subsequent interventions. In one study, freedom from valve replacement was 81% at 5  years and 41% at 15  years, and younger age was a risk factor for decreased time to redo surgery [43]. Patients with severe RV dilatation should be considered for outflow tract remodelling for volume reduction and restoring the geometry of the right ventricle [44]. Percutaneous balloon pulmonary valvuloplasty was introduced in 1982 and consists in balloon inflation with diluted contrast material across the stenotic pulmonary valve [45]. The recommended balloon size is 1.2–1.25 × annulus size [46]. Percutaneous balloon valvuloplasty is the treatment of choice in patients with doming pulmonary valve stenosis and some authors support the utilisation of this procedure even in patients with dysplastic pulmonary valves [47].

B. A. Popescu et al.

The reported procedural success rate is 88% [48] and freedom from reoperation at 10  years is 80–90% [49, 50]. The main complication of this procedure is pulmonary regurgitation and the reported incidence of severe pulmonary regurgitation after balloon valvuloplasty is 5–6% [51, 52] (Fig. 10.8). Percutaneous pulmonary valve implantation is a newer method for severe pulmonary valve disease correction [53] and the world-wide experience is continuously increasing. The first valve used in 2000 was the Melody valve formed by a bare metal platinum iridium stent (16 or 18 mm) and a manually sewn valved segment of bovine jugular vein. In 2006 [54] the Edwards valve for aortic position was used in the pulmonary position as well. The Edwards SAPIEN valves are composed by radiopaque stainless-steel stent (23 and 26  mm) and trileaflet bovine pericardial tissue valves. The Edwards SAPIEN XT valve is also available in 29  mm cobalt chromium frame and SAPIEN 3 has a pericardial cover for minimizing perivalvular leak. Contraindications for percutaneous pulmonary valve implantation are severe stenosis that cannot be expanded through catheter balloon, active infection, inappropriate annulus size for the prosthesis (e.g. less than 16  mm) [55], or ­coronary compression during balloon inflation [56]. The risks of the procedure are related to utilization of rigid guides and large introducers (e.g. risk of tricuspid valve damage), to dilatation of a rigid and possibly calcified structure (e.g. homograft rupture, compression of coronary arteries [57]), and to the possibility of stent migration or fracture during the procedure [58]. Valve stent fracture may be present in almost 30% of PV implantation cases [59], but the majority are not clinically relevant type I (no loss of stent integrity). Type II (loss of stent integrity) fractures are generally treated by valve in valve implantation, while type III fracture (separation or embolization of fractured part) may require surgical treatment. The percutaneous PV implantation requires general anaesthesia and follows several steps: right heart catheterization through the femoral, jugular, or subclavian vein; right ventricle outflow tract dimension assessment by angiogra-

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157

a

c

b

d

Fig. 10.8  Pulmonary valvuloplasty for pulmonary valve stenosis. The intervention was performed in a patient with pulmonary valve stenosis with restricted and doming valve opening visualized by transthoracic echocardiography (a, systolic frame). The pre-procedural peak gradient across the valve was 75 mmHg (b). After balloon valvulo-

plasty (c, angiographic view of the balloon during inflation) the peak gradient across the valve decreased to less than 20 mmHg (d). After the procedure the signal of pulmonary regurgitation can be seen on the continuous Doppler recording (d)

phy; estimation of minimal diameter using low pressure balloon inflation; coronary artery flow assessment during balloon inflation and valve implantation [60]. Pre-stenting in the same procedure or 2–3 months previously has decreased the incidence of stent fracture [61, 62]. The hospitalisation time is generally 4–5 days and the procedural success rate is 94–98% [63] (Fig. 10.9). The late complications of PV implantation are infective endocarditis and the need for reintervention. The risk of endocarditis is 2.4% per patient per year. It generally responds to antibiotic therapy with no need for reintervention [64]. The risk factors for infective endocarditis are residual turbulent flow in the RV outflow tract, in situ thrombosis, or lack of antibiotic prophylaxis [65, 66]. Compared to surgical pulmonary valve prosthesis, infective endocarditis is 4.5-fold more frequent after transcatheter pulmonary valve

implantation [67] and the main explanation for this is the possible target for germs represented by micro lesions observed on Melody valve leaflets [68]. Percutaneous pulmonary valve implantation has been accepted as a therapeutic solution being proved a safe and effective solution, but no direct comparisons with surgical treatment are available. The reported data for freedom from reintervention are 90%, 80% and 76% for 1, 2 and 5 years respectively [69–71]. Although the initial data are promising, this procedure cannot be used in a category of patients with complex RV tract morphology or in patients with RV outflow tract diameter more than 22 mm for Melody valve and 27 mm for Sapien valve (the majority of patients with right ventricle outflow patch augmented have larger dimensions) [60].

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a

b

c

d

e

f

Fig. 10.9  Percutaneous pulmonary valve implantation. The first step during pulmonary valve implantation procedure is the visualization of pulmonary artery and pulmonary valve by angiography (a) and a rigid wire is passed through the valve. Most of the operators perform a pre-­

stenting of the pulmonary artery (b, c). Subsequently the artificial pulmonary valve (d, Melody valve) is delivered (e) and inflated at the level of the stent (f). The final result is appreciated by pulmonary artery contrast injection for the evaluation of pulmonary regurgitation (f)

Conclusions

3. Stamm C, Anderson RH, Ho SY.  Clinical anatomy of the normal pulmonary root compared with that in isolated pulmonary valvular stenosis. Journal of the American College of Cardiology. 1998;6:1420–5. 4. Benninghoff A, Hartmann A, Hellmann T. Handbuch der mikroskopischen Anatomie des Menschen. Berlin: Springer; 1930. 5. Stradins P, Lacis R, Ozolanta I, Purina B, Ose V, Feldmane L, Kasyanov V.  Comparison of biomechanical and structural properties between human aortic and pulmonary valve. Eur J Cardiothorac Surg. 2004;26(3):634–9. 6. Ross DN. Replacement of aortic and mitral valves with a pulmonary autograft. Lancet. 1967;2(7523):956–8. 7. Misfle M, Sievers HH. Heart valve macro and microstructure. Philos Trans R Soc Lond Ser B Biol Sci. 2007;362(1484):1421–36. 8. Abadir S, Edouard T, Julia S. Severe aortic valvar stenosis in familial Noonan syndrome with mutation of the PTPN11 gene. Cardiol Young. 2007;17(1):95–7. 9. DePace N, Nestico P.  Acute severe pulmonic valve regurgitation: pathophysiology, diagnosis, and treatment. Am Heart J. 1984;108:567–73. 10. Noohi F, Sadeghpour A, Alizadehasl A. Chapter 25— valvular heart disease. In: Maleki M, Alizadehasl A, Haghjoo M, editors. Practical cardiology. Amsterdam: Elsevier; 2018. p. 395–441.

Although the pulmonary valve is still the least studied among the cardiac valves, its importance is increasingly recognized in recent years. Advances in cardiac imaging (e.g. 3D echocardiography, cardiac MR) as well as the treatment options (e.g. percutaneous pulmonary valve implantation) offer the possibility to treat patients with pulmonary valve disease timely and effectively.

References 1. Fathallah M, Krasuski R.  Pulmonic valve disease: review of pathology and current treatment options. Curr Cardiol Rep. 2017;19:108–20. 2. Jonas SN, Kligerman SJ, Burke AP, Frazier AA, White CS.  Pulmonary valve anatomy and abnormalities: a pictorial essay of radiography, computed tomography (CT), and magnetic resonance imaging (MRI). J Thorac Imaging. 2016;31(1):W4–12.

10  Pulmonic Valve Diseases 11. Oxorn DC, Otto CM. Adult congenital heart disease. In: Oxorn DC, Otto CM, editors. Intraoperative and interventional echocardiography. 2nd ed. Amsterdam: Elsevier; 2017. 12. O’Connor BK, Beekman RH, Lindauer A, et  al. Intermediate-term outcome after pulmonary balloon valvuloplasty: comparison with a matched surgical control group. J Am Coll Cardiol. 1992;20:169–73. 13. Murphy JG, Gersh BJ, Mair DD, et al. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med. 1993;329:593–9. 14. Nollert G, Fischlein T, Bouterwek S, et  al. Long-­ term survival in patients with repair of tetralogy of Fallot: 36-year follow-up of 490 survivors of the first year after surgical repair. J Am Coll Cardiol. 1997;30:1374–83. 15. Davlouros PA, Kilner PJ, Hornung TS, et  al. Right ventricular function in adults with repaired tetralogy of Fallot assessed with cardiovascular magnetic resonance imaging: detrimental role of right. J Am Coll Cardiol. 2002;40(11):2044–52. 16. Baumgartner H, Bonhoeffer P, De Grott NM, et  al. ESC guidelines for the management of grown-up congential heart disease. Eur Heart J. 2010;31:2915–57. 17. Calin A.  Stenoza pulmonara. In: Ginghina C, editor. Mic tratat de cardiologie. Bucharest: Editura Academiei; 2016. 18. Warnes CA, Williams RG, Bashore TM, et al. ACC/ AHA 2008 guidelines for the management of adults with congenital heart disease. J Am Coll Cardiol. 2008;52:e143–263. 19. Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet. 2000;356:975–81. 20. Natalie FA.  Feasibilty of pulmonary valve imaging using three-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2010;23:1076–80. 21. Silvilairat S, Cabalka A, Cetta F, et  al. Echocardiographic assessment of isolated pulmonary valve stenosis: which out patient Doppler gradient has the most clinical validity? J Am Soc Echocardiogr. 2005;18:1137–42. 22. Nishimura RA, Otto CM, Bonow RO, et  al. Management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(23):244. 23. Lancellotti P, Tribouilloy C, Hagendorff A.  Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the european association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging. 2013;14:611–44. 24. Savu O, Ginghia C.  Regurgitarea pulmonara. In: Popescu BA, Ginghina C, editors. Ecocardiografia Doppler. Bucuresti: Editura Medicala; 2011. p. 247–50. 25. Saremi F, Gera A, Ho SY, Hijazi ZM, Sánchez-­ Quintana D.  CT and MR imaging of the pulmonary valve. Radiographics. 2014;34(1):51–71.

159 26. Kerl JM, Ravenel JG, Nguyen SA, et al. Right heart: split-bolus injection of diluted contrast medium for visualization at coronary CT angiography. Radiology. 2008;247(2):356–64. 27. Krauss T, Berchem L, Blake P, et  al. 4D-Cine CT imaging of a bicuspid pulmonary valve. J Cardiovasc Comput Tomogr. 2014;8:170–1. 28. Chen JJ, Manning MA, Frazier AA, et  al. CT angiography of the cardiac valves: normal, diseased, and postoperative appearances. Radiographics. 2009;29:1393–412. 29. Myerson SG.  Heart valve disease: investigation by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:7. 30. Popescu BA, Gurzun MM, Ginghina C. Tricuspid and pulmonary valve disease. In: The ESC textbook of cardiovascular imaging. Oxford: Oxford University Press; 2015. p. 171–80. 31. Sugeng L, Mor-Avi V, Weinert L, Niel J, Ebner C, Steringer-Mascherbauer R, et al. Multimodality comparison of quantitative volumetric analysis of the right ventricle. JACC Cardiovasc Imaging. 2010;3:10–8. 32. Therrien J, Siu SC, Harris L, et  al. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation. 2001;103:2489–94. 33. Therrien J, Siu SC, McLaughlin PR, et al. Pulmonary valve replacement in adults late after repair of tetralogy of fallot: are we operating too late? J Am Coll Cardiol. 2000;36(5):1670–5. 34. Vliegen HW, van Straten A, de Roos A, et al. Magnetic resonance imaging to assess the hemodynamic effects of pulmonary valve replacement in adults late after repair of tetralogy of fallot. Circulation. 2002;106:1703–7. 35. Oosterhof T, van Straten A, Vliegen HW, et  al. Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance. Circulation. 2007;116:545–51. 36. Geva T. Indications for pulmonary valve replacement in repaired tetralogy of Fallot: the quest continues. Circulation. 2013;128(17):1855–7. 37. Geva T, Gauvreau K, Powell AJ, Cecchin F, Rhodes J, Geva J, del Nido P. Randomized trial of pulmonary valve replacement with and without right ventricular remodeling surgery. Circulation. 2010;122:S201–8. 38. Buechel ER, Dave HH, Kellenberger CJ, Dodge-­ Khatami A, Pretre R, Berger F, Bauersfeld U. Remodelling of the right ventricle after early pulmonary valve replacement in children with repaired tetralogy of fallot. Eur Heart J. 2005;26:2721–7. 39. Geva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJ.  Factors associated with impaired clinical status in long-term survivors of tetralogy of fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol. 2004;43:1068–74. 40. Knauth AL, Gauvreau K, Powell AJ, Landzberg MJ, Walsh EP, Lock JE, del Nido PJ, Geva T. Ventricular size and function assessed by cardiac MRI predict

160 major adverse clinical outcomes late after tetralogy of fallot repair. Heart. 2008;94:211–6. 41. Kawachi Y, Masuda M, Tominaga R, et  al. Comparative study between St. Jude Medical and bioprosthetic valves in the right side of the heart. Jpn Circ J. 1991;55:553–62. 42. Caldarone CA, McCrindle BW, Van Arsdell GS, et al. Independent factors associated with longevity of prosthetic pulmonary valves and valved conduits. J Thorac Cardiovasc Surg. 2000;120(6):1022–30. 43. d’Udekem d’Acoz Y, Pasquet A, Van Caenegem O, et  al. Reoperation for severe right ventricular dilatation after tetralogy of Fallot repair: pulmonary infundibuloplasty should be added to homograft implantation. J Heart Valve Dis. 2004;13:307–12. 44. Rao PS.  Percutaneous balloon pulmonary valvuloplasty: state of the art. Catheter Cardiovasc Interv. 2007 Apr;69(5):747–63. 45. Masura J, Burch M, Deanfield JE, Sullivan ID. Five-­ year follow-up after balloon pulmonary valvuloplasty. J Am Coll Cardiol. 1993;21(1):132–6. 46. Musewe NN, Robertson MA, Benson LN, Smallhorn JF, Burrows PE, Freedom RM, et  al. The dysplastic pulmonary valve: echocardiographic features and results of balloon dilatation. Br Heart J. 1987;57:364–70. 47. Holzer RJ, Gauvreau K, Kreutzer J, Trucco SM, Torres A, Shahanavaz S, et al. Safety and efficacy of balloon pulmonary valvuloplasty: a multicenter experience. Catheter Cardiovasc Interv. 2012;80:663–72. 48. Rao PS.  Percutaneous balloon pulmonary valvuloplasty: state of the art. Catheter Cardiovasc Interv. 2007;69:747–63. 49. Garty Y, Veldtman G, Lee K, Benson L.  Late outcomes after pulmonary valve balloon dilatation in neonates, infants and children. J Invasive Cardiol. 2005;17:318–22. 50. Berman W, Fripp RR, Raisher BD, Yabek SM.  Significant pulmonary valve incompetence following oversize balloon pulmonary valveplasty in small infants: a long-term follow-up study. Catheter Cardiovasc Interv. 1999;48:61–5. 51. Rao PS.  Late pulmonary insufficiency after bal loon dilatation of the pulmonary valve. Catheter Cardiovasc Interv. 2000;49:118–9. 52. Bonhoeffer P, Boudjemline Y, Qureshi SA, et  al. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. 2002;39:1664–9. 53. Garay F, Webb J, Hijazi ZM. Percutaneous replacement of pulmonary valve using the Edwards-Cribier percutaneous heart valve: first report in a human patient. Catheter Cardiovasc Interv. 2006;67(5):659–62. 54. Griona J, Betrian P, Marti G.  Percutaneous implantation of a pulmonary valve. Rev Esp Cardiol. 2009;62(09):1072–4. 55. Ansari M, Cardoso R, Garcia D, et  al. Percutanous pulmonary valve implantation- present status and evolving future. J Am Coll Cardiol. 2015;66:2246–55.

B. A. Popescu et al. 56. Morray BH, McElhinney DB, Cheatham JP, et  al. Risk of coronary artery compression among patients referred for transcatheter pulmonary valve implantation: a multicenter experience. Circ Cardiovasc Interv. 2013;6(5):535–42. 57. Lurz P, Bonhoeffer P, Taylor AM. Percutaneous pulmonary valve implantation: an update. Expert Rev Cardiovasc Ther. 2009;7(7):823–33. 58. Nordmeyer J, Khambadkone S, Coats L, et  al. Risk stratification, systematic classification, and anticipatory management strategies for stent fracture after percutaneous pulmonary valve implantation. Circulation. 2007;115:1392–7. 59. Biernacka W, Ruzyllo W, Demkow M. Percutaneous pulmonary valve implantation—state of the art and polish experience. Postepy Kardiol Interwencyjnej. 2017;13(1):3–9. 60. Nordmeyer J, Lurz P, Khambadkone S, et  al. Pre-­ stenting with a bare metal stent before percutaneous pulmonary valve implantation: acute and 1-year outcomes. Heart. 2011;97:118–23. 61. McElhinney DB, Cheatham JP, Jones TK, et al. Stent fracture, valve dysfunction, and right ventricular outflow tract reintervention after transcatheter pulmonary valve implantation: patient-related and procedural risk factors in the US Melody. Circ Cardiovasc Interv. 2011;4:602–14. 62. Kenny D, Hijazi ZM, Kar S, et  al. Percutaneous implantation of the Edwards SAPIEN transcatheter heart valve for conduit failure in the pulmonary position: early phase 1 results from an international multicenter clinical trial. J Am Coll Cardiol. 2011;58(21):2248–56. 63. McElhinney DB, Benson LN, Eicken A, et  al. Infective endocarditis after transcatheter pulmonary valve replacement using the Melody valve: combined results of 3 prospective North American and European studies. Circ Cardiovasc Interv. 2013;6:292–300. 64. Khambadkone S, Coats L, Taylor A, et al. Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients. Circulation. 2005;112:1189–97. 65. Butera G, Milanesi O, Spadoni I, et  al. Melody transcatheter pulmonary valve implantation. Results from the registry of the Italian Society of Pediatric Cardiology. Catheter Cardiovasc Interv. 2013;81:310–6. 66. Van Dijck I, Budts W, Cools B, et al. Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants. Heart. 2015;101:788–93. 67. Jalal Z, Galmiche L, Beloin C, Boudjemline Y. Impact of percutaneous pulmonary valve implantation procedural steps on leaflets histology and mechanical behaviour: an in  vitro study. Arch Cardiovasc Dis. 2016;109:465–75. 68. Lurz P, Coats L, Khambadkone S, et al. Percutaneous pulmonary valve implantation: impact of evolving technology and learning curve on clinical outcome. Circulation. 2008;117:1964–72.

10  Pulmonic Valve Diseases 69. Vezmar M, Chaturvedi R, Lee K-J, et al. Percutaneous pulmonary valve implantation in the young: 2-year follow-up. J Am Coll Cardiol Intv. 2010;3:439–48. 70. Cheatham JP, Hellenbrand WE, Zahn EM, et  al. Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in

161 the US Melody valve investigational device exemption trial. Circulation. 2015;131:1960–70. 71. Kheiwa A, Divanji P, Mahadevan VS.  Transcatheter pulmonary valve implantation: will it replace surgical pulmonary valve replacement? Expert Rev Cardiovasc Ther. 2018 Mar;16(3):197–207.

Acute Rheumatic Fever and Rheumatic Heart Disease

11

G. Itzikowitz, E. A. Prendergast, B. D. Prendergast, and L. Zühlke

Introduction Acute rheumatic fever (ARF) is a post-infectious, non-suppurative sequel of untreated Group A streptococcal (GAS) pharyngitis. It is a systemic disease which presents with an array of clinical manifestations, including arthralgia or arthritis, Sydenham’s chorea, fever, skin lesions (such as erythema marginatum) and subcutaneous nodules, and heart valve disease (with associated risk of secondary heart failure). Whilst most symptoms will resolve, there is potential for heart valve damage to persist. Repeated GAS infections increase the risk of repeated episodes of ARF and progression to permanent

G. Itzikowitz Division of Paediatric Cardiology, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa E. A. Prendergast Cambridge University Clinical School, Cambridge, UK B. D. Prendergast (*) Department of Cardiology, St Thomas’ Hospital, London, UK e-mail: [email protected] L. Zühlke Division of Paediatric Cardiology, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa Division of Cardiology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

heart valve damage—rheumatic heart disease (RHD)—which carries significant morbidity and mortality.

Epidemiology Global Burden The mid twentieth century saw a decline in the incidence and prevalence of ARF and RHD in developed countries, owing to major advances in the treatment of ARF with penicillin and the use of benzathine penicillin G (BPG) for secondary prevention of RHD. However, both ARF and RHD continue to pose significant public health concerns amongst young people living in lowand middle-income countries (LMICs) [1, 2]. In 2005, a systematic review estimated the global incidence of ARF to be 471,000 new cases per  annum, with peak incidence between 5 and 15 years of age (336,000 new cases per annum in this group) [3]. The global prevalence of RHD was estimated at 15.6–19.6 million cases, with peak prevalence amongst adults aged 25–45  years. The review also demonstrated that approximately 60% of people living with ARF in endemic areas would go on to develop RHD. Mortality related to ARF or RHD was estimated at 350,000 deaths/ annum, almost all of these occurring in people living in LMICs.

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More recent data accumulated using more robust collection methods coordinated by the Global Burden of Disease consortium and ­following an increase in the use of echocardiographic screening have demonstrated even higher prevalence amongst individuals living in LMICs: approximately 33  million prevalent cases and 275,000 deaths/annum [4].

 lobal Trends in Rheumatic Heart G Disease Areas with the highest prevalence of RHD include Africa, the Pacific region, Latin America, the Middle East and Asia, and disadvantaged communities in high-income countries such as Australia and North America [4]. A recent review heighted the geographic distribution of RHD in 2013 and change in age standardized RHD prevalence 1990–2013. Of concern, was as much as 20% increase in prevalence in RHD in some areas of the world [2]. The age-standardised global prevalence of ARF depicts two contrasting epidemics. The first occurred in high-income countries in the first half of the twentieth century, where there are now very few incident cases and most surviving individuals (prevalent cases) are adults aged >50 years. The second epidemic is ongoing in LMICs with significantly higher incidence in younger individuals and lower prevalence in older populations owing to the poor survival of those affected by ARF.

 isk Factors for ARF and RHD R (Table 11.1) The global rheumatic heart disease registry (REMEDY), a multi-centre hospital-based prospective registry of patients with RHD, demonstrated that most patients living with the disease are young and largely unemployed, a high proportion of whom are women of childbearing age with severe manifestations and complications of the disease [9]. The increased relative risk of

Table 11.1  Established risk factors for ARF and RHD Risk factor Age

ARF Initial cases: 5–14 years Recurrent episodes: older children and adolescents Sex Equal prevalence Socioeconomic Household overcrowding

RHD 25–45 years

1.6-2x greater risk in females [5, 6] Household overcrowding [7, 8] Unemployment Income 4 km from nearest healthcare facility [8]

women developing RHD is thought to be due to greater autoimmune susceptibility (as observed in systemic lupus erythematosus), greater exposure to GAS infection related to child-rearing, and inadequate access to primary and secondary ARF prophylaxis compared with men and boys. Further study is required for confirmation of distinct and preventable factors. Of concern, however, RHD is a leading cause of indirect obstetric death, accounting for 25% of all maternal deaths in developing countries [10], related to worsening pre-existing cardiovascular disease as a result of haemodynamic changes occuring during pregnancy [11].

Economic Burden A systematic review of available studies concerning RHD health system costs demonstrates wide global variation in economic burden [12]. In Fiji, for example, RHD health system costs are US$2 per patient screened by echocardiography, whereas they are US$2900 per hospital admission with ARF in South Africa (and US$10,900 per patient requiring valve surgery). Average yearly cost per patient with RHD in Brazil is about US$1500. The number of disability-­adjusted life years (DALYs) lost is estimated at >nine million, and larger indirect societal costs of RHD occur routinely through absence from school and work [13].

11  Acute Rheumatic Fever and Rheumatic Heart Disease

Pathogenesis of ARF The development of ARF following infection with Group A β-hemolytic streptococcus is believed to involve interplay between a triad of factors: 1. Infection with a rheumatogenic strain of streptococcus 2. Host genetic susceptibility 3. Aberrant immune response and molecular mimicry

 olecular Mimicry (Type II M Hypersensitivity Reaction) Following GAS pharyngitis, neutrophils, macrophages and dendritic cells phagocytose bacteria and present the antigen to human T cells. Both B and T cells respond to GAS infection by initial antibody production (IgM and IgG) and subsequent T cell activation (mainly CD4+ T cells). In genetically susceptible individuals, the host response against GAS triggers autoimmune reactions against host tissues through a process called molecular mimicry [1]. Molecular mimicry is the sharing of antibody or T cell epitopes between host and microorganism, i.e. the antibodies or T cells generated by the infection also recognise and interact with host antigens. In ARF, the streptococcal M protein shares an α-helical coiled structure with myosin (found in myocardial tissue), laminin (found in basement membranes and the endothelial lining of cardiac valves), and keratin (found in human skin). Antibodies isolated from patients with ARF crossreact with both streptococcal M protein (foreign antigen) and host tissue, including human heart tissue, basal ganglia and skin. Repeated GAS throat infections are important in generating molecular mimicry, breaking immune tolerance and inducing epitope spreading, which leads to recognition of more epitopes in cardiac myosin and other heart proteins [14–16]. The site of immune complex deposition determines clinical manifestation:

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• Formation of immune complexes that bind to the synovial membrane and/or collagen in joints leads to inflammatory cell recruitment manifest as transient migratory polyarthritis • Antibody binding to the basal ganglia with subsequent neuronal cell release of excess dopamine leads to Sydenham’s chorea • Antibodies that bind to keratin result in subcutaneous nodules and erythema marginatum • Antibody deposition in the myocardial tissue and cardiac valves manifests as rheumatic carditis

 olecular Mimicry and Rheumatic M Carditis The antibody-mediated immune response to GAS is mainly responsible for initiating rheumatic carditis. Identification of streptococcus-­ specific monoclonal antibodies isolated from patients with rheumatic carditis supports the theory that antibodies against the streptococcal group A carbohydrate epitope recognise cross-­ reactive structures on heart valve endothelium and/or endocardium. The inflammatory cascade in ARF has structural and functional effects on the epicardium, myocardium and endocardium (pancarditis). Acute and chronic inflammation of the myocardium (characterized by interstitial granulomas or Aschoff’s bodies) and epicardium (characterized by fibrinous pericarditis) often resolve without permanent damage (Fig.  11.1) [17]. However, rheumatic carditis can result in damage to the heart valves that persists after initial inflammation has subsided, resulting in established RHD (Fig.  11.2). Pathological consequences include: 1. Annular dilation and elongation of the chordae tendinae 2. Incomplete leaflet coaptation leading to valvular regurgitation 3. Fibrinous vegetations and leaflet scarring (with potential to cause valvular stenosis)

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Fig. 11.1  Histological features of Aschoff bodies (granulomatous structures, consisting of acute fibrinoid changes, lymphocytic infiltration, plasma cells and abnormal macrophages surrounding necrotic centres) that are a pathognomonic feature of acute and chronic rheumatic fever

but also CD8+ T cells) via the endothelium to produce inflammatory cytokines and valvular injury [18]. VCAM-1 also interacts with numerous other cellular adhesion molecules, chemokines and their receptors. The valvular autoimmune reaction increases production of matrix/structural proteins (vimentin and lumican) and apolipoprotein A1, while levels of collagen VI, haptoglobin-­ related protein, prolargin, biglycan and cartilage oligomeric matrix protein are reduced. The overall consequence is loss of structural integrity and subsequent valve dysfunction [19].

Anti-Collagen Antibodies and Valvular Dysfunction

Fig. 11.2  Anatomical appearances of severe mitral stenosis secondary to rheumatic fever demonstrating leaflet thickening, commissural fusion and restricted valve orifice

Potential late complications include cardiac failure, arrhythmias, systemic embolism and infective endocarditis.

 olecular Mimicry and Valvular M Endothelial Activation CD4+ and CD8+ T-cells, produced during the cellular autoimmune response to ARF, infiltrate the valvular endothelium through activity of vascular cell adhesion protein-1 (VCAM-1). IgG antibodies that react with valvular endothelium up-regulate VCAM-1 through a process known as valvular endothelial activation and promote T-cell infiltration (primarily CD4+,

Autoantibodies against valvular collagen I produced in ARF are not cross-reactive, raising the possibility of an alternative pathogenic pathway that does not rely on molecular mimicry. Animal models, where only cardiac myosin and M protein (but not collagen) induce valvulitis, demonstrate that molecular mimicry is important in impeding immune tolerance and initiating rheumatic carditis. Production of anti-collagen antibodies is thought to occur after initial damage because of immune system exposure to collagen—a process that continues during RHD [20, 21].

Molecular Mimicry and the Brain Sydenham’s chorea is the neurological manifestation of ARF.  The clinical picture, characterized by irregular and involuntary movement of the limbs, trunk and facial muscles, arises as a result of neuron specific antibodies produced in response to GAS infection. These IgG antibodies target the basal ganglia, leading to release of excess dopamine [22]. Human monoclonal antibodies cross-react with the group A carbohydrate epitope N­acetyl-β­d­glucosamine [22] and a group of antigens found in the basal ganglia, including D1 and D2 dopamine receptors, lysoganglioside and tubulin [23]. Cross-reactive neuron-specific antibodies are generated by the response against

11  Acute Rheumatic Fever and Rheumatic Heart Disease

group A streptococcal carbohydrate and recognize both host and microbial antigens.

Genetic Susceptibility A role for genetic susceptibility in the development of ARF and RHD is supported by evidence that the lifetime cumulative incidence of ARF amongst people infected with untreated rheumatogenic strains of GAS is constant (3–6%), irrespective of ethnicity or geographical location. Twin studies have been pivotal in assessing the extent to which familial occurrence of ARF is due to genetic and environmental factors. Phenotypic concordance among dizygotic twins suggests that susceptibility to ARF has an inherited component but that this inheritance does not follow a classic Mendelian pattern. Class II HLA molecules expressed on the surface of antigen presenting cells (APCs) are crucial in triggering adaptive immune responses via the T cell receptor. HLA class II alleles (particularly DR7) have been associated with ARF and RHD around the world [24]. In addition, the class I HLA allele HLA∗B5 is associated with development of ARF and associated immune complex formation. These observations indicate that alterations of Fc receptor (FcR) genes and potential failure of immune complex clearance may play an important role in pathogenesis. Thus far, gene polymorphisms coding for immune-related proteins (including MBL2, FCN2, FCGR2A, TLR2, TNF, IL-1RN, TGF-β1 and CRLA4) have been associated with susceptibility to ARF and RHD. Screening for such genetic variants may be useful in identifying high-risk individuals who would benefit from penicillin prophylaxis or vaccination against Group A β-hemolytic streptococci [25].

Clinical Manifestations ARF typically presents 2–4  weeks after GAS pharyngitis - fever (>90%) and arthritis (>75%) are the most common symptoms.

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Arthritis Single large joint migratory polyarthritis is the most common rheumatological manifestation of ARF. However, this poses a significant diagnostic challenge given the numerous causes of arthritis in children. Exclusion of septic arthritis (that can cause permanent joint damage and disability if left untreated) is imperative. Arthritis in ARF is highly responsive to anti-inflammatory drugs (aspirin and NSAIDs), and alternative diagnoses should be sought if the patient fails to respond within 48–72  h. Polyarthralgia is a less severe manifestation.

Carditis Pan-carditis arises in >50% of patients with ARF and valvulitis is the most common manifestation. Most patients present with mitral regurgitation, whilst a minority may develop isolated aortic regurgitation. Symptoms range from mild sub-­clinical involvement (detected by echocardiography) to severe carditis and heart failure. Cardiomegaly may complicate moderate/severe valvular regurgitation. Importantly, sub-clinical carditis is now recognised as a major manifestation of ARF [26].

 rythema Marginatum (EM) E and Subcutaneous Nodules (SN) Cutaneous manifestations of ARF are infrequently observed and occur in only 10% of patients. Erythema marginatum is described as bright pink blanching macules or papules that usually present on the trunk and proximal limbs. Subcutaneous nodules are small (0.5–2  cm ­diameter), round and painless, and located over bony prominences or extensor tendons.

Sydenham’s Chorea Chorea typically occurs 1–8  months after GAS infection in up to 30% of patients with

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ARF.  Choreiform movements are rhythmic, involuntary and often asymmetrical, and disappear with sleep. Chorea may present without evidence of recent streptococcal infection. Exclusion of other causes is important, including certain drug reactions, systemic lupus erythematosus and Wilsons disease. Echocardiography should be performed in every patient with chorea to exclude carditis associated with ARF. Symptoms usually resolve within 12–15 weeks, but relapse in one third of patients and may persist for years. Treatment is recommended when associated with significant motor impairment. Corticosteroids may shorten the disease course but do not influence the rate of relapse - antipsychotic and neuroleptic medications are reserved for patients with resistant symptoms (Table 11.2) [27].

 iagnosis (The Revised Jones D Criteria) The diagnosis of ARF is based upon the Jones Criteria, which include a combination of major and minor clinical findings and assist in the exclusion of other differential diagnoses. Confirmation of ARF requires appropriate symptoms combined with evidence of recent streptococcal infection (positive serology) plus 2 major criteria or 1 major and 2 minor criteria (Table  11.3). Exceptions include presentation with Sydenham’s chorea or indolent carditis, as symptoms may be delayed after initial streptococcal infection (by which time serology may be normal). The Jones criteria were revised in 2015 to include the use of echocardiography for diagnosis of carditis and to differentiate patients into low- and moderate-high risk groups (moderate–high risk: populations with ARF incidence >2/100,000 school aged children/year OR all-­age RHD prevalence >1 per 1000 people/year). The intention of this distinction was to improve diagnostic sensitivity in areas where ARF is endemic (i.e. to ensure accurate diagnosis of those who have ARF) whilst maintaining diagnostic specificity in low-risk areas (i.e. to ensure accurate exclusion of ARF). Clinicians are directed to the

moderate-high risk pathway if there is uncertainty. Echocardiographic evaluation (Fig.  11.3) is recommended for all patients with suspected ARF in the 2015 revised Jones Criteria, and both clinical and subclinical carditis are major criteria (even in the absence of classical auscultatory findings) [29]. In addition to the modified Jones Criteria, there are established New Zealand criteria that divide the diagnosis of ARF into ‘definite’, ‘probable’ and ‘possible’ ARF (Table 11.4).

Clinical Management A single intramuscular dose of BPG (or 10-day course of oral penicillin/amoxicillin) should be administered to eliminate GAS alongside education concerning the importance of secondary prophylaxis. For example, the Uganda Heart Institute has established a support group where long-term RHD patients support clinicians in counselling newly diagnosed subjects. Patients with acute valve disease should mobilise gradually during the first 4  weeks or until inflammatory marker levels (C reactive protein and erythrocyte sedimentation rate) have reduced or normalised. Those in whom carditis is mild or absent should only remain in bed as long as necessary to manage arthritis and other symptoms. Aspirin is used as a first-line anti-­inflammatory agent, although naproxen has equivalent efficacy with fewer side-effects. Glucocorticoids may provide therapeutic benefit in severe carditis, although a recent systematic review concluded that corticosteroids had no impact on the risk of heart valve lesions in patients with ARF [31, 32]. Treatment of RHD requires secondary prevention with penicillin prophylaxis, regular review by a specialist in RHD care, access to echocardiography, adequate anticoagulant monitoring in patients with atrial fibrillation or prosthetic valves, access to dental healthcare, and timely referral for heart surgery if required. Warfarin is recommended for patients with prosthetic heart valves (Table 11.5) and the international normalized ratio (INR) must be monitored on a regular basis (with dose adjustment as required) [1].

9

18

Harel et al. (2000)

Pena et al. (2002)

Not specified

2 years

16

14

3 months

15

7–15

Not specified

7–240 days

1–3 weeks

9–12

7–16

1–104 weeks

5–13

12–16 2 weeks–6 months

11–18 5 days–130 weeks

8 weeks

2 weeks–7 months

Duration of chorea before treatment 2 weeks–8 years

19

9–21

8

McLachlan 1 (1981) Sandyk 1 (1983) Harries-­ 1 Jones (1985) Dhanaraj 5 et al. (1990) Shannon and 2 Fernichel (1990) Daoud et al. 15 (1990) Kulkarni 5 (1992) Appleton and 1 Jan (1998)

Author/year Shenker et al. (1973) Green (1978)

Age range (yrs) 8–15

Number of cases 4

Table 11.2  Pharmacotherapy for Sydenham’s chorea

14–21

5–10

2

14

2

Corticosteroids 2–5 Prednisone 1–2

Response (days) 4–7

Carbamazepine (n = 6) haloperidol (n = 6) Valproic acid (n = 6)

7 (non-responders: Carbamazepine, n = 1; haloperidol, n = 3)

No response Valproic acid 25 mg/kg/day (haloperidol if no response after 3 weeks) Carbamazepine 4–10 mg/kg/ 2–14 day

Sodium valproate 15–20 mg/ 4–8 kg/day Sodium valproate 20 mg/kg/day 2

Sodium valproate 15–20 mg/ kg/day Pimozide 2 mg bd

Sodium valproate 300 mg od and baclofen 15 mg od Pimozide 2 mg bd

Corticotrophin 30–40 U/day (3–9 days) and prednisone 30–75 mg od Valproic acid 250 mg bd

Medication/Dose Haloperidol 1–3 mg od

3

2

Not specified

Not documented

Nil

2

Not documented

Nil

Not documented Nil

Nil

Relapse Not documented Nil

1–27 months

1 year on haloperidol

Not specified

6–7 weeks

7 months

Not specified

Not specified

3+ months

34 days

21–90 days

Duration of treatment 3–7 months

Blockade of dopamine receptors or stimulation of cholinergic pathways Blockade of dopamine receptors, stimulation of cholinergic pathways, and increase GABA (continued)

Increase GABA

Increase GABA

Increase GABA

Dopamine receptor antagonist

Dopamine receptor antagonist Increase GABA

Increase GABA

Increase GABA

Mechanism of action Dopamine receptor antagonist Anti-inflammatory

11  Acute Rheumatic Fever and Rheumatic Heart Disease 169

6–17

11–13 Not specified

65

2

Demiroren et al. (2007)

Van Immerzeel et al. (2010) Sabui and Pant (2010)

3–60 days

2–4000 days

2–84 days

Not specified

Immune modulating IVIG 3 Plasma exchange 2 prednisone 2

5

Not documented Nil

Not specified

12 weeks

Not documented

29 days

Pimozide 84.3 (SD 102.6), haloperidol 51 (SD 22.5)

Prednisone 3 Placebo 4

Increase GABA

Immune modulating

Dopamine receptor antagonist

Immune modulating

Immune modulating

Not documented

Nil

Mechanism of action Increase GABA, blockade of dopamine receptors and increase in acetylcholine Immune modulating

Relapse 1,3

Prednisone remission 28 days time 54, placebo 119.9

Duration of Response (days) treatment Valproate 2–30, Valproate carbamazepine 4–14 1.5–9 months; carbamazepine 2–10 months 1–2 3 weeks full, 3 weeks taper 30–90 Dependent on clinical course (all cases severe) All assessed at 2 days 1 month 5 treatments or 10 days (according to treatment regime)

Sodium valproate 20 mg/kg/day 3 (n = 4) 4 (n = 4) plus phenbarbitone in initial 7 (n = 2) phases

Methylprednisolone 25 mg/kg/ day IV for 5 days and prednisone 1 mg/kg/day IVIG 1 mg/kg/day for 2 days (n = 4) Daily plasma exchange 5–6 days (n = 8) Prednisone 1 mg/kg/day for 10 days (n = 6) Prednisone 2 mg/kg/day (max 60 mg) for 4 weeks then tapered dose; placebo controls (n = 15) Pimozide (n = 26) haloperidol (n = 23) Phenobarbitone (n = 2) Carbamazepine (n = 1) Haloperidol + pimozide (n = 1) No medication (n = 12) IVIG 400 mg/kg for 5 days

Prednisone 2 mg/kg/day

Medication/Dose Sodium valproate 20–25 mg/ kg/day (n = 7), carbamazepine 15 mg/kg/day (n = 17)

Adapted from ‘An update on the treatment of Sydenham’s chorea: the evidence for established and evolving interventions’ [28]

7–9

7–11

22

Paz et al. (2006)

10

5–14

Garvey et al. 18 (2005)

4–8 weeks

4–13

4

2–30 days

Duration of chorea before treatment 2–180 days

4–11

Age range (yrs) 5–14

5

Barash et al. (2005) Teixeira et al. (2005)

Author/year Genel et al. (2002)

Number of cases 24

Table 11.2 (continued)

170 G. Itzikowitz et al.

171

11  Acute Rheumatic Fever and Rheumatic Heart Disease Table 11.3  The modified 2015 Jones criteria [29]

Evidence of preceding GAS infection 1. Elevated or rising levels of anti-streptolysin O titre or other streptococcal antibodies (anti-DNAase B). A rise in titre is better evidence than a single result 2.  Positive throat culture for group A β -hemolytic streptococci 3. Positive rapid group A streptococcal carbohydrate antigen test in a child whose clinical presentation suggests high pre-test probability of streptococcal pharyngitis Low risk Moderate-high risk Major Carditis (clinical/subclinical) Carditis (clinical/subclinical) Arthritis (polyarthritis only) Arthritis (monoarthritis/polyarthritis/ polyarthralgia) Chorea Chorea Erythema marginatum Erythema marginatum Subcutaneous nodules Subcutaneous nodules Minor Polyarthralgia Monoarthralgia Fever (≥38.5 °C) Fever (≥38 °C) ESR ≥60 mm/h +/or CRP ≥3.0 mg/dL ESR ≥30 mm/h +/or CRP ≥ 3.0 mg/dL Prolonged age-corrected PR interval Prolonged age-corrected PR interval (unless carditis is a major criterion) (unless carditis is a major criterion)

a

c

b

e

d

f

Fig. 11.3  Echocardiographic images from a patient with rheumatic heart disease affecting all four cardiac valves: (a) severe mitral stenosis and incompetence, (b) severe

aortic regurgitation, (c, d) severe pulmonary stenosis with a peak gradient of 50 mmHg, (e, f) severe tricuspid stenosis and regurgitation

Surgery

and valve gradient. Valve repair is the preferred operation for patients with mitral regurgitation due to lower risk of procedural complications and need for repeat surgery. If valve anatomy is unsuitable for repair, treatment options include valve replacement with a mechanical or bioprosthetic valve. Women of childbearing age who are planning pregnancy should be offered a bioprosthetic valve due to the harmful risks of warfarin to the fetus and of heparin regimes to the mother.

Intervention during the acute phase is associated with poor outcomes and usually deferred until acute inflammation has subsided. Referral for surgery is required in adults with severe mitral regurgitation, aortic regurgitation, or mitral stenosis. Valve regurgitation is evaluated based on symptoms and left ventricular size while stenosis is assessed based on symptoms

G. Itzikowitz et al.

172

The management of rheumatic heart valve disease in women remains a major challenge, particularly in areas with scarce resources where young females still have limited access to valve repair and aortic homograft techniques [33, 34]. Table 11.4  New Zealand guidelines for the diagnosis of ARF Diagnostic requirements Category Definite 2 major or 1 major ARF and 2 minor manifestations plus evidence of preceding GAS infection Probable Initial episode of 1 major and 2 minor ARF (including evidence of ARF preceding GAS infection as a minor manifestation) Possible Initial episode of 2 major or 1 major ARF and 2 minor or several ARF minor plus evidence of preceding GAS infection Recurrent ARF and 2 major or 1 major and 2 minor previous ARF/RHD or several minor plus evidence of preceding GAS infection Carditis (including Major echocardiographic evidence of manifestations subclinical rheumatic valve modified from disease) original Jones criteria (1992) Polyarthritis or aseptic monoarthritis with history of NSAID use Chorea (can be stand-alone for diagnosis of ARF) Erythema marginatum Subcutaneous nodules Minor Fever manifestations Raised ESR or CRP Polyarthralgia Prolonged PR interval Variables Initial episode of ARF

Adapted from ‘Rheumatic fever diagnosis, management and secondary prevention: a New Zealand guideline [30]

Patients with severe symptomatic mitral stenosis should be considered for percutaneous balloon valvuloplasty or cardiac surgery according to anatomical criteria. Intervention is also increasingly used in asymptomatic individuals with moderate-to-severe disease  – particularly if exercise testing demonstrates restricted functional capacity. Importantly, young patients have a better chance of successful balloon valvuloplasty and early referral is recommended.

Women with RHD Women with moderate-to-severe RHD are at risk of obstetric complications (such as premature delivery) and fetal complications (such as growth restriction). Complete cardiac assessment is therefore essential before pregnancy in women with known RHD and those with symptoms should be considered for intervention before conception [35]. Pregnant women with RHD should be monitored by a multidisciplinary team (comprising an obstetrician, cardiologist and/or obstetric physician) and those with severe RHD should deliver at a referral centre with on-site cardiac and intensive care facilities [36].

Prevention Primordial Prevention Primordial prevention entails prophylactic strategies to avoid GAS infection. Since ARF is triggered by GAS pharyngitis and transmission is facilitated by close personal contact, improved living conditions and education concerning the

Table 11.5  Antithrombotic regimes in patients with bioprosthetic heart valves Risk factorsa No risk factors Target INR

Aortic valve replacement Aspirin + anticoagulation for 3–6 months Subclinical thrombosis: Aspirin + consider anticoagulation No subclinical thrombosis: Aspirin only 2.0 (range 1.5–2.5)

Mitral valve replacement Aspirin + anticoagulation Aspirin + anticoagulation 2.5 (range 2.0–3.0)

Adapted from ‘Anticoagulation after bioprosthetic valve replacement: What should we do?’ [37] a Risk factors include atrial fibrillation, previous thromboembolic event, hypercoagulable condition, and, possibly, severely reduced left ventricular systolic function

173

11  Acute Rheumatic Fever and Rheumatic Heart Disease

symptoms of GAS infection and mechanisms of disease transmission are integral to the control of ARF. Studies in a low-resource inner city area within a developed country outline how alleviation of household crowding can reduce ARF incidence, irrespective of population ethnicity and race [37].

Primary Prevention Primary prevention comprises active case detection and treatment of streptococcal pharyngitis. These strategies are well established in New Zealand where school-based sore throat clinics target high-risk populations.

Table 11.6 Clinical presentation in a registry-based study of urban African adults with RHD 1 2 3 4 5

Clinical presentation Dyspnoea Palpitations/chest pain Peripheral oedema NYHA functional class III/IV Raised jugular venous pressure

Clinical profile Renal dysfunction Atrial fibrillation Anaemia

Adapted from ‘Incidence and characteristics of newly diagnosed rheumatic heart disease in urban African adults: insights from the Heart of Soweto Study’ [39]

Screening

Echocardiography is particularly effective in identifying RHD, as demonstrated by multiple studies demonstrating a tenfold increase in detection in schoolchildren compared with ausSecondary Prevention cultation alone [40]. Portable echocardiography machines make large-scale field assessment posSecondary prevention overcomes the practi- sible, particularly when using smartphone-size cal challenges associated with primary preven- hand-held machines that are efficient, mobile and tion and is a more popular strategy in affected cost-effective. Training of frontline medical perpopulations due to its proven efficacy and cost-­ sonnel is crucial for effective screening and the effectiveness. Treatment entails 4-weekly intra- addition of biomarkers (e.g. B-type natriuretic muscular BPG injections, which reduce ARF peptides and streptococcal antibodies) could recurrence and the severity of rheumatic valve increase specificity and sensitivity. lesions, and are associated with regression of valve lesions over time. Integration of primary and secondary preven- Control Programmes tion is effective and affordable in low-income settings. For example, one study estimated Registry-based programmes are integral in guidthat Cuba’s combined ARF/RHD programme ing patient care and providing epidemiological reduced the burden of RHD by >90% and signifi- data. For example, in New Zealand, where ­ARF/ cantly reduced long-term treatment costs follow- RHD registers have been in place for some years, ing initial investment of approximately US$0.07 recurrence rates have fallen to less than 10% per child per year [12, 38]. [41]. The last decade has also seen increased However, patients frequently present with recognition of the complex factors contributestablished RHD, particularly in resource-poor ing to the development and pathogenesis of settings, by which time secondary prevention is RHD, accompanied by a rise in interdisciplinineffective and surgery the only remaining treat- ary approaches. For example, the Awareness, ment option (Table 11.6). Heart failure is the most Surveillance, Advocacy and Prevention (ASAP) frequent presentation, although embolic stroke, programme draws on several disciplines to creinfective endocarditis and arrhythmias (usually ate a multi-faceted approach to the eradication atrial fibrillation) are also common. Established of RHD, incorporating public health principles RHD may also be detected in asymptomatic and appropriate community- based intervenpatients with a newly noted heart murmur. tions [42].

174

Integrated Health Policy Initiatives International Health Ministers have advocated: (1) prospective RHD registers at sentinel sites, (2) consistent provision of high-quality BPG in areas at risk, (3) integration of healthcare providers from primary care and maternal and child health, and (4) improved access to reproductive health services for women with RHD at risk during the peri-partum period [43]. Future decentralization of technical expertise and point of care technologies to primary and district level will improve detection, secondary prevention and treatment of RHD.  Centres of excellence for heart valve disease will deliver intervention for RHD with additional benefit for the treatment of other cardiac conditions. Multi-sectorial integrated national RHD control programmes, led by the Ministry of Health in partnership with other government departments, academia, civic society and people living with and affected by RHD, are necessary to tackle the disease on all fronts. Finally (and perhaps most importantly), a binding World Health Organisation resolution on global control measures is required for progress in eradicating RHD.

References 1. Carapetis JR, Beaton A, Cunningham MW, Guilherme L, Karthikeyan G, Mayosi BM, et  al. Acute rheumatic fever and rheumatic heart disease. Nat Rev Dis Primers. 2016;2:15084. 2. Zuhlke LJ, Beaton A, Engel ME, Hugo-Hamman CT, Karthikeyan G, Katzenellenbogen JM, et  al. Group A Streptococcus, acute rheumatic fever and rheumatic heart disease: epidemiology and clinical considerations. Curr Treat Options Cardiovasc Med. 2017;19:15. 3. Carapetis JR, Steer AC, Mulholland EK, Weber M.  The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005;5:685–94. 4. Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, Bukhman G, et al. Global, regional, and national burden of rheumatic heart disease, 1990-2015. N Engl J Med. 2017;377:713–22. 5. Mehta A, Saxena A, Juneja R, Ramakrishnan S, Gupta S, Kothari SS. Characteristics and outcomes of Indian children enrolled in a rheumatic heart disease registry. Int J Cardiol. 2016;222:1136–40.

G. Itzikowitz et al. 6. Sudeep DD, Sredhar K. The descriptive epidemiology of acute rheumatic fever and rheumatic heart disease in low and middle-income countries. Am J Epidemiol Infect Dis. 2013;1:34–40. 7. Alkhalifa MS, Ibrahim SA, Osman SH.  Pattern and severity of rheumatic valvular lesions in children in Khartoum. Sudan East Mediterr Health J. 2008;14:1015–21. 8. Okello E, Kakande B, Sebatta E, Kayima J, Kuteesa M, Mutatina B, et  al. Socioeconomic and environmental risk factors among rheumatic heart disease patients in Uganda. PLoS One. 2012;7:e43917. 9. Zuhlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, et  al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J. 2015;36:1115–22. 10. Watkins DA, Sebitloane M, Engel ME, Mayosi BM.  The burden of antenatal heart disease in South Africa: a systematic review. BMC Cardiovasc Disord. 2012;12:23. 11. Sliwa K, Johnson MR, Zilla P, Roos-Hesselink JW. Management of valvular disease in pregnancy: a global perspective. Eur Heart J. 2015;36:1078–89. 12. Watkins DA, Mvundura M, Nordet P, Mayosi BM. A cost-effectiveness analysis of a program to control rheumatic fever and rheumatic heart disease in Pinar del Rio, Cuba. PLoS One. 2015;10:e0121363. 13. Watkins D, Lubinga SJ, Mayosi B, Babigumira JB. A cost-effectiveness tool to guide the prioritization of interventions for rheumatic fever and rheumatic heart disease control in African nations. PLoS Negl Trop Dis. 2016;10:e0004860. 14. Guilherme L, Kalil J.  Rheumatic fever and rheu matic heart disease: cellular mechanisms leading autoimmune reactivity and disease. J Clin Immunol. 2010;30:17–23. 15. Guilherme L, Kohler KF, Kalil J. Rheumatic heart disease: mediation by complex immune events. Adv Clin Chem. 2011;53:31–50. 16. Azevedo PM, Pereira RR, Guilherme L. Understanding rheumatic fever. Rheumatol Int. 2012;32:1113–20. 17. Tandon R, Sharma M, Chandrashekhar Y, Kotb M, Yacoub MH, Narula J.  Revisiting the pathogenesis of rheumatic fever and carditis. Nat Rev Cardiol. 2013;10:171–7. 18. Martins TB, Hoffman JL, Augustine NH, Phansalkar AR, Fischetti VA, Zabriskie JB, et al. Comprehensive analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever. Int Immunol. 2008;20:445–52. 19. Martins CO, Demarchi L, Ferreira FM, Pomerantzeff PM, Brandao C, Sampaio RO, et al. Rheumatic heart disease and myxomatous degeneration: differences and similarities of valve damage resulting from autoimmune reactions and matrix disorganization. PLoS One. 2017;12:e0170191.

11  Acute Rheumatic Fever and Rheumatic Heart Disease 20. Dinkla K, Nitsche-Schmitz DP, Barroso V, Reissmann S, Johansson HM, Frick IM, et  al. Identification of a streptococcal octapeptide motif involved in acute rheumatic fever. J Biol Chem. 2007;282:18686–93. 21. Dinkla K, Talay SR, Morgelin M, Graham RM, Rohde M, Nitsche-Schmitz DP, et al. Crucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever. PLoS One. 2009;4:e4666. 22. Kirvan CA, Swedo SE, Heuser JS, Cunningham MW.  Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 2003;9:914–20. 23. Cox CJ, Sharma M, Leckman JF, Zuccolo J, Zuccolo A, Kovoor A, et  al. Brain human monoclonal autoantibody from sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease. J Immunol. 2013;191:5524–41. 24. Engel ME, Stander R, Vogel J, Adeyemo AA, Mayosi BM.  Genetic contribution to rheumatic fever: a systematic review and meta-analysis of twin studies. S Afr Med J. 2007;97:1094. 25. Parks T, Mirabel MM, Kado J, Auckland K, Nowak J, Rautanen A, et  al. Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. Nat Commun. 2017;8:14946. 26. Tubridy-Clark M, Carapetis JR.  Subclinical carditis in rheumatic fever: a systematic review. Int J Cardiol. 2007;119:54–8. 27. Walker KG, de Vries PJ, Stein DJ, Wilmshurst JM. Sydenham chorea and PANDAS in South Africa: review of evidence and recommendations for management in resource-poor countries. J Child Neurol. 2015;30:850–9. 28. Walker KG, Wilmshurst JM. An update on the treatment of Sydenham's chorea: the evidence for established and evolving interventions. Ther Adv Neurol Disord. 2010;3:301–9. 29. Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation. 2015;131:1806–18. 30. Atatoa-Carr P, Lennon D, Wilson N. Rheumatic fever diagnosis, management, and secondary prevention: a New Zealand guideline. N Z Med J. 2008;121:59–69. 31. Cilliers A, Manyemba J, Adler AJ, Saloojee H. Anti-­ inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev. 2012.

175 32. Cilliers A, Adler AJ, Saloojee H.  Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev. 2015;(5):CD003176. 33. Grimaldi A, Ammirati E, Karam N, Vermi AC, de Concilio A, Trucco G, et  al. Cardiac surgery for patients with heart failure due to structural heart disease in Uganda: access to surgery and outcomes. Cardiovasc J Afr. 2014;25:204–11. 34. Russell EA, Tran L, Baker RA, Bennetts JS, Brown A, Reid CM, et al. A review of valve surgery for rheumatic heart disease in Australia. BMC Cardiovasc Disord. 2014;14:134. 35. Zuhlke L, Acquah L.  Pre-conception counselling for key cardiovascular conditions in Africa: optimising pregnancy outcomes. Cardiovasc J Afr. 2016;27:79–83. 36. Sliwa K, Libhaber E, Elliott C, Momberg Z, Osman A, Zuhlke L, et  al. Spectrum of cardiac disease in maternity in a low-resource cohort in South Africa. Heart. 2014;100:1967–74. 37. Jaine R, Baker M, Venugopal K.  Acute rheu matic fever associated with household crowding in a developed country. Pediatr Infect Dis J. 2011;30:315–9. 38. Nordet P, Lopez R, Duenas A, Sarmiento L. Prevention and control of rheumatic fever and rheumatic heart disease: the Cuban experience (1986-1996-2002). Cardiovasc J Afr. 2008;19:135–40. 39. Sliwa K, Carrington M, Mayosi BM, Zigiriadis E, Mvungi R, Stewart S.  Incidence and characteristics of newly diagnosed rheumatic heart disease in urban African adults: insights from the heart of Soweto study. Eur Heart J. 2010;31:719–27. 40. Saxena A, Zühlke L, Wilson N.  Echocardiographic screening for rheumatic heart disease. Glob Heart. 2013;8:197–202. 41. Oliver J, Pierse N, Baker MG.  Improving rheu matic fever surveillance in New Zealand: results of a surveillance sector review. BMC Public Health. 2014;14:528. 42. Mayosi B. The four pillars of rheumatic heart disease control. S Afr Med J. 2009;100:506. 43. Mocumbi AO, Jamal KK, Mbakwem A, Shung-King M, Sliwa K. The Pan-African Society of Cardiology position paper on reproductive healthcare for women with rheumatic heart disease. Cardiovasc J Afr. 2018;29:1–10.

Infective Endocarditis

12

Gilbert Habib and Maria Abellas-Sequeiros

Introduction Infective endocarditis (IE) is a changing disease, with new high-risk patients, new diagnostic procedures, new microorganisms involved and new therapeutic methods [1]. Despite considerable improvements in its diagnostic and therapeutic strategies, IE is still a severe disease [2, 3]. The high morbidity and mortality rate of IE is the consequence of both the destructive valvular lesions causing valve regurgitation and heart failure, and valvular vegetations with their high embolic potential. Although the incidence of IE is relatively stable, the patients affected by the disease are older, sicker and with higher comorbidity rates [3]. The key issues in IE are the following: –– Epidemiology: population at risk. –– Diagnosis: frequently delayed, causing progressive and irreparable valvular damage. –– Prognosis: high in-hospital mortality, ranging from 16 to 25% and high incidence of

G. Habib (*) Cardiology Department, APHM, La Timone Hospital, Marseille, France IRD, APHM, MEPHI, IHU-­Méditerranée Infection, Aix Marseille University, Marseille, France M. Abellas-­Sequeiros Cardiology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain

embolic events (EE), ranging from 10 to 49%, source of severe complications and sequels [4, 5]. –– Management: the optimal therapeutic strategy in these patients is still to be defined, may vary in the individual patient, and needs a multidisciplinary approach. –– Surgery: some patients present with specific features or complications and need a specific management. –– Prevention: best prevention and prophylaxis of IE is still debated. These 6 issues will be addressed in the following chapter.

Epidemiology It has been described a rising incidence of IE over the last years, to a maximum of 15 per 100,000 in 2011 [6]. But this augmentation in developed countries has come along with differences both in the predisposing conditions and the route of entry. Thereby, a diminishing number of IE over rheumatic valvulopathy [7] has been accompanied by an increasing IE involving health care and cardiac implantable electronic devices (CIEDs) [8–10]. We are heading to an era where  prophylaxis will be specially relevant. Staphylococcus aureus remains to be the most frequent microorganism of IE in developped countries [11].

© Springer Nature Switzerland AG 2020 J. Zamorano et al. (eds.), Heart Valve Disease, https://doi.org/10.1007/978-3-030-23104-0_12

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Pathophysiology and Pathogenesis

Diagnosis

In most cases, IE needs both an injured endothelium and transient bacteraemia. On the one hand, a mechanical stimulus damages the outer layer of the valve, the endothelium, leading to the so-called nonbacterial thrombotic endocarditis (NBTE) lesions, consisting in fibrin and platelets. On the other hand, a microorganism with the ability to adhere to that bulk is needed. For example, Streptococcus mutans belongs to common oral flora, harmless to healthy people. In those patients with predisposing conditions (such as prosthetic heart valves, for example), these bacteria are  able to get attached to that harmed valve-endothelium, leading to an infective vegetation. 10–20% of all S. mutans have cell surface collagen-binding proteins (CBPs), essential for platelet aggregation and  mass formation [12]. Another example:  Staphylococcus aureus has also  an important virulence factor: the cell-­ wall collagen adhesin CNA.  CNA belongs to the named MSCRAMM (microbial surface component recognizing adhesive matrix molecules) adhesins, critical for the pathogenesis of staphylococcal infection [13, 14]. Besides, genetic susceptibility may not be forgotten. Recently, two single nucleotide polymorphisms (SNPs) (rs115231074: p = 1.3 × 10–10 and rs35079132: p = 3.8 × 10–8) has been significantly associated with S. aureus infection [15].

Clinical Presentation

Fig. 12.1 Cutaneous manifestations in infective endocarditis. (a) Osler’s node in a patient with hypertrophic obstructive cardiomyopathy and streptococcal endocarditis. (b) Severe purpuric lesions in a woman with staphylococcal pacemaker endocarditis

a

The clinical presentation of IE may differ from one patient to another. Fever is the most frequent symptom of IE (up to 90%) but may be absent in elderly patients and in case of previous antibiotic therapy. Fever is frequently intermittent in IE and may be associated with weight loss, fatigue and anorexia. Cardiac manifestations include congestive heart failure, new heart murmur and atrioventricular block. Severe heart failure in the context of IE is generally the consequence of severe valvular lesions. These patients require close follow-­up and frequently urgent surgery is mandatory. Finally, extracardiac manifestations may be the first sign of IE, including cutaneous manifestations (Fig. 12.1), splenomegaly, rheumatological symptoms  and neurological manifestations. The latter, may be an embolic phenomena (the most common), related to meningitis or secondary to treatment. The peripheral stigmata of IE (Osler nodes, splinter hemorrhages, Janeway lesions) are dwindling. Osler nodes are non-specific small, painful nodules on the fingertips. Its aetiology has been discussed, but they are thought to depend of an inmunologic mechanism. On the opposite, Janeway lesions are painless and they appear on the palms of the hands and the soles of the feet. They have an embolic origin, as the splinter hemorrhages do. In right-side and pacemaker lead endocarditis, clinical presentation is frequently atypical, includ-

b

179

12  Infective Endocarditis Table 12.1  Clinical endocarditis Symptom/sign Fever Heart murmur Weight loss Embolic phenomena Splinter haemorrhages Roth spots Osler nodes Splenomegaly

manifestations

of

infective

Prevalence (%) 58–96% 70–85% 25–35% 17–25% 3–8% 2% 2–3% 11%

ing local and pulmonary symptoms as first manifestations of the disease [16]. Finally, IE must be suspected both in very acute situations including cardiogenic or septic shock (fulminant endocarditis) representing life-threatening situations, as well as in case of more insidious presentations, for example prolonged unexplained fever, in which case the diagnosis of IE is the main challenge. In all these situations, echocardiography and blood cultures must be performed. Table  12.1 summarizes clinical findings and their prevalence [7, 17, 18].

 aboratory Findings and Blood L Cultures IE may be suspected when non-specific laboratory abnormalities are present, including anaemia, leucocytosis, elevated C-reactive protein, procalcitonin and erythrocyte sedimentation rate and markers of end-organ dysfunction (lactataemia). These parameters are useful to stratify the severity of the ongoing infection, but not to rule-in or rule-out the diagnosis [19]. Laboratory data are included in different risk scores used in IE, such as EuroSCORE II (including creatinine clearance), SOFA score (including creatinine and platelet number), RISK-E score (renal function, platelet count) [20]. The diagnosis of IE is mainly based on blood cultures. Blood cultures are positive in about 90% cases but may be negative in cases of intracellular or fastidious pathogens or after previous antibiotic therapy. Performing blood cultures before any antibiotic therapy is thus mandatory when IE is suspected. PCT is not diagnostic [19].

Echocardiography Echocardiography plays a key role in both the diagnosis and management of infective endocarditis. Echocardiography is also useful for the prognostic assessment of patients with IE, for their follow-up under therapy, and during surgery.

 hen to Perform Echocardiography W in IE? IE is not a single disease but may present with several very different initial symptoms, including heart failure, cerebral embolism, pacemaker infection or isolated fever. IE must be suspected in the presence of fever associated with regurgitant heart murmur, known cardiac disease, bacteraemia, new conduction disturbance and embolic events of unknown origin [21]. In all these situations, echocardiography is the first-line diagnostic technique. Transthoratic echocrdiogram (TTE) must be performed firstly in all cases, because it is a non-invasive technique giving useful information both for the diagnosis and the assessment of severity of IE. In most circumstances, trasoesophageal echocardiogram (TOE) must also be performed. The ESC Guidelines for the management of infective endocarditis recommends TOE in four situations related to IE diagnosis: 1 . TTE positive, to exclude local complications 2. Prosthetic valve/intracardiac device 3. Non-diagnosis TTE 4. Negative TTE with high suspicion of IE There is one case when TOE might be avoided: isolated-right sided IE, confirmed with TTE. In case of S. aureus bacteraemia, due to its strong association and its devastating virulence, it is recommended to perform TTE or TOE. Echocardiography plays a key role not only in IE diagnosis, but also during follow-up, being repeated when needed.

Duke “Echocardiographic” Criteria In 1994, Durack et al. proposed a new classification of criteria for IE called Duke criteria [22], including for the first time echocardiography as

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a major criterion for IE. The major echocardiographic criteria for IE are vegetation, abscess and new dehiscence of a prosthetic valve. Vegetation: (Fig. 12.2) Typically, vegetation presents as an oscillating mass attached on a valvular structure, with a motion independent to that of this valve [23]. However, vegetation may also present as a non-­ oscillating mass and with an atypical location. Vegetations are usually localized on the atrial side of the atrioventricular valves, and on the ventricular side of the aortic and pulmonary valves. Less frequently, vegetations are localized on mural endocardium, papillary muscles, or ascending aorta. They also may be localized on intracardiac devices, such as peacemaker leads. TTE has a sensitivity of about 75% for the diagnosis of vegetations. However, the sensitivity of TTE may be reduced in case of low echogenicity, very small vegetations, and in IE affecting intracardiac devices. TOE is mandatory in case of doubtful transthoracic examination, in prosthetic and pacemaker IE, and when an abscess is suspected [24]. TOE enhances the sensitivity of TTE to about 85–90% for the diagnosis of vegetations. In addiFig. 12.2 Large vegetation on the anterior mitral leaflet (arrow) (TOE). (a) Two-dimensional TOE. (b) 3D TOE. LA left atrium, LV left ventricle, Ao aorta, AML anterior mitral leaflet, PML posterior mitral leaflet

a

a

tion, both TTE and TOE are useful to assess the size and mobility of the vegetation, as well as its evolution under antibiotic therapy [23]. Non infective aethiologies of intracardiac masses must be ruled out. In those cases, clinical context may be assessed. Abscess Formation: (Fig. 12.3) The second major echocardiographic criterion for endocarditis is the presence of perivalvular abscesses. They are more frequently observed in aortic valve IE and in prosthetic valve IE.  Abscess typically presents as a perivalvular zone of reduced echo density, without colour flow detected inside. The diagnosis may be more difficult at the early stage of the disease when only a thickening of the aortic root is evidenced (Fig.  12.3). The sensitivity of TTE is about 50%, that of TOE 90% [25]. Other perivalvular lesions include pseudoaneurysm and fistula. Pseudoaneurysm is described as a pulsatile perivalvular lession, with inner colour-Doppler flow. Fistula is a communication between two cavities. All these perivalvular lesions are more frequently observed in aortic endocarditis and then involve the mitral-aortic intervalvular fibrosa [26]. b

b

Fig. 12.3  Perivalvular abscess in a patient with a bioprosthetic aortic valve endocarditis. (a) TOE: Initial normal bioprosthetic aortic valve—doubtful thickening of the posterior aortic root (arrow). (b) Positive PET/CT intense

c

uptake on the bioprosthesis. (c) Follow-up TOE: typical posterior abscess (arrow). LA left atrium, LV left ventricle, Ao aorta

12  Infective Endocarditis

New Dehiscence of a Prosthetic Valve It represents the third main diagnostic  criteria for IE [22]. IE must be suspected in the presence of a new perivalvular regurgitation, even in the absence of vegetation or abscess. For this reason, systematic postoperative echocardiography must be performed after any valve replacement in order to serve as reference for better interpretation of future echocardiographic abnormalities. Other Echocardiographic Findings in IE Other echocardiographic features are not main criteria for IE but may be suggestive of the diagnosis. These include valve destruction and prolapse, aneurysm and/or perforation of a valve. Valve perforation and aneurysm have recently been included as major criteria in the most recent ESC guidelines [21]. In addition, both TTE and TOE are useful for the assessment of the underlying valve disease, and for the assessment of consequences of IE, including left ventricular size and function, quantification of valve regurgitation or obstruction, assessment of right ventricular function, and estimation of pulmonary pressures.

Limitations of Echocardiography In clinical practice, the echocardiographic diagnosis of IE remains difficult in IE affecting intracardiac devices and in patients with prosthetic valve infective endocarditis (PVIE). In these situations, echographic findings, positive or negative, must be interpreted with caution, taking into account the clinical presentation and the likelihood of IE. In doubtful cases, repeat TTE/ TOE examination must be performed 7/10 days after the first examination when the clinical level of suspicion is still high. Other imaging modalities (CT scan and PET CT) should also be used in those situations (see below). Conversely, false diagnosis of IE may occur in other situations; for example, it may be difficult to differentiate between vegetations and thrombi, cusp prolapse, cardiac tumors, myxomatous changes, Lambl’s excrescences, strands, Libman-Sacks lessions (related to systemic lupus erythematosus) or non infective vegetations (marantic endocarditis) [27].

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Prognostic Value of Echocardiography In addition to its role in diagnosing IE, echocardiography also has a major prognostic value in IE, for both prediction of death and embolic events. Echocardiography Predicts Both In– Hospital and Long-Term Prognosis in IE Mortality is still high in IE, although it has declined in the recent years. Several factors have been associated with an increased risk of death in IE including patients’ characteristics (diabetes, comorbidity), presence of complications (heart failure, stroke, renal failure), and type of microorganism [28]. Echocardiography also plays a very important prognostic role in IE.  Several echocardiographic features have been associated with worse prognosis, including periannular complications, severe valve regurgitation or obstruction, low LV ejection fraction, pulmonary hypertension, intracardiac abscess, and premature mitral valve closure [23, 29]. Risk of Embolism Embolic events (EE) are a frequent and life-­ threatening complication of IE, related to the migration of cardiac vegetations. and are associated with an increased morbidity and mortality [4]. Total embolic risk is very high in IE, with EE occurring in 20–50% of IE. However, the risk of new EE (i.e. occurring after initiation of antibiotic therapy) is only 6–21% [1]. Echocardiography plays a key-role in predicting embolic events [30, 31], although this prediction remains difficult in the individual patient. Several factors should be considered in assessing the embolic risk. One of those factors is vegetetation size [32]. In a recent meta analysis of 21 studies conducted by Mohananey et al., vegetations >10 mm were associated with high risk of embolic events (OR, 2.28; 95% CI, 1.71–3.05; P  12 h apart; or     –  All of 3 or a majority of ≥4 separate cultures of blood (with first and last samples drawn ≥1 h apart); or  (c)  Single positive blood culture for Coxiella burnetii or phase I IgG antibody titre >1:800 2. Imaging positive for IE  (a)  Echocardiogram positive for IE:    – Vegetation;     –  Abscess, pseudoaneurysm, intracardiac fistula;     –  Valvular perforation or aneurysm;     –  New partial dehiscence of prosthetic valve   (b) Abnormal activity around the site of prosthetic valve implantation detected by 18F-FDG PET/CT (only if the prosthesis was implanted for > 3 months) or radiolabelled leukocytes SPECT/CT   (c)  Definite paravalvular lesions by cardiac CT Minor criteria 1.  Predisposition such as predisposing heart condition, or injection drug use 2.  Fever defined as temperature > 38 °C 3. Vascular phenomena (including those detected only by imaging): major arterial emboli, septic pulmonary infarcts, infectious (mycotic) aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway’s lesions 4.  Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor 5. Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE

G. Habib and M. Abellas-Sequeiros

184 Fig. 12.4 European Society of Cardiology 2015 algorithm for diagnosis of infective endocarditis. CT computed tomography; FDG fluorodeoxyglucose; IE infective endocarditis; PET positron emission tomography; SPECT single photon emission computerized tomography; TOE transoesophageal echocardiography; TTE transthoracic echocardiography

Clinical suspicion of IE Modified Duke criteria (Li) Definite IE

Possible/rejected IE but high suspicion Native valve

Rejected IE Low suspicion

Prosthetic valve 1 - Repeat echo (TTE + TOE)/microbiology 2 - 18F-FDG PET/CT or Leucocytes labeled SPECT/CT 3 - Cardiac CT 4 - Imaging for embolic events

1 - Repeat echo (TTE + TOE)/microbiology 2 - Imaging for embolic events 3 - Cardiac CT

ESC 2015 modified diagnostic criteria Definite IE

Possible IE

 SC 2015 Modified Criteria E for Diagnosis of IE Major criteria 1. Blood cultues positive for IE a. Typical microorganisms consistent with IE from 2 separate blood cultures: • Viridans streptococci, Streptococcus gallolyticus (Streptococcus bovis), HACEK group, Staphylococcus aureus; or • Community-acquired enterococci, in the absence of a primary focus; or b. Microorganisms consistent with IE from persistently positive blood cultures: • ≥2 positive blood cultures of blood samples drawn >12 h apart; or • All of 3 or a majority of ≥4 separate cultures of blood (with first and last samples drawn ≥1 h apart);or c. Single positive blood culture for Coxiella burnetii or phase 1 IgG antibody titre > 1:800 2. Imaging positive for IE a. Echocardiogram positive for IE: • Vegetation; • Abscess. pseudoaneurysm, intracardiac fistula; • Valvular perforation or aneurysm; • New partial dehiscence of prosthetic valve. b. Abnormal activity around the site of prosthetic valve implantation detected by 18F-FDG PET/CT (only if the prosthesis was implanted for >3 months) or radiolabelled leukocytes SPECT/CT. c. Definite paravalvular lesions by cardiac CT. Minor criteria 1. Predisposition such as predisposing heart condition, or injection drug use. 2. Fever defined as temperature >38°C. 3. Vascular phenomena (including those detected by imaging only): major arterial emboli, septic pulmonary infarcts. infectious (mycotic) aneurysm. intracranial haemorrhage, conjunctival haemorrhages, and Janeway’s lesions. 4. Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor. 5. Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE.

Rejected IE

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Management of Infective Endocarditis: The Endocarditis Team

Complications of Infective Endocarditis and Indications for Surgery

In 2015, the ESC guidelines introduced the concept of the “endocarditis team”. A multidisciplinary approach is mandatory for the treatment of patients with infective endocarditis, including cardiologists, cardiac surgeons, and specialists of infectious diseases. They must be treated in highly specialized centres with dedicated surgical facilities. This team approach has been shown to significantly reduce the 1-year mortality [49] and has been recommended recently as class IB in the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guideline for the management of patients with valvular heart disease [50] and is a class IIa, level B recommendations in the 2015 ESC guidelines [21]. The main characteristics of the ‘Endocarditis Team’ and the referring indications are summarized in Table 12.3.

Surgical treatment is used in approximately half of patients with IE because of severe complications. Early consultation with a cardiac surgeon is recommended to determine the best therapeutic approach. Identification of patients requiring early surgery is frequently difficult and is an important scope of the ‘Heart Team’. Quantification of risk associated with surgery may be a first step to take. In some cases, surgery needs to be performed on an emergency basis (within 24  h), urgent basis (within a few days, 10 mm after ≥1 embolic episodes despite appropriate antibiotic therapy Aortic or mitral NVE with large vegetations >10 mm, associated with severe valve stenosis or regurgitation, and low operative risk Aortic or mitral NVE or PVE with isolated very large vegetations (>30 mm) Aortic or mitral NVE or PVE with isolated large vegetations (>15 mm) and no other indication for surgeryd

Timinga

Classb Levelc

Emergency

I

B

Urgent

I

B

Urgent Urgent/ elective Urgent

I I

B C

IIa

B

Urgent/ elective

IIa

C

Urgent

I

B

Urgent

IIa

B

Urgent Urgent

IIa IIb

B C

Emergency surgery: surgery performed within 24 h; urgent surgery: within a few days; elective surgery: after at least one or 2 weeks of antibiotic therapy b Class of recommendation c Level of evidence d Surgery may be preferred if a procedure preserving the native valve is feasible a

12  Infective Endocarditis

Candida infections, recent publications orient to similar outcomes in both treated medically with and without surgery [54, 55]. Recent studies have remarked that not all S. aureus IE might benefit from surgery [56, 57]. Each particular case must be assessed individually. –– “Embolic” indications for surgery are more controversial. The exact role of early surgery in preventing embolic events remains debated. A randomized trial demonstrated that early surgery in patients with large vegetations significantly reduced the risk of death and embolic events as compared with conventional therapy [31]. Another recent study found that a vegetation size ≥3  cm was an independent risk factor of neurological complications (hazard ratio [HR] 1.91) in a large series of 340 patients with IE and neurological complication [58]. –– Finally, the decision to operate early for prevention embolism must consider the presence of previous embolic events, other complications of IE, the size and mobility of the vegetation, the likelihood of conservative surgery, and the duration of antibiotic therapy [21]. The ESC guidelines [21] recommend surgery in case of vegetation >10 mm following one or more embolic episodes, when a vegetation >10 mm is associated with severe valve stenosis or regurgitation and low operative risk, and in IE with isolated very large vegetations (>30  mm). The decision to operate early in smaller vegetations (> 15 mm) is more difficult. In this situation, surgery may be preferred when a valve repair seems possible, particularly in mitral valve IE.  But the most crucial point is that surgery, if needed, must be performed on an urgent basis, during the first few days following initiation of antibiotic therapy, since the risk of embolism is highest at this time. –– Surgery should be considered in some cases of right-sided IE, such as HF due to severe tricuspid regurgitation (TR), large vegetations (> 20 mm) responsible for pulmonary embolism and persistent positive blood cultures despite optimal treatment.

187

–– Conservative surgery is more and more frequently performed in mitral valve IE.  In a series of 78 patients operated on between 1990 and 1999 for IE [24], 63 (81%) could beneficiate conservative surgery with good both short and long-term results. In aortic IE, homograft surgery is frequently used, and has been shown to be particularly useful in patients with perivalvular involvement. In summary, early surgery associated with prompt antibiotic therapy are the keys of successful treatment of IE.  The ESC guidelines recommend that the 3 indications for surgery (infectious, hemodynamic, embolic) should be recognized urgently by the multidisciplinary endocarditis team and should be individualized in each patient depending on his clinical status, operative risk, and comorbidities.

 ndocarditis in Specific Subgroups/ E The Example of Neurological Complications Cerebral complications represent the second cause of death in IE, after congestive heart failure. The incidence of cerebral complications varies from 25 to 56% and mortality ranges from 21 to 83% in these patients [44, 59–62]. Cerebral complications may result from the migration of cardiac valvular vegetations into the cerebral arteries, causing cerebral infarction. Cerebral arteries and spleen are the most frequent sites of embolization in left-side IE, cerebral embolims being observed in 20% of patients with IE in our experience. Cerebral embolism may present as a stroke of various severity associated with fever, or may be silent, and found only by systematic CT-scan. Cerebral hemorrhage may complicate cerebral infarction or be the consequence of the rupture of a mycotic aneurysm. Mycotic aneurysms can be detected either by CT-scan, or magnetic resonance angiography, but the gold standard remains conventional cerebral angiography. Mycotic aneurysms may heal under antibiotic therapy in 50% of cases.

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188

The main problem in these patients is the optimal timing of valve surgery, when needed. The best therapeutic strategy in patients with cerebral complications is still debated. All patients with neurological signs or abnormal cerebral imaging findings should be referred to a reference centre and their management discussed within the endocarditis team. After a stroke, the ESC guidelines recommend cardiac surgery to be performed, when indicated, if coma is absent, and the presence of cerebral haemorrhage has been excluded. Following intracranial haemorrhage, surgery should generally be postponed for ≥1  month. Figure 12.5 represents the algorithm we use facing any neurological complication in infective endocarditis.

Antimicrobial Treatment Empirical treatment must be initiated within first hours. Bactericidal antibiotics will be preferred over bacteriostic. Treatment regimen in PVE will be longer than NVE (because of the existence of biofilms). That duration will be counted since the first negative-blood culture day.

Empirical Therapy Empirical treatment must take into account clinical and epidemiological characteristics of the patient. NVE and >  12- month-PVE must cover Staphylococcus, Streptococcus and Enterococcus:

Left-sided Infective Endocarditis • Clinical assessment • TTE / TEE

No neurological symptom Normal cerebral imaging

• Immediate Cerebral CT scan / MRI

Neurological symptoms or Abnormal cerebral imaging

Suspected intracardial mycotic aneurysm

Refer the patient to a reference center

Refer the patient to a reference center

Immediate discussion within the endocarditis team* No indication for surgery**

Catheter-based cerebral angiography

Indication for surgery** • Intracranial haemorrhage

Yes • Coma

• Severe comorbidities • Stroke with severe damage

Management of the patient according to current endocarditis guidelines

Conservative treatment and monitoring

Management according to the endocarditis team* decision

No Urgent surgery

* Includes cardiac surgeon, cardiologist, specialist of infectious diseases, neurologist, neuro-surgeons, and interventional neuroradiologists ** Heart failure, Uncontrolled infection, Abscess, High embolic risk

Fig. 12.5 Diagnostic algorithm and management of patients with endocarditis and neurological complications. CT computed tomography; MRI magnetic reso-

nance imaging; TEE transesophageal echocardiography; TTE transthoracic echocardiography

189

12  Infective Endocarditis

ampicilin plus cloxalicin or vancomycin with gentamicin. Early PVE regimen may be more aggressive: vancomycin with gentamicin and rifampicin. When the causal organism is identified, treatment must be orientated. In case of NVE due to S. aureus, treatment would be cloxacilin in susceptible staphylococci, vancomycin if resistant or allergic. On the other hand, PVE must add rifampicin and gentamicin to above. Standard treatment of IE due to oral streptoccoci consists of penicilin or ceftriaxone (vancomycin in case of allergic patients). In case of strain penicillin-resistance, treatment shoul be enhanced with gentamicin.

Prevention and Prophylaxis Most guidelines now agree on the same principles concerning prophylaxis and prevention –– The principle of antibiotic prophylaxis when performing procedures at risk of IE in patients with predisposing cardiac conditions is maintained –– Antibiotic prophylaxis must be limited to patients with the highest risk of IE (including prosthetic valves) undergoing the highest risk dental procedures (dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa) [63]. –– Good oral hygiene and regular dental review are more important than antibiotic prophylaxis to reduce the risk of IE. –– Aseptic measures are mandatory during venous catheter manipulation and during any invasive procedures in order to reduce the rate of health care-associated IE. ESC 2015 guidelines [21] maintained the principle of antibiotic prophylaxis in high-risk patients and focused on non-specific prevention. Those measures include strict dental and cutaneous hygiene, dental follow-up, no self-­medication with antibiotics, strict infection control measures for any at-risk procedure, discouraging piercing

and tattooing, and limitation in the use of infusion catheters and invasive procedure when possible. These measures should not only be applied in high-risk patients but should also be part of routine care in all patients since IE occurring in patients without previously known heart disease now accounts for a substantial and increasing incidence. This means that, although antibiotic prophylaxis should be restricted to the highest-­risk patients, preventive measures should be applied in all patients with predisposing cardiac disease, and, ideally, to the general population [60].

Conclusion Infective endocarditis (IE) is a severe form of valve disease still associated with an unacceptably high mortality (10–30% in-hospital mortality), quite similar than 20  years ago, although improvements in antibiotic therapy and surgery are fantastic. This can be explained by the completely changing epidemiological profile of IE, with more valve prostheses and new intracardiac devices, less  intravenous drug abuse, and more elderly patients. The only objective for the following years is to reduce morbidity and mortality in IE.  This can be done using a better prevention, particularly oriented towards nosocomial diseases, earlier diagnosis using modern imaging tools, earlier therapy and surgery if needed. The management of IE by an endocarditis team in a reference center is probably one of the most important new recommendations. The physicians should keep in mind the need for management of these patients with IE in close relationship with “endocarditis centers”, and that they should send the patients for an early surgical assessment as soon as possible, since surgery is the major part of therapy in more than half patients with IE.

References 1. Habib G.  Management of infective endocarditis. Heart. 2006;92:124–30. 2. Hasbun R, Vikram HR, Barakat LA, Buenconsejo J, Quagliarello VJ. Complicated left-sided native valve

190 endocarditis in adults: risk classification for mortality. JAMA. 2003;289(15):1933–40. 3. 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. J Am Coll Cardiol. 2012;59(22):1968–76. 4. Hubert S, Thuny F, Resseguier N, et al. Prediction of symptomatic embolism in infective endocarditis: construction and validation of a risk calculator in a multicenter cohort. J Am Coll Cardiol. 2013;62:1384–92. 5. Habib G. Embolic risk in subacute bacterial endocarditis. Role of transesophageal echocardiography. Curr Cardiol Rep. 2003;5:129–36. 6. Pant S, Patel NJ, Deshmukh A, et al. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am Coll Cardiol. 2015;65(19):2070–6. https://doi. org/10.1016/j.jacc.2015.03.518. 7. Murdoch DR, Corey GR, Hoen B, et  al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009;169(5):463–73. 8. Athan E, Chu VH, Tattevin P, et  al. Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices. JAMA. 2012;307(16):1727–35. 9. Zlug D, Lacroix D, Savoye C, et al. Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management. Circulation. 1997;95(8):2098–107. 10. Fernandez-Hidalgo N, Almirante B, Tornos P, Pigrau C, Sambola A, Igual A, Pahissa A. Contemporary epidemiology and prognosis of health care-­associated infective endocarditis. Clin Infect Dis. 2008;47:1287–97. 11. Wang A, Gaca JG, Chu VH.  Management considerations in infective endocarditis: a review. JAMA. 2018;320(1):72–83. 12. Otsugu M, et al. Contribution of streptococcus mutans strains with collagen-binding proteins in the presence of serum to the pathogenesis of infective endocarditis. Infect Immun. 2017;85(12). 13. Madani A, Garakani K, Mofrad MRK.  Molecular mechanics of Staphylococcus aureus adhesin, CNA, and the inhibition of bacterial adhesion by stretching collagen. PLoS One. 2017;12(6):e0179601. 14. Hienz SA, Schennings T, Heimdahl A, Flock J-I.  Collagen binding of Staphylococcus aureus is a virulence factor in experimental endocarditis. J Infect Dis. 1996;174:83–8. pmid: 8656018. 15. DeLorenze GN, Nelson CL, Scott WK, Allen AS, Ray GT, Tsai A-L, et  al. Polymorphisms in HLA Class II genes are associated with susceptibility to Staphylococcus aureus infection in a white population. J Infect Dis. 2016;213:816–23. 16. Klug D, Lacroix D, Savoye C, et al. Systemic infection related to endocarditis on pacemaker leads: clinical presentation and management. Circulation. 1997;95:2098–107.

G. Habib and M. Abellas-Sequeiros 17. Thuny F, Di Salvo G, Belliard O, Avierinos JF, Pergola V, Rosenberg V, Casalta JP, Gouvernet J, Derumeaux G, Iarussi D, Ambrosi P, Calabro R, Riberi A, Collart F, Metras D, Lepidi H, Raoult D, Harle JR, Weiller PJ, Cohen A, Habib G. Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study. Circulation. 2005;112:69–75. 18. Gursul NC, Vardar I, Demirdal T, Gursul E, Ural S, Yesil M.  Clinical and microbiological findings of infective endocarditis. J Infect Dev Ctries. 2016;10(5):478–87. 19. Yu CW, Juan LI, Hsu SC, Chen CK, Wu CW, Lee CC, Wu JY. Role of procalcitonin in the diagnosis of infective endocarditis: a meta-analysis. Am J Emerg Med. 2013;31:935–41. 20. Olmos C, et  al. Risk score for cardiac surgery in active left-sided infective endocarditis. Heart. 2017;103(18):1435–42. 21. Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC guidelines for the management of infective endocarditis: the task force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36:3075–128. 22. Durack DT, Lukes AS, Bright DK.  New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med. 1994;96:200–9. 23. Habib G, Badano L, Tribouilloy C, Vilacosta I, Zamorano JL, On behalf of the European Association of Echocardiography. Recommendations for the practice of echocardiography in infective endocarditis. Eur J Echocardiogr. 2010;11:202–19. 24. Habib G, Derumeaux G, Avierinos JF, et  al. Value and limitations of the Duke criteria for the diagnosis of infective endocarditis. J Am Coll Cardiol. 1999;33:2023–9. 25. Bai AD, 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(7):639–646.e8. 26. Evangelista A, Gonzalez-Alujas MT. Echocar­ diography in infective endocarditis. Heart. 2004;90:614–7. 27. Lambl V.  Papillare exkreszenzen an der semilunar-­ klappe der aorta. Wien Med Wochenschr. 1856;6:244–7. 28. San Roman JA, Lopez J, Vilacosta I, et al. Prognostic stratification of patients with left-sided endocarditis determined at admission. Am J Med. 2007;120:369 e361–7. 29. Lauridsen TK, et  al. Echocardiographic findings predict in-hospital and 1-year mortality in left-sided native valve Staphylococcus aureus endocarditis: analysis from the international collaboration on endocarditis-prospective Echo cohort study. Circ Cardiovasc Imaging. 2015;8(7):e003397.

12  Infective Endocarditis 30. Di Salvo G, Habib G, Pergola V, et  al. Echocar­ diography predicts embolic events in infective endocarditis. J Am Coll Cardiol. 2001;37:1069–76. 31. Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366:2466–73. 32. Tischler MD, Vaitkus PT.  The ability of vegetation size on echocardiography to predict clinical complications: a meta-analysis. J Am Soc Echocardiogr. 1997;10:562–8. 33. Mohananey D, et  al. Association of vegetation size with embolic risk in patients with infective endocarditis: a systematic review and meta-analysis. JAMA Intern Med. 2018;178(4):502–10. 34. Narducci ML, Pelargiono G, Russo E, et al. Usefulness of intracardiac echocardiography for the diagnosis of cardiovascular implantable electronic device-related endocarditis. J Am Coll Cardiol. 2013;61:1398–405. 35. Pfister R, et  al. Three-dimensional compared to two-dimensional transesophageal echocardiography for diagnosis of infective endocarditis. Infection. 2016;44(6):725–31. 36. Sungur A, et  al. The advantages of live/real time three-dimensional transesophageal echocardiography in the assessment of tricuspid valve infective endocarditis. Echocardiography. 2014;31(10):1293–309. 37. Karwhar RB, et  al. Ruptured anterior mitral leaflet aneurysm in aortic valve infective endocarditis— evaluation by three-dimensional echocardiography. Echocardiography. 2014;31(3):E72–6. 38. Feuchtner GM, Stolzmann P, Dichtl W, et  al. Multislice computed tomography in infective endocarditis: comparison with transesophageal echocardiography and intraoperative findings. J Am Coll Cardiol. 2009;53(5):436–44. 39. Fagman E, Perrotta S, Bech-Hanssen O, et al. ECG-­ gated computed tomography: a new role for patients with suspected aortic prosthetic valve endocarditis. Eur Radiol. 2012;22(11):2407–14. 40. Koo HJ, et al. Demonstration of infective endocarditis by cardiac CT and transoesophageal echocardiography: comparison with intra-operative findings. Eur Heart J Cardiovasc Imaging. 2018;19(2):199–207. 41. Kim IC, et  al. Comparison of cardiac computed tomography with transesophageal echocardiography for identifying vegetation and intracardiac complications in patients with infective endocarditis in the era of 3-dimensional images. Circ Cardiovasc Imaging. 2018;11(3):e006986. 42. Hekimian G, Kim M, Passefort S, Duval X, Wolff M, Leport C, Leplat C, Steg G, Iung B, Vahanian A, Messika-Zeitoun D.  Preoperative use and safety of coronary angiography for acute aortic valve infective endocarditis. Heart. 2010;96:696–700. 43. Duval X, Iung B, Klein I, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study. Ann Intern Med. 2010;152:497–504. 44. Snygg-Martin U, Gustafsson L, Rosengren L, et  al. Cerebrovascular complications in patients with left-­

191 sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis. 2008;47:23–30. 45. Iung B, Klein I, Mourvillier B, Olivot JM, Detaint D, Longuet P, Ruimy R, Fourchy D, Laurichesse JJ, Laissy JP, Escoubet B, Duval X.  Respective effects of early cerebral and abdominal magnetic resonance imaging on clinical decisions in infective endocarditis. Eur Heart J Cardiovasc Imaging. 2012;13:703–10. 46. Thuny F, Gaubert JY, Jacquier A, et  al. Imaging investigations in infective endocarditis: current approach and perspectives. Arch Cardiovasc Dis. 2013;106:52–62. 47. Saby L, Laas O, Habib G, et  al. Positron emission tomography/computed tomography for diagnosis of prosthetic valve endocarditis: increased valvular 18F-fluorodeoxyglucose uptake as a novel major criterion. J Am Coll Cardiol. 2013;61:2374–82. 48. Tattevin P, et  al. Update on blood culture-negative endocarditis. Med Mal Infect. 2015;45(1–2):1–8. 49. Botelho-Nevers E, Thuny F, Casalta JP, et al. Dramatic reduction in infective endocarditis-related m ­ ortality with a management-based approach. Arch Intern Med. 2009;169:1290–8. 50. Nishimura RA, Otto CM, Bonow RO, et  al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2014;63:2438–88. 51. Tornos P, Iung B, Permanyer-Miralda G, Baron G, Delahaye F, Gohlke-Barwolf C, Butchart EG, Ravaud P, Vahanian A.  Infective endocarditis in Europe: lessons from the Euro Heart Survey. Heart. 2005;91:571–5. 52. Vikram HR, Buenconsejo J, Hasbun R, Quagliarello VJ. Impact of valve surgery on 6-month mortality in adults with complicated, left-sided native valve endocarditis. A propensity analysis. JAMA. 2003;290:3207–14. 53. Bashore TM, Cabell C, Fowler V Jr. Update on infective endocarditis. Curr Probl Cardiol. 2006;31:274–352. 54. Steinbach WJ, Perfect JR, Cabell CH, et al. A meta-­ analysis of medical versus surgical therapy for Candida endocarditis. J Infect. 2005;51(3):230247. 55. Arnold CJ, Johnson M, Bayer AS, et al. Candida infective endocarditis: an observational cohort study with a focus on therapy. Antimicrob Agents Chemother. 2015;59(4):2365–73. 56. Chirouze C, Alla F, Fowler VG Jr, et  al. Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study. Clin Infect Dis. 2015;60(5):741–9. 57. Sohail MR, Martin KR, Wilson WR, Baddour LM, Harmsen WS, Steckelberg JM.  Medical

192 versus surgical management of Staphylococcus aureus prosthetic valve endocarditis. Am J Med. 2006;119(2):147–54. 58. Garcia-Cabrera E, Fernandez-Hidalgo N, Almirante B, et  al. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation. 2013;127:2272–84. 59. Iung B, Rousseau-Paziaud J, Cormier B, et  al. Contemporary results of mitral valve repair for infective endocarditis. J Am Coll Cardiol. 2004;43:386–92. 60. Duval X, Iung B, Klein I, Brochet E, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study. Ann Intern Med. 2010;152:497–504, W175.

G. Habib and M. Abellas-Sequeiros 61. Cooper HA, Thompson EC, Laureno R, et  al. Subclinical brain embolization in left-sided infective endocarditis: results from the evaluation by MRI of the brains of patients with left-sided intracardiac solid masses (EMBOLISM) pilot study. Circulation. 2009;120:585–91. 62. Iung B, Tubiana S, Klein I, et  al. Determinants of cerebral lesions in endocarditis on systematic cerebral magnetic resonance imaging: a prospective study. Stroke. 2013;44:3056–62. 63. Tubiana S, et al. Dental procedures, antibiotic prophylaxis, and endocarditis among people with prosthetic heart valves: nationwide population based cohort and a case crossover study. BMJ. 2017; 358:j3776.

Multiple Valve Disease

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Philippe Unger and Mauro Pepi

Etiology and Prevalence Multiple valvular heart disease (MVD) is a highly prevalent condition, affecting 20% of all patients with native valve disease included in the Euro Heart Survey [1]. In a Swedish nationwide study, 11% of all patients with a first diagnosis of valvular heart disease presented with MVD [2]. Moreover, 17% of the patients undergoing intervention in the Euro Heart Survey had MVD [1]. In the Society of Thoracic Surgeons Database, 11% of all valvular surgeries were double valve procedures [3]. However, the heterogeneity of these conditions in terms of combinations, etiology, severity, surgical risk, reparability, and suitability for transcatheter therapies likely limits the availability of data and, therefore, contributes to the low level of evidence supporting the decision-making. Most MVD are acquired, mainly resulting from rheumatic fever and degenerative etiologies (Fig.  13.1) [4, 5]. Much lesser commonly, it may result from infective endocarditis, radiation therapy, drug-induced valvular disease, and

P. Unger (*) Université Libre de Bruxelles, CHU Saint-Pierre, Brussels, Belgium e-mail: [email protected] M. Pepi Department of Cardiovascular Imaging, Centro Cardiologico Monzino IRCCS, Milan, Italy e-mail: [email protected]

inflammatory diseases. As a consequence of ageing and of the overall decrease incidence of rheumatic fever, degenerative etiologies become increasingly prevalent in industrialized countries. Downstream valvular lesions may induce secondary mitral regurgitation (MR) and tricuspid regurgitation (TR). Although quite unusual, significant pulmonary regurgitation (PR) may occur, as a result from endocarditis or carcinoid disease, and, even more rarely, from left-sided valvular disease-related pulmonary hypertension. Because of the high prevalence of coronary artery disease and remote myocardial infarction in patients with degenerative valvular disease, ischemic MR is not uncommon in patients with aortic valve disease. Congenital etiologies are by far less frequent than acquired etiologies [4].

Pathophysiology and Diagnosis Hemodynamic and clinical consequences of a single valvular lesion may vary according to the concomitant presence of a stenotic or regurgitant lesion on another valve [4]. Several factors, including the specific combination of MVD, the severity and timing of onset of each individual lesion, the loading conditions, and the ventricular systolic and diastolic performance may modulate the expression of these lesions. As in single valve disease, Doppler-­ echocardiography is the cornerstone of the diagnosis and, hence, of the management of MVD.

© Springer Nature Switzerland AG 2020 J. Zamorano et al. (eds.), Heart Valve Disease, https://doi.org/10.1007/978-3-030-23104-0_13

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194 Fig. 13.1 Degenerative calcified mitral and aortic valve disease observed in an elderly patient (systolic and diastolic frames, Panel a and b, respectively), and rheumatic valve disease in a young patient (systolic and diastolic frames, Panel c and d, respectively)

A

B

C

D

It provides detailed and non-invasive information about the etiology, mechanisms, severity, progression and repercussions of each valvular lesion, and thus contributes to determine the indication and timing for intervention, as well as the choice of therapeutic procedure (surgical versus transcatheter approach). However, several methods routinely used to assess valvular disease have only been validated in single valve disease. If not correctly interpreted, echocardiography may be misleading in the setting of MVD.  The main hemodynamic interactions and consequences of MVD, that may impact the echocardiographic diagnosis, are as follows: (1) Low flow, low gradient stenosis is frequent in the setting of MVD; (2) The continuity equation is inapplicable when transvalvular flows are unequal; (3) Any severe valvular lesion may induce or increase upstream MR and/or TR; and (4) Pressure half-time- derived methods may be invalid in the presence of altered left ventricular diastolic properties due to another valvular disease. The main diagnostic pitfalls are presented in Table 13.1 [4]. When non-invasive evaluation is inconclusive or discordant with clinical findings, cardiac catheterization remains a recommended alternative

[6]. However, in patients with severe TR and/or with very low cardiac output, the calculation of aortic or of mitral valve area may be inaccurate with the Gorlin formula using cardiac output assessment by either the thermodilution or the Fick method [7]. When conventional echocardiography is inconclusive, other imaging modalities can be helpful. However, there is currently only limited data supporting a role for multimodality imaging in the setting of MVD.  Alternative techniques may prove useful in selected challenging cases, particularly in the setting of low flow states. These include three-dimensional echocardiography, low dose dobutamine stress echocardiography, and multidetector computed tomography (MDCT). In patients with inadequate acoustic windows or in case of discrepant results, cardiac magnetic resonance (CMR) allows to assess the severity of valvular lesions, particularly in regurgitant lesions, as well as ventricular volumes and systolic function [8]. However, similarly to echocardiography, the assessment of regurgitant fraction and volume by calculating ventricular volumes may be inaccurate in the presence of MVD, as it assumes that only one valve is affected [9].

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13  Multiple Valve Disease Table 13.1  Main diagnostic caveats in the echocardiographic diagnosis of multiple valve disease

Aortic stenosis

Aortic regurgitation

Mitral stenosis Mitral regurgitation

Might impair the diagnosis of Mitral stenosis MS pressure half-time method unreliable Low-flow, low-gradient mitral stenosis can occur Aortic regurgitant jet can be mistaken for mitral stenosis jet Continuity equation is unreliable to calculate mitral valve area if aortic valve is used as the reference flow MS pressure half-time method unreliable Aortic stenosis Low-flow, low-gradient aortic stenosis is common Low-flow, low-gradient aortic stenosis is common Mitral regurgitant jet should not be mistaken for the aortic stenosis jet

Mitral regurgitation Increased mitral regurgitant volume Increased area of mitral regurgitant jet using colour-flow mapping Mitral effective regurgitant orifice less affected than mitral regurgitant volume and colour-flow mapping parameters Doppler volumetric method using left-sided assessment of net forward flow invalid Mitral to aortic velocity time integral ratio unreliable

Aortic regurgitation MS can blunt the increase in pulse pressure and the LV dilation associated with AR Doppler volumetric method using left-sided assessment of net forward flow invalid Pressure half-time method can be unreliable

This table presents the caveats in the echocardiographic diagnosis of a given valvular lesion (horizontal rows) in presence of concomitant valvular lesion (vertical columns)

 ortic Stenosis and Mitral A Regurgitation The long-standing increased afterload associated with severe aortic stenosis (AS) may eventually result in LV dilatation, dysfunction, and hypertrophic remodeling. These morphological and functional changes may lead to mitral leaflet tethering and mitral annular dilatation, and thus, promote the development of secondary MR.  In addition, concomitant coronary artery disease is highly prevalent in the elderly, and the combination of aortic valve disease and ischemic MR is not uncommon. Primary MR may result from degenerative and calcified mitral valve disease whose prevalence is also high in the elderly [10]. Less frequently, mitral valve prolapse may occur in patients with severe degenerative AS. AS and MR jets should be differentiated. MR jet has a higher velocity than the AS jet, and includes the isovolumic contraction and relaxation periods, therefore starting earlier and lasting longer than the latter (Fig. 13.2, top panel).

AS increases LV systolic pressure, and, therefore, the systolic pressure gradient across the mitral valve also increases, resulting in a higher mitral regurgitant volume and a larger colour-­flow mapping area, whereas mitral regurgitant orifice is usually lesser affected [11]. In addition, significant MR may decrease the net forward flow, thereby reducing the transaortic pressure gradient, and, among patients with AS and normal LV ejection fraction, is independently associated with low flow [12]. Three-dimensional echocardiography and MDCT may provide more accurate left ventricular outflow tract assessment, and thereby can be used to improve the accuracy of aortic valve area assessment [13]. Dobutamine stress echocardiography (if ejection fraction is reduced) and aortic valve calcium scoring by MDCT (if ejection fraction is preserved) can be used to distinguish true severe from pseudo-­severe AS and to confirm its severity. A calcium scores of >2000 AU in men and >1200 AU in women are strongly suggestive of severe AS [6]. A typical example of a patient with a low flow state associated with coexistent MR in whom MDCT allowed to confirm severe AS is presented in Fig. 13.3.

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Fig. 13.2  Continuous wave Doppler flows recorded from the apex in a patient presenting a combination of mixed aortic valve disease and mixed mitral valve disease. Top panel: aortic flow demonstrating the timing of anterograde (peak aortic velocity 4 m/s) and regurgitant flows. Lower panel: mitral flow recorded from the apex, demonstrating

the timing of mitral regurgitation (peak systolic velocity: 6.8 m/s) and forward flow. Unlike regurgitant flows, aortic and mitral forward flows do not include the isovolumic contraction and relaxation periods (red and yellow asterisks, respectively)

Aortic Stenosis and Mitral Stenosis

used to measure mitral valve anatomic area and confirm MS severity [14].

The reduction in cardiac output, observed in combined AS and mitral stenosis (MS), is usually greater than what is seen in isolated AS or MS, and this infrequent combination is usually poorly tolerated. Due to their mutual effect, stroke volume may be markedly reduced and, hence, both aortic and mitral pressure gradients may be lower than expected even if LV ejection fraction is preserved. In this situation, aortic valve calcium scoring by MDCT can be used to confirm AS severity. Due to altered LV diastolic properties, the pressure half-time method is unreliable for assessing mitral valve area. In the absence of concomitant MR and/or AR, the assessment of mitral valve area should include the use of the continuity equation. In selected patients, 3D echocardiography can be

 ortic Regurgitation and Mitral A Stenosis MS and AR induce opposed effects on LV preload. Indeed, preload is decreased by MS, while it is increased by AR. Hence, LV volumes [15], stroke volume, and regurgitant volume may be lower than in isolated AR [16], which may blunt the typical clinical signs of AR. AR and MS jets should be differentiated. The AR jet has a higher velocity than the MS jet and includes the isovolumic relaxation and contraction periods, and therefore starts earlier and lasts longer than the latter (Fig.  13.2, lower panel). Both the continuity equation and

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a

b

f c

d

e

Fig. 13.3 Panel a: Mid-systolic transthoracic echocardiographic parasternal long-axis view showing severe mitral regurgitation due to mitral valve prolapse. Left ventricular (LV) ejection fraction is 70%. The aortic valve is severely calcified (Panel b). Panel c shows the continuous wave Doppler interrogation of the aortic valve, with a 26 mmHg mean pressure gradient and a 340 cm/s maximal velocity. With a LVOT diameter of 21 mm (Panel d) and a LVOT velocity-time integral of 13.7 cm by pulsed wave Doppler (Panel e), the calculated forward stroke vol-

ume in the LVOT is 47 mL (indexed stroke volume 30 mL/ m2), consistent with a low flow state. Aortic valve area is 0.61 cm2. Panel f: Non-contrast multi-detector computed tomography shows severe valve calcification (aortic valve calcium score 4500 AU), consistent with true severe aortic stenosis. Thus, computed tomography allows confirming true severe paradoxical aortic stenosis, with the low gradient and the low flow state being related to the coexistence of severe mitral regurgitation

the pressure half-time method to assess mitral valve area are unreliable in this setting. 3D echocardiography may be useful to determine MS severity [17].

although LV function may improve after surgery [20], persisting symptoms are more frequent than in patients operated for isolated AR.  Survival rates are lower in combined AVR and MVR compared to patients operated for isolated symptomatic MR [21]. Both Doppler volumetric methods using left-­ sided assessment of forward flow and cardiac magnetic resonance imaging using volumetric methods are invalid in this setting.

 ortic Regurgitation and Mitral A Regurgitation Aortic regurgitation (AR) and MR both contribute to volume overload, which may result in marked LV dilatation and dysfunction [18]. Currently, normal mitral valve competence protects the left atrium from the deleterious effects of increased LV pressure in patients with AR.  However, the presence of concomitant MR may contribute to poor clinical tolerance, resulting in pressure overload on left atrium, pulmonary circulation and right heart chambers. Postoperative LV dysfunction is frequent after AVR for AR [19], and

 ricuspid Regurgitation and T Left-­Sided VHD Secondary TR is highly prevalent among patients presenting with left-sided VHD, and may occur as a result of mitral and of aortic valve disease [22, 23]. Secondary TR impacts both long-term functional capacity and survival after treatment of the

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left-sided VHD [23]. In the setting of downstream VHD, many factors including pulmonary hypertension, atrial fibrillation, right ventricular dilatation and dysfunction, leaflet tethering, annular dilatation towards the right ventricular free wall, and/ or right atrial enlargement may contribute to the occurrence and severity of TR. TR is highly sensitive to changes in loading conditions; therefore, rather than TR severity itself, annular dilatation and leaflet coaptation might be better predictors for the subsequent development of TR [24, 25].

Management Strategy Current evidence on the management of MVD is limited, and most American Heart Association/ American College of Cardiology (AHA/ACC)

and European Society of Echocardiography/ European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines have been given a C level of evidence [6, 26, 27]. The number of possible combinations, and the heterogeneity in terms of etiology and severity currently preclude a standardized approach, and the management of these patients remains particularly challenging. Nevertheless, three main clinical scenarios may be encountered [28] (Fig. 13.4): 1. When two or more severe lesions are present, the likelihood of severe functional intolerance is high if one of the lesions is left untreated, and all severe lesions are usually being addressed. Current ACC/AHA guidelines on the management of VHD have given to severe AS, AR, MS, primary MR, TR and TS a class

Clinical scenarios

³ 2 severe lesions

One severe and ³ 1 non severe lesion

³ 2 non severe lesions

Is the patient symptomatic? Are valvular lesions causing these symptoms? Are there repercussions (LV/RV systolic dysfunction, pulmonary hypertension, atrial fibrillation)? Heart team Surgical risk score Frailty Natural history of unoperated valve(s) Age Likelihood and risk of reintervention Assess the indication and select the type and the timing of valve procedure(s) Feasibility of Transcatheter approaches?

Double valve procedure usually considered

Severe valvular lesion: follow current recommendations for single valve lesion Non severe lesion(s): case-by-case management

Case-by-case management determinedby the global consequences of all lesions

Fig. 13.4  Clinical scenarios and decision-making in the management of patients with multiple valve disease

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I recommendation for concomitant procedure while undergoing other cardiac surgery [26, 27], whereas mitral valve surgery for severe secondary MR (stage C and D) in patients undergoing aortic valve replacement has received a class of recommendation IIa [27]. Similarly, 2017 ESC/EACTS guidelines have given a class of recommendation I for concomitant valve surgery in patients with severe AS, AR, secondary MR and TR [6]. 2 . When one severe lesion is associated with one or more non-severe lesion(s), the most severely diseased valve should be managed

according to current guidelines. However, the management of the less-than severe lesion(s) is less straightforward, and, in most situations, a class II recommendation has been given for intervention [6, 26, 27] (Table 13.2). 3 . Two or more moderate lesions may induce a significant overall hemodynamic burden and may cause symptoms and/or LV systolic dysfunction. The exact prevalence of this scenario is unknown, and it is not covered by current guidelines. Before considering intervention, it is of particular importance to determine the global consequences of all lesions, which may

Table 13.2  Indications for concomitant valve surgery on a less than severe valve lesion in patients undergoing surgery on another valve, according to the AHA/ACC and ESC/EACTS guidelines [6, 26, 27] Valve lesion Moderate AS

Moderate AR

2014–2017 AHA/ACC guidelines AVR is reasonable for patients who are undergoing other cardiac surgery (Class IIa, LOE C)

AVR is reasonable in patients who are undergoing other cardiac surgery (Class IIa, LOE C) Moderate MS Concomitant mitral valve surgery may be considered for patients undergoing other cardiac surgery (Class IIb, level of evidence C) Moderate MR Concomitant MV repair is reasonable in patients with chronic moderate primary MR (stage B) undergoing cardiac surgery for other indications (Class IIa, LOE C) MV repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery (Class IIb, LOE C) Non-­severe Tricuspid valve repair can be beneficial for TR patients with mild, moderate, or greater functional TR (stage B) at the time of left-sided valve surgery with either (1) tricuspid annular dilation or (2) prior evidence of right heart failure (Class IIa, LOE B) Tricuspid valve repair may be considered for patients with moderate functional TR (stage B) and pulmonary artery hypertension at the time of left-sided valve surgery (Class IIb, LOE C) Non severe Not mentioned TS

2017 ESC/EACTS guidelines SAVR should be considered in patients undergoing surgery of the ascending aorta or another valve, after heart team decision (Class IIa, LOE C) In cases with severe MS, PMC can be performed in order to postpone the surgical treatment of both valves Not mentioned

Not mentioned

Primary MR: not mentioned The potential impact of mitral valve intervention (surgery and catheter intervention) on survival in patients with secondary MR needs to be evaluated

Surgery should be considered in patients with moderate primary TR undergoing left-sided valve surgery (Class IIa, LOE C) Surgery should be considered in patients with mild or moderate secondary TR with dilated annulus (≥40 mm or >21 mm/m2) undergoing left-sided valve surgery (Class IIa, LOE C) Surgery may be considered in patients undergoing left-sided valve surgery with mild or moderate secondary TR, even in the absence of annular dilatation when previous recent right-heart failure has been documented (Class IIb, LOE C) Not mentioned

AS aortic stenosis, AR aortic regurgitation, MS mitral stenosis, MR mitral regurgitation, TR tricuspid regurgitation, TS tricuspid stenosis, AVR aortic valve replacement, PMC percutaneous mitral commissurotomy, MV mitral valve, LOE level of evidence

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include the assessment of natriuretic peptides levels, of maximal exercise capacity and of peak oxygen consumption, in addition to conventional imaging parameters.

• The natural history of an untreated valve may help to predict the likelihood and timing of a potential reoperation [31]. For instance, the progression rates of moderate AS are faster in patients with degenerative disease [32–35] than in those with rheumatic or congenital AS Decision-Making in MVD, [36–38] as well as in patients with higher degree of valvular calcifications and higher and the Role of the Heart Team degree of severity [35, 38]. The progression European guidelines recommend a Heart Team-­ rate of isolated AR is low, in particular in based management strategy [6] and highlight the rheumatic AR [37, 39, 40]. The rate of proimportance of a collaborative multidisciplinary gression of MS of rheumatic etiology is highly inpatient team approach including cardiolovariable, but is faster with higher transmitral gists and cardiac surgeons in the setting of Heart pressure gradient and echocardiographic Valve Centers [29], linked to dedicated and strucscores [41, 42]. Importantly, the expected protured outpatient Heart Valve Clinics [30]. The gression rate of the non-severe lesion should decision-­making in patients with MVD should be balanced again the estimated life expecinclude imaging and clinical factors and has to tancy, but inter-individual variability is high, be individually tailored. For instance, whether and unexpected progression rate may occur or not leaving unoperated a less-than-severe (Fig. 13.5). valve lesion at the time of treating another valve • Treatment of a downstream valve lesion may requires the integration of numerous factors, impact the severity of MR and/or TR.  Even which include the followings: severe MR may improve following surgical or

a

d

b

e

Fig. 13.5  At the time of mitral valve repair, this patient presented mild aortic regurgitation. Despite excellent mitral valve repair results (Panel a: normal diastolic opening of the MV valve; Panels b and c: trivial residual mitral regurgitation), moderate to severe aortic regurgitation

c

f

developed during a 10  years follow up (Panel d and e: 3-Chamber apical TTE views showing aortic regurgitant jet; Panel f: Continuous wave Doppler demonstrating an aortic regurgitation slope of 3.5 m/s

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transcatheter aortic valve replacement (TAVR). Although the degree of severity of secondary MR tends to decrease after aortic valve replacement—particularly in the absence of pulmonary hypertension, of left atrial dilatation, of atrial fibrillation and of low aortic mean gradient-, individual responses may be variable, and pre-procedural identification of the responders remains challenging (Fig.  13.6) [43]. A marked decrease in MR severity is unlikely for primary degenerative MR. • Secondary TR is highly load-dependent. However, the presence of tricuspid annular dilatation despite moderate or lesser degrees of TR at the time of left-sided valve surgery is associated with a risk of TR progression and of redo surgery for severe TR. This has led to lower down the threshold for performing concomitant restrictive ring annuloplasty ­ repair, despite limited evidence supporting

Fig. 13.6  Examples of improvement (Panel a and b) and of deterioration in mitral regurgitation post TAVR (Panel c and d)

current recommendations (Fig. 13.7). In addition to annular dilatation, evidence of right heart failure, leaflet tethering and atrial fibrillation should also be considered in the decision-­making. Similarly, TR may spontaneously improve after transcatheter pulmonary valve replacement but predictors and long-term durability of this improvement remain largely unknown [44]. • The individual surgical risk profile markedly influences the decision-making. Improved perioperative and postoperative care achieved in the last decades have contributed to better long-term survival after multiple valve surgery [45], but operative mortality of double valve replacement remains on average two-­ ­ fold greater than that of single valve replacement [1, 3, 46–48]. Several risk factors influencing the operative risk and outcomes after multiple valve surgery have been identified, which include age, New  York Heart

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P. Unger and M. Pepi

202 Fig. 13.7 Panel a: Moderate tricuspid regurgitation detected by color flow Doppler in apical 4 chamber view obtained in a patient with severe mitral regurgitation due to mitral valve prolapse. Panel b: End-diastolic tricuspid annulus measures 40 mm. This clinical situation represents a class IIa indication for concomitant tricuspid annuloplasty according to both the AHA/ACC and ESC/EACTS guidelines

a

Association class IV, pulmonary hypertension, reduced LV ejection fraction, atrial fibrillation, emergency presentation, reoperation and associated coronary artery disease [45, 46, 49–51]. Noticeably, both the Society of Thoracic Surgeons scoring system and EuroSCORE II have been shown to reliably assess operative mortality for single-valve surgery [52, 53], but their role in multiple valve surgery have not been validated [52]. • The possibility of valve repair and the feasibility of transcatheter approaches should be evaluated. Mitral valve repair plus aortic valve replacement has been shown in some series to lower operative mortality and to improve late survival as compared to double-valve replacement [54] but this observation was not confirmed by others [55]. Therefore, repairing or replacing mitral valve in patients undergoing aortic valve surgery remains a matter of debate. As in single valve disease, a “case by case” management strategy should be followed, considering: valve anatomy and likelihood of successful and durable valve repair, the availability of surgical expertise, and patient’s condition [6]. The role of transcatheter interventions in MVD is currently ill-defined. Small series on highly selected patients have shown the feasibil-

b

ity of combining TAVR and percutaneous edge-­ to-­edge procedure, usually as staged procedures (Fig. 13.8). More recently, there has been some experience of concomitant TR and MR correction with the percutaneous edge-to-edge procedure [56]. The time delay between the two procedures might be longer for secondary as compared to primary MR, as further MR improvement may occur several months after the TAVR procedure. Patients whose severe MR persists after TAVR and presenting favorable ­ anatomic conditions might benefit from percutaneous mitral procedures (Fig. 13.8) [57]. TAVI is usually targeted at degenerative AS and percutaneous mitral commissurotomy at rheumatic MS.  Therefore, there is usually no indication for combining these two procedures. Preliminary reports have shown the feasibility of transcatheter mitral valve implantation in highly selected patients with MS or MR presenting with extensive mitral valve calcifications who had undergone previous aortic valve replacement [58]. Transcatheter implantation of both aortic and mitral valves might become an option for the treatment of severe degenerative AS and MS in patients with a prohibitive surgical risk [56, 59, 60]. Percutaneous mitral commissurotomy may be indicated in patients with severe MS and moderate aortic valve disease, thereby allow-

13  Multiple Valve Disease

a

203

Numerous new percutaneous techniques addressing mitral, aortic, and tricuspid VHD are currently under development and will likely change the therapeutic paradigm, but further studies are needed to clarify their respective role.

References

b

c

Fig. 13.8  MitraClip procedure in a patient with persisting symptomatic severe mitral regurgitation due to flail anterior mitral leaflet after a TAVR procedure (Panel a), with minimal residual mitral regurgitation (Panel b). Panel c: fluoroscopic appearance of the aortic valvular prosthesis and of the MitraClip

ing postponing surgery. Although current guidelines list severe TR among unfavorable anatomical characteristics for performing percutaneous mitral commissurotomy [6], this procedure might be considered in patients presenting contraindications to- or being at high risk for- surgery.

1. Iung B, Baron G, Butchart EG, et  al. A prospective survey of patients with valvular heart disease in Europe: the euro heart survey on valvular heart disease. Eur Heart J. 2003;24:1231–43. 2. Andell P, Li X, Martinsson A, et  al. Epidemiology of valvular heart disease in a Swedish nationwide hospital-­ based register study. Heart. 2017;103:1696–703. 3. Lee R, Li S, Rankin JS, et  al. Society of Thoracic Surgeons Adult Cardiac Surgical Database. Fifteen-­ year outcome trends for valve surgery in North America. Ann Thorac Surg. 2011;91:677–84. 4. Unger P, Rosenhek R, Dedobbeleer C, Berrebi A, Lancellotti P. Management of multiple valve disease. Heart. 2011;97:272–7. 5. Iung B, Baron G, Tornos P, Gohlke-Bärwolf C, Butchart EG, Vahanian A.  Valvular heart disease in the community: a European experience. Curr Probl Cardiol. 2007;32:609–61. 6. Baumgartner H, Falk V, Bax JJ, et  al. 2017 ESC/ EACTS guidelines for the management of valvular heart disease: the task force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017;38:2739–91. 7. van Grondelle A, Ditchey RV, Groves BM, Wagner WW Jr, Reeves JT.  Thermodilution method overestimates low cardiac output in humans. Am J Physiol. 1983;245:H690–2. 8. American College of Cardiology Foundation Task Force on Expert Consensus Documents, Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA, Friedrich MG, Ho VB, Jerosch-Herold M, Kramer CM, Manning WJ, Patel M, Pohost GM, Stillman AE, White RD, Woodard PK.  ACCF/ACR/AHA/ NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation task force on expert consensus documents. Circulation. 2010;121:2462–508. 9. Cawley PJ, Maki JH, Otto CM.  Cardiovascular magnetic resonance imaging for valvular heart disease: technique and validation. Circulation. 2009;119:468–78. 10. Abramowitz Y, Jilaihawi H, Chakravarty T, Mack MJ, Makkar RR. Mitral annulus calcification. J Am Coll Cardiol. 2015;66:1934–41.

204 11. Unger P, Plein D, Van Camp G, Cosyns B, Pasquet A, Henrard V, de Cannière D, Melot C, Piérard LA, Lancellotti P.  Effects of valve replacement for aortic stenosis on mitral regurgitation. Am J Cardiol. 2008;102:1378–82. 12. Leong DP, Pizzale S, Haroun MJ, et al. Factors associated with low flow in aortic valve stenosis. J Am Soc Echocardiogr. 2016;29:158–65. 13. Baumgartner H, Hung J, Bermejo J, Chambers JB, Edvardsen T, Goldstein S, Lancellotti P, LeFevre M, Miller F Jr, Otto CM. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18:254–75. 14. Wunderlich NC, Beigel R, Siegel RJ. Management of mitral stenosis using 2D and 3D echo-Doppler imaging. JACC Cardiovasc Imaging. 2013;6:1191–205. 15. Gash AK, Carabello BA, Kent RL, Frazier JA, Spann JF.  Left ventricular performance in patients with coexistent mitral stenosis and aortic insufficiency. J Am Coll Cardiol. 1984;3:703–11. 16. Cohn LH, Mason DT, Ross J Jr, Morrow AG, Braunwald E.  Preoperative assessment of aortic regurgitation in patients with mitral valve disease. Am J Cardiol. 1967;19:177–82. 17. Flachskampf FA, Weyman AE, Gillam L, Liu CM, Abascal VM, Thomas JD. Aortic regurgitation shortens Doppler pressure half-time in mitral stenosis: clinical evidence, in  vitro simulation and theoretic analysis. J Am Coll Cardiol. 1990;16:396–404. 18. Shine KI, DeSanctis RW, Sanders CA, Austen WG. Combined aortic and mitral incompetence: clinical features and surgical management. Am Heart J. 1968;76:728–35. 19. Gentles TL, Finucane AK, Remenyi B, Kerr AR, Wilson NJ. Ventricular function before and after surgery for isolated and combined regurgitation in the young. Ann Thorac Surg. 2015;100:1383–9. 20. Skudicky D, Essop MR, Sareli P.  Time-related changes in left ventricular function after double valve replacement for combined aortic and mitral regurgitation in a young rheumatic population. Predictors of postoperative left ventricular performance and role of chordal preservation. Circulation. 1997;95:899–904. 21. Niles N, Borer JS, Kamen M, Hochreiter C, Devereux RB, Kligfield P. Preoperative left and right ventricular performance in combined aortic and mitral regurgitation and comparison with isolated aortic or mitral regurgitation. Am J Cardiol. 1990;65:1372–8. 22. Dreyfus GD, Corbi PJ, Chan KMJ, Bahrami T.  Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair? Ann Thorac Surg. 2005;79:127–32. 23. Dumont C, Galli E, Oger E, Fournet M, Flecher E, Leclercq C, Verhoye JP, Donal E.  Pre- and postoperative tricuspid regurgitation in patients with severe symptomatic aortic stenosis: importance of

P. Unger and M. Pepi pre-operative tricuspid annulus diameter. Eur Heart J Cardiovasc Imaging. 2018;19:319–28. 24. Lindman BR, Maniar HS, Jaber W, et  al. Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the PARTNER II inoperable cohort. Circ Cardiovasc Interv. 2015;8:e002073. 25. Dreyfus GD, Martin RP, Chan KM, Dulguerov F, Alexandrescu C. Functional tricuspid regurgitation: a need to revise our understanding. J Am Coll Cardiol. 2015;65:2331–6. 26. Nishimura RA, Otto CM, Bonow RO, et  al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521–643. 27. Nishimura RA, Otto CM, Bonow RO, et  al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2017;135:e1159–95. 28. Unger P, Clavel MA, Lindman BR, Mathieu P, Pibarot P. Pathophysiology and management of multivalvular disease. Nat Rev Cardiol. 2016;13:429–40. 29. Chambers JB, Prendergast B, Iung B, Rosenhek R, Zamorano JL, Piérard LA. Standards defining a ‘Heart Valve Centre’: ESC Working Group on Valvular Heart Disease and European Association for Cardiothoracic Surgery Viewpoint. Eur Heart J. 2017;38:2177–83. 30. Lancellotti P, Rosenhek R, Pibarot P, et  al. ESC Working Group on Valvular Heart Disease position paper-heart valve clinics: organization, structure, and experiences. Eur Heart J. 2013;34:1597–606. 31. Fukunaga N, Okada Y, Konishi Y, et al. Clinical outcomes of redo valvular operations: a 20-year experience. Ann Thorac Surg. 2012;94:2011–6. 32. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95:2262–70. 33. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation. 2010;121:151–6. 34. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343:611–7. 35. Rosenhek R, Klaar U, Schemper M, et al. Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. Eur Heart J. 2004;25:199–205. 36. Wagner S, Selzer A.  Patterns of progression of aortic stenosis: a longitudinal hemodynamic study. Circulation. 1982;65:709–12. 37. Vaturi M, Porter A, Adler Y, et al. The natural history of aortic valve disease after mitral valve surgery. J Am Coll Cardiol. 1999;33:2003–8.

13  Multiple Valve Disease 38. Tastet L, Enriquez-Sarano M, Capoulade R, et  al. Impact of aortic valve calcification and sex on hemodynamic progression and clinical outcomes in aortic stenosis. J Am Coll Cardiol. 2017;69:2096–8. 39. Weisenberg D, Omelchenko A, Shapira Y, et al. Mid-­ term echocardiographic progression of patients with moderate aortic regurgitation: implications for aortic valve surgery. J Heart Valve Dis. 2013;22:192–4. 40. Borer JS, Bonow RO.  Contemporary approach to aortic and mitral regurgitation. Circulation. 2003;108:2432–8. 41. Gordon SP, Douglas PS, Come PC, Manning WJ.  Two-dimensional and Doppler echocardiographic determinants of the natural history of mitral valve narrowing in patients with rheumatic mitral stenosis: implications for follow-up. J Am Coll Cardiol. 1992;19:968–7. 42. Sagie A, Freitas N, Padial LR, et  al. Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: valve area and right heart disease. J Am Coll Cardiol. 1996;28:472–9. 43. Nombela-Franco L, Ribeiro HB, Urena M, et  al. Significant mitral regurgitation left untreated at the time of aortic valve replacement: a comprehensive review of a frequent entity in the transcatheter aortic valve replacement era. J Am Coll Cardiol. 2014;63:2643–58. 44. Jones TK, Rome JJ, Armstrong AK, et al. Transcatheter pulmonary valve replacement reduces tricuspid regurgitation in patients with right ventricular volume/pressure overload. J Am Coll Cardiol. 2016;68:1525–35. 45. Alsoufi B, Rao V, Borger MA, et al. Short- and long-­ term results of triple valve surgery in the modern era. Ann Thorac Surg. 2006;81:2172–7. 46. Rankin JS, He X, O’Brien SM, et al. The Society of Thoracic Surgeons risk model for operative mortality after multiple valve surgery. Ann Thorac Surg. 2013;95:1484–90. 47. Vassileva CM, Li S, Thourani VH, et  al. Outcome characteristics of multiple-valve surgery: comparison with single-valve procedures. Innovations (Phila). 2014;9:27–32. 48. Hannan EL, Racz MJ, Jones RH, et  al. Predictors of mortality for patients undergoing cardiac valve replacements in New  York state. Ann Thorac Surg. 2000;70:1212–8. 49. Leavitt BJ, Baribeau YR, DiScipio AW, et  al.; Northern New England Cardiovascular Disease Study Group. Outcomes of patients undergoing concomi-

205 tant aortic and mitral valve surgery in northern new England. Circulation. 2009;120(11 Suppl):S155–62. 50. Schulenberg R, Antonitsis P, Stroebel A, Westaby S. Chronic atrial fibrillation is associated with reduced survival after aortic and double valve replacement. Ann Thorac Surg. 2010;89:738–44. 51. Akay TH, Gultekin B, Ozkan S, et  al. Triple-­ valve procedures: impact of risk factors on midterm in a rheumatic population. Ann Thorac Surg. 2006;82:1729–34. 52. Guida P, Mastro F, Scrascia G, Whitlock R, Paparella D.  Performance of the European system for cardiac operative risk evaluation II: a meta-analysis of 22 studies involving 145,592 cardiac surgery procedures. J Thorac Cardiovasc Surg. 2014;148:3049–57. 53. Osnabrugge RL, Speir AM, Head SJ, et al. Performance of EuroSCORE II in a large US database: implications for transcatheter aortic valve implantation. Eur J Cardiothorac Surg. 2014;46:400–8. 54. Gillinov AM, Blackstone EH, Cosgrove DM III, et al. Mitral valve repair with aortic valve replacement is superior to double valve replacement. J Thorac Cardiovasc Surg. 2003;125:1372–87. 55. Coutinho GF, Correia PM, Antunes MJ. Concomitant aortic and mitral surgery: to replace or repair the mitral valve? J Thorac Cardiovasc Surg. 2014;148:1386–92. 56. Ando T, Takagi H, Briasoulis A, Telila T, Slovut DP, Afonso L, Grines CL, Schreiber T.  A systematic review of reported cases of combined transcatheter aortic and mitral valve interventions. Catheter Cardiovasc Interv. 2018;91:124–34. 57. Cortés C, Amat-Santos IJ, Nombela-Franco L, et al. Mitral regurgitation after transcatheter aortic valve replacement: prognosis, imaging predictors, and potential management. JACC Cardiovasc Interv. 2016;9:1603–14. 58. Guerrero M, Dvir D, Himbert D, et al. Transcatheter mitral valve replacement in native mitral valve disease with severe mitral annular calcification: results from the first multicenter global registry. JACC Cardiovasc Interv. 2016;9:1361–71. 59. Witkowski A, Kuśmierski K, Chmielak Z, et  al. First-in-man simultaneous transcatheter aortic and mitral valve replacement to treat severe native aortic and mitral valve stenoses. JACC Cardiovasc Interv. 2015;8:1399–401. 60. Weich H, Janson J, Pecoraro A, et  al. First case of transcatheter native mitral and aortic valve replacement. EuroIntervention. 2016;12:1196.

Prosthetic Heart Valves

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John Chambers

Introduction Preventing the development and progression of calcific aortic valve disease remains an unattainable goal. Rheumatic valve disease is preventable and treatable but this is all too often economically or organisationally hard [1]. Valve replacements are therefore an important treatment for severe valve disease and approximately 500,000 replacement procedures are performed every year world-wide with a global commercial value in 2017 estimated at $4.84 billion [2]. However replacing a stenotic or regurgitant heart valve is not curative since the replacement is usually at least mildly stenotic compared to a normal native valve and has its own natural history and complications. Therefore where feasible a durable repair is preferable to replacement and this is now routine for severe mitral regurgitation caused by mitral valve prolapse. The decision on the timing of surgery and what type of valve to use or whether a percutaneous procedure would be preferable requires specialist competencies in heart valve disease. Therefore best practice is for patients to be followed in a specialist valve clinic [3] and for complex decisions to be made by a heart valve team working in a heart valve centre [4, 5]. The essence of a centre is to attain sufficient volumes, expertise and processes to ensure the best results availJ. Chambers (*) Guy’s and St. Thomas Hospitals, London, UK

able (Table 14.1). The question of what constitutes sufficient individual surgeon and centre volumes is controversial and highly dependent on political and organisational realities so it is agreed that being able to demonstrate excellent results is more important than exceeding arbitrary volume thresholds. For this reason detailed audit of a broad range of outcome measures (Table  14.2) should be available for external scrutiny by patients and commissioning authorities. This chapter describes the types of replacement valve, choice of valve type for individual patients, clinical follow-up, and management of complications.

Types of Replacement Valves The ideal valve would have unlimited durability without the need for anticoagulation and would function haemodynamically as well as a normal native valve. No current replacement valve is ideal and all have limitations as well as strengths. Replacement valves [6] are broadly classified as biological or mechanical (Fig.  14.1). Biological valves comprise approximately 80% of all valve implantations. Biological. The most commonly implanted biological valves are made from animal tissue (‘xenografts’) (Table 14.3) usually manufactured using either pig aortic valve cusps or bovine pericardium. Early porcine valves used the whole pig aortic valve sewn within the stents but this led to

© Springer Nature Switzerland AG 2020 J. Zamorano et al. (eds.), Heart Valve Disease, https://doi.org/10.1007/978-3-030-23104-0_14

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208 Table 14.1  Requirements of a comprehensive heart valve centre [4] Minimum Specialist valve clinic Imaging Echocardiography: 2D/3D, stress, transoesophageal, intraoperative CMR, cardiac CT, CT-PET Departments and individual imagers accredited by recognised national or international systems Procedures available Surgical: Replacement of all valves, mitral valve repair, tricuspid valve repair, surgery for aortic root and ascending aorta, atrial fibrillation ablation Percutaneous: TAVI, mitral edge to edge procedures (e.g., MitraClip) Links with hospitals offering superspecialist techniques Collaborative services Other specialist cardiac services including heart failure, and electrophysiology Intensive care (dedicated beds, ExtraCorporeal membrane oxygenation) Extracardiac specialties: vascular surgery, general surgery, neurology, renal, stroke and elderly care medicine, psychology, genetics and dental surgery Processes Organisation into multidisciplinary teams including endocarditis 24 h, 7 day cover allowing for annual leave and sickness Culture of safety (e.g. World Health Organisation checklist, review of complications) Training Job-planning to include valve related sessions including continuing education Data review Internal audit processes including rates of repair and haemodynamic results on, complications, durability of repair and rates of reoperation assessed annually and summarised at 5 and 10 years Involvement in national databases with mandatory external review

Additional at selected centres

Surgical: Ross procedure, aortic valve repair, robotic mitral valve repair, heart transplant Percutaneous: Balloon mitral valvotomy, closure of paraprosthetic regurgitation, developing mitral and tricuspid valve interventions Percutaneous extraction of electronic devices

Research programmes

CMR cardiac magnetic resonance, CT computed tomography, PET positron emission tomography, TAVI transcatheter aortic valve implantation

high transaortic gradients because of the prominent muscle bar at the base of the right coronary cusp (Fig.  14.2). Later designs substituted this with a cusp from another animal or used three individual cusps matched for size and shape from three separate pigs. For pericardial valves, cusps cut using a template from bovine pericardium (occasionally horse or kangaroo) are sewn either inside or less commonly outside the stents. The stents consist of a plastic or polymer (e.g. Polytetrafluoroethylene) or metal (e.g. Elgiloy wire) crown-shaped platform covered in tissue (e.g. pericardium) or fabric (e.g. Dacron) and with a sewing ring at their base used for sewing to the patient tissue annulus. The biological tissue is

fixed in glutaraldehyde to render it less antigenic but this and the method of attachment to the stents makes it prone to degeneration. The developmental history of these valves has revolved around improved methods of tissue fixation, anticalcification treatment, attachment to the stents and stent design to minimise stresses. Stentless biological valves were introduced in the hope of improving haemodynamic function and complication rates. They were prepared from a sculpted (e.g. St Jude Toronto) or whole pig aorta (e.g. Medtronic Freestyle) or from sheets of pericardium (e.g. Sorin Pericarbon) and were implanted either in a subcoronary position, as a mini-root requiring the reimplantation of the coronary arter-

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14  Prosthetic Heart Valves Table 14.2  Data for collection in repair and replacement for primary mitral or aortic valve disease [4]

Preoperative  Demographic data, comorbidities  Grading of valve lesion  Preoperative risk assessment and stratification using validated multivariate scores Early clinical results  Operative mortality and morbidity at 30 days including stroke, mediastinitis, myocardial infarction, acute kidney injury  Repair rates based on preoperative multidisciplinary team classification for repair as ‘likely’, ‘unlikely’ or ‘not feasible’  Time on intensive therapy unit In hospital haemodynamic function  Transvalve velocity and mean gradient (all positions) and effective orifice area (aortic position) of replacement or transcatheter valves  Presence and grade of paraprosthetic regurgitation  Residual regurgitation and new obstruction after surgical or transcatheter repair or systolic anterior motion of the anterior mitral leaflet Follow-up  Complications: infection, valve thrombosis  Mortality: At 1 and 5 years  Durability of repairs based on routine annual echocardiography (more frequent if significant regurgitation present). Proportion per year developing moderate or worse regurgitation  Incidence and timing of structural valve degeneration and non structural valve degeneration  Rates of redo procedure per year

a

b

Fig. 14.1  Types of replacement valves. Reproduced with permission from Chambers JB, Pibarot P, Rosenhek R. Replacement Heart Valves in The EACVI Textbook of

Echocardiography. 978-0-19-872601-2

ies or as a whole root. The elimination of the stents was expected to lead to a larger orifice available for flow. Stresses between the cusp and stent posts were thought to reduce durability and the stent was

also implicated in ­complications such as thrombosis. The stentless design was therefore expected to give a step-change in durability and complications but this has largely not been realised [7, 8].

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Fig. 14.1 (continued)

Furthermore implantation is technically more challenging than for stented valves and the bypass and cross-clamp times are longer. These valves are therefore not frequently used. The homograft (or allograft) is effectively a subset of stentless valves. These showed early promise in terms of durability but latterly [9] 10  year outcomes have been similar to stented valves probably partly as a result of imperfect

preservation because of delayed harvesting. Redo procedures proved difficult before the availability of valve in valve TAVI because of calcification of the aortic root and ascending aorta. Homografts remain useful in patients with endocarditis with aortic root abscesses. They include the base of the anterior mitral leaflet which can be particularly useful to repair a perforation in the base of the recipient valve damaged by endocarditis.

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14  Prosthetic Heart Valves Table 14.3  Common types of replacement biological heart valve Stented xenograft Porcine Pericardial Sutureless Transcatheter Stentless valves Pulmonary autograft Pulmonary or aortic homograft Heterograft

Hancock, Mosaic, Carpentier–Edwards (standard and supra-annular porcine), Intact, Labcor (porcine tricomposite), Biocor (porcine tri-composite) Baxter Perimount, Mitroflow (bovine pericardial), Labcor pericardial, Trifecta, C-E biophysio, Sorin More, Sorin Soprano Perceval S, Edwards Intuity Elite, 3F Enable, Trilogy SAPIEN, CoreValve, Accurate, Centera, Direct Flow, Engager, JenaValve, Lotus, Portico

These may be implanted as: Subcoronary inclusion, e.g. Toronto (St Jude Medical), Cryolife-O’Brien, Sorin Pericarbon (pericardial), Baxter Prima, Labcor stentless, Biocor PSB tricomposite Miniroot, e.g. Cryolife-O’Brien, Baxter Prima Root, e.g. Freestyle (Medtronic), Baxter Prima, Cryolife-O’Brien root

Fig. 14.2  Pig aortic root showing the prominent muscle bar at the base of the right coronary cusp

The Ross procedure consists of replacing the diseased native aortic valve with the patient’s own pulmonary valve. The pulmonary valve is then replaced usually by a cryopreserved cadaveric pulmonary valve. This surgical procedure is indicated for children because the autograft may sometimes grow and reduce the need for repeated surgical procedures. Anticoagulation is not required and it is therefore a valid alternative for younger patients requiring aortic valve replacement wanting to avoid anticoagulation. It has better durability than xenografts to 15 years [10] with a reintervention rate of 17% at 15  years in the German Ross Registry [11]. A propensity matched comparison with mechanical valves [12] showed a re-intervention rate for the Ross procedure of 8% at 15  years and 13% at 20  years compared

with 6% for the mechanical valves at both 15 and 20  years. It has been hoped that it might resist infection if used to correct endocarditis since it lacks artificial materials but a recurrence rate of 1 (3.6%) in 28 cases has been reported [13] which is similar for other replacement valves. There are limitations. It cannot be used in patients with aortic dilatation because of the risk of regurgitation [14] and the operation is complicated and relatively lengthy. It requires a super-specialist surgeon so it is not widely available. Transcatheter valves are an important new class currently limited mainly to the aortic position (Table  14.4) although mitral and tricuspid devices are being evaluated. These are broadly either balloon (e.g. Edwards SAPIEN) or self-­ expandable (e.g. Medtronic Corevalve). Sutureless valves [15] were developed to speed the implantation process to limit bypass time in high-risk patients and also to facilitate minimally-­ invasive surgery using a limited thoracotomy. In effect they are a hybrid between the transcatheter techniques and conventional valve implantation using a balloon-expandable steel frame (Intuity) or self-expanding nitinol frame (3F enable, Perceval S) usually with a small number of anchoring sutures. Early results are acceptable [16] with 30 day mortality 2.1% and 1 year mortality 4.9%, comparable or better than for TAVI in a propensity scored analysis [17]. Mechanical. There are three general types of mechanical valve, the caged-ball, tilting disk and bileaflet mechanical valve (Table 14.4).

212 Table 14.4  Types of mechanical replacement valve

J. Chambers

biopolymers and in tissue engineering [18, 19]. Tissue engineering techniques aim to grow valves from stem-cells or to seed circulating progenitor cells onto biological, synthetic or hybrid scaffolds. Another line of research is genetic engineering targeted gene-editing in the hope of making a pig aortic valve less antigenic. This may be done using zinc-finger nucleases or clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 technology [20] which cuts the genome where desired and adds a new The Starr-Edwards caged-ball valve was gene. 3D printing techniques may also be used to implanted from 1960. These were obstructive and construct biological valves with different tissues thrombogenic but durable and low in cost. Early in cusp and stent or may be used to model polytilting disk valves were developed throughout the mer valves although currently it is used to model 1960s  for better haemodynamic function and the heart to plan interventions particularly percuthrombogenicity and the commonly-used Bjork-­ taneous closure of dehiscences [21]. Shiley valve was introduced in 1968. The final stage in the evolution of mechanical valves occurred from the late 1960s culminating Choice of Valve in the clinical introduction of the St Jude Medical bileaflet mechanical valve in 1977. Bileaflet Guideline indications are given in Tables 14.5 and valves are the most frequently implanted type of 14.6 [22]. The choice needs to take account of indimechanical valve. They have flow profiles that vidual patient characteristics. For example, patients most closely mimic normal native valve and have may have contraindications to anticoagulation or surfaces or whole components made from pyro- life-limiting comorbidity reducing the advantage of lytic carbon polished to a glassy smoothness that a mechanical valve. Biological valves are also a is relatively resistant of thrombosis. The various choice for a woman planning pregnancy to avoid designs of bileaflet mechanical valve differ in the the problems of anticoagulation and despite the composition and purity of the pyrolytic carbon need for a redo procedure. It is also important to used in their manufacture, in the shape and open- involve the patient in the choice of valve since apart ing angle of the leaflets, in the design of the from simple courtesy and inclusiveness this also ­pivots, the size and shape of the housing and the leads to better results [23]. Abnormal psychologidesign of the sewing ring. The valve can be cal processes should be identified and addressed in placed within the patient tissue annulus advance of the surgery [24]. This together with (Carbomedics standard) or above the annulus patient education is an important aspect of the work (Edwards Mosaic, Carbomedics TopHat). Some of the heart valve clinic [3, 4]. have both intra-annular and supra-annular comAn informed patient may choose a biological ponents (On-X). valve against guideline advice. Unfortunately the Local national variations on the generic types definition of an informed patient is open and have been developed (e.g. the Jyros bileaflet there are major market pressures towards using mechanical valve and Minsk tilting disc valves in biological valves with the understanding that Russia and the TTK Chitra tilting disk in India) durability is good and that valve failure can be but there have been no step-changes in the design managed with valve-in-valve TAVI.  This may of replacement valves for 40  years. Research have contributed to the strong trend to using bioaims for the holy grail of excellent durability logical valves in younger patients in the US [25] without the need for anticoagulation. The main and UK [19]. The proportion of isolated aortic areas of research are in the use of polymers or valve replacements using biological valve in peoBall-cage Starr–Edwards, Macgovern-Cromie, Smeloff-Cutter Bjork–Shiley monostrut, Hall-Kaster, Single Kay-Shiley, Medtronic Hall, Sorin tilting Monoleaflet Allcarbon, Omnicarbon, disc Kehler Ultracor. TLK Chitra Bileaflet St Jude Medical (standard, HP, Masters and Regent), Carbomedics, On-X, ATS, Sorin Bicarbon, Medtronic Advantage, Edwards Tekna and Edwards Mira, Jyros

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Table 14.5  Reasons for favouring a mechanical replacement [22] Who are informed and request a mechanical valve provided there is no

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contraindication to long-term anticoagulation With a risk of accelerated failure of a biological valve

I

Who already has a mechanical valve in another position

IIa

Aged 65 in the aortic position or >70 in the mitral position or life

IIa

expectancy lower than the presumed durability of the valve

ple aged 56–60 increased from 25% in 2004 to 40% in 2008 [26]. In the US 31% of adult-sized children suitable for a mechanical valve between 2009 and 2013 elected to have a biological valve [27]. However durability is limited in younger patients particularly aged under 40 [28, 29]. In a series from Ottowa, the 10  year freedom compared with 99.7% aged >60 [29]. Furthermore the results from valve in valve TAVI are not certain and patient prosthesis mismatch results if the failing valve is small [30].

The pattern of use of replacement valves is also affected by economic and organisational concerns. In the under-developed world safe anticoagulation may not be feasible leading to an 8.45 times relative risk for dying for a Maori or Pacific Islander compared with a white New Zealander [31] implanted with a mechanical valve. Therefore repair may be performed even in rheumatic valves in preference to the implantation of a replacement mechanical valve although 90% survival 14  years has been reported [32].

J. Chambers

214

Reoperation for structural degeneration of biological replacement valves is a more common reason for surgery than in industrially developed areas occurring in 41% of operations in Sao Paolo [33] compared with 7% in the UK [26]. The challenge is a cheap, transcatheter ideally renewable prosthesis for patients with rheumatic disease [19].

Table 14.7 Checklist routine annual assessment in replacement heart valves Any cardiac symptom or change in exercise capacity? Any bleeding or TIA/stroke? Any general symptom requiring an opinion from a non-cardiac physician? Anticoagulation control. Discuss diet if control poor. Consider home-testing Check dental surveillance occurring usually 6 monthly Confirm indications for antibiotic prophylaxis for dental procedures (extractions, scaling, deep fillings, gum incisions) Examination for signs of valve dysfunction, other valve disease, endocarditis, blood pressure and rhythm ECG if new irregular rhythm Consider echocardiography for new symptom, abnormal sign or as indicated routinely (Table 14.10)

Routine Clinical Management The first postoperative visit is usually to the surgeon at about 4–6  weeks to check recovery including sternal wound healing. A full echocardiogram should be done then unless the local protocol is to perform one before discharge. The advantage of a 4–6 week study is that image quality is better and the findings are more representative when the chest wound has healed, chest wall oedema has resolved, and LV systolic function has recovered. Every valve is different and the baseline study acts as a ‘fingerprint’ against which to compare future studies. For example, there may be mild paraprosthetic regurgitation. If the patient presents later with fever, the finding of a paraprosthetic jet might be a sign of endocarditis if it is new, but not necessarily if it has already been documented. Many centres at this point offer a rehabilitation course. Patients report uncertainty about who is in charge of their care between discharge and the first postoperative visit and some centres offer support from a nurse usually by telephone. If recovery is uneventful and there is no residual valve disease or other cardiac problem routine follow-up should then be offered annually. This should be in a specialist valve clinic usually led by a cardiologist. However follow-up in some countries, particularly the UK is often devolved to a cardiac nurse or, if routine echocardiography is indicated, to a clinical scientist with oversight from a cardiologist [34, 35]. Unfortunately discharge to a general practitioner is common, at least in the UK [36], with uncertain follow-up likely to increase the risk of complications.

Table 14.8  Guideline INR targets [22] Aortic with no added risk factorsa 2.5

Low-risk design (Carbomedics, Medtronic-­ Hall, ATS, Medtronic Open-Pivot, On-Xb, St Jude, Sorin Bicarbon Medium-risk design 3.0 (other bileaflet valves) 3.5 High-risk design (Lillehei-Kaster, Omniscience, Starr-­ Edwards, Bjork-Shiley and other tilting disc valves)

Mitral or tricuspid or aortic with ≥1 risk factora 3.0

3.5 4.0

Risks: Previous thromboembolism, atrial fibrillation, LV ejection fraction 60 cannot be assumed. Furthermore the durability of new valves cannot be assumed from data in established designs and must be established by observation. A balance incorporating these concerns has been suggested by the ESC working group in valve disease [37] (Table  14.10). Table 14.9  Onset after implantation of routine annual echocardiography: summary of international guidelines

ESC valve disease 2017 [22] AHA valve disease 2014 [42] ESC prosthetic valves 2016 [43] ESC valve disease 2012 [44] ASE/EAE prosthetic valves 2009 [45]

Biological Mechanical aortic – Immediate

Biological mitral –

–

>10 years

–

Not routinely

>5 or 10 years

–

–

>5 yearsa

–

Not routinely

>5 years

–

– not stated a Earlier in young patients

Table 14.10  Recommended frequency of routine TTE after the baseline postoperative study [37] Mechanical valve in aortic or mitral position No routine follow-up usually needed Biological valve Annual from implantation: TAVI, new designs for which durability data do not exist, Ross procedure Annual ≥5 years: mitral or tricuspid position, aortic xenograft age 41 mm at the time of surgery Other valves Appearance, grade of stenosis and regurgitation Table 14.12 Spectral obstruction

Doppler

signs

suggesting

Aortic Mitral Tricuspid Pulmonary >4.0 >2.0 >1.4 >2.0 homograft >3.0 all other Mean gradient >35 >5 >5 (mmHg) Doppler 2.2 velocity index Effective 130 >240 half-time (ms) Peak velocity (m/s)

and can be accessed using Apps (e.g. British Society of Echocardiography or American Society of Echocardiography). Pathological obstruction is suggested by abnormal thickness or motion of the cusps or occluder together with constriction of the colour Doppler signal. However the possibility of pathological obstruction is suggested by parameters in Table 14.12 [1, 45].

In addition the shape of the signal may be useful in the aortic position. Obstruction is suggested by a rounded symmetrical continuous wave-form (this may be quantified by a peak to mean pressure gradient ratio 0.37 [48]. The interpretation of quantitative Doppler is often difficult. Over-interpretation must be avoided if the patient is well. High velocities are common especially in size 19 or 21 prostheses. The challenge is to differentiate a small, but normally-­ functioning valve from a pathologically obstructive valve (Fig.  14.3). The key is imaging of the cusps or occluder (Table 14.13). Imaging may be difficult on TTE and even on TEE. Fluoroscopy may then be used to image movement (Fig.  14.4) of the occluders of mechanical valves while CT is useful for biological valve cusps and the leaflets of bileaflet mechanical valves. Patient prosthesis mismatch is common and only causes a problem if causing symptoms (see below). It is defined by the criteria in Table 14.13 [49] which includes a correction for obesity. A change from immediate postoperative values is also supportive of acquired prosthetic valve obstruction. For example an increase in mean gradient ≥5  mmHg with similar heart rates is suggestive of the occurrence of valve obstruction. In less severe obstruction, particularly with restriction of only one leaflet in a bileaflet mechanical mitral valve, the pressure half-time may be only mildly prolonged, to around 150 ms. A change from immediate postoperative values may be obvious. Normal ranges are less variable than for the aortic position [50]. TEE is essential for determining the cause of obstruction in mechanical valves: thrombosis, pannus, mechanical obstruction by septal hypertrophy or retained chordae, or vegetations as a result of endocarditis (see complications below). Minor regurgitation is normal in virtually all mechanical valves (Fig. 14.5). Early valves had a closing volume as the leaflet closed followed by true regurgitation around the occluder. The single tilting disc valves have both types of regurgitation, but the pattern may vary. The Bjork–Shiley valve has a minor and major jet from the two orifices while the Medtronic Hall valve has a single

14  Prosthetic Heart Valves

217

Peak Prosthetic Aortic Jet Velocity > 3m/s and/or mean pressure gradient ≥ 20 mmHg

Measure EOA by continuity equation and compare to normal EOA reference value

Measured EOA ~ reference value

Measured EOA < reference value

Change in EOA & DVI during follow-up? YES

NO

Calculate indexed EOA

Decrease in EOA & DVI

Indexed EOA >0.85cm2/m2 DVI≥0.35

Indexed EOA ≤0.85cm2/m2

Abnormal disk/ leaflet motion# YES

Consider PPM

AT/ET>0.37 Rounded Jet

Consider • Subvalvular acceleration • Aortic regurgitation*** • Technical error##

NO

AT/ET≤0.37 Triangular Jet

DVI0.37 Rounded Jet

DVI0.70)b >1.2 (>1.0)b

Moderate 0.65–0.85 (0.6–0.70)b 0.9–1.2 (0.8–1.0)b

Severe