دليل أمراض صمامات القلب

ia_gov_sa · guide · processed · 525 chunks

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
© 2021 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION AND THE
AMERICAN HEART ASSOCIATION, INC.
PUBLISHED BY ELSEVIER
VOL. 77, NO. 4, 2021
CLINICAL PRACTICE GUIDELINE: FULL TEXT
2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease

A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons
Writing Committee Members*
Catherine M. Otto, MD, FACC, FAHA, Co-Chair
Rick A. Nishimura, MD, MACC, FAHA, Co-Chair
Robert O. Bonow, MD, MS, MACC, FAHA
Blase A. Carabello, MD, FACC, FAHA
John P. Erwin III, MD, FACC, FAHA
Federico Gentile, MD, FACC
Hani Jneid, MD, FACC, FAHA
Eric V. Krieger, MD, FACC
Michael Mack, MD, MACC
Christopher McLeod, MBCHB, PhD, FAHA
Patrick T. O'Gara, MD, MACC, FAHA†
Vera H. Rigolin, MD, FACC, FAHA
Thoralf M. Sundt III, MD, FACC, FAHA
Annemarie Thompson, MD
Christopher Toly
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.
†ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison.
The American College of Cardiology Foundation requests that this document be cited as follows: Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021;77:e25-197.
This document was approved by the American College of Cardiology Clinical Policy Approval Committee in August 2020, the American Heart Association Science Advisory and Coordinating Committee in August 2020, and the American Heart Association Executive Committee in September 2020.
This article has been copublished in Circulation.
Copies: This document is available on the websites of the American College of Cardiology (www.acc.org) and the American Heart Association (professional.heart.org). For copies of this document, please contact Elsevier Inc. Reprint Department via fax (212) 633-3820 or e-mail (reprints@elsevier.com).
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site https://www.elsevier.com/about/policies/copyright/permissions.
ISSN 0735-1097/$36.00
https://doi.org/10.1016/j.jacc.2020.11.018

e26
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
ACC/AHA Joint
Committee
Members
Patrick T. O'Gara, MD, MACC, FAHA, Chair
Joshua A. Beckman, MD, MS, FAHA, Chair-Elect
Glenn N. Levine, MD, FACC, FAHA, Immediate Past Chair‡
Sana M. Al-Khatib, MD, MHS, FACC, FAHA‡
Anastasia Armbruster, PharmD, AACC
Kim K. Birtcher, PharmD, MS, AACC
Joaquin Ciggaroa, MD, FACC
Anita Deswal, MD, MPH, FACC, FAHA
Dave L. Dixon, PharmD, FACC
Lee A. Fleisher, MD, FACC, FAHA‡
Lisa de las Fuentes, MD, MS, FAHA, FASE
Federico Gentile, MD, FACC‡
Zachary D. Goldberger, MD, MSc, FACC, FAHA
Bulent Gorenek, MD, FACC, FESC
Norrisa Haynes, MD, MPH
Adrian F. Hernandez, MD, MHS
Mark A. Hlatky, MD, FACC, FAHA‡
José A. Joglar, MD, FACC, FAHA
W. Schuyler Jones, MD, FACC
Joseph E. Marine, MD, FACC‡
Daniel Mark, MD, MPH, FACC, FAHA
Latha Palaniappan, MD, MS, FAHA, FACC
Mariann R. Piano, RN, PhD, FAHA
Erica S. Spatz, MD, MHS, FACC
Jacqueline Tamis-Holland, MD, FACC
Duminda N. Wijeysundera, MD, PhD‡
Y. Joseph Woo, MD, FAHA, FACC
‡Former Joint Committee member; current member during the writing effort.
TABLE OF CONTENTS
<table><tr><td>TOP 10 TAKE-HOME MESSAGES</td><td>e28</td></tr><tr><td>PREAMBLE</td><td>e29</td></tr><tr><td>1. INTRODUCTION</td><td>e30</td></tr><tr><td>1.1. Methodology and Evidence Review</td><td>e30</td></tr><tr><td>1.2. Organization of the Writing Committee</td><td>e30</td></tr><tr><td>1.3. Document Review and Approval</td><td>e31</td></tr><tr><td>1.4. Scope of the Guideline</td><td>e31</td></tr><tr><td>1.5. Class of Recommendation and Level of Evidence</td><td>e32</td></tr><tr><td>1.6. Abbreviations</td><td>e33</td></tr><tr><td>2. GENERAL PRINCIPLES</td><td>e33</td></tr><tr><td>2.1. Evaluation of the Patient With Known or Suspected Native VHD</td><td>e33</td></tr><tr><td>2.2. Definitions of Severity of Valve Disease</td><td>e33</td></tr><tr><td>2.3. Diagnosis and Follow-Up</td><td>e35</td></tr><tr><td>2.3.1. Diagnostic Testing: Initial Diagnosis</td><td>e35</td></tr><tr><td>2.3.2. Diagnostic Testing: Changing Signs or Symptoms</td><td>e35</td></tr><tr><td>2.3.3. Diagnostic Testing: Routine Follow-Up</td><td>e35</td></tr><tr><td>2.3.4. Diagnostic Testing: Cardiac Catheterization</td><td>e35</td></tr><tr><td>2.3.5. Diagnostic Testing: Exercise Testing</td><td>e36</td></tr></table>
2.4. Basic Principles of Medical Therapy ..... e36
2.4.1. Secondary Prevention of Rheumatic Fever e36
2.4.2. IE Prophylaxis e37
2.4.3. Anticoagulation for AF in Patients With VHD e38
2.5. Evaluation of Surgical and Interventional Risk e40
2.6. The Multidisciplinary Heart Valve Team and Heart Valve Centers e42
2.7. Management of Patients With VHD After Valve Intervention e44
2.7.1. Procedural Complications e44
2.7.2. Primary and Secondary Risk Factor Evaluation and Treatment ..... e44
2.7.3. Persistent Symptoms After Valve Intervention e44
2.7.4. Periodic Imaging After Valve Intervention e44
3. AORTIC STENOSIS e45
3.1. Stages of Valvular AS e45
3.2. Aortic Stenosis e46
3.2.1. Diagnosis and Follow-Up e46
3.2.2. Medical Therapy e49
3.2.3. Timing of Intervention e50
3.2.4. Choice of Intervention e53

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e27
4. AORTIC REGURGITATION e60
4.1. Acute Aortic Regurgitation ..... e60
4.1.1. Diagnosis of Acute AR ..... e60
4.1.2. Intervention for ACUTE AR ..... e60
4.2. Stages of Chronic AR e61
4.3. Chronic AR e62
4.3.1. Diagnosis of Chronic AR e62
4.3.2. Medical Therapy e62
4.3.3. Timing of Intervention e63
5. BICUSPID AORTIC VALVE e66
5.1. BAV and Associated Aortopathy e66
5.1.1. Diagnosis and Follow-Up of BAV ..... e66
5.1.2. Interventions for Patients With BAV ..... e68
6. MITRAL STENOSIS e70
6.1. Stages of MS e71
6.2. Rheumatic MS e71
6.2.1. Diagnosis and Follow-Up of Rheumatic MS e71
6.2.2. Medical Therapy e73
6.2.3. Intervention e74
6.3. Nonrheumatic Calcific MS e77
7. MITRAL REGURGITATION e77
7.1. Acute MR e77
7.1.1. Diagnosis of Acute MR e78
7.1.2. Medical Therapy e78
7.1.3. Intervention e79
7.2. Chronic Primary MR e79
7.2.1. Stages of Chronic Primary MR e79
7.2.2. Diagnosis and Follow-Up of Chronic Primary MR e79
7.2.3. Medical Therapy e82
7.2.4. Intervention e83
7.3. Chronic Secondary MR e86
7.3.1. Stages of Chronic Secondary MR e86
7.3.2. Diagnosis of Chronic Secondary MR e87
7.3.3. Medical Therapy e88
7.3.4. Intervention e89
8. TRICUSPID VALVE DISEASE e91
8.1. Classification and Stages of TR e91
8.2. Tricuspid Regurgitation e92
8.2.1. Diagnosis of TR e92
8.2.2. Medical Therapy e93
8.2.3. Timing of Intervention e93
9. PULMONIC VALVE DISEASE e96
10. MIXED VALVE DISEASE e96
10.1. Diagnosis of Mixed VHD e96
10.2. Timing of Intervention for Mixed VHD e97
10.2.1. Intervention for Mixed AS and AR e97
10.2.2. Intervention for Mixed AS and MR e97
10.2.3. Intervention for Mixed MS and MR e99
10.2.4. Intervention for Mixed MS and AR e99
10.2.5. Intervention for Mixed MS and AS e99
11. PROSTHETIC VALVES e99
11.1. Evaluation and Selection of Prosthetic Valves . e99
11.1.1. Diagnosis and Follow-Up of Prosthetic Valves e99
11.1.2. Selection of Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve . e101
11.2. Antithrombotic Therapy e105
11.3. Bridging Therapy e109
11.4. Excessive Anticoagulation and Serious Bleeding With Prosthetic Valves e110
11.5. Thromboembolic Events With Prosthetic Valves e111
11.6. Acute Mechanical Valve Thrombosis e113
11.6.1. Diagnosis of Acute Mechanical Valve Thrombosis e113
11.6.2. Intervention e113
11.7. Bioprosthetic Valve Thrombosis e114
11.7.1. Diagnosis of Bioprosthetic Valve Thrombosis e114
11.7.2. Medical Therapy e114
11.8. Prosthetic Valve Stenosis e115
11.8.1. Diagnosis of Prosthetic Valve Stenosis e115
11.8.2. Intervention for Prosthetic Valve Stenosis e116
11.9. Prosthetic Valve Regurgitation e117
11.9.1. Diagnosis of Prosthetic Valve
Regurgitation e118
11.9.2. Medical Therapy e118
11.9.3. Intervention 119

e28
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
12. INFECTIVE ENDOCARDITIS e120
12.1. Classification of Endocarditis ..... e120
12.2. Diagnosis of IE ..... e120
12.3. Medical Therapy 125
12.4. Intervention 127
13. PREGNANCY AND VHD e131
13.1. Initial Management of Women With VHD Before and During Pregnancy e131
13.1.1. Medical Therapy for Women With VHD Before and During Pregnancy e132
13.1.2. Intervention for Women With Native VHD Before and During Pregnancy e133
13.2. Prosthetic Valves in Pregnant Women ..... e136
13.2.1. Initial Management ..... e136
13.2.2. Anticoagulation for Pregnant Women With Mechanical Prosthetic Heart Valves e137
14. SURGICAL CONSIDERATIONS e141
14.1. Evaluation and Management of CAD in Patients With VHD e141
14.1.1. Management of CAD in Patients Undergoing TAVI e141
14.1.2. Management of CAD in Patients Undergoing Valve Surgery e143
14.2. Intervention for AF in Patients With VHD . .e144
15. NONCARDIAC SURGERY IN PATIENTS WITH VHD e146
15.1. Diagnosis of Patients With VHD Undergoing Noncardiac Surgery e146
15.2. Management of the Symptomatic Patient . . . e147
15.3. Management of the Asymptomatic Patient . . . e147
16. EVIDENCE GAPS AND FUTURE DIRECTIONS . e149
16.1. Prevention of Valve Disease: Stage A e149
16.2. Medical Therapy to Treat or Prevent Disease Progression: Stage B e149
16.3. Optimal Timing of Intervention: Stage C e150
16.4. Better Options for Intervention: Stage D e151
REFERENCES e152
APPENDIX 1
Author Relationships With Industry and Other Entities (Relevant) e190
APPENDIX 2
Reviewer Relationships With Industry and Other Entities (Comprehensive) e192
TOP 10 TAKE-HOME MESSAGES
1. Disease stages in patients with valvular heart disease should be classified (Stages A, B, C, and D) on the basis of symptoms, valve anatomy, the severity of valve dysfunction, and the response of the ventricle and pulmonary circulation.
2. In the evaluation of a patient with valvular heart disease, history and physical examination findings should be correlated with the results of noninvasive testing (ie, ECG, chest x-ray, transthoracic echocardiogram). If there is discordance between the physical examination and initial noninvasive testing, consider further noninvasive (computed tomography, cardiac magnetic resonance imaging, stress testing) or invasive (transesophageal echocardiography, cardiac catheterization) testing to determine optimal treatment strategy.
3. For patients with valvular heart disease and atrial fibrillation (except for patients with rheumatic mitral stenosis or a mechanical prosthesis), the decision to use oral anticoagulation to prevent thromboembolic events, with either a vitamin K antagonist or a non-vitamin K antagonist anticoagulant, should be made in a shared decision-making process based on the CHA \( _{2} \) DS \( _{2} \) -VASc score. Patients with rheumatic mitral stenosis or a mechanical prosthesis and atrial fibrillation should receive oral anticoagulation with a vitamin K antagonist.
4. All patients with severe valvular heart disease being considered for valve intervention should be evaluated by a multidisciplinary team, with either referral to or consultation with a Primary or Comprehensive Valve Center.
5. Treatment of severe aortic stenosis with either a transcatheter or surgical valve prosthesis should be based primarily on symptoms or reduced ventricular systolic function. Earlier intervention may be considered if indicated by results of exercise testing, biomarkers, rapid progression, or the presence of very severe stenosis.
6. Indications for transcatheter aortic valve implantation are expanding as a result of multiple randomized trials of transcatheter aortic valve implantation versus surgical aortic valve replacement. The choice of type of intervention for a patient with severe aortic stenosis should be a shared decision-making process that considers the lifetime risks and benefits associated

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e29
with type of valve (mechanical versus bioprosthetic) and type of approach (transcatheter versus surgical).
7. Indications for intervention for valvular regurgitation are relief of symptoms and prevention of the irreversible long-term consequences of left ventricular volume overload. Thresholds for intervention now are lower than they were previously because of more durable treatment options and lower procedural risks.
8. A mitral transcatheter edge-to-edge repair is of benefit to patients with severely symptomatic primary mitral regurgitation who are at high or prohibitive risk for surgery, as well as to a select subset of patients with secondary mitral regurgitation who remain severely symptomatic despite guideline-directed management and therapy for heart failure.
9. Patients presenting with severe symptomatic isolated tricuspid regurgitation, commonly associated with device leads and atrial fibrillation, may benefit from surgical intervention to reduce symptoms and recurrent hospitalizations if done before the onset of severe right ventricular dysfunction or end-organ damage to the liver and kidney.
10. Bioprosthetic valve dysfunction may occur because of either degeneration of the valve leaflets or valve thrombosis. Catheter-based treatment for prosthetic valve dysfunction is reasonable in selected patients for bioprosthetic leaflet degeneration or paravalvular leak in the absence of active infection.
PREAMBLE
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cardiovascular care. The ACC and AHA sponsor the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. For some guidelines, the ACC and AHA partner with other organizations.
Intended Use
Clinical practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in
the United States, but these guidelines are relevant to patients throughout the world. Although guidelines may be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients' interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment.
Clinical Implementation
Management, in accordance with guideline recommendations, is effective only when followed by both practitioners and patients. Adherence to recommendations can be enhanced by shared decision-making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities.
Methodology and Modernization
The ACC/AHA Joint Committee on Clinical Practice Guidelines (Joint Committee) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations, including the Institute of Medicine, (1,2) and on the basis of internal reevaluation. Similarly, presentation and delivery of guidelines are reevaluated and modified in response to evolving technologies and other factors to optimally facilitate dissemination of information to healthcare professionals at the point of care.
Numerous modifications to the guidelines have been implemented to make them shorter and enhance “user-friendliness.” Guidelines are written and presented in a modular “knowledge chunk” format, in which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review. Word limit targets and a web supplement for useful but noncritical tables and figures are 2 recent modifications.
In recognition of the importance of cost-value considerations, in certain guidelines, when appropriate and feasible, an analysis of value for a drug, device, or intervention may be performed in accordance with the ACC/AHA methodology (3).
To ensure that guideline recommendations remain current, new data will be reviewed on an ongoing basis by the writing committee and staff. Going forward, targeted sections or knowledge chunks will be revised dynamically after publication and timely peer review of potentially

e30
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
practice-changing science. The previous designations of “full revision” and “focused update” will be phased out. For additional information and policies on guideline development, readers may consult the ACC/AHA guideline methodology manual (4) and other methodology articles (5-7).
Selection of Writing Committee Members
The Joint Committee strives to ensure that the guideline writing committee members have requisite content expertise and are representative of the broader cardiovascular community. Experts are selected across a spectrum of backgrounds, representing different geographic regions, sexes, races, ethnicities, intellectual perspectives or biases, and clinical practice settings. Organizations and professional societies with related interests and expertise are invited to participate as partners or collaborators.
Relationships With Industry and Other Entities
The ACC and AHA have rigorous policies and methods to ensure that documents are developed without bias or improper influence. The complete policy on relationships with industry and other entities (RWI) can be found online. Appendix 1 of the guideline lists writing committee members' relevant RWI; for the purposes of full transparency, their comprehensive disclosure information is available online. Comprehensive disclosure information for the Joint Committee is also available online.
Evidence Review and Evidence Review Committees
In developing recommendations, the writing committee uses evidence-based methodologies that are based on all available data (4,5). Literature searches focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only key references are cited.
An independent evidence review committee is commissioned when there are one or more questions deemed of utmost clinical importance that merit formal systematic review to determine which patients are most likely to benefit from a drug, device, or treatment strategy, and to what degree. Criteria for commissioning an evidence review committee and formal systematic review include absence of a current authoritative systematic review, feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline, relevance to a substantial number of patients, and likelihood
that the findings can be translated into actionable recommendations. Evidence review committee members may include methodologists, epidemiologists, clinicians, and biostatisticians. Recommendations developed by the writing committee on the basis of the systematic review are marked “SR.”
Guideline-Directed Management and Therapy
The term guideline-directed management and therapy (GDMT) encompasses clinical evaluation, diagnostic testing, and both pharmacological and procedural treatments. For these and all recommended drug treatment regimens, the reader should confirm dosage with product insert material and evaluate for contraindications and interactions. Recommendations are limited to drugs, devices, and treatments approved for clinical use in the United States.
Patrick T. O'Gara, MD, MACC, FAHA, Chair, ACC/AHA Joint Committee on Clinical Practice Guidelines
1. INTRODUCTION
11. Methodology and Evidence Review
The recommendations listed in this document are, whenever possible, evidence based. An extensive review was conducted on literature published through March 1, 2020. Searches were extended to studies, reviews, and other evidence involving human subjects that were published in English and indexed in PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this guideline. Key search words included but were not limited to the following: valvular heart disease, aortic stenosis, aortic regurgitation, bicuspid aortic valve, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonic stenosis, pulmonic regurgitation, prosthetic valves, anticoagulation therapy, infective endocarditis, cardiac surgery, transcatheter aortic valve replacement or implantation, and percutaneous mitra-clip. Additionally, the committee reviewed documents related to the subject matter previously published by the ACC and AHA. The references selected and published in this document are representative and not all-inclusive.
1.2. Organization of the Writing Committee
The writing committee was composed of clinicians, which included cardiologists, interventionalists, surgeons,

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e31
TABLE 1 Associated Guidelines and Related References
<table><tr><td>Title</td><td colspan="2">Organization Publication Year (Reference)</td></tr><tr><td>Recommendations for Evaluation of the Severity of Native Valvular Regurgitation With Two-Dimensional and Doppler Echocardiography</td><td>ASE</td><td>2017 (5)</td></tr><tr><td>European Association of Echocardiography Recommendations for the Assessment of Valvular Regurgitation, Part 2: Mitral and Tricuspid Regurgitation (Native Valve Disease)</td><td>EAE</td><td>2010 (6)</td></tr><tr><td>Guidelines for the Management of Patients With Atrial Fibrillation</td><td>ACC/AHA/ESC</td><td>2006, 2008, 2019 (7-9)</td></tr><tr><td>Guidelines for the Management of Adults With Congenital Heart Disease</td><td>ACC/AHA</td><td>2018 (10)</td></tr><tr><td>Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice</td><td>EAE/ASE</td><td>2009 (11)</td></tr><tr><td>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</td><td>EACI/ASE</td><td>2017 (12)</td></tr><tr><td>Guidelines for the Evaluation of Valvular Regurgitation After Percutaneous Valve Repair or Replacement: A Report from the American Society of Echocardiography</td><td>ASE</td><td>2019 (13)</td></tr><tr><td>Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound</td><td>ASE</td><td>2009 (14)</td></tr><tr><td>Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy</td><td>ACCF/AHA</td><td>2011 (15)2020 (16)</td></tr><tr><td>Guidelines on the Management of Cardiovascular Diseases During Pregnancy</td><td>ESC</td><td>2011, 2018 (17,18)</td></tr><tr><td>Antithrombotic and Thrombolytic Therapy for Valvular Disease: Antithrombotic Therapy and Prevention of Thrombosis</td><td>ACCP</td><td>2012 (19)</td></tr><tr><td>Guidelines on the Management of Valvular Heart Disease</td><td>ESC/EACTS</td><td>2012 (20) 2017 (21)</td></tr><tr><td>Guideline for the Management of Heart Failure</td><td>ACCF/AHA</td><td>2017 (22)</td></tr></table>
ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; ACCP, American College of Chest Physicians; AHA, American Heart Association; ASE, American Society of Echocardiography; EACI, European Association of Cardiovascular Imaging; EACTS, European Association of Cardio Thoracic Surgery; EAE, European Association of Echocardiography; and ESC, European Society of Cardiology.
anesthesiologists, and a patient representative. Members were required to disclose all RWI relevant to the data under consideration.
1.3. Document Review and Approval
This document was reviewed by 2 official reviewers each nominated by the ACC and the AHA, as well as content reviewers nominated by the ACC and AHA. Reviewers' RWI information was distributed to the writing committee and is published in this document (Appendix 2).
1.4. Scope of the Guideline
The focus of this guideline is the diagnosis and management of adult patients with valvular heart disease (VHD). A full revision of the original 1998 VHD guideline was made in 2006, and an update was made in 2008 (1). Another full revision was made in 2014 (2), with an update in 2017 (3). There was an additional statement of clarification specifically for surgery for aortic dilation in patients with bicuspid aortic valves (BAV) in 2016 (4). The present guideline will replace the
2014 guideline and 2017 focused update. Some recommendations from the earlier VHD guidelines have been updated as warranted by new evidence or a better understanding of earlier evidence, whereas others that were inaccurate, irrelevant, or overlapping were deleted or modified. Throughout, our goal was to provide the clinician with concise, evidence-based, contemporary recommendations and the supporting documentation to encourage their use. Where applicable, sections were divided into subsections of 1) diagnosis and follow-up, 2) medical therapy, and 3) intervention. The purpose of these subsections is to categorize the Class of Recommendation according to the clinical decision-making pathways that caregivers use in the management of patients with VHD.
The document recommends a combination of lifestyle modifications and medications that constitute components of GDMT. For both GDMT and other recommended drug treatment regimens, the reader is advised to confirm dosages with product insert material and to carefully evaluate for contraindications and drug-drug interactions. Table 1 is a list of associated guidelines that may be of interest to the reader.

e32
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
TABLE 2
Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*
<table><tr><td colspan="2">CLASS (STRENGTH) OF RECOMMENDATION</td></tr><tr><td>CLASS 1 (STRONG)</td><td>Benefit &gt;&gt;&gt; Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is recommended/Is indicated/useful/effective/beneficialShould be performed/administered/otherComparative-Effectiveness Phrases+- Treatment/strategy A is recommended/indicated in preference to treatment B- Treatment A should be chosen over treatment B</td></tr></table>
<table><tr><td>CLASS 2a (MODERATE)</td><td>Benefit &gt;&gt; Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is reasonableCan be useful/effective/beneficialComparative-Effectiveness Phrases+- Treatment/strategy A is probably recommended/indicated in preference to treatment B- It is reasonable to choose treatment A over treatment B</td></tr></table>
<table><tr><td>CLASS 2b (WEAK)</td><td>Benefit ≥ Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:May/might be reasonableMay/might be consideredUsefulness/effectiveness is unknown/unclear/uncertain or not well-established</td></tr></table>
<table><tr><td>CLASS 3: No Benefit (MODERATE)(Generally, LOE A or B use only)</td><td>Benefit = Risk</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Is not recommendedIs not indicated/useful/effective/beneficialShould not be performed/administered/other</td></tr></table>
<table><tr><td>Class 3: Harm (STRONG)</td><td>Risk &gt; Benefit</td></tr><tr><td colspan="2">Suggested phrases for writing recommendations:Potentially harmfulCauses harmAssociated with excess morbidity/mortalityShould not be performed/administered/other</td></tr></table>
LEVEL (QUALITY) OF EVIDENCE‡
LEVEL A
• High-quality evidence‡ from more than 1 RCT
• Meta-analyses of high-quality RCTs
• One or more RCTs corroborated by high-quality registry studies
LEVEL B-R
(Randomized)
• Moderate-quality evidence‡ from 1 or more RCTs
• Meta-analyses of moderate-quality RCTs
LEVEL B-NR
(Nonrandomized)
- Moderate-quality evidence‡ from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies
• Meta-analyses of such studies
LEVEL C-LD
(Limited Data)
- Randomized or nonrandomized observational or registry studies with limitations of design or execution
• Meta-analyses of such studies
• Physiological or mechanistic studies in human subjects
LEVEL C-EO
(Expert Opinion)
• Consensus of expert opinion based on clinical experience
COR and LOE are determined independently (any COR may be paired with any LOE).
A recommendation with LOE C does not imply that the recommendation is weak. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.
* The outcome or result of the intervention should be specified (an improved clinical outcome or increased diagnostic accuracy or incremental prognostic information).
† For comparative-effectiveness recommendations (COR 1 and 2a; LOE A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.
‡ The method of assessing quality is evolving, including the application of standardized, widely-used, and preferably validated evidence grading tools; and for systematic reviews, the incorporation of an Evidence Review Committee.
COR indicates Class of Recommendation; EO, expert opinion; LD, limited data; LOE, Level of Evidence; NR, nonrandomized; R, randomized; and RCT, randomized controlled trial.
1.5. Class of Recommendation and Level of Evidence
The Class of Recommendation (COR) indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to
risk. The Level of Evidence (LOE) rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 2) (1).

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e33
1.6. Abbreviations
<table><tr><td>Abbreviation</td><td>Meaning/Phrase</td></tr><tr><td>2D</td><td>2-dimensional</td></tr><tr><td>3D</td><td>3-dimensional</td></tr><tr><td>ACE</td><td>angiotensin-converting enzyme</td></tr><tr><td>AF</td><td>atrial fibrillation</td></tr><tr><td>ARB</td><td>angiotensin receptor blocker</td></tr><tr><td>aPTT</td><td>activated partial thromboplastin time</td></tr><tr><td>AR</td><td>aortic regurgitation</td></tr><tr><td>AS</td><td>aortic stenosis</td></tr><tr><td>AVR</td><td>aortic valve replacement</td></tr><tr><td>BAV</td><td>bicuspid aortic valve</td></tr><tr><td>BNP</td><td>B-type natriuretic peptide</td></tr><tr><td>CABG</td><td>coronary artery bypass graft surgery</td></tr><tr><td>CAD</td><td>coronary artery disease</td></tr><tr><td>CMR</td><td>cardiac magnetic resonance</td></tr><tr><td>COR</td><td>Class of Recommendation</td></tr><tr><td>CT</td><td>computed tomography</td></tr><tr><td>ECG</td><td>electrocardiogram</td></tr><tr><td>GDMT</td><td>guideline-directed management and therapy</td></tr><tr><td>HF</td><td>heart failure</td></tr><tr><td>IE</td><td>infective endocarditis</td></tr><tr><td>INR</td><td>international normalized ratio</td></tr><tr><td>LA</td><td>left atrium (left atrial)</td></tr><tr><td>LMWH</td><td>low-molecular-weight heparin</td></tr><tr><td>LOE</td><td>Level of Evidence</td></tr><tr><td>LV</td><td>left ventricle (left ventricular)</td></tr><tr><td>LVEDD</td><td>left ventricular end-diastolic dimension</td></tr><tr><td>LVEF</td><td>left ventricular ejection fraction</td></tr><tr><td>LVESD</td><td>left ventricular end-systolic dimension</td></tr><tr><td>MDT</td><td>multidisciplinary team</td></tr><tr><td>MR</td><td>mitral regurgitation</td></tr><tr><td>MS</td><td>mitral stenosis</td></tr><tr><td>NOAC</td><td>non-vitamin K oral anticoagulant</td></tr><tr><td>NYHA</td><td>New York Heart Association</td></tr><tr><td>PCI</td><td>percutaneous coronary intervention</td></tr><tr><td>PET</td><td>positron emission tomography</td></tr><tr><td>PMBC</td><td>percutaneous mitral balloon commissurotomy</td></tr><tr><td>RCT</td><td>randomized controlled trial</td></tr><tr><td>RV</td><td>right ventricle (right ventricular)</td></tr><tr><td>SAVR</td><td>surgical aortic valve replacement</td></tr><tr><td>TAVI</td><td>transcatheter aortic valve implantation</td></tr><tr><td>TEE</td><td>transesophageal echocardiography (echocardiogram)</td></tr><tr><td>TEER</td><td>transcatheter edge-to-edge repair</td></tr><tr><td>TR</td><td>tricuspid regurgitation</td></tr><tr><td>TTE</td><td>transthoracic echocardiography (echocardiogram)</td></tr><tr><td>UFH</td><td>unfractionated heparin</td></tr><tr><td>VHD</td><td>valvular heart disease</td></tr><tr><td>ViV</td><td>valve-in-valve</td></tr><tr><td>VKA</td><td>vitamin K antagonist</td></tr></table>
2. GENERAL PRINCIPLES
2.1. Evaluation of the Patient With Known or Suspected Native VHD
Patients with VHD may present with a heart murmur, symptoms, or incidental findings of valvular abnormalities on noninvasive testing. Irrespective of the presentation, all patients with known or suspected VHD should undergo an initial meticulous history and physical examination. A detailed physical examination should be performed to diagnose and assess the severity of valve lesions. An electrocardiogram (ECG) to confirm heart rhythm and a chest x-ray to assess the presence or absence of pulmonary congestion or other lung pathology may be helpful in the initial assessment of patients with known or suspected VHD. A comprehensive transthoracic echocardiogram (TTE) with 2-dimensional (2D) imaging and Doppler interrogation should be performed for diagnosis and evaluation of known or suspected VHD. The TTE also provides additional information, such as the effect of the valve lesion on the cardiac chambers and great vessels, as well as an assessment of other valve lesions. To determine the optimal treatment for a patient with VHD, ancillary testing may be required, such as transesophageal echocardiography (TEE), computed tomography (CT), cardiac magnetic resonance (CMR) imaging, stress testing, Holter monitoring, diagnostic hemodynamic cardiac catheterization, or positron emission tomography (PET) combined with CT imaging. If intervention is contemplated, surgical or procedural risk should be estimated and other factors also considered, including comorbidities, frailty, and patient preferences and values (Table 3).
2.2. Definitions of Severity of Valve Disease
Classification of valve disease severity is based on multiple criteria, including symptoms, valve anatomy, valve hemodynamics and the effects of valve dysfunction on ventricular and vascular function (eg, end-organ damage). Surgical and transcatheter interventions are performed primarily on patients with severe VHD, but diagnosis, patient education, periodic monitoring, and medical therapy are essential elements in the management of patients at risk of VHD and with mild to moderate valve dysfunction. This document provides a classification of the progression of VHD, with 4 stages (A to D). Indications for intervention and periodic monitoring are dependent on 1) the presence or absence of symptoms, 2) the severity of VHD, 3) the response of the LV and/or RV to volume or pressure overload caused by VHD, and 4) the effects on the pulmonary or systemic circulation (Table 4). The purpose of valvular intervention is to improve

e34
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
TABLE 3 Evaluation of Patients With Known or Suspected VHD
<table><tr><td>Reason</td><td colspan="2">Test</td><td>Indication</td></tr><tr><td rowspan="3">Initial evaluation: All patients with known or suspected valve disease</td><td>TTE*</td><td>Establishes chamber size and function, valve morphology and severity, and effect on pulmonary and systemic circulation</td><td></td></tr><tr><td>History and physical</td><td>Establishes symptom severity, comorbidities, valve disease presence and severity, and presence of HF</td><td></td></tr><tr><td>ECG</td><td>Establishes rhythm, LV function, and presence or absence of hypertrophy</td><td></td></tr><tr><td rowspan="5">Further diagnostic testing: Information required for equivocal symptom status, discrepancy between examination and echocardiogram, further definition of valve disease, or assessing response of the ventricles and pulmonary circulation to load and to exercise</td><td>Chest x-ray</td><td>Important for the symptomatic patient, establishes heart size and presence or absence of pulmonary vascular congestion, intrinsic lung disease, and calcification of aorta and pericardium</td><td></td></tr><tr><td>TEE</td><td>Provides high-quality assessment of mitral and prosthetic valve, including definition of intracardiac masses and possible associated abnormalities (eg, intracardiac abscess, LA thrombus)</td><td></td></tr><tr><td>CMR</td><td>Provides assessment of LV volumes and function, valve severity, and aortic disease</td><td></td></tr><tr><td>PET CT</td><td>Aids in determination of active infection or inflammation</td><td></td></tr><tr><td>Stress testing</td><td>Gives an objective measure of exercise capacity</td><td></td></tr><tr><td rowspan="6">Further risk stratification: Information on future risk of the valve disease, which is important for determination of timing of intervention</td><td>Catheterization</td><td>Provides measurement of intracardiac and pulmonary pressures, valve severity, and hemodynamic response to exercise and drugs</td><td></td></tr><tr><td>Biomarkers</td><td>Provide indirect assessment of filling pressures and myocardial damage</td><td></td></tr><tr><td>TTE strain</td><td>Helps assess intrinsic myocardial performance</td><td></td></tr><tr><td>CMR</td><td>Assesses fibrosis by gadolinium enhancement</td><td></td></tr><tr><td>Stress testing</td><td>Provides prognostic markers</td><td></td></tr><tr><td>Procedural risk</td><td>Quantified by STS (Predicted Risk of Mortality) and TAVI scores</td><td></td></tr><tr><td rowspan="5">Preprocedural testing: Testing required before valve intervention</td><td>Frailty score</td><td>Provides assessment of risk of procedure and chance of recovery of quality of life</td><td></td></tr><tr><td>Dental examination</td><td>Rules out potential infection sources</td><td></td></tr><tr><td>CT coronary angiogram or invasive coronary angiogram</td><td>Gives an assessment of coronary anatomy</td><td></td></tr><tr><td>CT: Peripheral</td><td>Assesses femoral access for TAVI and other transcatheter procedures</td><td></td></tr><tr><td>CT: Cardiac</td><td>Assesses suitability for TAVI and other transcatheter procedures</td><td></td></tr></table>
*TTE is the standard initial diagnostic test in the initial evaluation of patients with known or suspected VHD.
CMR indicates cardiac magnetic resonance; CT, computed tomography; ECG, electrocardiogram; HF, heart failure; LV, left ventricular; PET, positron emission tomography; STS, Society of Thoracic Surgeons; TAVI, transcatheter aortic valve implantation; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; and VHD, valvular heart disease.
symptoms, prolong survival, and minimize the risk of VHD-related complications, such as irreversible ventricular dysfunction, pulmonary hypertension, stroke, and atrial fibrillation (AF). Thus, the criteria for “severe” VHD are based on predictors of clinical outcome from observational studies, registry data, and randomized clinical trials (RCTs) of patients with VHD. Of course, severity is a continuous variable; categorizing disease into stages, from A to D, simply provides a framework, or starting point, for diagnosis and management, and it is recognized that not all patients will fit perfectly into a specific stage. Some patients will have symptoms or end-organ damage with valve hemodynamics that do not quite meet specific disease severity criteria, and numerical measures may not match exactly across all categories. Conversely, other patients may remain asymptomatic without obvious evidence of end-organ damage despite apparently severe VHD. Criteria for the stages of each individual valve lesion
are listed in Section 3.1 (Table 13), Section 4.2 (Table 15), Section 6.1 (Table 16), Section 7.2 (Table 17), Section 7.3 (Table 18), and Section 8.1 (Table 20).
TABLE 4 Stages of VHD
<table><tr><td>Stage</td><td>Definition</td><td>Description</td></tr><tr><td>A</td><td>At risk</td><td>Patients with risk factors for development of VHD</td></tr><tr><td>B</td><td>Progressive</td><td>Patients with progressive VHD (mild to moderate severity and asymptomatic)</td></tr><tr><td>C</td><td>Asymptomatic severe</td><td>Asymptomatic patients who have the criteria for severe VHD:C1: Asymptomatic patients with severe VHD in whom the LV or RV remains compensatedC2: Asymptomatic patients with severe VHD with decompensation of the LV or RV</td></tr><tr><td>D</td><td>Symptomatic severe</td><td>Patients who have developed symptoms as a result of VHD</td></tr></table>
LV indicates left ventricle; RV, right ventricle; and VHD, valvular heart disease.

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e35
TABLE 5 Frequency of Echocardiograms in Asymptomatic Patients With VHD and Normal LV Function
<table><tr><td colspan="5">Type of Valve Lesion</td></tr><tr><td>Stage</td><td>Aortic Stenosis*</td><td>Aortic Regurgitation</td><td>Mitral Stenosis</td><td>Mitral Regurgitation</td></tr><tr><td rowspan="2">Progressive (Stage B)</td><td>■ Every 3-5 y (mild severity; \( V_{max} \) 2.0-2.9 m/s)</td><td>■ Every 3-5 y (mild severity)</td><td>Every 3-5 y (MV area &gt;1.5 cm2)</td><td>■ Every 1-2 y (moderate severity)</td></tr><tr><td>■ Every 1-2 y moderate severity; \( V_{max} \) 3.0-3.9 m/s)</td><td>■ Every 1-2 y (moderate severity)</td><td></td><td>■ Every 3-5 y (mild severity)</td></tr><tr><td>Severe asymptomatic (Stage C1)</td><td>Every 6-12 mo (\( V_{max} \) ≥4 m/s)</td><td>Every 6-12 mo Dilating LV: More frequently</td><td>■ Every 1-2 y (MV area 1.0-1.5 cm2)■ Every year (MV area &lt;1.0 cm2)</td><td>Every 6-12 mo Dilating LV: More frequently</td></tr></table>
Patients with mixed valve disease may require serial evaluations at intervals earlier than recommended for single-valve lesions. These intervals apply to most patients with each valve lesion and do not take into consideration the etiology of the valve disease.
*With normal stroke volume.
LV indicates left ventricle; MV, mitral valve; VHD, valvular heart disease; and \( V_{max} \) , maximum velocity.
2.3. Diagnosis and Follow-Up
2.3.1. Diagnostic Testing: Initial Diagnosis
TTE is the standard diagnostic test in the initial evaluation of patients with known or suspected VHD (1-4). TTE allows accurate assessment of valve anatomy and etiology, concurrent valve disease, and associated abnormalities, such as aortic dilation. Left ventricular (LV) anatomy and function are characterized by linear dimensions, as well as by 2D and 3D volumes and ejection fraction (LVEF), and it is recognized that decisions are most robust when based on sequential studies, given the inherent measurement variability for these parameters (5). Doppler echocardiography provides accurate noninvasive determination of valve hemodynamics (1,2,6). For stenotic lesions, key measurements are maximum velocity, mean gradient, and valve area. For regurgitant lesions, calculation of regurgitant orifice area, volume, and fraction is performed, when possible in the context of a multiparameter severity grade based on color Doppler imaging, continuous- and pulsed-wave Doppler recordings, and the presence or absence of distal flow reversals. Pulmonary systolic pressure also is estimated, along with qualitative evaluation of right ventricular (RV) size and function (7). In selected patients, additional testing, such as stress testing, TEE, cardiac catheterization, and CT or CMR imaging, might be indicated. However, both the performance and interpretation of these diagnostic tests require meticulous attention to detail, as well as expertise in cardiac imaging and evaluation of hemodynamics. Because echocardiography remains the mainstay of the initial evaluation of all patients with VHD, it is recommended that the laboratory be an Intersocietal Accreditation Commission (IAC)-accredited program (8).
2.3.2. Diagnostic Testing: Changing Signs or Symptoms
Patients with VHD should be instructed to promptly report any change in symptom status. The onset of symptoms or a change in the physical examination should
raise concern about the cardiac response to the valve lesion, necessitating a repeat TTE. A repeat comprehensive TTE study can determine whether symptoms are caused by progressive valve dysfunction, deterioration of the ventricular response to the volume or pressure overload, or another etiology. New signs on physical examination also warrant a repeat TTE (1-7). This requires that patients with known VHD have access to a primary care provider and a cardiovascular specialist.
2.3.3. Diagnostic Testing: Routine Follow-Up
After initial evaluation of an asymptomatic patient with VHD, the clinician should continue regular follow-up with periodic examinations and TTE. The purpose of follow-up is to prevent the irreversible consequences of severe VHD, primarily affecting the status of the ventricles and pulmonary circulation, which may occur in the absence of symptoms. At a minimum, a yearly history and physical examination are necessary. The frequency of repeat 2D and Doppler echocardiography is based on the type and severity of the valve lesion, the known rate of progression of the specific valve lesion, and the effect of the valve lesion on the affected ventricle (Table 5) (1-14). Patients with Stages C2 and D disease are not included in this table because they would be considered candidates for intervention. The follow-up interval may be extended in patients with mild regurgitation who show no change over a 10- to 15-year period. In addition to routine periodic imaging, the onset of symptoms or a change in the physical examination should raise concern about the cardiac response to the valve lesion, necessitating a repeat TTE.
2.3.4. Diagnostic Testing: Cardiac Catheterization
Although TTE is now able to provide the required anatomic and hemodynamic information in most patients with VHD, there is still a subset of patients in whom hemodynamic catheterization is necessary to ensure that the proper decision about treatment is made. If noninvasive testing yields inconclusive data, particularly in the

e36
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
symptomatic patient, or if there is a discrepancy between the noninvasive tests and clinical findings, a hemodynamic cardiac catheterization with direct intracardiac measurements of transvalvular pressure gradients and cardiac output measurements provides valuable clinical information. Severity of stenosis may be underestimated when imaging is difficult or when the Doppler beam is not aligned parallel to the direction of the high-velocity jet. Severity of valve regurgitation may be overestimated or underestimated if the image or Doppler data quality is suboptimal. Contrast angiography is sometimes useful for a semiquantitative assessment of the severity of regurgitation in those instances in which the noninvasive results are discordant with the physical examination (1). A major advantage of cardiac catheterization is the measurement of intracardiac pressures and pulmonary vascular resistance, which may further aid in decision-making about valve intervention. Diagnostic interventions that can be performed in the catheterization laboratory include the use of dobutamine in low-flow states, pulmonary vasodilators in pulmonary hypertension, and exercise hemodynamics in patients with discrepant symptoms (1,2). A hemodynamic catheterization needs to be done with meticulous attention to detail by persons with knowledge and expertise in assessing patients with VHD.
2.3.5. Diagnostic Testing: Exercise Testing
In a subset of patients, exercise stress testing will be of additional value in determining optimal therapy. Because of the slow, insidious rate of progression of many valve lesions, patients may deny symptoms as they gradually limit their activity level over several years to match the gradual limitations imposed by the valve lesion. In patients with an equivocal history of symptoms, exercise testing helps identify those who are truly symptomatic (1,2). Exercise stress testing (ie, examining the exercise capacity and blood pressure response) is of prognostic value in patients with asymptomatic valve disease and provides further information about the timing of a potential intervention (3-11). It is important that exercise
testing in patients with severe VHD always be performed by trained operators, with continuous monitoring of the ECG and blood pressure.
2.4. Basic Principles of Medical Therapy
In patients being evaluated for VHD, standard GDMT for cardiac risk factors, including hypertension, diabetes mellitus, and hyperlipidemia, should not be neglected. Heart-healthy lifestyle factors (exercising, consuming a healthy diet, not smoking, and maintaining a normal body size) are no different for patients with VHD than for the general population. Many patients with asymptomatic VHD feel better with regular aerobic exercise to improve cardiovascular fitness (1-3). Although heavy isometric repetitive training might increase LV afterload, resistive training with small free weights or repetitive isolated muscle training may be used to strengthen individual muscle groups. Most patients with LV systolic dysfunction and severe VHD will undergo intervention for the valve itself. However, if intervention is declined or not feasible, standard GDMT drug therapy for LV systolic dysfunction should be continued, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta blockers, aldosterone antagonists, and/or sacubitril/valsartan and biventricular pacing, as indicated in the guidelines for heart failure (HF) (1). In patients with stenotic valve lesions, abrupt lowering of blood pressure should be avoided (1). Rheumatic fever prophylaxis and infective endocarditis (IE) prophylaxis should be provided to appropriate groups of patients, as outlined in Sections 2.4.1 and 2.4.2. The maintenance of optimal oral health remains the most important component of an overall healthcare program in preventing IE. Influenza and pneumococcal vaccinations should follow standard recommendations in patients with VHD. For subsets of patients with AF and VHD, anticoagulation is discussed in Section 2.4.3.
2.4.1. Secondary Prevention of Rheumatic Fever
Recommendation for Secondary Prevention of Rheumatic Fever
<table><tr><td>COR</td><td>LOE</td><td>RECOMMENDATION</td></tr><tr><td>1</td><td>C-EO</td><td>1. In patients with rheumatic heart disease, secondary prevention of rheumatic fever is indicated (Tables 6 and 7) (1).</td></tr></table>
Synopsis
Rheumatic fever is an important cause of VHD worldwide, although it is less common in high-income countries. Rapid detection and treatment of streptococcal pharyngitis constitute primary prevention of rheumatic
fever. For patients with previous episodes of rheumatic fever or in those with evidence of rheumatic heart disease, long-term antistreptococcal prophylaxis is indicated for secondary prevention (1).

JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
e37
TABLE 6 Secondary Prevention of Rheumatic Fever
<table><tr><td>Antibiotics for Prevention</td><td>Dosage*</td></tr><tr><td>Penicillin G benzathine</td><td>1.2 million U intramuscularly every 4 wk†</td></tr><tr><td>Penicillin V potassium</td><td>200 mg orally twice daily</td></tr><tr><td>Sulfadiazine</td><td>1 g orally once daily</td></tr><tr><td>Macrolide or azalide antibiotic (for patients allergic to penicillin and sulfadiazine)‡</td><td>Varies</td></tr></table>
Adapted from Gerber et al. (1)
*In patients with documented valvular heart disease, the duration of rheumatic fever prophylaxis should be ≥10 y or until the patient is 40 y of age (whichever is longer). Lifelong prophylaxis may be recommended if the patient is at high risk of group A streptococcus exposure. Secondary rheumatic heart disease prophylaxis is required even after valve replacement.
†Administration every 3 wk is recommended in certain high-risk situations.
‡Macrolide antibiotics should not be used in persons taking other medications that inhibit cytochrome P450 3A, such as azole antifungal agents, HIV protease inhibitors, and some selective serotonin reuptake inhibitors.
Recommendation-Specific Supportive Text
1. Recurrent rheumatic fever is associated with a worsening of rheumatic heart disease. However, infection with group A streptococcus does not have to be symptomatic to trigger a recurrence, and rheumatic fever can recur even when the symptomatic infection is treated.
Recommendations for IE Prophylaxis
Referenced studies that support the recommendations are summarized in Online Data Supplement 1.
<table><tr><td>COR</td><td>LOE</td><td>RECOMMENDATIONS</td></tr><tr><td>2a</td><td>C-LD</td><td>1. Antibiotic prophylaxis is reasonable before dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa in patients with VHD who have any of the following (1-9):a. Prosthetic cardiac valves, including transcatheter-implanted prostheses and homografts.b. Prosthetic material used for cardiac valve repair, such as annuloplasty rings, chords, or clips.c. Previous iE.d. Unrepaired cyanotic congenital heart disease or repaired congenital heart disease, with residual shunts or valvular regurgitation at the site of or adjacent to the site of a prosthetic patch or prosthetic device.e. Cardiac transplant with valve regurgitation attributable to a structurally abnormal valve.</td></tr><tr><td>3: No Benefit</td><td>B-NR</td><td>2. In patients with VHD who are at high risk of IE, antibiotic prophylaxis is not recommended for nondental procedures (eg, TEE, esophagogastroduodenoscopy, colonoscopy, or cystoscopy) in the absence of active infection (10,11).</td></tr></table>
Synopsis
With the absence of RCTs addressing the efficacy of antibiotic prophylaxis for prevention of IE (1,12-14) and given uncertainty about which patient populations are at highest risk, these recommendations are based on pathophysiological considerations, limited data, and clinical expertise. A prospective study demonstrated that prophylactic antibiotics given to patients for what is typically considered a high-risk dental procedure reduced but did not eliminate the incidence of bacteremia (2). A 2013 Cochrane Database systematic review of antibiotic prophylaxis for the prevention of IE in dentistry concluded
that there is no evidence to determine whether antibiotic prophylaxis is effective or ineffective, highlighting the need for further study of this long-standing clinical dilemma (1). Epidemiological data conflict with regard to changes in the incidence of IE after adoption of more limited antibiotic prophylaxis guidelines (15-22). The consensus of the writing committee is that antibiotic prophylaxis is reasonable for the subset of patients at highest risk of developing IE and at high risk of experiencing adverse outcomes from IE. There is no evidence for IE prophylaxis in gastrointestinal procedures or genitourinary procedures, in the absence of known active infection.

e38
Otto et al.
2020 ACC/AHA Guideline for the Management of Valvular Heart Disease
JACC VOL. 77, NO. 4, 2021
FEBRUARY 2, 2021:e25-197
Recommendation-Specific Supportive Text
1. The risk of developing IE is highest in patients with a prosthetic valve, prior IE, or congenital heart disease with residual flow disturbances (3). IE has been reported to occur after transcatheter aortic valve implantation (TAVI) at rates equal to or exceeding those associated with surgical aortic valve replacement (SAVR) and is associated with a high 1-year mortality rate of 75% (23,24). IE may also occur after valve repair with prosthetic material, which results in high in-hospital and 1-year mortality rates, even with surgical intervention (25,26). IE appears to be more common in heart transplant recipients than in the general population, according to limited data (3). The risk of IE is highest in the first 6 months after transplantation because of endothelial disruption, high-intensity immunosuppressive therapy, frequent central venous catheter access, and frequent endomyocardial biopsies (3). Persons at risk of IE can reduce potential sources of bacterial seeding by maintaining optimal oral health through regular professional dental care and the use of appropriate dental products, such as manual, powered, and ultrasonic toothbrushes; dental floss; and other plaque-removal devices.
2. Transient bacteremia is commonly seen in routine activities such as brushing teeth and flossing (20% to 68%), using toothpicks (20% to 40%), and simply
chewing food (7% to 51%). The incidence of IE after most procedures is low, with no controlled data supporting the benefit of antibiotic prophylaxis. Indiscriminate use of antibiotics can be associated with the development of resistant organisms, Clostridium difficile colitis, unnecessary expense, and drug toxicity. The rate of transient bacteremia during or immediately after endoscopy is 2% to 5%, and the organisms typically identified are unlikely to cause IE (11,27,28). The rate of bacteremia does not increase with biopsy, polypectomy, or sphincterotomy. Some gastrointestinal procedures are associated with 

…(851,765 more chars)