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 2020 by the American College of Cardiology Foundation and the American Heart Association, Inc. ACC/AHA CLINICAL PRACTICE GUIDELINE 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 Circulation https://www.ahajournals.org/journal/circ 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 ACC/AHA Joint Committee on Clinical Practice Guidelines Members, see page *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 Heart Association 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. Circulation. 2021;143:e72-e227. doi: 10.1161/CIR.0000000000000923 Key Words: AHA Scientific Statements anticoagulation therapy aortic regurgitation aortic stenosis bicuspid aortic valve cardiac surgery guidelines infective endocarditis mitral regurgitation mitral stenosis mitral transcatheter edge-to-edge repair prosthetic valve pulmonic regurgitation pulmonic stenosis transcatheter aortic valve replacement or implantation tricuspid regurgitation tricuspid stenosis valvular heart disease CLINICAL STATEMENTS AND GUIDELINES TABLE OF CONTENTS Top 10 Take-Home Messages . . . . . . . . . . . . . . . . . . . . . . . . e74 Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e75 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e76 1.1. Methodology and Evidence Review . . . . . . . . . . . . e76 1.2. Organization of the Writing Committee . . . . . . . . e76 1.3. Document Review and Approval . . . . . . . . . . . . . . e76 1.4. Scope of the Guideline . . . . . . . . . . . . . . . . . . . . . . e76 1.5. Class of Recommendation and Level of Evidence e77 1.6. Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e77 2. General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e78 2.1. Evaluation of the Patient With Known or Suspected Native VHD . . . . . . . . . . . . . . . . . . . . . . . e78 2.2. Definitions of Severity of Valve Disease . . . . . . . . . e78 2.3. Diagnosis and Follow-Up e78 2.3.1. Diagnostic Testing: Initial Diagnosis 30 . . . e78 2.3.2. Diagnostic Testing: Changing Signs or Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . e80 2.3.3. Diagnostic Testing: Routine Follow-Up . . . . e80 2.3.4. Diagnostic Testing: Cardiac Catheterization . e81 2.3.5. Diagnostic Testing: Exercise Testing . . . . . . e81 2.4. Basic Principles of Medical Therapy . . . . . . . . . . . . e81 2.4.1. Secondary Prevention of Rheumatic Fever . e82 2.4.2. IE Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . e82 2.4.3. Anticoagulation for AF in Patients With VHD e83 2.5. Evaluation of Surgical and Interventional Risk . . . e85 2.6. The Multidisciplinary Heart Valve Team and Heart Valve Centers . . . . . . . . . . . . . . . . . . . . . . . . . e86 2.7. Management of Patients With VHD After Valve Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e88 2.7.1. Procedural Complications . . . . . . . . . . . . . . e89 2.7.2. Primary and Secondary Risk Factor Evaluation and Treatment . . . . . . . . . . . . . . e89 2.7.3. Persistent Symptoms After Valve Intervention . e89 2.7.4. Periodic Imaging After Valve Intervention . e89 3. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e90 3.1. Stages of Valvular AS . . . . . . . . . . . . . . . . . . . . . . . . e90 3.2. Aortic Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e90 3.2.1. Diagnosis and Follow-Up . . . . . . . . . . . . . . . e90 3.2.2. Medical Therapy . . . . . . . . . . . . . . . . . . . . . . e93 3.2.3. Timing of Intervention . . . . . . . . . . . . . . . . . e94 3.2.4. Choice of Intervention . . . . . . . . . . . . . . . . . e97 4. Aortic Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . e104 4.1. Acute Aortic Regurgitation . . . . . . . . . . . . . . . . . . e104 4.1.1. Diagnosis of AR . . . . . . . . . . . . . . . . . . . . . e104 4.1.2. Intervention . . . . . . . . . . . . . . . . . . . . . . . . . e104 4.2. Stages of Chronic AR . . . . . . . . . . . . . . . . . . . . . . . e104 4.3. Chronic AR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e106 4.3.1. Diagnosis of Chronic AR . . . . . . . . . . . . . . e106 4.3.2. Medical Therapy . . . . . . . . . . . . . . . . . . . . . e106 4.3.3. Timing of Intervention . . . . . . . . . . . . . . . . e107 5. Bicuspid Aortic Valve . . . . . . . . . . . . . . . . . . . . . . . . . . . e109 5.1. BAV and Associated Aortopathy . . . . . . . . . . . . . e109 5.1.1. Diagnosis and Follow-Up of BAV . . . . . . . e109 5.1.2. Interventions for Patients With BAV . . . . . e109 6. Mitral Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e112 6.1. Stages of MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e113 6.2. Rheumatic MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . e113 6.2.1. Diagnosis and Follow-Up of Rheumatic MS e113 6.2.2. Medical Therapy . . . . . . . . . . . . . . . . . . . . . e115 6.2.3. Intervention . . . . . . . . . . . . . . . . . . . . . . . e116 6.3. Nonrheumatic Calcific MS . . . . . . . . . . . . . . . . . e118 7. Mitral Regurgitation . . . . . . . . . . . . . . . . . . . . . . . . . . . e119 7.1. Acute MR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e119 7.1.1. Diagnosis of Acute MR . . . . . . . . . . . . . . e119 7.1.2. Medical Therapy . . . . . . . . . . . . . . . . . . . . e119 7.1.3. Intervention . . . . . . . . . . . . . . . . . . . . . . . e119 7.2. Chronic Primary MR . . . . . . . . . . . . . . . . . . . . . . e119 7.2.1. Stages of Chronic Primary MR . . . . . . . . e119 7.2.2. Diagnosis and Follow-Up of Chronic Primary MR . . . . . . . . . . . . . . . . . . . . . . . . e120 7.2.3. Medical Therapy . . . . . . . . . . . . . . . . . . . . e123 7.2.4. Intervention . . . . . . . . . . . . . . . . . . . . . . . e124 7.3. Chronic Secondary MR . . . . . . . . . . . . . . . . . . . . e126 7.3.1. Stages of Chronic Secondary MR . . . . . . e126 7.3.2. Diagnosis of Chronic Secondary MR . . . e127 7.3.3. Medical Therapy . . . . . . . . . . . . . . . . . . . . e128 7.3.4. Intervention . . . . . . . . . . . . . . . . . . . . . . . e129 8. Tricuspid Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . e131 8.1. Classification and Stages of TR . . . . . . . . . . . . . e131 8.2. Tricuspid Regurgitation . . . . . . . . . . . . . . . . . . . . e131 8.2.1. Diagnosis of TR . . . . . . . . . . . . . . . . . . . . e131 8.2.2. Medical Therapy . . . . . . . . . . . . . . . . . . . . e132 8.2.3. Timing of Intervention . . . . . . . . . . . . . . . e133 9. Pulmonic Valve Disease e135 10. Mixed Valve Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . e135 10.1. Diagnosis of Mixed VHD . . . . . . . . . . . . . . . . . . e135 10.2. Timing of Intervention for Mixed VHD . . . . . . . e136 10.2.1. Intervention for Mixed AS and AR e136 10.2.2. Intervention for Mixed AS and MR . . . e136 10.2.3. Intervention for Mixed MS and MR . . . e137 10.2.4. Intervention for Mixed MS and AR . . . e137 10.2.5. Intervention for Mixed MS and AS . . . e137 11. Prosthetic Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e137 11.1. Evaluation and Selection of Prosthetic Valves . e137 11.1.1. Diagnosis and Follow-Up of Prosthetic Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . e137 11.1.2. Selection of Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve . e139 11.2. Antithrombotic Therapy . . . . . . . . . . . . . . . . . . . e142 11.3. Bridging Therapy e146 11.4. Excessive Anticoagulation and Serious Bleeding With Prosthetic Valves . . . . . . . . . . . . e148 11.5. Thromboembolic Events With Prosthetic Valves . e148 11.6. Acute Mechanical Valve Thrombosis . . . . . . . . e149 11.6.1. Diagnosis of Acute Mechanical Valve Thrombosis . . . . . . . . . . . . . . . . . . . . . . e149 11.6.2. Intervention . . . . . . . . . . . . . . . . . . . . . e150 11.7. Bioprosthetic Valve Thrombosis . . . . . . . . . . . . . e150 11.7.1. Diagnosis of Bioprosthetic Valve Thrombosis . . . . . . . . . . . . . . . . . . . . . . e150 11.7.2. Medical Therapy . . . . . . . . . . . . . . . . . . e150 11.8. Prosthetic Valve Stenosis . . . . . . . . . . . . . . . . . . e151 11.8.1.Diagnosis of Prosthetic Valve Stenosis . . . . e151 11.8.2. Intervention for Prosthetic Valve Stenosis . e152 11.9. Prosthetic Valve Regurgitation . . . . . . . . . . . . . . e152 11.9.1. Diagnosis of Prosthetic Valve Regurgitation e153 11.9.2. Medical Therapy . . . . . . . . . . . . . . . . . . e154 11.9.3. Intervention . . . . . . . . . . . . . . . . . . . . . . e154 CLINICAL STATEMENTS AND GUIDELINES 12. Infective Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . e155 12.1. Classification of Endocarditis . . . . . . . . . . . . . . e155 12.2. Diagnosis of IE . . . . . . . . . . . . . . . . . . . . . . . . . . e156 12.3. Medical Therapy . . . . . . . . . . . . . . . . . . . . . . . . e160 12.4. Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . e162 13. Pregnancy and VHD . . . . . . . . . . . . . . . . . . . . . . . . . . . e165 13.1. Initial Management of Women With VHD Before and During Pregnancy . . . . . . . . . . . . . e165 13.1.1. Medical Therapy for Women With VHD Before and During Pregnancy e166 13.1.2. Intervention for Women With Native VHD Before and During Pregnancy e166 13.2. Prosthetic Valves in Pregnant Women . . . . . . . e169 13.2.1. Initial Management . . . . . . . . . . . . . . . e169 13.2.2. Anticoagulation for Pregnant Women With Mechanical Prosthetic Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . e170 14. Surgical Considerations . . . . . . . . . . . . . . . . . . . . . . . . e174 14.1. Evaluation and Management of CAD in Patients With VHD . . . . . . . . . . . . . . . . . . . . . . . e174 14.1.1. Management of CAD in Patients Undergoing TAVI . . . . . . . . . . . . . . . . . e174 14.1.2. Management of CAD in Patients Undergoing Valve Surgery . . . . . . . . . e176 14.2. Intervention for AF in Patients With VHD . . . . e177 15. Noncardiac Surgery in Patients With VHD . . . . . . . . . e178 15.1. Diagnosis of Patients With VHD Undergoing Noncardiac Surgery . . . . . . . . . . . . . . . . . . . . . . e178 15.2. Management of the Symptomatic Patient . . . e179 15.3. Management of the Asymptomatic Patient . . e180 16. Evidence Gaps and Future Directions . . . . . . . . . . . . . e181 16.1. Prevention of Valve Disease: Stage A . . . . . . . e181 16.2. Medical Therapy to Treat or Prevent Disease Progression: Stage B . . . . . . . . . . . . . . . . . . . . . e182 16.3. Optimal Timing of Intervention: Stage C . . . . e182 16.4. Better Options for Intervention: Stage D e182 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e184 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) . . . . . . . . . . . . . . . . . . . . . . . . . e222 Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive) . . . . . . . . . . . . . . . . . . . e224 TOP 10 TAKE-HOME MESSAGES 1. Disease stages in patients with valvular heart dis- ease 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 find- ings should be correlated with the results of noninvasive testing (ie, ECG, chest x-ray, trans- thoracic echocardiogram). If there is discordance between the physical examination and initial noninvasive testing, consider further noninva- sive (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 anti- coagulant, should be made in a shared decision- making process based on the CHA2 -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 ven- tricular 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 implan- tation are expanding as a result of multiple randomized trials of transcatheter aortic valve implantation versus surgical aortic valve replace- ment. 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 with type of valve (mechanical versus bioprosthetic) and type of approach (transcatheter versus surgical). 7. Indications for intervention for valvular regurgi- tation are relief of symptoms and prevention of the irreversible long-term consequences of left ventricular volume overload. Thresholds for inter- vention 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 regurgi- tation who remain severely symptomatic despite guideline-directed management and therapy for heart failure. 9. Patients presenting with severe symptomatic iso- lated tricuspid regurgitation, commonly associ- ated with device leads and atrial fibrillation, may benefit from surgical intervention to reduce symp- toms and recurrent hospitalizations if done before CLINICAL STATEMENTS AND GUIDELINES 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 sci- entific evidence into clinical practice guidelines with recom- mendations to improve cardiovascular health. These guide- lines, 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 guide- lines 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 car- diovascular 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 in- tent 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, cir- cumstances, and should not replace clinical judgment. Clinical Implementation Management, in accordance with guideline recom- mendations, is effective only when followed by both practitioners and patients. Adherence to recommen- dations can be enhanced by shared decision-making between clinicians and patients, with patient engage- ment in selecting interventions on the basis of individ- ual values, preferences, and associated conditions and comorbidities. Methodology and Modernization The ACC/AHA Joint Committee on Clinical Practice Guidelines (Joint Committee) continuously reviews, up- dates, and modifies guideline methodology on the ba- sis 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 fa- cilitate dissemination of information to healthcare pro- fessionals 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 con- siderations, in certain guidelines, when appropriate and feasible, an analysis of value for a drug, device, or in- tervention may be performed in accordance with the To ensure that guideline recommendations remain current, new data will be reviewed on an ongoing ba- sis 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 practice-changing science. The previous designations of full revision and focused update will be phased out. For additional information and poli- cies on guideline development, readers may consult the ACC/AHA guideline methodology manual4 and other Selection of Writing Committee Members The Joint Committee strives to ensure that the guide- line writing committee members have requisite content expertise and are representative of the broader cardio- vascular community. Experts are selected across a spec- trum 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 meth- ods to ensure that documents are developed without bias or improper influence. The complete policy on re- lationships with industry and other entities (RWI) can be found at https://www.acc.org/guidelines/about- guidelines-and-clinical-documents/relationships-with- industry-policy. Appendix 1 of the guideline lists writing committee members relevant RWI; for the purposes of CLINICAL STATEMENTS AND GUIDELINES full transparency, their comprehensive disclosure infor- mation is available online (https://www.ahajournals.org/ hensive disclosure information for the Joint Commit- tee is also available at https://www.acc.org/guidelines/ about-guidelines-and-clinical-documents/guidelines- and-documents-task-forces. Evidence Review and Evidence Review Committees In developing recommendations, the writing com- mittee uses evidence-based methodologies that are based on all available data.4 5 Literature searches fo- cus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and descriptive studies, case series, cohort studies, sys- tematic reviews, and expert opinion. Only key refer- ences are cited. An independent evidence review committee is commissioned when there are one or more questions deemed of utmost clinical importance that merit for- mal 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 bio- statisticians. Recommendations developed by the writing committee on the basis of the systematic re- view are marked SR . Guideline-Directed Management and Therapy The term guideline-directed management and therapy (GDMT) encompasses clinical evaluation, diagnos- tic testing, and both pharmacological and procedural treatments. For these and all recommended drug treat- ment regimens, the reader should confirm dosage with product insert material and evaluate for contraindica- tions 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 1.1. 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 limit- ed to the following: valvular heart disease, aortic steno- sis, aortic regurgitation, bicuspid aortic valve, mitral ste- nosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonic stenosis, pulmonic regurgita- tion, 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, sur- geons, 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 commit- tee and is published in this document (Appendix 2). 1.4. Scope of the Guideline The focus of this guideline is the diagnosis and man- agement of adult patients with valvular heart disease (VHD). A full revision of the original 1998 VHD guide- line was made in 2006, and an update was made in 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 war- ranted by new evidence or a better understanding of CLINICAL STATEMENTS AND GUIDELINES 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 recommenda- tions 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 sub- sections 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 life- style modifications and medications that constitute components of GDMT. For both GDMT and other rec- ommended drug treatment regimens, the reader is advised to confirm dosages with product insert mate- rial 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. 1.5. Class of Recommendation and Level of Evidence The Class of Recommendation (COR) indicates the strength of recommendation, encompassing the esti- mated 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 Table 1. Associated Guidelines and Related References Title Organization Publication Year (Reference) Recommendations for Evaluation of the Severity of Native Valvular Regurgitation With Two-Dimensional and Doppler Echocardiography European Association of Echocardiography Recommendations for the Assessment of Valvular Regurgitation, Part 2: Mitral and Tricuspid Regurgitation (Native Valve Disease) Guidelines for the Management of Patients With Atrial Fibrillation ACC/AHA/ESC 2006, 2008, 20197 9 Guidelines for the Management of Adults With Congenital Heart Disease ACC/AHA 201810 Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice EAE/ASE 200911 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 Guidelines for the Evaluation of Valvular Regurgitation After Percutaneous Valve Repair or Replacement: A Report from the American Society of Echocardiography Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound ASE 200914 Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ACCF/AHA 201115 Guidelines on the Management of Cardiovascular Diseases During Pregnancy ESC 2011, 201817, 18 Antithrombotic and Thrombolytic Therapy for Valvular Disease: Antithrombotic Therapy and Prevention of Thrombosis ACCP 201219 Guidelines on the Management of Valvular Heart Disease ESC/EACTS 201220 Guideline for the Management of Heart Failure ACCF/AHA 201722 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. Abbreviation Meaning/Phrase ACE angiotensin-converting enzyme AF atrial fibrillation ARB angiotensin receptor blocker aPTT activated partial thromboplastin time AR aortic regurgitation AS aortic stenosis AVR aortic valve replacement BAV bicuspid aortic valve BNP B-type natriuretic peptide CABG coronary artery bypass graft surgery CAD coronary artery disease CMR cardiac magnetic resonance COR Class of Recommendation CT computed tomography ECG electrocardiogram GDMT guideline-directed management and therapy HF heart failure IE infective endocarditis INR international normalized ratio LA left atrium (left atrial) LMWH low-molecular-weight heparin CLINICAL STATEMENTS AND GUIDELINES 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 abnormali- ties on noninvasive testing. Irrespective of the presenta- tion, all patients with known or suspected VHD should undergo an initial meticulous history and physical ex- amination. 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 ab- sence of pulmonary congestion or other lung pathology may be helpful in the initial assessment of patients with known or suspected VHD. A comprehensive transtho- racic echocardiogram (TTE) with 2-dimensional (2D) im- aging 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 treat- ment 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 moni- toring, diagnostic hemodynamic cardiac catheteriza- tion, or positron emission tomography (PET) combined with CT imaging. If intervention is contemplated, surgi- cal 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 hemo- dynamics and the effects of valve dysfunction on ven- tricular and vascular function (eg, end-organ damage). Surgical and transcatheter interventions are performed primarily on patients with severe VHD, but diagnosis, pa- tient education, periodic monitoring, and medical thera- py are essential elements in the management of patients at risk of VHD and with mild to moderate valve dysfunc- tion. This document provides a classification of the pro- gression 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 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 pa- tients with VHD. Of course, severity is a continuous vari- able; 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 hemo- dynamics that do not quite meet specific disease severity criteria, and numerical measures may not match exactly across all categories. Conversely, other patients may re- main asymptomatic without obvious evidence of end- organ damage despite apparently severe VHD. Criteria for the stages of each individual valve lesion are listed in and Section 8.1 (Table 20). 2.3. Diagnosis and Follow-Up 2.3.1. Diagnostic Testing: Initial Diagnosis TTE is the standard diagnostic test in the initial evalu- ation of patients with known or suspected VHD.1 4 LOE Level of Evidence LV left ventricle (left ventricular) LVEDD left ventricular end-diastolic dimension LVEF left ventricular ejection fraction LVESD left ventricular end-systolic dimension MDT multidisciplinary team MR mitral regurgitation MS mitral stenosis NOAC non vitamin K oral anticoagulant NYHA New York Heart Association PCI percutaneous coronary intervention PET positron emission tomography PMBC percutaneous mitral balloon commissurotomy RCT randomized controlled trial RV right ventricle (right ventricular) SAVR surgical aortic valve replacement TAVI transcatheter aortic valve implantation TEE transesophageal echocardiography (echocardiogram) TEER transcatheter edge-to-edge repair TR tricuspid regurgitation TTE transthoracic echocardiography (echocardiogram) UFH unfractionated heparin VHD valvular heart disease ViV valve-in-valve VKA vitamin K antagonist CLINICAL STATEMENTS AND GUIDELINES TTE allows accurate assessment of valve anatomy and etiology, concurrent valve disease, and associated ab- normalities, such as aortic dilation. Left ventricular (LV) anatomy and function are characterized by linear di- mensions, as well as by 2D and 3D volumes and ejec- tion fraction (LVEF), and it is recognized that decisions are most robust when based on sequential studies, giv- en the inherent measurement variability for these pa- 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 regurgi- tant lesions, calculation of regurgitant orifice area, vol- ume, 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 inter- pretation of these diagnostic tests require meticulous attention to detail, as well as expertise in cardiac imag- ing and evaluation of hemodynamics. Because echocar- diography remains the mainstay of the initial evaluation of all patients with VHD, it is recommended that the laboratory be an Intersocietal Accreditation Commis- sion (IAC) accredited program.8 Table 2. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)* CLINICAL STATEMENTS AND GUIDELINES 2.3.2. Diagnostic Testing: Changing Signs or Symptoms Patients with VHD should be instructed to promptly re- port any change in symptom status. The onset of symp- toms or a change in the physical examination should raise concern about the cardiac response to the valve lesion, necessitating a repeat TTE. A repeat comprehen- sive 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 le- sion 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 inter- vention. The follow-up interval may be extended in pa- tients 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 physi- cal 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 Table 3. Evaluation of Patients With Known or Suspected VHD Reason Test Indication Initial evaluation: All patients with known or suspected valve disease TTE* Establishes chamber size and function, valve morphology and severity, and effect on pulmonary and systemic circulation History and physical Establishes symptom severity, comorbidities, valve disease presence and severity, and presence of HF ECG Establishes rhythm, LV function, and presence or absence of hypertrophy 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 Chest x-ray 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 TEE Provides high-quality assessment of mitral and prosthetic valve, including definition of intracardiac masses and possible associated abnormalities (eg, intracardiac abscess, LA thrombus) CMR Provides assessment of LV volumes and function, valve severity, and aortic disease PET CT Aids in determination of active infection or inflammation Stress testing Gives an objective measure of exercise capacity Catheterization Provides measurement of intracardiac and pulmonary pressures, valve severity, and hemodynamic response to exercise and drugs Further risk stratification: Information on future risk of the valve disease, which is important for determination of timing of intervention Biomarkers Provide indirect assessment of filling pressures and myocardial damage TTE strain Helps assess intrinsic myocardial performance CMR Assesses fibrosis by gadolinium enhancement Stress testing Provides prognostic markers Procedural risk Quantified by STS (Predicted Risk of Mortality) and TAVI scores Frailty score Provides assessment of risk of procedure and chance of recovery of quality of life Preprocedural testing: Testing required before valve intervention Dental examination Rules out potential infection sources CT coronary angiogram or invasive coronary angiogram Gives an assessment of coronary anatomy CT: Peripheral Assesses femoral access for TAVI and other transcatheter procedures CT: Cardiac Assesses suitability for TAVI and other transcatheter procedures *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. CLINICAL STATEMENTS AND GUIDELINES 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 symptomatic patient, or if there is a discrepancy between the noninvasive tests and clinical findings, a hemodynamic cardiac cath- eterization with direct intracardiac measurements of transvalvular pressure gradients and cardiac output measurements provides valuable clinical information. Severity of stenosis may be underestimated when im- aging 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 overesti- mated 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 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 symp- 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 pres- sure response) is of prognostic value in patients with asymptomatic valve disease and provides further in- formation about the timing of a potential interven- It is important that exercise testing in patients with severe VHD always be performed by trained op- erators, 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 asymp- tomatic VHD feel better with regular aerobic exercise to improve cardiovascular fitness.1 3 Although heavy iso- metric repetitive training might increase LV afterload, resistive training with small free weights or repetitive Table 4. Stages of VHD Stage Definition Description A At risk Patients with risk factors for development of VHD B Progressive Patients with progressive VHD (mild to moderate severity and asymptomatic) C Asymptomatic severe Asymptomatic patients who have the criteria for severe VHD: C1: Asymptomatic patients with severe VHD in whom the LV or RV remains compensated C2: Asymptomatic patients with severe VHD with decompensation of the LV or RV D Symptomatic severe Patients who have developed symptoms as a result of VHD LV indicates left ventricle; RV, right ventricle; and VHD, valvular heart disease. Table 5. Frequency of Echocardiograms in Asymptomatic Patients With VHD and Normal LV Function Stage Type of Valve Lesion Aortic Stenosis* Aortic Regurgitation Mitral Stenosis Mitral Regurgitation Progressive (Stage B) Every 3 5 y (mild severity; Vmax Every 3 5 y (mild severity) Every 3 5 y (MV area >1.5 ) Every 3 5 y (mild severity) Every 1 2 y moderate severity; Vmax Every 1 2 y (moderate severity) Every 1 2 y (moderate severity) Severe asymptomatic Every 6 12 mo (Vmax 4 m/s) Every 6 12 mo Every 1 2 y (MV area 1.0 ) Every 6 12 mo Dilating LV: More frequently Every year (MV area <1.0 cm2 ) Dilating LV: More frequently 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 Vmax , maximum velocity. CLINICAL STATEMENTS AND GUIDELINES isolated muscle training may be used to strengthen in- dividual 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 sys- tolic dysfunction should be continued, including diuret- ics, 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 endocardi- tis (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 COR LOE Recommendation In patients with rheumatic heart disease, secondary prevention of rheumatic fever is indicated (Tables 6 Synopsis Rheumatic fever is an important cause of VHD world- wide, although it is less common in high-income coun- tries. 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 dis- ease, long-term antistreptococcal prophylaxis is indicat- ed for secondary prevention.1 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. Prevention of recurrent rheumatic fever requires long-term anti- microbial prophylaxis rather than recognition and treatment of acute episodes of group A strepto- coccus pharyngitis. The recommended treatment regimens and duration of secondary prophylaxis are shown in Tables 6 and 7. 2.4.2. IE Prophylaxis Recommendations for IE Prophylaxis Referenced studies that support the recommendations are summarized in Online Data Supplement 1. COR LOE Recommendations 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 : 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. Benefit B-NR 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 Table 6. Secondary Prevention of Rheumatic Fever Antibiotics for Prevention Dosage* Penicillin G benzathine 1.2 million U intramuscularly every 4 wk Penicillin V potassium 200 mg orally twice daily Sulfadiazine 1 g orally once daily Macrolide or azalide antibiotic (for patients allergic to penicillin and sulfadiazine) Varies *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. Adapted from Gerber et al.1 Table 7. Duration of Secondary Prophylaxis for Rheumatic Fever Type Duration After Last Attack* Rheumatic fever with carditis and residual heart disease (persistent VHD ) 10 y or until patient is 40 y of age (whichever is longer) Rheumatic fever with carditis but no residual heart disease (no valvular disease ) 10 y or until patient is 21 y of age (whichever is longer) Rheumatic fever without carditis 5 y or until patient is 21 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. Clinical or echocardiographic evidence. VHD indicates valvular heart disease. Adapted from Gerber et al.1 CLINICAL STATEMENTS AND GUIDELINES Synopsis With the absence of RCTs addressing the efficacy of anti- biotic prophylaxis for prevention of IE1,12 14 and given un- certainty about which patient populations are at highest risk, these recommendations are based on pathophysio- logical considerations, limited data, and clinical expertise. A prospective study demonstrated that prophylactic anti- biotics 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 Data- base 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 Epidemio- logical data conflict with regard to changes in the in- cidence of IE after adoption of more limited antibiotic 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. Recommendation-Specific Supportive Text 1. The risk of developing IE is highest in patients with a prosthetic valve, prior IE, or congenital heart dis- ease 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 replace- ment (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 lim- The risk of IE is highest in the first 6 months after transplantation because of endothe- lial 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 bac- terial seeding by maintaining optimal oral health through regular professional dental care and the use of appropriate dental products, such as man- ual, powered, and ultrasonic toothbrushes; dental floss; and other plaque-removal devices. 2. Transient bacteremia is commonly seen in rou- tine activities such as brushing teeth and floss- ing (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 anti- biotics 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 rates of bacteremia higher than that for simple endoscopy; these procedures include esophageal dilation (as high as 45%), sclerotherapy (31%), and endoscopic retrograde cholangiopancreatog- However, no studies have shown reduced rates of IE with antibiotic prophy- laxis. Surgery, instrumentation, or diagnostic pro- cedures that involve the genitourinary tract may cause bacteremia. In the absence of infection, the rate of bacteremia after urinary tract procedures is low. In patients with bacteriuria, antimicrobial therapy before elective procedures, including lith- otripsy, typically is provided.30 2.4.3. Anticoagulation for AF in Patients With VHD Recommendations for Anticoagulation for AF in Patients With VHD Referenced studies that support the recommendations are summarized in Online Data Supplement 2. COR LOE Recommendations For patients with AF and native valve heart disease (except rheumatic mitral stenosis [MS]) or who received a bioprosthetic valve >3 months ago, a non vitamin K oral anticoagulant (NOAC) is an effective alternative to VKA anticoagulation and should be administered on the basis of the patient s CHA2 For patients with AF and rheumatic MS, long-term VKA oral anticoagulation is recommended. For patients with new-onset AF 3 months after surgical or transcatheter bioprosthetic valve replacement, anticoagulation with a VKA 3: Harm B-R In patients with mechanical heart valves with or without AF who require long-term anticoagulation with VKA to prevent valve thrombosis, NOACs are not recommended.7 Synopsis Patients with VHD and AF should be evaluated for risk of thromboembolic events and to treat them with oral anticoagulation if they are at high risk. VKAs are the anticoagulation drugs of choice for patients with rheu- matic MS and mechanical heart valves. NOACs are an alternative to VKAs in patients with AF and 1) with CLINICAL STATEMENTS AND GUIDELINES bioprosthetic valves >3 months after implantation or, 2) with native VHD excluding rheumatic MS (Figure 1). Recommendation-Specific Supportive Text comparing NOACs with war- farin included small numbers of patients with VHD, prior valve repair, and bioprosthetic valves (excluding moderate to severe rheumatic MS and mechanical heart valves). In addition to the examinations of insurance claims data and large registries18 have consistently confirmed no signal for a differen- tial effect between NOAC and VKA therapy.19,20 More consistently observed is a net clinical ben- efit, with fewer events in patients using NOACs than in patients on VKA therapy. Validation of the -VASc risk schema in patients with VHD (excluding moderate to severe rheumatic MS and mechanical heart valves) has been performed in confirming the applicability of this score. Bioprosthetic valves do not appear to be independent predictors of thromboembolic events in patients with AF.19 2. The coexistence of AF and rheumatic MS is com- mon and confers a substantial risk of throm- boembolic events. These patients have been specifically excluded from NOAC trials, yet a single registry study and a US claims database analysis do suggest that NOACs may be poten- These findings need further validation, and currently the use of NOACs can- not be supported over VKA (target international normalized ratio [INR] of 2.5). 3. Postoperative AF after VHD intervention is associated with increased stroke and mortality irrespective of the CHA2 -VASc score. Anticoagulation in this setting may reduce these endpoints. There are conflicting data about the safety and efficacy of NOAC therapy in patients early after implantation of a bioprosthesis.5,6,23 Until more data are available, the writing com- mittee favors using VKA for patients with AF in the first 3 months after surgical or transcath- eter bioprosthetic valve implantation to prevent thromboembolic events. The optimal duration of anticoagulation is not well defined. Repeat evaluation is encouraged in all patients to detect arrhythmia recurrence in the context of their -VASc scores. 4. The phase II study comparing dabigatran to warfarin (RE-ALIGN [Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement]) was halted prematurely because of excess stroke and Figure 1. 