Author + information
- Published online August 1, 2006.
- Robert O. Bonow, MD, FACC, FAHA, Chair, Writing Committee Member,
- Blase A. Carabello, MD, FACC, FAHA, Writing Committee Member,
- Kanu Chatterjee, MB, FACC, Writing Committee Member,
- Antonio C. de Leon Jr, MD, FACC, FAHA, Writing Committee Member,
- David P. Faxon, MD, FACC, FAHA, Writing Committee Member,
- Michael D. Freed, MD, FACC, FAHA, Writing Committee Member,
- William H. Gaasch, MD, FACC, FAHA, Writing Committee Member,
- Bruce Whitney Lytle, MD, FACC, Writing Committee Member,
- Rick A. Nishimura, MD, FACC, FAHA, Writing Committee Member,
- Patrick T. O’Gara, MD, FACC, FAHA, Writing Committee Member,
- Robert A. O’Rourke, MD, MACC, FAHA, Writing Committee Member,
- Catherine M. Otto, MD, FACC, FAHA, Writing Committee Member,
- Pravin M. Shah, MD, MACC, FAHA, Writing Committee Member,
- Jack S. Shanewise, MD, Writing Committee Member⁎,
- Sidney C. Smith Jr, MD, FACC, FAHA, Chair, Task Force Member,
- Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair, Task Force Member,
- Cynthia D. Adams, MSN, APRN-BC, FAHA, Task Force Member,
- Jeffrey L. Anderson, MD, FACC, FAHA, Task Force Member,
- Elliott M. Antman, MD, FACC, FAHA, Task Force Member†,
- David P. Faxon, MD, FACC, FAHA, Task Force Member‡,
- Valentin Fuster, MD, PhD, FACC, FAHA, Task Force Member‡,
- Jonathan L. Halperin, MD, FACC, FAHA, Task Force Member,
- Loren F. Hiratzka, MD, FACC, FAHA, Task Force Member‡,
- Sharon A. Hunt, MD, FACC, FAHA, Task Force Member,
- Bruce W. Lytle, MD, FACC, FAHA, Task Force Member,
- Rick Nishimura, MD, FACC, FAHA, Task Force Member,
- Richard L. Page, MD, FACC, FAHA, Task Force Member and
- Barbara Riegel, DNSc, RN, FAHA, Task Force Member
Table of contents
1.1 Organization of the Committee and Evidence Review......e5
1.2 Scope of the Document......e6
2. GENERAL PRINCIPLES......e8
2.1 Evaluation of the Patient With a Cardiac Murmur......e8
2.1.2 Classification of Murmurs......e9
18.104.22.168 Dynamic Cardiac Auscultation......e9
22.214.171.124 Other Physical Findings......e9
126.96.36.199 Associated Symptoms......e10
2.1.3 Electrocardiography and Chest Roentgenography......e11
2.1.5 Cardiac Catheterization......e12
2.1.6 Exercise Testing......e12
2.1.7 Approach to the Patient......e12
2.2 Valve Disease Severity Table......e13
2.3 Endocarditis and Rheumatic Fever Prophylaxis......e13
2.3.1 Endocarditis Prophylaxis......e13
2.3.2 Rheumatic Fever Prophylaxis......e16
188.8.131.52 General Considerations......e16
184.108.40.206 Primary Prevention......e16
220.127.116.11 Secondary Prevention......e17
3. SPECIFIC VALVE LESIONS......e17
3.1 Aortic Stenosis......e17
18.104.22.168 Grading the Degree of Stenosis......e18
3.1.3 Natural History......e20
3.1.4 Management of the Asymptomatic Patient......e20
22.214.171.124 Echocardiography (Imaging, Spectral, and Color Doppler) in Aortic Stenosis......e20
126.96.36.199 Exercise Testing......e22
188.8.131.52 Serial Evaluations......e22
184.108.40.206 Medical Therapy......e22
220.127.116.11 Physical Activity and Exercise......e23
3.1.5 Indications for Cardiac Catheterization......e23
3.1.6 Low-Flow/Low-Gradient Aortic Stenosis......e23
3.1.7 Indications for Aortic Valve Replacement......e24
18.104.22.168 Symptomatic Patients......e25
22.214.171.124 Asymptomatic Patients......e25
126.96.36.199 Patients Undergoing Coronary Artery Bypass or Other Cardiac Surgery......e26
3.1.8 Aortic Balloon Valvotomy......e26
3.1.9 Medical Therapy for the Inoperable Patient......e27
3.1.10 Evaluation After Aortic Valve Replacement......e27
3.1.11 Special Considerations in the Elderly......e27
3.2 Aortic Regurgitation......e27
3.2.2 Acute Aortic Regurgitation......e28
3.2.3 Chronic Aortic Regurgitation......e28
188.8.131.52 Natural History......e29
184.108.40.206.1 Asymptomatic Patients With Normal Left Ventricular Function.......e29
220.127.116.11.2 Asymptomatic Patients With Depressed Systolic Function.......e32
18.104.22.168.3 Symptomatic Patients.......e32
22.214.171.124 Diagnosis and Initial Evaluation......e32
126.96.36.199 Medical Therapy......e33
188.8.131.52 Physical Activity and Exercise......e35
184.108.40.206 Serial Testing......e35
220.127.116.11 Indications for Cardiac Catheterization......e36
18.104.22.168 Indications for Aortic Valve Replacement or Aortic Valve Repair......e37
22.214.171.124.1 Symptomatic Patients With Normal Left Ventricular Systolic Function.......e37
126.96.36.199.2 Symptomatic Patients With Left Ventricular Dysfunction.......e37
188.8.131.52.3 Asymptomatic Patients.......e38
3.2.4 Concomitant Aortic Root Disease......e39
3.2.5 Evaluation of Patients After Aortic Valve Replacement......e40
3.2.6 Special Considerations in the Elderly......e40
3.3 Bicuspid Aortic Valve With Dilated Ascending Aorta......e40
3.4 Mitral Stenosis......e41
3.4.1 Pathophysiology and Natural History......e41
3.4.2 Indications for Echocardiography in Mitral Stenosis......e42
3.4.3 Medical Therapy......e45
184.108.40.206 Medical Therapy: General......e45
220.127.116.11 Medical Therapy: Atrial Fibrillation......e45
18.104.22.168 Medical Therapy: Prevention of Systemic Embolization......e46
3.4.4 Recommendations Regarding Physical Activity and Exercise......e46
3.4.5 Serial Testing......e47
3.4.6 Evaluation of the Symptomatic Patient......e47
3.4.7 Indications for Invasive Hemodynamic Evaluation......e47
3.4.8 Indications for Percutaneous Mitral Balloon Valvotomy......e50
3.4.9 Indications for Surgery for Mitral Stenosis......e53
3.4.10 Management of Patients After Valvotomy or Commissurotomy......e54
3.4.11 Special Considerations......e55
22.214.171.124 Pregnant Patients......e55
126.96.36.199 Older Patients......e55
3.5 Mitral Valve Prolapse......e55
3.5.1 Pathophysiology and Natural History......e55
3.5.2 Evaluation and Management of the Asymptomatic Patient......e56
3.5.3 Evaluation and Management of the Symptomatic Patient......e57
3.5.4 Surgical Considerations......e59
3.6 Mitral Regurgitation......e59
3.6.2 Acute Severe Mitral Regurgitation......e59
188.8.131.52 Medical Therapy......e59
3.6.3 Chronic Asymptomatic Mitral Regurgitation......e60
184.108.40.206 Pathophysiology and Natural History......e60
220.127.116.11 Indications for Transthoracic Echocardiography......e60
18.104.22.168 Indications for Transesophageal Echocardiography......e61
22.214.171.124 Serial Testing......e61
126.96.36.199 Guidelines for Physical Activity and Exercise......e62
188.8.131.52 Medical Therapy......e62
184.108.40.206 Indications for Cardiac Catheterization......e62
3.6.4 Indications for Surgery......e63
220.127.116.11 Types of Surgery......e63
18.104.22.168 Indications for Mitral Valve Operation......e63
22.214.171.124.1 Symptomatic Patients With Normal Left Ventricular Function......e64
126.96.36.199.2 Asymptomatic or Symptomatic Patients With Left Ventricular Dysfunction......e64
188.8.131.52.3 Asymptomatic Patients With Normal Left Ventricular Function......e66
184.108.40.206.4 Atrial Fibrillation......e66
3.6.5 Ischemic Mitral Regurgitation......e67
3.6.6 Evaluation of Patients After Mitral Valve Replacement or Repair......e67
3.6.7 Special Considerations in the Elderly......e67
3.7 Multiple Valve Disease......e68
3.7.2 Mixed Single Valve Disease......e68
220.127.116.11.1 Two-Dimensional and Doppler Echocardiographic Studies......e68
18.104.22.168.2 Cardiac Catheterization.......e68
3.7.3 Combined Mitral Stenosis and Aortic Regurgitation......e69
3.7.4 Combined Mitral Stenosis and Tricuspid Regurgitation......e69
3.7.5 Combined Mitral Regurgitation and Aortic Regurgitation......e69
22.214.171.124 Diagnosis and Therapy......e70
3.7.6 Combined Mitral Stenosis and Aortic Stenosis......e70
126.96.36.199 Diagnosis and Therapy......e70
3.7.7 Combined Aortic Stenosis and Mitral Regurgitation......e70
188.8.131.52 Diagnosis and Therapy......e70
3.8 Tricuspid Valve Disease......e70
3.9 Drug-Related Valvular Heart Disease......e72
3.10 Radiation Heart Disease......e72
4. EVALUATION AND MANAGEMENT OF INFECTIVE ENDOCARDITIS......e73
4.1 Antimicrobial Therapy......e73
4.2 Culture-Negative Endocarditis......e74
4.3 Endocarditis in HIV-Seropositive Patients......e76
4.4 Indications for Echocardiography in Suspected or Known Endocarditis......e76
4.4.1 Transthoracic Echocardiography in Endocarditis......e77
4.4.2 Transesophageal Echocardiography in Endocarditis......e78
4.5 Outpatient Treatment......e80
4.6 Indications for Surgery in Patients With Acute Infective Endocarditis......e80
4.6.1 Surgery for Native Valve Endocarditis......e82
4.6.2 Surgery for Prosthetic Valve Endocarditis......e82
5. MANAGEMENT OF VALVULAR DISEASE IN PREGNANCY......e83
5.1 Physiological Changes of Pregnancy......e83
5.2 Physicial Examination......e83
5.4 General Management Guidelines......e84
5.5 Specific Lesions......e84
5.5.1 Mitral Stenosis......e84
5.5.2 Mitral Regurgitation......e86
5.5.3 Aortic Stenosis......e86
5.5.4 Aortic Regurgitation......e84
5.5.5 Pulmonic Stenosis......e86
5.5.6 Tricuspid Valve Disease......e86
5.5.7 Marfan Syndrome......e86
5.6 Endocarditis Prophylaxis......e87
5.7 Cardiac Valve Surgery......e88
5.8 Anticoagulation During Pregnancy......e88
5.8.2 Unfractionated Heparin......e88
5.8.3 Low-Molecular-Weight Heparins......e88
5.8.4 Selection of Anticoagulation Regimen in Pregnant Patients With Mechanical Prosthetic Valves......e89
5.9 Selection of Valve Prostheses in Young Women......e90
6. MANAGEMENT OF CONGENITAL VALVULAR HEART DISEASE IN ADOLESCENTS AND YOUNG ADULTS......e90
6.1 Aortic Stenosis......e91
6.1.2 Evaluation of Asymptomatic Adolescents or Young Adults With Aortic Stenosis......e91
6.1.3 Indications for Aortic Balloon Valvotomy in Adolescents and Young Adults......e92
6.2 Aortic Regurgitation......e93
6.3 Mitral Regurgitation......e94
6.4 Mitral Stenosis......e95
6.5 Tricuspid Valve Disease......e95
6.5.2 Evaluation of Tricuspid Valve Disease in Adolescents and Young Adults......e96
6.5.3 Indications for Intervention in Tricuspid Regurgitation......e96
6.6 Pulmonic Stenosis......e97
6.6.2 Evaluation of Pulmonic Stenosis in Adolescents and Young Adults......e97
6.6.3 Indications for Balloon Valvotomy in Pulmonic Stenosis......e97
6.7 Pulmonary Regurgitation......e98
7. SURGICAL CONSIDERATIONS......e99
7.1 American Association for Thoracic Surgery/Society of Thoracic Surgeons Guidelines for Clinical Reporting of Heart Valve Complications......e99
7.2 Aortic Valve Surgery......e101
7.2.1 Risks and Strategies in Aortic Valve Surgery......e101
7.2.2 Mechanical Aortic Valve Prostheses......e101
184.108.40.206 Antithrombotic Therapy for Patients With Aortic Mechanical Heart Valves......e101
7.2.3 Stented and Nonstented Heterografts......e102
220.127.116.11 Aortic Valve Replacement With Stented Heterografts......e102
18.104.22.168 Aortic Valve Replacement With Stentless Heterografts......102
7.2.4 Aortic Valve Homografts......e102
7.2.5 Pulmonic Valve Autotransplantation......e104
7.2.6 Aortic Valve Repair......e104
7.2.7 Left Ventricle–to–Descending Aorta Shunt......e104
7.2.8 Comparative Trials and Selection of Aortic Valve Prostheses......e104
7.2.9 Major Criteria for Aortic Valve Selection......e105
7.3 Mitral Valve Surgery......e106
7.3.1 Mitral Valve Repair......e106
22.214.171.124 Myxomatous Mitral Valve......e106
126.96.36.199 Rheumatic Heart Disease......e107
188.8.131.52 Ischemic Mitral Valve Disease......e107
184.108.40.206 Mitral Valve Endocarditis......e107
7.3.2 Mitral Valve Prostheses (Mechanical or Bioprostheses)......e107
220.127.116.11 Selection of an Mitral Valve Prosthesis......e108
7.4 Tricuspid Valve Surgery......e108
7.5 Valve Selection for Women of Childbearing Age......e109
8. INTRAOPERATIVE ASSESSMENT......e109
8.1 Specific Valve Lesions......e110
8.1.1 Aortic Stenosis......e110
8.1.2 Aortic Regurgitation......e110
8.1.3 Mitral Stenosis......e110
8.1.4 Mitral Regurgitation......e111
8.1.5 Tricuspid Regurgitation......e111
8.1.6 Tricuspid Stenosis......e111
8.1.7 Pulmonic Valve Lesions......e111
8.2 Specific Clinical Scenarios......e111
8.2.1 Previously Undetected Aortic Stenosis During CABG......e111
8.2.2 Previously Undetected Mitral Regurgitation During CABG......e111
9. MANAGEMENT OF PATIENTS WITH PROSTHETIC HEART VALVES......e112
9.1 Antibiotic Prophylaxis......e112
9.1.1 Infective Endocarditis......e112
9.1.2 Recurrence of Rheumatic Carditis......e112
9.2 Antithrombotic Therapy......e112
9.2.1 Mechanical Valves......e113
9.2.2 Biological Valves......e114
9.2.3 Embolic Events During Adequate Antithrombotic Therapy......e114
9.2.4 Excessive Anticoagulation......e114
9.2.5 Bridging Therapy in Patients With Mechanical Valves Who Require Interruption of Warfarin Therapy for Noncardiac Surgery, Invasive Procedures, or Dental Care......e114
9.2.6 Antithrombotic Therapy in Patients Who Need Cardiac Catheterization/Angiography......e115
9.2.7 Thrombosis of Prosthetic Heart Valves......e115
9.3 Follow-Up Visits......e116
9.3.1 First Outpatient Postoperative Visit......e117
9.3.2 Follow-Up Visits in Patients Without Complications......e117
9.3.3 Follow-Up Visits in Patients With Complications......e118
9.4 Reoperation to Replace a Prosthetic Valve......e118
10. EVALUATION AND TREATMENT OF CORONARY ARTERY DISEASE IN PATIENTS WITH VALVULAR HEART DISEASE......e118
10.1 Probability of Coronary Artery Disease in Patients With Valvular Heart Disease......e118
10.2 Diagnosis of Coronary Artery Disease......e119
10.3 Treatment of Coronary Artery Disease at the Time of Aortic Valve Replacement......e120
10.4 Aortic Valve Replacement in Patients Undergoing Coronary Artery Bypass Surgery......e120
10.5 Management of Concomitant MV Disease and Coronary Artery Disease......e121
It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting the absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.
The American College of Cardiology (ACC) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. This effort is directed by the ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures. Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop and update written recommendations for clinical practice.
Experts in the subject under consideration are selected from both organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups where appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered, as well as frequency of follow-up. When available, information from studies on cost will be considered; however, review of data on efficacy and clinical outcomes will be the primary basis for preparing recommendation in these guidelines.
The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing committee. Specifically, all members of the writing committee and peer reviewers of the document are asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. Writing committee members are also strongly encouraged to declare a previous relationship with industry that might be perceived as relevant to guideline development. If a writing committee member develops a new relationship with industry during his or her tenure, he or she is required to notify guideline staff in writing. The continued participation of the writing committee member will be reviewed. These statements are reviewed by the parent task force, reported orally to all members of the writing panel at each meeting, and updated and reviewed by the writing committee as changes occur. Please refer to the methodology manual for the ACC/AHA guideline writing committees for further description and the relationships with industry policy, available on ACC and AHA World Wide Web sites (http://www.acc.org/clinical/manual/manual_introltr.htmand http://circ.ahajournals.org/manual). See Appendix 1for a list of writing committee member relationships with industry and Appendix 2for a listing of peer reviewer relationships with industry that are pertinent to this guideline.
These practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available, current scientific evidence and are intended to improve patient care. If these guidelines are used as the basis for regulatory/payer decisions, the ultimate goal is quality of care and serving the patient’s best interests. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all of the circumstances presented by that patient. There are circumstances in which deviations from these guidelines are appropriate.
The “ACC/AHA 2006 Guideline for the Management of Patients With Valvular Heart Disease” was approved for publication by the ACC Foundation (ACCF) board of trustees in May 2006 and the AHA Science Advisory and Coordinating Committee in May 2006. The executive summary and recommendations are published in the August 1, 2006 issue of the Journal of the American College of Cardiologyand the August 1, 2006 issue of Circulation. The full-text guideline is e-published in the same issues of each journal and is posted on the World Wide Web sites of the ACC (www.acc.org) and the AHA (www.americanheart.org). The guidelines will be reviewed annually by the ACC/AHA Task Force on Practice Guidelines and will be considered current unless they are updated, revised, or sunsetted and withdrawn from distribution. Copies of the full text and the executive summary are available from both organizations.
Sidney C. Smith, Jr., MD, FACC, FAHA, Chair, ACC/AHA Task Force on Practice Guidelines
1.1 Organization of the Committee and Evidence Review
The ACC and the AHA have long been involved in the joint development of practice guidelines designed to assist healthcare providers in the management of selected cardiovascular disorders or the selection of certain cardiovascular procedures. The determination of the disorders or procedures to develop guidelines for is based on several factors, including importance to healthcare providers and whether there are sufficient data from which to derive accepted guidelines. One important category of cardiac disorders that affect a large number of patients who require diagnostic procedures and decisions regarding long-term management is valvular heart disease.
During the past 2 decades, major advances have occurred in diagnostic techniques, the understanding of natural history, and interventional cardiology and surgical procedures for patients with valvular heart disease. These advances have resulted in enhanced diagnosis, more scientific selection of patients for surgery or catheter-based intervention versus medical management, and increased survival of patients with these disorders. The information base from which to make clinical management decisions has greatly expanded in recent years, yet in many situations, management issues remain controversial or uncertain. Unlike many other forms of cardiovascular disease, there is a scarcity of large-scale multicenter trials addressing the diagnosis and treatment of patients with valvular disease from which to derive definitive conclusions, and the information available in the literature represents primarily the experiences reported by single institutions in relatively small numbers of patients.
The 1998 Committee on Management of Patients With Valvular Heart Disease reviewed and compiled this information base and made recommendations for diagnostic testing, treatment, and physical activity. For topics for which there was an absence of multiple randomized, controlled trials, the preferred basis for medical decision making in clinical practice (evidence-based medicine), the committee’s recommendations were based on data derived from single randomized trials or nonrandomized studies or were based on a consensus opinion of experts. The current writing committee was charged with revising the guidelines published in 1998. The committee reviewed pertinent publications, including abstracts, through a computerized search of the English literature since 1998 and performed a manual search of final articles. Special attention was devoted to identification of randomized trials published since the original document. A complete listing of all publications covering the treatment of valvular heart disease is beyond the scope of this document; the document includes those reports that the committee believes represent the most comprehensive or convincing data that are necessary to support its conclusions. However, evidence tables were updated to reflect major advances over this time period. Inaccuracies or inconsistencies present in the original publication were identified and corrected when possible. Recommendations provided in this document are based primarily on published data. Because randomized trials are unavailable in many facets of valvular heart disease treatment, observational studies and, in some areas, expert opinions form the basis for recommendations that are offered.
All of the recommendations in this guideline revision were converted from the tabular format used in the 1998 guideline to a listing of recommendations that has been written in full sentences to express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document, would still convey the full intent of the recommendation. It is hoped that this will increase the readers’ comprehension of the guidelines. Also, the level of evidence, either A, B, or C, for each recommendation is now provided.
Classification of recommendations and level of evidence are expressed in the ACC/AHA format as follows:
• Class I:Conditions for which there is evidence for and/or general agreement that the procedure or treatment is beneficial, useful, and effective.
• Class II:Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.
• Class IIa:Weight of evidence/opinion is in favor of usefulness/efficacy.
• Class IIb:Usefulness/efficacy is less well established by evidence/opinion.
• Class III:Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful.
In addition, the weight of evidence in support of the recommendation is listed as follows:
• Level of Evidence A:Data derived from multiple randomized clinical trials.
• Level of Evidence B:Data derived from a single randomized trial or nonrandomized studies.
• Level of Evidence C:Only consensus opinion of experts, case studies, or standard-of-care.
The schema for classification of recommendations and level of evidence is summarized in Figure 1,which also illustrates how the grading system provides an estimate of the size of the treatment effect and an estimate of the certainty of the treatment effect.
Writing committee membership consisted of cardiovascular disease specialists and representatives of the cardiac surgery and cardiac anesthesiology fields; both the academic and private practice sectors were represented. The Society of Cardiovascular Anesthesiologists assigned an official representative to the writing committee.
This document was reviewed by 2 official reviewers nominated by the ACC; 2 official reviewers nominated by the AHA; 1 official reviewer from the ACC/AHA Task Force on Practice Guidelines; reviewers nominated by the Society of Cardiovascular Anesthesiologists, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons (STS); and individual content reviewers, including members of the ACCF Cardiac Catheterization and Intervention Committee, ACCF Cardiovascular Imaging Committee, ACCF Cardiovascular Surgery Committee, AHA Endocarditis Committee, AHA Cardiac Clinical Imaging Committee, AHA Cardiovascular Intervention and Imaging Committee, and AHA Cerebrovascular Imaging and Intervention Committee.
1.2 Scope of the Document
The guidelines attempt to deal with general issues of treatment of patients with heart valve disorders, such as evaluation of patients with heart murmurs, prevention and treatment of endocarditis, management of valve disease in pregnancy, and treatment of patients with concomitant coronary artery disease (CAD), as well as more specialized issues that pertain to specific valve lesions. The guidelines focus primarily on valvular heart disease in the adult, with a separate section dealing with specific recommendations for valve disorders in adolescents and young adults. The diagnosis and management of infants and young children with congenital valvular abnormalities are significantly different from those of the adolescent or adult and are beyond the scope of these guidelines.
This task force report overlaps with several previously published ACC/AHA guidelines about cardiac imaging and diagnostic testing, including the guidelines for the clinical use of cardiac radionuclide imaging (1), the clinical application of echocardiography (2), exercise testing (3), and percutaneous coronary intervention (4). Although these guidelines are not intended to include detailed information covered in previous guidelines on the use of imaging and diagnostic testing, an essential component of this report is the discussion of indications for these tests in the evaluation and treatment of patients with valvular heart disease.
The committee emphasizes the fact that many factors ultimately determine the most appropriate treatment of individual patients with valvular heart disease within a given community. These include the availability of diagnostic equipment and expert diagnosticians, the expertise of interventional cardiologists and surgeons, and notably, the wishes of well-informed patients. Therefore, deviation from these guidelines may be appropriate in some circumstances. These guidelines are written with the assumption that a diagnostic test can be performed and interpreted with skill levels consistent with previously reported ACC training and competency statements and ACC/AHA guidelines, that interventional cardiological and surgical procedures can be performed by highly trained practitioners within acceptable safety standards, and that the resources necessary to perform these diagnostic procedures and provide this care are readily available. This is not true in all geographic areas, which further underscores the committee’s position that its recommendations are guidelines and not rigid requirements.
2 General principles
2.1 Evaluation of the Patient With a Cardiac Murmur
Cardiac auscultation remains the most widely used method of screening for valvular heart disease. The production of murmurs is due to 3 main factors:
• high blood flow rate through normal or abnormal orifices
• forward flow through a narrowed or irregular orifice into a dilated vessel or chamber
• backward or regurgitant flow through an incompetent valve
Often, more than 1 of these factors is operative (5–7).
A heart murmur may have no pathological significance or may be an important clue to the presence of valvular, congenital, or other structural abnormalities of the heart (8). Most systolic heart murmurs do not signify cardiac disease, and many are related to physiological increases in blood flow velocity (9). In other instances, a heart murmur may be an important clue to the diagnosis of undetected cardiac disease (e.g., valvular aortic stenosis [AS]) that may be important even when asymptomatic or that may define the reason for cardiac symptoms. In these situations, various noninvasive or invasive cardiac tests may be necessary to establish a firm diagnosis and form the basis for rational treatment of an underlying disorder. Echocardiography is particularly useful in this regard, as discussed in the “ACC/AHA/ASE 2003 Guidelines for the Clinical Application of Echocardiography” (2). Diastolic murmurs virtually always represent pathological conditions and require further cardiac evaluation, as do most continuous murmurs. Continuous “innocent” murmurs include venous hums and mammary souffles.
The traditional auscultation method of assessing cardiac murmurs has been based on their timing in the cardiac cycle, configuration, location and radiation, pitch, intensity (grades 1 through 6), and duration (5–9). The configuration of a murmur may be crescendo, decrescendo, crescendo-decrescendo (diamond-shaped), or plateau. The precise times of onset and cessation of a murmur associated with cardiac pathology depend on the period of time in the cardiac cycle in which a physiologically important pressure difference between 2 chambers occurs (5–9). A classification of cardiac murmurs is listed in Table 1.
2.1.2 Classification of Murmurs
Holosystolic (pansystolic) murmurs are generated when there is flow between chambers that have widely different pressures throughout systole, such as the left ventricle and either the left atrium or right ventricle. With an abnormal regurgitant orifice, the pressure gradient and regurgitant jet begin early in contraction and last until relaxation is almost complete.
Midsystolic (systolic ejection) murmurs, often crescendo-decrescendo in configuration, occur when blood is ejected across the aortic or pulmonic outflow tracts. The murmurs start shortly after S1, when the ventricular pressure rises sufficiently to open the semilunar valve. As ejection increases, the murmur is augmented, and as ejection declines, it diminishes.
In the presence of normal semilunar valves, this murmur may be caused by an increased flow rate such as that which occurs with elevated cardiac output (e.g., pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula), ejection of blood into a dilated vessel beyond the valve, or increased transmission of sound through a thin chest wall. Most innocent murmurs that occur in children and young adults are midsystolic and originate either from the aortic or pulmonic outflow tracts. Valvular, supravalvular, or subvalvular obstruction (stenosis) of either ventricle may also cause a midsystolic murmur, the intensity of which depends in part on the velocity of blood flow across the narrowed area. Midsystolic murmurs also occur in certain patients with functional mitral regurgitation (MR) or, less frequently, tricuspid regurgitation (TR). Echocardiography is often necessary to separate a prominent and exaggerated (grade 3) benign midsystolic murmur from one due to valvular AS.
Early systolic murmurs are less common; they begin with the first sound and end in midsystole. An early systolic murmur is often due to TR that occurs in the absence of pulmonary hypertension, but it also occurs in patients with acute MR. In large ventricular septal defects with pulmonary hypertension and small muscular ventricular septal defects, the shunting at the end of systole may be insignificant, with the murmur limited to early and midsystole.
Late systolic murmurs are soft or moderately loud, high-pitched murmurs at the left ventricular (LV) apex that start well after ejection and end before or at S2. They are often due to apical tethering and malcoaptation of the mitral leaflets due to anatomic and functional changes of the annulus and ventricle. Late systolic murmurs in patients with midsystolic clicks result from late systolic regurgitation due to prolapse of the mitral leaflet(s) into the left atrium. Such late systolic murmurs can also occur in the absence of clicks.
Early diastolic murmurs begin with or shortly after S2, when the associated ventricular pressure drops sufficiently below that in the aorta or pulmonary artery. High-pitched murmurs of aortic regurgitation (AR) or pulmonic regurgitation due to pulmonary hypertension are generally decrescendo, consistent with the rapid decline in volume or rate of regurgitation during diastole. The diastolic murmur of pulmonic regurgitation without pulmonary hypertension is low to medium pitched, and the onset of this murmur is slightly delayed because regurgitant flow is minimal at pulmonic valve closure, when the reverse pressure gradient responsible for the regurgitation is minimal. Such murmurs are common late after repair of tetralogy of Fallot.
Middiastolic murmurs usually originate from the mitral and tricuspid valves, occur early during ventricular filling, and are due to a relative disproportion between valve orifice size and diastolic blood flow volume. Although they are usually due to mitral or tricuspid stenosis, middiastolic murmurs may also be due to increased diastolic blood flow across the mitral or tricuspid valve when such valves are severely regurgitant, across the normal mitral valve (MV) in patients with ventricular septal defect or patent ductus arteriosus, and across the normal tricuspid valve in patients with atrial septal defect. In severe, chronic AR, a low-pitched, rumbling diastolic murmur (Austin-Flint murmur) is often present at the LV apex; it may be either middiastolic or presystolic. An opening snap is absent in isolated AR.
Presystolic murmurs begin during the period of ventricular filling that follows atrial contraction and therefore occur in sinus rhythm. They are usually due to mitral or tricuspid stenosis. A right or left atrial myxoma may cause either middiastolic or presystolic murmurs similar to tricuspid or mitral stenosis (MS).
Continuous murmurs arise from high- to low-pressure shunts that persist through the end of systole and the beginning of diastole. Thus, they begin in systole, peak near S2, and continue into all or part of diastole. There are many causes of continuous murmurs, but they are uncommon in patients with valvular heart disease (5–9).
18.104.22.168 Dynamic Cardiac Auscultation
Attentive cardiac auscultation during dynamic changes in cardiac hemodynamics often enables the observer to deduce the correct origin and significance of a cardiac murmur (10–13). Changes in the intensity of heart murmurs during various maneuvers are indicated in Table 2.
22.214.171.124 Other Physical Findings
The presence of other physical findings, either cardiac or noncardiac, may provide important clues to the significance of a cardiac murmur and the need for further testing (Fig. 2).For example, a right heart murmur in early to midsystole at the lower left sternal border likely represents TR without pulmonary hypertension in an injection drug user who presents with fever, petechiae, Osler’s nodes, and Janeway lesions.
Associated cardiac findings frequently provide important information about cardiac murmurs. Fixed splitting of the second heart sound during inspiration and expiration in a patient with a grade 2/6 midsystolic murmur in the pulmonic area and left sternal border should suggest the possibility of an atrial septal defect. A soft or absent A2or reversed splitting of S2may denote severe AS. An early aortic systolic ejection sound heard during inspiration and expiration suggests a bicuspid aortic valve, whereas an ejection sound heard only in the pulmonic area and at the left sternal border during expiration usually denotes pulmonic valve stenosis. LV dilatation on precordial palpation and bibasilar pulmonary rales favor the diagnosis of severe, chronic MR in a patient with a grade 2/6 holosystolic murmur at the cardiac apex. A slow-rising, diminished arterial pulse suggests severe AS in a patient with a grade 2/6 midsystolic murmur at the second right intercostal space. The typical parvus et tardus pulse may be absent in the elderly, even in those with severe AS, secondary to the effects of aging on the vasculature. Pulsus parvus may also occur with severely reduced cardiac output from any cause. Factors that aid in the differential diagnosis of LV outflow tract obstruction are listed in Table 3(14). Examination of the jugular venous wave forms may provide additional or corroborative information. For example, regurgitant cv waves are indicative of TR and are often present without an audible murmur.
126.96.36.199 Associated Symptoms
An important consideration in the patient with a cardiac murmur is the presence or absence of symptoms (15) (Fig. 2). For example, symptoms of syncope, angina pectoris, or heart failure in a patient with a midsystolic murmur will usually result in a more aggressive diagnostic approach than in a patient with a similar midsystolic murmur who has none of these symptoms. An echocardiogram to rule in or rule out the presence of significant AS should be obtained. A history of thromboembolism will also usually result in a more extensive workup. In patients with cardiac murmurs and clinical findings suggestive of endocarditis, echocardiography is indicated (2).
Conversely, many asymptomatic children and young adults with grade 2/6 midsystolic murmurs and no other cardiac physical findings need no further workup after the initial history and physical examination (Fig. 2). A particularly important group is the large number of asymptomatic older patients, many with systemic hypertension, who have midsystolic murmurs, usually of grade 1 or 2 intensity, related to sclerotic aortic valve leaflets; flow into tortuous, noncompliant great vessels; or a combination of these findings. Such murmurs must be distinguished from those caused by more significant degrees of aortic valve thickening, calcification, and reduced excursion that result in milder or greater degrees of valvular AS. The absence of LV hypertrophy on the electrocardiogram (ECG) may be reassuring, but echocardiography is frequently necessary. Aortic sclerosis can be defined by focal areas of increased echogenicity and thickening of the leaflets without restriction of motion and a peak velocity of less than 2.0 m per second. The recognition of aortic valve sclerosis may prompt the initiation of more aggressive programs of coronary heart disease prevention. In patients with AS, it is difficult to assess the rate and severity of disease progression on the basis of auscultatory findings alone.
2.1.3 Electrocardiography and Chest Roentgenography
Although echocardiography usually provides more specific and often quantitative information about the significance of a heart murmur and may be the only test needed, the ECG and chest X-ray are readily available and may have been obtained previously. The absence of ventricular hypertrophy, atrial enlargement, arrhythmias, conduction abnormalities, prior myocardial infarction, and evidence of active ischemia on the ECG provides useful negative information at a relatively low cost. Abnormal ECG findings in a patient with a heart murmur, such as ventricular hypertrophy or a prior infarction, should lead to a more extensive evaluation that includes echocardiography (Fig. 2).
Posteroanterior and lateral chest roentgenograms often yield qualitative information on cardiac chamber size, pulmonary blood flow, pulmonary and systemic venous pressure, and cardiac calcification in patients with cardiac murmurs. When abnormal findings are present on chest X-ray, echocardiography should be performed (Fig. 2). A normal chest X-ray and ECG are likely in asymptomatic patients with isolated midsystolic murmurs, particularly in younger age groups, when the murmur is grade 2 or less in intensity and heard along the left sternal border (16–18). Routine ECG and chest radiography are not recommended in this setting.
1. Echocardiography is recommended for asymptomatic patients with diastolic murmurs, continuous murmurs, holosystolic murmurs, late systolic murmurs, murmurs associated with ejection clicks or murmurs that radiate to the neck or back. (Level of Evidence: C)
2. Echocardiography is recommended for patients with heart murmurs and symptoms or signs of heart failure, myocardial ischemia/infarction, syncope, thromboembolism, infective endocarditis, or other clinical evidence of structural heart disease. (Level of Evidence: C)
3. Echocardiography is recommended for asymptomatic patients who have grade 3 or louder midpeaking systolic murmurs. (Level of Evidence: C)
1. Echocardiography can be useful for the evaluation of asymptomatic patients with murmurs associated with other abnormal cardiac physical findings or murmurs associated with an abnormal ECG or chest X-ray. (Level of Evidence: C)
2. Echocardiography can be useful for patients whose symptoms and/or signs are likely noncardiac in origin but in whom a cardiac basis cannot be excluded by standard evaluation. (Level of Evidence: C)
Echocardiography is not recommended for patients who have a grade 2 or softer midsystolic murmur identified as innocent or functional by an experienced observer. (Level of Evidence: C)
Echocardiography with color flow and spectral Doppler evaluation is an important noninvasive method for assessing the significance of cardiac murmurs. Information regarding valve morphology and function, chamber size, wall thickness, ventricular function, pulmonary and hepatic vein flow, and estimates of pulmonary artery pressures can be readily integrated.
Although echocardiography can provide important information, such testing is not necessary for all patients with cardiac murmurs and usually adds little but expense in the evaluation of asymptomatic younger patients with short grade 1 to 2 midsystolic murmurs and otherwise normal physical findings. At the other end of the spectrum are patients with heart murmurs for whom transthoracic echocardiography proves inadequate. Depending on the specific clinical circumstances, transesophageal echocardiography, cardiac magnetic resonance, or cardiac catheterization may be indicated for better characterization of the valvular lesion.
It is important to note that Doppler ultrasound devices are very sensitive and may detect trace or mild valvular regurgitation through structurally normal tricuspid and pulmonic valves in a large percentage of young, healthy subjects and through normal left-sided valves (particularly the MV) in a variable but lower percentage of patients (16,19–22).
General recommendations for performing echocardiography in patients with heart murmurs are provided. Of course, individual exceptions to these indications may exist.
2.1.5 Cardiac Catheterization
Cardiac catheterization can provide important information about the presence and severity of valvular obstruction, valvular regurgitation, and intracardiac shunting. It is not necessary in most patients with cardiac murmurs and normal or diagnostic echocardiograms, but it provides additional information for some patients in whom there is a discrepancy between the echocardiographic and clinical findings. Indications for cardiac catheterization for hemodynamic assessment of specific valve lesions are given in Section 3, “Specific Valve Lesions,” in these guidelines. Specific indications for coronary angiography to screen for the presence of CAD are given in Section 10.2.
2.1.6 Exercise Testing
Exercise testing can provide valuable information in patients with valvular heart disease, especially in those whose symptoms are difficult to assess. It can be combined with echocardiography, radionuclide angiography, and cardiac catheterization. It has a proven track record of safety, even among asymptomatic patients with severe AS. Exercise testing has generally been underutilized in this patient population and should constitute an important component of the evaluation process.
2.1.7 Approach to the Patient
The evaluation of the patient with a heart murmur may vary greatly depending on many of the considerations discussed above (23,24). These include the timing of the murmur in the cardiac cycle, its location and radiation, and its response to various physiological maneuvers (Table 2). Also of importance is the presence or absence of cardiac and noncardiac symptoms and other findings on physical examination that suggest the murmur is clinically significant (Fig. 2).
Patients with diastolic or continuous heart murmurs not due to a cervical venous hum or a mammary souffle during pregnancy are candidates for echocardiography. If the results of echocardiography indicate significant heart disease, further evaluation may be indicated. An echocardiographic examination is also recommended for patients with apical or left sternal edge holosystolic or late systolic murmurs, for patients with midsystolic murmurs of grade 3 or greater intensity, and for patients with softer systolic murmurs in whom dynamic cardiac auscultation suggests a definite diagnosis (e.g., hypertrophic cardiomyopathy).
Echocardiography is also recommended for patients in whom the intensity of a systolic murmur increases during the Valsalva maneuver, becomes louder when the patient assumes the upright position, and decreases in intensity when the patient squats. These responses suggest the diagnosis of either hypertrophic obstructive cardiomyopathy or MV prolapse (MVP). Additionally, further assessment is indicated when a systolic murmur increases in intensity during transient arterial occlusion, becomes louder during sustained handgrip exercise, or does not increase in intensity either in the cardiac cycle that follows a premature ventricular contraction or after a long R-R interval in patients with atrial fibrillation. The diagnosis of MR or ventricular septal defect in these circumstances is likely.
In many patients with grade 1 or 2 midsystolic murmurs, an extensive workup is not necessary. This is particularly true for children and young adults who are asymptomatic, have an otherwise normal cardiac examination, and have no other physical findings associated with cardiac disease.
However, echocardiography is indicated in certain patients with grade 1 or 2 midsystolic murmurs, including patients with symptoms or signs consistent with infective endocarditis, thromboembolism, heart failure, myocardial ischemia/infarction, or syncope. Echocardiography also usually provides an accurate diagnosis in patients with other abnormal physical findings, including widely split second heart sounds, systolic ejection sounds, and specific changes in intensity of the systolic murmur during certain physiological maneuvers (Table 2).
Although echocardiography is an important test for patients with a moderate to high likelihood of a clinically important cardiac murmur, it must be re-emphasized that trivial, minimal, or physiological valvular regurgitation, especially affecting the mitral, tricuspid, or pulmonic valves, is detected by color flow imaging techniques in many otherwise normal patients, including many patients who have no heart murmur at all (16,19–22). This observation must be considered when the results of echocardiography are used to guide decisions in asymptomatic patients in whom echocardiography was used to assess the significance of an isolated murmur.
Very few data address the cost-effectiveness of various approaches to the patient undergoing medical evaluation of a cardiac murmur. Optimal auscultation by well-trained examiners who can recognize an insignificant midsystolic murmur with confidence (by dynamic cardiac auscultation as indicated) results in less frequent use of expensive additional testing to define murmurs that do not indicate cardiac pathology.
Characteristics of innocent murmurs in asymptomatic adults that have no functional significance include the following:
• grade 1 to 2 intensity at the left sternal border
• a systolic ejection pattern
• normal intensity and splitting of the second heart sound
• no other abnormal sounds or murmurs
• no evidence of ventricular hypertrophy or dilatation and the absence of increased murmur intensity with the Valsalva maneuver or with standing from a squatting position (12).
Such murmurs are especially common in high-output states such as anemia and pregnancy (25,26). When the characteristic features of individual murmurs are considered together with information obtained from the history and physical examination, the correct diagnosis can usually be established (24). In patients with ambiguous clinical findings, the echocardiogram can often provide a definite diagnosis, rendering a chest X-ray and/or ECG unnecessary.
In the evaluation of heart murmurs, the purposes of echocardiography are to
• define the primary lesion in terms of cause and severity
• define hemodynamics
• define coexisting abnormalities
• detect secondary lesions
• evaluate cardiac chamber size and function
• establish a reference point for future comparisons
• re-evaluate the patient after an intervention.
Throughout these guidelines, treatment recommendations will often derive from specific echocardiographic measurements of LV size and systolic function. Accuracy and reproducibility are critical, particularly when applied to surgical recommendations for asymptomatic patients with MR or AR. Serial measurements over time, or reassessment with a different imaging technology (radionuclide ventriculography or cardiac magnetic resonance), are often helpful for counseling individual patients. Lastly, although handheld echocardiography can be used for screening purposes, it is important to note that its accuracy is highly dependent on the experience of the user. The precise role of handheld echocardiography for the assessment of patients with valvular heart disease has not been elucidated.
As valuable as echocardiography may be, the basic cardiovascular physical examination is still the most appropriate method of screening for cardiac disease and will establish many clinical diagnoses. Echocardiography should not replace the cardiovascular examination but can be useful in determining the cause and severity of valvular lesions, particularly in older and/or symptomatic patients.
2.2 Valve Disease Severity Table
Classification of the severity of valve disease in adults is listed in Table 4(27). The classification for regurgitant lesions is adapted from the recommendations of the American Society of Echocardiography (27). For full recommendations of the American Society of Echocardiography, please refer to the original document. Subsequent sections of the current guidelines refer to the criteria in Table 4(27) to define severe valvular stenosis or regurgitation.
2.3 Endocarditis and Rheumatic Fever Prophylaxis
The following information is based on recommendations made by the AHA in 1997 (28). These recommendations are currently under revision and subject to change. Recommendations for prophylaxis against and treatment of nonvalvular cardiac device–related infections have been published previously (29).
2.3.1 Endocarditis Prophylaxis
Prophylaxis against infective endocarditis is recommended for the following patients:
• Patients with prosthetic heart valves and patients with a history of infective endocarditis. (Level of Evidence: C)
• Patients who have complex cyanotic congenital heart disease (e.g., single-ventricle states, transposition of the great arteries, tetralogy of Fallot). (Level of Evidence: C)
• Patients with surgically constructed systemic-pulmonary shunts or conduits. (Level of Evidence: C)
• Patients with congenital cardiac valve malformations, particularly those with bicuspid aortic valves, and patients with acquired valvular dysfunction (e.g., rheumatic heart disease). (Level of Evidence: C)
• Patients who have undergone valve repair. (Level of Evidence: C)
• Patients who have hypertrophic cardiomyopathy when there is latent or resting obstruction. (Level of Evidence: C)
• Patients with MVP and auscultatory evidence of valvular regurgitation and/or thickened leaflets on echocardiography.* (Level of Evidence: C)
Prophylaxis against infective endocarditis is not recommended for the following patients:
• Patients with isolated secundum atrial septal defect. (Level of Evidence: C)
• Patients 6 or more months after successful surgical or percutaneous repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus. (Level of Evidence: C)
• Patients with MVP without MR or thickened leaflets on echocardiography.* (Level of Evidence: C)
• Patients with physiological, functional, or innocent heart murmurs, including patients with aortic valve sclerosis as defined by focal areas of increased echogenicity and thickening of the leaflets without restriction of motion and a peak velocity less than 2.0 m per second. (Level of Evidence: C)
• Patients with echocardiographic evidence of physiologic MR in the absence of a murmur and with structurally normal valves. (Level of Evidence: C)
• Patients with echocardiographic evidence of physiological TR and/or pulmonary regurgitation in the absence of a murmur and with structurally normal valves. (Level of Evidence: C)
*Patients with MVP without regurgitation require additional clinical judgment. Indications for antibiotic prophylaxis in MVP are discussed in Section 3.5.2. Patients who do not have MR but who do have echocardiographic evidence of thickening and/or redundancy of the valve leaflets, and especially men 45 years of age or older, may be at increased risk for infective endocarditis (30). Additionally, approximately one third of patients with MVP without MR at rest may have exercise-induced MR (31). Some patients may exhibit MR at rest on one occasion and not on another. There are no data available to address this latter issue, and at present, the decision must be left to clinical judgment, taking into account the nature of the invasive procedure, the previous history of endocarditis, and the presence or absence of valve thickening and/or redundancy.
Infective endocarditis is a serious illness associated with significant morbidity and mortality. Its prevention by the appropriate administration of antibiotics before procedures expected to produce bacteremia merits serious consideration. Experimental studies suggest that endothelial damage leads to platelet and fibrin deposition and the formation of a nonbacterial thrombotic endocardial lesion. In the presence of bacteremia, the organisms may adhere to these lesions and multiply within the platelet-fibrin complex, leading to an infective vegetation (30,32). Valvular and congenital abnormalities, especially those that result in abnormal high-velocity jet streams, can damage the endothelial lining and predispose to platelet aggregation and fibrin deposition at those sites, which are thus at higher risk for bacterial colonization.
Several issues must be considered in generating recommendations for endocarditis prophylaxis (33). The rationale for antimicrobial prophylaxis is based on the following:
• Clinical experience documents endocarditis after bacteremia.
• Bacteremia by organisms known to produce endocarditis follows various procedures, such as dental procedures, endoscopy, and cystoscopy.
• Antibiotics to which known offending organisms are sensitive are available.
• Antibiotics prevent Streptococcus viridans endocarditis in experimental endocarditis.
• Small clinical studies in humans suggest benefit from prophylaxis against endocarditis (34,35).
The following evidence raises questions about the value of prophylaxis:
• Lack of any randomized, controlled clinical trials to support the application of the results of animal studies to humans.
• The evidence that dental and other procedures cause endocarditis is circumstantial. With the incidence of bacteremia (positive blood culture) varying from 8% (urethral catheterization) to as high as 94% (periodontal surgery/extractions) (38), the actual incidence of endocarditis is low (10 to 60 cases per 1 million persons per year) (33). Studies suggest that dental treatment alone is not a risk factor for endocarditis (39,40).
• In specific circumstances, such as prophylaxis for all cases of MVP, the risk of death due to penicillin is estimated to be greater than the risk of infective endocarditis (41,42).
In view of these issues, and until the AHA’s recommendations have been revised, the committee continues to recommend that the risk of endocarditis in patients with pre-existing cardiac disorders be classified as relatively high, moderate, or low, as determined primarily by the underlying cardiac disorder (28).
Various dental and surgical procedures are associated with varying degrees and frequencies of bacteremia. The frequency of bacteremia is highest with dental and oral procedures, intermediate with procedures that involve the genitourinary tract, and lowest with gastrointestinal procedures (33). Recommendations for endocarditis prophylaxis, as determined by dental, surgical, and other procedures, are listed in Tables 5 through 8⇓⇓⇓⇓(28). Anecdotal reports of infective endocarditis complicating body piercing and tattoo application underscore the changing nature of this disease.
The procedure—and thus, the portal of entry—determines the type of organisms involved in the resulting bacteremia and dictates the choice of antibiotic for prophylaxis. Because streptococci are normal inhabitants of the oral cavity, the antibiotic prophylaxis regimen for dental and oral procedures is directed against these organisms. For genitourinary and lower gastrointestinal tract procedures, the antibiotic prophylactic regimen is designed primarily to cover enterococci.
2.3.2 Rheumatic Fever Prophylaxis
188.8.131.52 General Considerations
Rheumatic fever is an important cause of valvular heart disease. In the United States (and Western Europe), cases of acute rheumatic fever have been uncommon since the 1970s. However, starting in 1987, an increase in cases has been observed (43,44). With the enhanced understanding of the causative organism, group A beta hemolytic streptococcus, its rheumatogenicity is attributed to the prevalence of M-protein serotypes of the offending organism. This finding has resulted in the development of kits that allow rapid detection of group A streptococci with specificity greater than 95% and more rapid identification of their presence in upper respiratory infection. Because the test has a low sensitivity, a negative test requires throat culture confirmation (44). Prompt recognition and treatment comprise primary rheumatic fever prevention. For patients who have had a previous episode of rheumatic fever, continuous antistreptococcal prophylaxis is indicated for secondary prevention.
184.108.40.206 Primary Prevention
220.127.116.11 Secondary Prevention
Patients who have had rheumatic fever with or without carditis (including patients with MS) should receive prophylaxis for recurrent rheumatic fever. (Level of Evidence: B)
Patients who have had an episode of rheumatic fever are at high risk of developing recurrent episodes of acute rheumatic fever. Patients who develop carditis are especially prone to similar episodes with subsequent attacks. Secondary prevention of rheumatic fever recurrence is thus of great importance. Continuous antimicrobial prophylaxis has been shown to be effective. Anyone who has had rheumatic fever with or without carditis (including patients with MS) should receive prophylaxis for recurrent rheumatic fever. The 1995 AHA guidelines for secondary prevention are shown in Table 10,and the 1995 AHA guidelines for duration of secondary prevention are shown in Table 11(45).
3 Specific valve lesions
3.1 Aortic Stenosis
The most common cause of AS in adults is calcification of a normal trileaflet or congenital bicuspid valve (46–49). This calcific disease progresses from the base of the cusps to the leaflets, eventually causing a reduction in leaflet motion and effective valve area without commissural fusion. Calcific AS is an active disease process characterized by lipid accumulation, inflammation, and calcification, with many similarities to atherosclerosis (50–60). Rheumatic AS due to fusion of the commissures with scarring and eventual calcification of the cusps is less common and is invariably accompanied by MV disease. A congenital malformation of the valve may also result in stenosis and is the more common cause in young adults. The management of congenital AS in adolescents and young adults is discussed in Section 6.1.
18.104.22.168 Grading the Degree of Stenosis
Although AS is best described as a disease continuum, and there is no single value that defines severity, for these guidelines, we graded AS severity on the basis of a variety of hemodynamic and natural history data (Table 4) (27,61), using definitions of aortic jet velocity, mean pressure gradient, and valve area as follows:
• Mild (area 1.5 cm2, mean gradient less than 25 mm Hg, or jet velocity less than 3.0 m per second)
• Moderate (area 1.0 to 1.5 cm2, mean gradient 25 to 40 mm Hg, or jet velocity 3.0 to 4.0 m per second)
• Severe (area less than 1.0 cm2, mean gradient greater than 40 mm Hg, or jet velocity greater than 4.0 m per second).
When stenosis is severe and cardiac output is normal, the mean transvalvular pressure gradient is generally greater than 40 mm Hg. However, when cardiac output is low, severe stenosis may be present with a lower transvalvular gradient and velocity, as discussed below. Some patients with severe AS remain asymptomatic, whereas others with only moderate stenosis develop symptoms. Therapeutic decisions, particularly those related to corrective surgery, are based largely on the presence or absence of symptoms. Thus, the absolute valve area (or transvalvular pressure gradient) is not the primary determinant of the need for aortic valve replacement (AVR).
In adults with AS, the obstruction develops gradually—usually over decades. During this time, the left ventricle adapts to the systolic pressure overload through a hypertrophic process that results in increased LV wall thickness, while a normal chamber volume is maintained (62–64). The resulting increase in relative wall thickness is usually enough to counter the high intracavitary systolic pressure, and as a result, LV systolic wall stress (afterload) remains within the range of normal. The inverse relation between systolic wall stress and ejection fraction is maintained; as long as wall stress is normal, the ejection fraction is preserved (65). However, if the hypertrophic process is inadequate and relative wall thickness does not increase in proportion to pressure, wall stress increases and the high afterload causes a decrease in ejection fraction (65–67). Depressed contractile state of the myocardium may also be responsible for a low ejection fraction, and it is often difficult clinically to determine whether a low ejection fraction is due to depressed contractility or to excessive afterload (68). When low ejection fraction is caused by depressed contractility, corrective surgery will be less beneficial than in patients with a low ejection fraction caused by high afterload (69).
As a result of increased wall thickness, low volume/mass ratio, and diminished compliance of the chamber, LV end-diastolic pressure increases without chamber dilatation (70–72). Thus, increased end-diastolic pressure usually reflects diastolic dysfunction rather than systolic dysfunction or failure (73). A forceful atrial contraction that contributes to an elevated end-diastolic pressure plays an important role in ventricular filling without increasing mean left atrial or pulmonary venous pressure (74). Loss of atrial contraction such as that which occurs with atrial fibrillation is often followed by serious clinical deterioration.
The development of concentric hypertrophy appears to be an appropriate and beneficial adaptation to compensate for high intracavitary pressures. Unfortunately, this adaptation often carries adverse consequences. The hypertrophied heart may have reduced coronary blood flow per gram of muscle and also exhibit a limited coronary vasodilator reserve, even in the absence of epicardial CAD (75–77). The hemodynamic stress of exercise or tachycardia can produce a maldistribution of coronary blood flow and subendocardial ischemia, which can contribute to systolic or diastolic dysfunction of the left ventricle. Hypertrophied hearts also exhibit an increased sensitivity to ischemic injury, with larger infarcts and higher mortality rates than are seen in the absence of hypertrophy (78–80). Another problem that is particularly common in elderly patients, especially women, is an excessive or inappropriate degree of hypertrophy; wall thickness is greater than necessary to counterbalance the high intracavitary pressures (81–84). As a result, systolic wall stress is low and ejection fraction is high; such inappropriate LV hypertrophy has been associated with high perioperative morbidity and mortality (81,83).
3.1.3 Natural History
The natural history of AS in the adult consists of a prolonged latent period during which morbidity and mortality are very low. The rate of progression of the stenotic lesion has been estimated in a variety of invasive and noninvasive studies (85). Once even moderate stenosis is present (jet velocity greater than 3.0 m per second) (Table 4) (27), the average rate of progression is an increase in jet velocity of 0.3 m per second per year, an increase in mean pressure gradient of 7 mm Hg per year, and a decrease in valve area of 0.1 cm2per year (86–96). However, there is marked individual variability in the rate of hemodynamic progression. Although it appears that the progression of AS can be more rapid in patients with degenerative calcific disease than in those with congenital or rheumatic disease (96–98), it is not possible to predict the rate of progression in an individual patient. For this reason, regular clinical follow-up is mandatory in all patients with asymptomatic mild to moderate AS. In addition, progression to AS may occur in patients with aortic sclerosis, defined as valve thickening without obstruction to ventricular outflow (99).
Aortic sclerosis, defined as irregular valve thickening without obstruction to LV outflow, is present in about 25% of adults over 65 years of age and is associated with clinical factors such as age, sex, hypertension, smoking, serum low-density lipoprotein and lipoprotein(a) levels, and diabetes mellitus (100). In the Cardiovascular Health Study, the presence of aortic sclerosis on echocardiography in subjects without known coronary disease was also associated with adverse clinical outcome, with an approximately 50% increased risk of myocardial infarction and cardiovascular death compared with subjects with a normal aortic valve (101). This has been confirmed in 2 additional studies (102,103). The association between aortic sclerosis and adverse cardiovascular outcomes persisted even when age, sex, known cardiovascular disease, and cardiovascular risk factors were taken into account. However, the mechanism of this association is unclear and is unlikely to be related to valve hemodynamics. Studies are in progress to evaluate potential mechanisms of this association, including subclinical atherosclerosis, endothelial dysfunction, and systemic inflammation.
In most patients with severe AS, impaired platelet function and decreased levels of von Willebrand factor can be demonstrated. The severity of the coagulation abnormality correlates with the severity of AS and resolves after valve replacement, except when the prosthetic valve area is small for patient size (less than 0.8 cm2per m2). This acquired von Willebrand syndrome is associated with clinical bleeding, most often epistaxis or ecchymoses, in approximately 20% of patients (104).
Eventually, symptoms of angina, syncope, or heart failure develop after a long latent period, and the outlook changes dramatically. After the onset of symptoms, average survival is 2 to 3 years (105–111), with a high risk of sudden death. Thus, the development of symptoms identifies a critical point in the natural history of AS. Management decisions are based largely on these data; most clinicians treat asymptomatic patients conservatively, whereas corrective surgery is generally recommended in patients with symptoms thought to be due to AS. It is important to emphasize that symptoms may be subtle and often are not elicited by the physician in taking a routine clinical history.
Sudden death is known to occur in patients with severe AS and, in older retrospective studies, has been reported to occur without prior symptoms (105,108,112,113). However, in prospective echocardiographic studies, sudden death in previously asymptomatic patients is rare (61,96,109,114–116). Therefore, although sudden death may occur in the absence of preceding symptoms in patients with AS (105,108,112,113,116), it is an uncommon event, estimated at less than 1% per year when patients with known AS are followed up prospectively.
3.1.4 Management of the Asymptomatic Patient
Asymptomatic patients with AS have outcomes similar to age-matched normal adults. However, disease progression with symptom onset is common, as detailed in Table 12(61,96,109,114–118). In a prospective study of 123 asymptomatic adults with an initial jet velocity of at least 2.6 m per second, the rate of symptom development was 38% at 3 years for the total group. However, clinical outcome was strongly dependent on AS severity, with an event-free survival of 84% at 2 years in those with a jet velocity less than 3 m per second compared with only 21% in those with a jet velocity more than 4 m per second (61,98). In another study of 128 asymptomatic adults with an initial aortic jet velocity of at least 4 m per second, event-free survival was 67% at 1 year and 33% at 4 years, with predictors of outcome that included age and the degree of valve calcification (96). A third study of patients with aortic jet velocities greater than 4 m per second provided similar results, with 33% remaining asymptomatic without surgery at 5 years (116). Therefore, patients with asymptomatic AS require frequent monitoring for development of symptoms and progressive disease.
22.214.171.124 Echocardiography (Imaging, Spectral, and Color Doppler) in Aortic Stenosis
1. Echocardiography is recommended for the diagnosis and assessment of AS severity. (Level of Evidence: B)
2. Echocardiography is recommended in patients with AS for the assessment of LV wall thickness, size, and function. (Level of Evidence: B)
3. Echocardiography is recommended for re-evaluation of patients with known AS and changing symptoms or signs. (Level of Evidence: B)
4. Echocardiography is recommended for the assessment of changes in hemodynamic severity and LV function in patients with known AS during pregnancy. (Level of Evidence: B)
5. Transthoracic echocardiography is recommended for re-evaluation of asymptomatic patients: every year for severe AS; every 1 to 2 years for moderate AS; and every 3 to 5 years for mild AS. (Level of Evidence: B)
Aortic stenosis typically is first suspected on the basis of the finding of a systolic ejection murmur on cardiac auscultation; however, physical examination findings are specific but not sensitive for the diagnosis of AS severity (119). The classic findings of a loud (grade 4/6), late-peaking systolic murmur that radiates to the carotids, a single or paradoxically split second heart sound (S2), and a delayed and diminished carotid upstroke confirm the presence of severe AS. However, in the elderly, the carotid upstroke may be normal because of the effects of aging on the vasculature, and the murmur may be soft or may radiate to the apex. The only physical examination finding that is reliable in excluding the possibility of severe AS is a normally split second heart sound (119).
Echocardiography is indicated when there is a systolic murmur that is grade 3/6 or greater, a single S2, or symptoms that might be due to AS. The 2-dimensional (2D) echocardiogram is valuable for evaluation of valve anatomy and function and determining the LV response to pressure overload. In nearly all patients, the severity of the stenotic lesion can be defined with Doppler echocardiographic measurements of maximum jet velocity, mean transvalvular pressure gradient, and continuity equation valve area, as discussed in the “ACC/AHA/ASE 2003 Guidelines for the Clinical Application of Echocardiography” (2). Doppler evaluation of AS severity requires attention to technical details, with the most common error being underestimation of disease severity due to a nonparallel intercept angle between the ultrasound beam and high-velocity jet through the narrowed valve. When measurement of LV outflow tract diameter is problematic, the ratio of outflow tract velocity to aortic jet velocity can be substituted for valve area, because this ratio is, in effect, indexed for body size. A ratio of 0.9 to 1.0 is normal, with a ratio less than 0.25 indicating severe stenosis. Echocardiography is also used to assess LV size and function, degree of hypertrophy, and presence of other associated valvular disease.
In some patients, it may be necessary to proceed with cardiac catheterization and coronary angiography at the time of initial evaluation. For example, this is appropriate if there is a discrepancy between clinical and echocardiographic examinations or if symptoms might be due to CAD.
126.96.36.199 Exercise Testing
Exercise testing in asymptomatic patients with AS may be considered to elicit exercise-induced symptoms and abnormal blood pressure responses. (Level of Evidence: B)
Exercise testing should not be performed in symptomatic patients with AS. (Level of Evidence: B)
Exercise testing in adults with AS has poor diagnostic accuracy for evaluation of concurrent CAD. Presumably, this is due to the presence of an abnormal baseline ECG, LV hypertrophy, and limited coronary flow reserve. Electrocardiographic ST depression during exercise occurs in 80% of adults with asymptomatic AS and has no known prognostic significance.
Exercise testing should not be performed in symptomatic patients owing to a high risk of complications. However, in asymptomatic patients, exercise testing is relatively safe and may provide information that is not uncovered during the initial clinical evaluation (61,117,118,120–124). When the medical history is unclear, exercise testing can identify a limited exercise capacity, abnormal blood pressure responses, or even exercise-induced symptoms (117,118,124). In one series (117), patients manifesting symptoms, abnormal blood pressure (less than 20-mm Hg increase), or ST-segment abnormalities with exercise had a symptom-free survival at 2 years of only 19% compared with 85% symptom-free survival in those with none of these findings with exercise. Four patients died during the course of this study (1.2% annual mortality rate); all had an aortic valve area less than 0.7cm2and an abnormal exercise test. In another series (118), exercise testing brought out symptoms in 29% of patients who where considered asymptomatic before testing; in these patients, spontaneous symptoms developed in 51% over the next year compared with only 11% of patients who had no symptoms on exercise testing. An abnormal hemodynamic response (e.g., hypotension or failure to increase blood pressure with exercise) in a patient with severe AS is considered a poor prognostic finding (117,125). Finally, in selected patients, the observations made during exercise may provide a basis for advice about physical activity. Exercise testing in asymptomatic patients should be performed only under the supervision of an experienced physician with close monitoring of blood pressure and the ECG.
188.8.131.52 Serial Evaluations
The frequency of follow-up visits to the physician depends on the severity of the valvular stenosis and on the presence of comorbid conditions. Recognizing that an optimal schedule for repeated medical examinations has not been defined, many physicians perform an annual history and physical examination on patients with asymptomatic AS of any degree. An essential component of each visit is patient education about the expected disease course and symptoms of AS. Periodic echocardiography may be appropriate as discussed below. Patients should be advised to promptly report the development of any change in exercise tolerance, exertional chest discomfort, dyspnea, lightheadedness, or syncope.
Serial echocardiography is an important part of an integrated approach that includes a detailed history, physical examination, and, in some patients, a carefully monitored exercise test. Because the rate of progression varies considerably, clinicians often perform an annual echocardiogram on patients known to have moderate to severe AS. Serial echocardiograms are helpful for assessing changes in stenosis severity, LV hypertrophy, and LV function. Therefore, in patients with severe AS, an echocardiogram every year may be appropriate. In patients with moderate AS, serial studies performed every 1 to 2 years are satisfactory, and in patients with mild AS, serial studies can be performed every 3 to 5 years. Echocardiograms should be performed more frequently if there is a change in signs or symptoms.
184.108.40.206 Medical Therapy
Antibiotic prophylaxis is indicated in all patients with AS for prevention of infective endocarditis and, in those with rheumatic AS, for prevention of recurrent rheumatic fever. Patients with associated systemic arterial hypertension should be treated cautiously with appropriate antihypertensive agents. With these exceptions, there is no specific medical therapy for patients who have not yet developed symptoms. Patients who develop symptoms require surgery, not medical therapy.
There are no medical treatments proven to prevent or delay the disease process in the aortic valve leaflets. However, the association of AS with clinical factors similar to those associated with atherosclerosis and the mechanisms of disease at the tissue level (50–60,99–103,126–129) have led to the hypothesis that intervention may be possible to slow or prevent disease progression in the valve leaflet (127,130). Specifically, the effect of lipid-lowering therapy on progression of calcific AS has been examined in several small retrospective studies using echocardiography or cardiac computed tomography to measure disease severity (131–136), suggesting a benefit of statins. However, a prospective, randomized, placebo-controlled trial in patients with calcific aortic valve disease failed to demonstrate a benefit of atorvastatin in reducing the progression of aortic valve stenosis over a 3-year period (137). It is noteworthy that the patients in this study had high levels of aortic valve calcification by computed tomography and evidence of moderate to severe AS at baseline, based on peak aortic valve gradient (48 to 50 mm Hg), aortic valve area (1.02 to 1.03 cm2), and peak jet velocity (3.39 to 3.45 m per second). It is possible that the calcific process was too advanced in these patients to be reversed by short-term statin therapy. Thus, further trials in patients with less severe aortic valve calcification, with longer follow-up periods, are needed. In the meanwhile, evaluation and modification of cardiac risk factors is important in patients with aortic valve disease to prevent concurrent CAD.
220.127.116.11 Physical Activity and Exercise
Recommendations for physical activity are based on the clinical examination, with special emphasis on the hemodynamic severity of the stenotic lesion. The severity can usually be judged by Doppler echocardiography, but in borderline cases, diagnostic cardiac catheterization may be necessary to accurately define the degree of stenosis.
Recommendations on participation in competitive sports have been published by the Task Force on Acquired Valvular Heart Disease of the 36th Bethesda Conference (138). Physical activity is not restricted in asymptomatic patients with mild AS; these patients can participate in competitive sports. Patients with moderate to severe AS should avoid competitive sports that involve high dynamic and static muscular demands. Other forms of exercise can be performed safely, but it is advisable to evaluate such patients with an exercise test before they begin an exercise or athletic program.
3.1.5 Indications for Cardiac Catheterization
1. Coronary angiography is recommended before AVR in patients with AS at risk for CAD (see Section 10.2). (Level of Evidence: B)
2. Cardiac catheterization for hemodynamic measurements is recommended for assessment of severity of AS in symptomatic patients when noninvasive tests are inconclusive or when there is a discrepancy between noninvasive tests and clinical findings regarding severity of AS. (Level of Evidence: C)
3. Coronary angiography is recommended before AVR in patients with AS for whom a pulmonary autograft (Ross procedure) is contemplated and if the origin of the coronary arteries was not identified by noninvasive technique. (Level of Evidence: C)
1. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of severity of AS before AVR when noninvasive tests are adequate and concordant with clinical findings. (Level of Evidence: C)
2. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of LV function and severity of AS in asymptomatic patients. (Level of Evidence: C)
In patients with AS, the indications for cardiac catheterization and angiography are essentially the same as in other conditions, namely, to assess the coronary circulation and confirm or clarify the clinical diagnosis. In preparation for AVR, coronary angiography is indicated in patients suspected of having CAD, as discussed in Section 10.2. If the clinical and echocardiographic data are typical of severe isolated AS, coronary angiography may be all that is needed before AVR. A complete left- and right-heart catheterization may be necessary to assess the hemodynamic severity of the AS if there is a discrepancy between clinical and echocardiographic data.
The pressure gradient across a stenotic valve is related to the valve orifice area and the transvalvular flow (139). Thus, in the presence of depressed cardiac output, relatively low pressure gradients may be obtained in patients with severe AS. On the other hand, during exercise or other high-flow states, significant pressure gradients can be measured in minimally stenotic valves. For these reasons, complete assessment of AS requires
• measurement of transvalvular flow
• determination of the mean transvalvular pressure gradient
• calculation of the effective valve area.
Attention to detail with accurate measurements of pressure and flow is important, especially in patients with low cardiac output or a low transvalvular pressure gradient.
3.1.6 Low-Flow/Low-Gradient Aortic Stenosis
1. Dobutamine stress echocardiography is reasonable to evaluate patients with low-flow/low-gradient AS and LV dysfunction. (Level of Evidence: B)
2. Cardiac catheterization for hemodynamic measurements with infusion of dobutamine can be useful for evaluation of patients with low-flow/low-gradient AS and LV dysfunction. (Level of Evidence: C)
Patients with severe AS and low cardiac output often present with a relatively low transvalvular pressure gradient (i.e., mean gradient less than 30 mm Hg). Such patients can be difficult to distinguish from those with low cardiac output and only mild to moderate AS. In the former (true anatomically severe AS), the stenotic lesion contributes to an elevated afterload, decreased ejection fraction, and low stroke volume. In the latter, primary contractile dysfunction is responsible for the decreased ejection fraction and low stroke volume; the problem is further complicated by reduced valve opening forces that contribute to limited valve mobility and apparent stenosis. In both situations, the low-flow state and low-pressure gradient contribute to a calculated effective valve area that can meet criteria for severe AS. Alternate measures of AS severity have been proposed as being less flow dependent than gradients or valve area. These include valve resistance and stroke work loss. However, all of these measures are flow dependent, have not been shown to predict clinical outcome, and have not gained widespread clinical use (140).
In selected patients with low-flow/low-gradient AS and LV dysfunction, it may be useful to determine the transvalvular pressure gradient and to calculate valve area during a baseline state and again during exercise or low-dose pharmacological (i.e., dobutamine infusion) stress, with the goal of determining whether stenosis is severe or only moderate in severity (123,141–147). Such studies can be performed in the echocardiography laboratory or in the cardiac catheterization laboratory. This approach is based on the notion that patients who do not have true anatomically severe stenosis will exhibit an increase in the valve area and little change in gradient during an increase in stroke volume (141,142). Thus, if a dobutamine infusion produces an increment in stroke volume and an increase in valve area greater than 0.2 cm2and little change in gradient, it is likely that baseline evaluation overestimated the severity of stenosis. In contrast, patients with severe AS will have a fixed valve area with an increase in stroke volume and an increase in gradient. These patients are likely to respond favorably to surgery. Patients who fail to show an increase in stroke volume with dobutamine (less than 20%), referred to as “lack of contractile reserve,” appear to have a very poor prognosis with either medical or surgical therapy (2,148). Dobutamine stress testing in patients with AS should be performed only in centers with experience in pharmacological stress testing and with a cardiologist in attendance.
The clinical approach to the patient with low-output AS relies on integration of multiple sources of data. In addition to measurement of Doppler velocity, gradient, and valve area, the extent of valve calcification should be assessed. Severe calcification suggests that AVR may be beneficial. When transthoracic images are suboptimal, transesophageal imaging or fluoroscopy may be used to assess the degree of valve calcification and orifice area. The risk of surgery and patient comorbidities also are taken into account. Although patients with low-output severe AS have a poor prognosis, in those with contractile reserve, outcome is still better with AVR than with medical therapy (148). Some patients without contractile reserve may also benefit from AVR, but decisions in these high-risk patients must be individualized because there are no data indicating who will have a better outcome with surgery.
3.1.7 Indications for Aortic Valve Replacement
1. AVR is indicated for symptomatic patients with severe AS.* (Level of Evidence: B)
2. AVR is indicated for patients with severe AS* undergoing coronary artery bypass graft surgery (CABG). (Level of Evidence: C)
3. AVR is indicated for patients with severe AS* undergoing surgery on the aorta or other heart valves. (Level of Evidence: C)
4. AVR is recommended for patients with severe AS* and LV systolic dysfunction (ejection fraction less than 0.50). (Level of Evidence: C)
AVR is reasonable for patients with moderate AS* undergoing CABG or surgery on the aorta or other heart valves (see Section 3.7 on combined multiple valve disease and Section 10.4 on AVR in patients undergoing CABG). (Level of Evidence: B)
1. AVR may be considered for asymptomatic patients with severe AS* and abnormal response to exercise (e.g., development of symptoms or asymptomatic hypotension). (Level of Evidence: C)
2. AVR may be considered for adults with severe asymptomatic AS* if there is a high likelihood of rapid progression (age, calcification, and CAD) or if surgery might be delayed at the time of symptom onset. (Level of Evidence: C)
3. AVR may be considered in patients undergoing CABG who have mild AS* when there is evidence, such as moderate to severe valve calcification, that progression may be rapid. (Level of Evidence: C)
4. AVR may be considered for asymptomatic patients with extremely severe AS (aortic valve area less than 0.6 cm2, mean gradient greater than 60 mm Hg, and jet velocity greater than 5.0 m per second) when the patient’s expected operative mortality is 1.0% or less. (Level of Evidence: C)
AVR is not useful for the prevention of sudden death in asymptomatic patients with AS who have none of the findings listed under the class IIa/IIb recommendations. (Level of Evidence: B)
In adults with severe, symptomatic, calcific AS, AVR is the only effective treatment. Younger patients with congenital or rheumatic AS may be candidates for valvotomy (see Section 6.1 under management of adolescents and young adults). Although there is some lack of agreement about the optimal timing of surgery in asymptomatic patients, it is possible to develop rational guidelines for most patients. A proposed management strategy for patients with severe AS is shown in Figure 3(149). Particular consideration should be given to the natural history of asymptomatic patients and to operative risks and outcomes after surgery. See also Section 7.2.
18.104.22.168 Symptomatic Patients
In symptomatic patients with AS, AVR improves symptoms and improves survival (106,150–155). These salutary results of surgery are partly dependent on LV function. The outcome is similar in patients with normal LV function and in those with moderate depression of contractile function. The depressed ejection fraction in many patients in this latter group is caused by excessive afterload (afterload mismatch) (66), and LV function improves after AVR in such patients. If LV dysfunction is not caused by afterload mismatch, survival is still improved, but improvement in LV function and resolution of symptoms might not be complete after AVR (150,154,156–158). Therefore, in the absence of serious comorbid conditions, AVR is indicated in virtually all symptomatic patients with severe AS. Because of the risk of sudden death, AVR should be performed promptly after the onset of symptoms. Age is not a contraindication to surgery, with several series showing outcomes similar to age-matched normal subjects in the very elderly. The operative risks can be estimated with readily available and well-validated online risk calculators from the Society of Thoracic Surgeons (www.sts.org) and the European System for Cardiac Operative Risk Evaluation (www.euroscore.org) (159–161), as well as the risk calculator developed specifically for valvular heart surgery by Ambler et al (162).
22.214.171.124 Asymptomatic Patients
Many clinicians are reluctant to proceed with AVR in an asymptomatic patient (163), whereas others are concerned about caring for a patient with severe AS without surgery. Although AVR is associated with low perioperative morbidity and mortality in many centers, the average perioperative mortality in the STS database is 3.0% to 4.0% for isolated AVR and 5.5% to 6.8% for AVR plus CABG (164,165). These rates are 33% higher in centers with low volume than in centers with the highest surgical volume (166). A review of Medicare data (167), involving 684 US hospitals and more than 142 000 patients, indicates that the average in-hospital mortality for AVR in patients over the age of 65 years is 8.8% (13.0% in low-volume centers and 6.0% in high-volume centers). In addition, despite improved longevity of current-generation bioprosthetic valves (168,169), AVR in young patients subjects them to the risks of structural valve deterioration of bioprostheses (168,170–174) and the appreciable morbidity and mortality of mechanical valves (172,174–178). Thus, the combined risk of surgery in older patients and the late complications of a prosthesis in younger patients needs to be balanced against the possibility of preventing sudden death, which, as noted above, occurs at a rate of less than 1.0% per year.
Despite these considerations, some difference of opinion persists among clinicians regarding the indications for AVR in asymptomatic patients with severe AS, because the probability of remaining free of cardiac symptoms without surgery is less than 50% at 5 years (61,96,116). Some argue that irreversible myocardial depression or fibrosis might develop during a prolonged asymptomatic stage and that this might preclude an optimal outcome. Such irreversibility has not been proved, but this concept has been used to support early surgery (152,179). Still others attempt to identify patients who are at especially high risk of sudden death without surgery, although data supporting this approach are limited. Currently, there is general agreement that the risk of AVR exceeds any potential benefit in patients with severe AS who are truly asymptomatic with normal LV systolic function. However, as improved valve substitutes are developed and methods of valve replacement become safer, the risk-benefit balance may change to favor earlier intervention in AS.
Studies suggest that patients at risk of rapid disease progression and impending symptom onset can be identified on the basis of clinical and echocardiographic parameters. The rate of hemodynamic progression is faster in patients with asymptomatic severe (96) or mild to moderate (98) AS when patient age is over 50 years and severe valve calcification or concurrent CAD is present. Adverse clinical outcomes are more likely in patients with a more rapid rate of hemodynamic progression, defined as an annual increase in aortic jet velocity greater than 0.3 m per second per year or a decrease in valve area greater than 0.1 cm2per year (61,96). The presence of left ventricular hypertrophy by ECG and smaller aortic valve area by Doppler echocardiography predict the development of symptoms (61,116). In addition, serum levels of B-type natriuretic peptide may provide important prognostic information (180). In situations in which there is delay between symptom onset and surgical intervention, patients are at high risk of adverse outcomes during the waiting period. These higher-risk patients might warrant more frequent echocardiography or earlier consideration of valve replacement.
In the 1998 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease, consideration was given to performing AVR in patients with AS and severe LV hypertrophy and those with ventricular tachycardia (Class IIb). The current committee determined that there was insufficient evidence to support those recommendations, which are not carried forward in the current document.
126.96.36.199 Patients Undergoing Coronary Artery Bypass or Other Cardiac Surgery
Patients with severe AS, with or without symptoms, who are undergoing CABG should undergo AVR at the time of the revascularization procedure. Similarly, patients with severe AS undergoing surgery on other valves (such as MV repair) or the aortic root should also undergo AVR as part of the surgical procedure. In patients with moderate AS, it is generally accepted practice to perform AVR at the time of CABG (181–185). Many clinicians also recommend AVR for moderate AS at the time of MV or aortic root surgery (for further detail, see Section 3.7, “Multiple Valve Disease”). However, there are no data to support a policy of AVR for mild AS at the time of CABG, with the exception of those patients with moderate to severe valvular calcification (98,181,182,185–187). Recommendations for AVR at the time of CABG are discussed in Section 10.4.
3.1.8 Aortic Balloon Valvotomy
1. Aortic balloon valvotomy might be reasonable as a bridge to surgery in hemodynamically unstable adult patients with AS who are at high risk for AVR. (Level of Evidence: C)
2. Aortic balloon valvotomy might be reasonable for palliation in adult patients with AS in whom AVR cannot be performed because of serious comorbid conditions. (Level of Evidence: C)
Aortic balloon valvotomy is not recommended as an alternative to AVR in adult patients with AS; certain younger adults without valve calcification may be an exception (see Section 6.1.3). (Level of Evidence: B)
Percutaneous balloon aortic valvotomy is a procedure in which 1 or more balloons are placed across a stenotic valve and inflated to decrease the severity of AS (188–190). This procedure has an important role in treating adolescents and young adults with AS (see Section 6.1.) but a very limited role in older adults. The mechanism underlying relief of the stenotic lesion in older adults is fracture of calcific deposits within the valve leaflets and, to a minor degree, stretching of the annulus and separation of the calcified or fused commissures (191–193). Immediate hemodynamic results include a moderate reduction in the transvalvular pressure gradient, but the postvalvotomy valve area rarely exceeds 1.0 cm2. Despite the modest change in valve area, an early symptomatic improvement is usually seen. However, serious acute complications occur with a frequency greater than 10% (194–200), and restenosis and clinical deterioration occur within 6 to 12 months in most patients (195,200–204). Therefore, in adults with AS, balloon valvotomy is not a substitute for AVR (204–207).
Some clinicians contend that despite the procedural morbidity and mortality and limited long-term results, balloon valvotomy can have a temporary role in the management of some symptomatic patients who are not initially candidates for AVR (207). For example, patients with severe AS and refractory pulmonary edema or cardiogenic shock might benefit from aortic valvuloplasty as a “bridge” to surgery; an improved hemodynamic state may reduce the risks of surgery. However, most clinicians recommend proceeding directly to AVR in these cases. The indications for palliative valvotomy in patients in whom AVR cannot be recommended because of serious comorbid conditions are even less well established, with no data to suggest improved longevity, although some patients do report a decrease in symptoms. Most asymptomatic patients with severe AS who require urgent noncardiac surgery can undergo surgery at a reasonably low risk with monitoring of anesthesia and attention to fluid balance (208–212). Balloon aortic valvotomy is not recommended for these patients. If preoperative correction of AS is needed, they should be considered for AVR.
3.1.9 Medical Therapy for the Inoperable Patient
Comorbid conditions (e.g., malignancy) or, on occasion, patient preferences might preclude AVR for severe AS. Under such circumstances, there is no therapy that prolongs life, and only limited medical therapies are available to alleviate symptoms. Patients with evidence of pulmonary congestion can benefit from cautious treatment with digitalis, diuretics, and angiotensin converting enzyme (ACE) inhibitors. Indeed, a cautious reduction in central blood volume and LV preload can be efficacious in some patients with heart failure symptoms. It should be recognized, however, that excessive preload reduction can depress cardiac output and reduce systemic arterial pressure; patients with severe AS are especially subject to this untoward effect due to a small hypertrophied ventricle. In patients with acute pulmonary edema due to AS, nitroprusside infusion may be used to reduce congestion and improve LV performance. Such therapy should be performed in an intensive care unit under the guidance of invasive hemodynamic monitoring (213). Digitalis should be reserved for patients with depressed systolic function or atrial fibrillation. Atrial fibrillation and other atrial arrhythmias have an adverse effect on atrial pump function and ventricular rate; if prompt cardioversion is unsuccessful, pharmacological control of the ventricular rate is essential. If angina is the predominant symptom, cautious use of nitrates and beta blockers can provide relief. There is no specific medical therapy for syncope unless it is caused by a bradyarrhythmia or tachyarrhythmia.
3.1.10 Evaluation After Aortic Valve Replacement
Considering the known complications of prosthetic aortic valves (168,170–178,214), patients require periodic clinical and selected laboratory examinations after AVR. A complete history and physical examination should be performed at least once a year. Indications for echocardiography are discussed in Section 9.3.
3.1.11 Special Considerations in the Elderly
Because there is no effective medical therapy and balloon valvotomy is not an acceptable alternative to surgery, AVR must be considered in all elderly patients who have symptoms caused by AS. Valve replacement is technically possible at any age (215), but the decision to proceed with such surgery depends on many factors, including the patient’s wishes and expectations. Older patients with symptoms due to severe AS, normal coronary arteries, and preserved LV function can expect a better outcome than those with CAD or LV dysfunction (110). Certainly advanced cancer and permanent neurological defects as a result of stroke or dementia make cardiac surgery inappropriate. Deconditioned and debilitated patients often do not return to an active existence, and the presence of the other comorbid disorders could have a major impact on outcome.
In addition to the confounding effects of CAD and the potential for stroke, other considerations are peculiar to older patients. For example, a narrow LV outflow tract and a small aortic annulus sometimes present in elderly women could require enlargement of the annulus. Heavy calcification of the valve, annulus, and aortic root may require debridement. Occasionally, a composite valve-aortic graft is needed. Likewise, excessive or inappropriate hypertrophy associated with valvular stenosis can be a marker for perioperative morbidity and mortality (81,83). Preoperative recognition of elderly patients with marked LV hypertrophy followed by appropriate perioperative management can reduce this morbidity and mortality substantially. There is no perfect method for weighing all of the relevant factors and identifying specifically high- and low-risk elderly patients, but this risk can be estimated well in individual patients (159–162,216). The decision to proceed with AVR depends on an imprecise analysis that considers the balance between the potential for improved symptoms and survival and the morbidity and mortality of surgery (217–219).
3.2 Aortic Regurgitation
There are a number of common causes of AR. These include idiopathic dilatation of the aorta, congenital abnormalities of the aortic valve (most notably bicuspid valves), calcific degeneration, rheumatic disease, infective endocarditis, systemic hypertension, myxomatous degeneration, dissection of the ascending aorta, and Marfan syndrome. Less common causes include traumatic injuries to the aortic valve, ankylosing spondylitis, syphilitic aortitis, rheumatoid arthritis, osteogenesis imperfecta, giant cell aortitis, Ehlers-Danlos syndrome, Reiter’s syndrome, discrete subaortic stenosis, and ventricular septal defects with prolapse of an aortic cusp. Recently, anorectic drugs have also been reported to cause AR (see Section 3.9.). The majority of these lesions produce chronic AR with slow, insidious LV dilation and a prolonged asymptomatic phase (Table 4) (27). Other lesions, in particular infective endocarditis, aortic dissection, and trauma, more often produce acute severe AR, which can result in sudden catastrophic elevation of LV filling pressures and reduction in cardiac output.
3.2.2 Acute Aortic Regurgitation
In acute severe AR, the sudden large regurgitant volume is imposed on a left ventricle of normal size that has not had time to accommodate the volume overload. With an abrupt increase in end-diastolic volume, the ventricle operates on the steep portion of a normal diastolic pressure-volume relationship, and LV end-diastolic and left atrial pressures may increase rapidly and dramatically. The Frank-Starling mechanism is used, but the inability of the ventricle to develop compensatory chamber dilatation acutely results in a decrease in forward stroke volume. Although tachycardia develops as a compensatory mechanism to maintain cardiac output, this is often insufficient. Hence, patients frequently present with pulmonary edema or cardiogenic shock. Acute AR creates especially marked hemodynamic changes in patients with pre-existing pressure overload hypertrophy, in whom the small, noncompliant LV cavity is set on an even steeper diastolic pressure-volume relationship and has reduced preload reserve. Examples of this latter situation include aortic dissection in patients with systemic hypertension, infective endocarditis in patients with pre-existing AS, and acute regurgitation after balloon valvotomy or surgical commissurotomy for congenital AS. Patients may also present with signs and symptoms of myocardial ischemia. As the LV end-diastolic pressure approaches the diastolic aortic and coronary artery pressures, myocardial perfusion pressure in the subendocardium is diminished. LV dilation and thinning of the LV wall result in increased afterload, and this combines with tachycardia to increase myocardial oxygen demand. Therefore, ischemia and its consequences, including sudden death, occur commonly in acute severe AR.
Many of the characteristic physical findings of chronic AR are modified or absent when valvular regurgitation is acute, which can lead to underestimation of its severity. LV size may be normal on physical examination, and cardiomegaly may be absent on chest X-ray. Pulse pressure may not be increased because systolic pressure is reduced and the aortic diastolic pressure equilibrates with the elevated LV diastolic pressure. Because this diastolic pressure equilibration between aorta and ventricle can occur before the end of diastole, the diastolic murmur may be short and/or soft and therefore poorly heard. The elevated LV diastolic pressure can close the MV prematurely, reducing the intensity of the first heart sound. An apical diastolic rumble can be present, but it is usually brief and without presystolic accentuation. Tachycardia is invariably present.
Echocardiography is indispensable in confirming the presence and severity of the valvular regurgitation, determining its cause, estimating the degree of pulmonary hypertension (if TR is present), and determining whether there is rapid equilibration of aortic and LV diastolic pressure. Evidence for rapid pressure equilibration includes a short AR diastolic half-time (less than 300 ms), a short mitral deceleration time (less than 150 ms), or premature closure of the MV.
Acute AR caused by aortic root dissection is a surgical emergency that requires particularly prompt identification and management. Transesophageal echocardiography is indicated when aortic dissection is suspected (220–222). In some settings, computed tomographic imaging or magnetic resonance imaging should be performed if this will lead to a more rapid diagnosis than can be achieved by transesophageal echocardiography (220,221,223). Cardiac catheterization, aortography, and coronary angiography are rarely required, are associated with increased risk, and might delay urgent surgery unnecessarily (221,224–227). Angiography should be considered only when the diagnosis cannot be determined by noninvasive imaging and when patients have known CAD, especially those with previous CABG (see Section 10.2).
Death due to pulmonary edema, ventricular arrhythmias, electromechanical dissociation, or circulatory collapse is common in acute severe AR, even with intensive medical management. Urgent surgical intervention is recommended. Nitroprusside, and possibly inotropic agents such as dopamine or dobutamine to augment forward flow and reduce LV end-diastolic pressure, may be helpful to manage the patient temporarily before surgery. Intra-aortic balloon counterpulsation is contraindicated. Although beta blockers are often used in treating aortic dissection, these agents should be used very cautiously, if at all, in the setting of acute AR because they will block the compensatory tachycardia. In patients with acute severe AR resulting from infective endocarditis, surgery should not be delayed, especially if there is hypotension, pulmonary edema, or evidence of low output. In patients with mild acute AR, antibiotic treatment may be all that is necessary if the patient is hemodynamically stable. Exceptions to this latter recommendation are discussed in Section 4.6.1.
3.2.3 Chronic Aortic Regurgitation
The left ventricle responds to the volume load of chronic AR with a series of compensatory mechanisms, including an increase in end-diastolic volume, an increase in chamber compliance that accommodates the increased volume without an increase in filling pressures, and a combination of eccentric and concentric hypertrophy. The greater diastolic volume permits the ventricle to eject a large total stroke volume to maintain forward stroke volume in the normal range. This is accomplished through rearrangement of myocardial fibers with the addition of new sarcomeres and development of eccentric LV hypertrophy (228). As a result, preload at the sarcomere level remains normal or near normal, and the ventricle retains its preload reserve. The enhanced total stroke volume is achieved through normal performance of each contractile unit along the enlarged circumference (229). Thus, LV ejection performance is normal, and ejection phase indexes such as ejection fraction and fractional shortening remain in the normal range. However, the enlarged chamber size, with the associated increase in systolic wall stress, also results in an increase in LV afterload and is a stimulus for further hypertrophy (228,230). Thus, AR represents a condition of combined volume overload and pressure overload (231). As the disease progresses, recruitment of preload reserve and compensatory hypertrophy permit the ventricle to maintain normal ejection performance despite the elevated afterload (232,233). The majority of patients remain asymptomatic throughout this compensated phase, which may last for decades. Vasodilator therapy has the potential to reduce the hemodynamic burden in such patients.
For purposes of the subsequent discussion, patients with normal LV systolic function will be defined as those with normal LV ejection fraction at rest. It is recognized that other indices of LV function may not be “normal” in chronic severe AR and that the hemodynamic abnormalities noted above may be considerable. It is also recognized that the transition to LV systolic dysfunction represents a continuum and that there is no single hemodynamic measurement that represents the absolute boundary between normal LV systolic function and LV systolic dysfunction.
In a large subset of patients, the balance between afterload excess, preload reserve, and hypertrophy cannot be maintained indefinitely. Preload reserve may be exhausted (233), and/or the hypertrophic response may be inadequate (63), so that further increases in afterload result in a reduction in ejection fraction, first into the low normal range and then below normal. Impaired myocardial contractility may also contribute to this process. Patients often develop dyspnea at this point in the natural history. In addition, diminished coronary flow reserve in the hypertrophied myocardium may result in exertional angina (234). However, this transition may be much more insidious, and it is possible for patients to remain asymptomatic until severe LV dysfunction has developed.
LV systolic dysfunction (defined as an ejection fraction below normal at rest) is initially a reversible phenomenon related predominantly to afterload excess, and full recovery of LV size and function is possible with AVR (235–246). With time, during which the ventricle develops progressive chamber enlargement and a more spherical geometry, depressed myocardial contractility predominates over excessive loading as the cause of progressive systolic dysfunction. This can progress to the extent that the full benefit of surgical correction of the regurgitant lesion, in terms of recovery of LV function and improved survival, can no longer be achieved (244,247–256).
A large number of studies have identified LV systolic function and end-systolic size as the most important determinants of survival and postoperative LV function in patients undergoing AVR for chronic AR (235,237–267). Studies of predictors of surgical outcome are listed in Table 13.
Among patients undergoing valve replacement for chronic AR with preoperative LV systolic dysfunction (defined as an ejection fraction below normal at rest), several factors are associated with worse functional and survival results after operation. These are listed in Table 14.
188.8.131.52 Natural History
184.108.40.206.1 Asymptomatic Patients With Normal Left Ventricular Function
There are no truly large-scale studies evaluating the natural history of asymptomatic patients in whom LV systolic function was known to be normal (as determined by invasive or noninvasive testing). The current recommendations are derived from 9 published series (268–277) involving a total of 593 such patients (range, 27 to 104 patients/series) with a mean follow-up period of 6.6 years (Table 15).This analysis is subject to the usual limitations of comparisons of different clinical series with different patient selection factors and different end points. For example, 1 series (270) represents patients receiving placebo in a randomized drug trial (278) that included some patients with “early” New York Heart Association (NYHA) functional class II symptoms (although none had “limiting” symptoms), and another (272) represents patients receiving digoxin in a long-term study comparing the effects of nifedipine with digoxin. In 2 studies (274,276), LV function was not reported in all patients, and it is unclear whether all had normal LV systolic function at baseline. In another study (275), 20% of patients were not asymptomatic but had “early” NYHA functional class II symptoms, and the presence of these symptoms was a significant predictor of death, LV dysfunction, or development of more severe symptoms. Some patients in this latter series had evidence of LV systolic dysfunction (fractional shortening as low as 18%).
The results of these 9 studies are summarized in Tables 15 and 16.⇓The rate of progression to symptoms and/or LV systolic dysfunction averaged 4.3% per year. Sudden death occurred in 7 of the 593 patients, for an average mortality rate of less than 0.2% per year. Seven of the 9 studies reported the rate of development of asymptomatic LV dysfunction, defined as an ejection fraction at rest below normal (269–273,275,276); 37 of a total of 535 patients developed depressed systolic function at rest without symptoms during a mean 5.9-year follow-up period, a rate of 1.2% per year.
Despite the low likelihood of patients developing asymptomatic LV dysfunction, it should also be emphasized that more than one fourth of patients who die or develop systolic dysfunction do so before the onset of warning symptoms (269–271,275). Thus, thorough questioning of patients regarding symptomatic status is not sufficient in the serial evaluation of asymptomatic patients; quantitative evaluation of LV function is also indispensable. Moreover, patients at risk of future symptoms, death, or LV dysfunction can also be identified on the basis of noninvasive testing. Five of the natural history studies provide concordant information on the variables associated with higher risk (270–272,275,276). These variables are age, LV end-systolic dimension (or volume), LV end-diastolic dimension (or volume), and the LV ejection fraction during exercise. In 1 study (275), the LV ejection fraction during exercise was an independent risk factor. However, the direction and magnitude of change in ejection fraction from rest to exercise is related not only to myocardial contractility (279) but also to severity of volume overload (271,278–280) and exercise-induced changes in preload and peripheral resistance (280). In 2 multivariate analyses (271,276), only age and end-systolic dimension on initial study were independent predictors of outcome, as were the rate of increase in end-systolic dimension and decrease in resting ejection fraction during serial longitudinal studies (271). During a mean follow-up period of 8 years, patients with initial end-systolic dimensions greater than 50 mm had a likelihood of death, symptoms, and/or LV dysfunction of 19% per year. In those with end-systolic dimensions of 40 to 50 mm, the likelihood was 6% per year, and when the dimension was less than 40 mm, it was zero (271).
220.127.116.11.2 Asymptomatic Patients With Depressed Systolic Function
The limited data in asymptomatic patients with depressed LV ejection fraction indicate that the majority develop symptoms that warrant AVR within 2 to 3 years (281–283). The average rate of symptom onset in such patients is greater than 25% per year (Table 16) (268–277,281–288).
18.104.22.168.3 Symptomatic Patients
There are no contemporary large-scale studies of the natural history of symptomatic patients with chronic AR, because the onset of angina or significant dyspnea is usually an indication for valve replacement. The data developed in the presurgical era indicate that patients with dyspnea, angina, or overt heart failure have a poor outcome with medical therapy, analogous to that of patients with symptomatic AS. Mortality rates of greater than 10% per year have been reported in patients with angina pectoris and greater than 20% per year in those with heart failure (284–286). LV function was not measured in these patients, so it is unclear whether symptomatic patients with normal ejection fractions have the same adverse outcome as symptomatic patients with LV dysfunction; however, subsequent data indicate a poor outcome for symptomatic patients with medical therapy, even among those with preserved LV systolic function (274,287,288).
22.214.171.124 Diagnosis and Initial Evaluation
1. Echocardiography is indicated to confirm the presence and severity of acute or chronic AR. (Level of Evidence: B)
2. Echocardiography is indicated for diagnosis and assessment of the cause of chronic AR (including valve morphology and aortic root size and morphology) and for assessment of LV hypertrophy, dimension (or volume), and systolic function. (Level of Evidence: B)
3. Echocardiography is indicated in patients with an enlarged aortic root to assess regurgitation and the severity of aortic dilatation. (Level of Evidence: B)
4. Echocardiography is indicated for the periodic re-evaluation of LV size and function in asymptomatic patients with severe AR. (Level of Evidence: B)
5. Radionuclide angiography or magnetic resonance imaging is indicated for the initial and serial assessment of LV volume and function at rest in patients with AR and suboptimal echocardiograms. (Level of Evidence: B)
6. Echocardiography is indicated to re-evaluate mild, moderate, or severe AR in patients with new or changing symptoms. (Level of Evidence: B)
1. Exercise stress testing for chronic AR is reasonable for assessment of functional capacity and symptomatic response in patients with a history of equivocal symptoms. (Level of Evidence: B)
2. Exercise stress testing for patients with chronic AR is reasonable for the evaluation of symptoms and functional capacity before participation in athletic activities. (Level of Evidence: C)
3. Magnetic resonance imaging is reasonable for the estimation of AR severity in patients with unsatisfactory echocardiograms. (Level of Evidence: B)
Exercise stress testing in patients with radionuclide angiography may be considered for assessment of LV function in asymptomatic or symptomatic patients with chronic AR. (Level of Evidence: B)
The diagnosis of chronic severe AR can usually be made on the basis of the diastolic murmur, displaced LV impulse, wide pulse pressure, and characteristic peripheral findings that reflect wide pulse pressure. A third heart sound is often heard as a manifestation of the volume load and is not necessarily an indication of heart failure. An Austin-Flint rumble is a specific finding for severe AR (289,290). In many patients with more mild to moderate AR, the physical examination will identify the regurgitant lesion but will be less accurate in determining its severity. When the diastolic murmur of AR is louder in the third and fourth right intercostal spaces than in the third and fourth left intercostal spaces, the AR likely results from aortic root dilatation rather than from a deformity of the leaflets alone (291). The chest X-ray and ECG are helpful in evaluating overall heart size and rhythm, evidence of LV hypertrophy, and evidence of conduction disorders.
Echocardiography is indicated
• to confirm the diagnosis of AR if there is an equivocal diagnosis based on physical examination
• to assess the cause of AR and to assess valve morphology
• to provide a semiquantitative estimate of the severity of AR
• to assess LV dimension, mass, and systolic function
• to assess aortic root size.
In asymptomatic patients with preserved systolic function, these initial measurements represent the baseline information with which future serial measurements can be compared. In addition to semiquantitative assessment of the severity of AR by color flow jet area and width by Doppler echocardiography, quantitative measurement of regurgitant volume, regurgitant fraction, and regurgitant orifice area can be performed in experienced laboratories (Table 4) (27). Indirect measures of severity of AR are helpful, using the rate of decline in regurgitant gradient measured by the slope of diastolic flow velocity, the degree of reversal in pulse wave velocity in the descending aorta, and the magnitude of LV outflow tract velocity (2,292,293). Comparison of stroke volumes at the aortic valve compared with another uninvolved valve may provide a quantitative measurement of regurgitant fraction (294), but this measurement is more technically demanding.
LV wall stress may also be estimated from blood pressure and echocardiographic measurements. However, such wall stress measurements are difficult to reproduce, have methodological and conceptual problems, and should not be used for diagnosis or management decision making in clinical practice.
For purposes of the subsequent discussion of management of patients with AR, severe AR is defined as clinical and Doppler evidence of severe regurgitation (Table 4) (27) in addition to LV cavity dilatation. If the patient is asymptomatic and leads an active lifestyle and the echocardiogram is of good quality, no other testing is necessary. If the patient has severe AR and is sedentary or has equivocal symptoms, exercise testing is helpful to assess functional capacity, symptomatic responses, and hemodynamic effects of exercise (Fig. 4).If the echocardiogram is of insufficient quality to assess LV function, radionuclide angiography or cardiac magnetic resonance should be used in asymptomatic patients to measure LV ejection fraction at rest and estimate LV volumes. In patients who are symptomatic on initial evaluation, it is reasonable to proceed directly to transesophageal echocardiography or cardiac catheterization and angiography if the echocardiogram is of insufficient quality to assess LV function or severity of AR.
The exercise ejection fraction and the change in ejection fraction from rest to exercise are often abnormal, even in asymptomatic patients (268,270–272,275,283,295–303); however, these have not been proved to have independent diagnostic or prognostic value when LV function at rest and severity of LV volume overload by echocardiography are already known. One study that did identify the LV ejection fraction response to exercise as a predictor of symptomatic deterioration or LV dysfunction (275) included many patients with NYHA functional class II symptoms, LV systolic dysfunction (fractional shortening as low as 18%), and severe LV dilatation (end-diastolic and end-systolic dimensions as high as 87 and 65 mm, respectively). Hence, the predictive nature of this response in asymptomatic patients with normal LV systolic function and without severe LV dilatation has not been fully demonstrated.
126.96.36.199 Medical Therapy
Vasodilator therapy is indicated for chronic therapy in patients with severe AR who have symptoms or LV dysfunction when surgery is not recommended because of additional cardiac or noncardiac factors. (Level of Evidence: B)
Vasodilator therapy is reasonable for short-term therapy to improve the hemodynamic profile of patients with severe heart failure symptoms and severe LV dysfunction before proceeding with AVR. (Level of Evidence: C)
Vasodilator therapy may be considered for long-term therapy in asymptomatic patients with severe AR who have LV dilatation but normal systolic function. (Level of Evidence: B)
1. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with mild to moderate AR and normal LV systolic function. (Level of Evidence: B)
2. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with LV systolic dysfunction who are otherwise candidates for AVR. (Level of Evidence: C)
3. Vasodilator therapy is not indicated for long-term therapy in symptomatic patients with either normal LV function or mild to moderate LV systolic dysfunction who are otherwise candidates for AVR. (Level of Evidence: C)
Therapy with vasodilating agents is designed to improve forward stroke volume and reduce regurgitant volume. These effects should translate into reductions in LV end-diastolic volume, wall stress, and afterload, resulting in preservation of LV systolic function and reduction in LV mass. The acute administration of sodium nitroprusside, hydralazine, nifedipine, or felodipine reduces peripheral vascular resistance and results in an immediate augmentation in forward cardiac output and a decrease in regurgitant volume (304–313). With nitroprusside and hydralazine, these acute hemodynamic changes lead to a consistent reduction in end-diastolic volume and an increase in ejection fraction (304–306,312). This is an inconsistent finding with a single oral dose of nifedipine (308–311). Reduced end-diastolic volume and increased ejection fraction have also been observed in small numbers of patients receiving long-term oral therapy with hydralazine and nifedipine for periods of 1 to 2 years (278,314); with nifedipine, these effects are associated with a reduction in LV mass (272,314). Less consistent results have been reported with ACE inhibitors, depending on the degree of reduction in arterial pressure and end-diastolic volume (315–317). Reduced blood pressure with enalapril and quinapril has been associated with decreases in end-diastolic volume and mass but no change in ejection fraction (316,317).
There are 3 potential uses of vasodilating agents in chronic AR. It should be emphasized that these criteria apply only to patients with severe AR. The first is long-term treatment of patients with severe AR who have symptoms and/or LV dysfunction who are considered poor candidates for surgery because of additional cardiac or noncardiac factors. The second is improvement in the hemodynamic profile of patients with severe heart failure symptoms and severe LV dysfunction with short-term vasodilator therapy before proceeding with AVR. In such patients, vasodilating agents with negative inotropic effects should be avoided. The third is prolongation of the compensated phase of asymptomatic patients who have volume-loaded left ventricles but normal systolic function.
Whether this latter effect can be achieved has been investigated in only 2 studies. The first study compared long-acting nifedipine versus digoxin in a prospective randomized trial (272). Over a 6-year period, fewer patients randomized to nifedipine required AVR because of symptoms or development of LV dysfunction (ejection fraction less than 0.50). This study enrolled a relatively small number of patients (143 patients); there were relatively few end points (20 patients in the digoxin group and 6 in the nifedipine group underwent AVR); and there was no placebo control group. A more recent study compared placebo, long-acting nifedipine, and enalapril in 95 consecutive patients, who were followed for 7 years (277). Neither nifedipine nor enalapril reduced the development of symptoms or LV dysfunction warranting AVR compared with placebo. Moreover, neither drug significantly altered LV dimension, ejection fraction, or mass over the course of time compared with placebo. Thus, definitive recommendations regarding the indications for long-acting nifedipine or ACE inhibitors cannot be made at this time.
If vasodilator therapy is used, the goal is to reduce systolic blood pressure, and drug dosage should be increased until there is a measurable decrease in systolic blood pressure or the patient develops side effects. It is rarely possible to decrease systolic blood pressure to normal because of the increased LV stroke volume, and drug dosage should not be increased excessively in an attempt to achieve this goal. Vasodilator therapy is of unknown benefit and is not indicated in patients with normal blood pressure or normal LV cavity size.
Vasodilator therapy is not recommended for asymptomatic patients with mild or moderate AR and normal LV function in the absence of systemic hypertension, because these patients have an excellent outcome with no therapy. In patients with severe AR, vasodilator therapy is not an alternative to surgery in asymptomatic or symptomatic patients with LV systolic dysfunction; such patients should be considered surgical candidates rather than candidates for long-term medical therapy unless AVR is not recommended because of additional cardiac or noncardiac factors. Whether symptomatic patients who have preserved systolic function can be treated safely with aggressive medical management and whether aggressive medical management is as good or better than AVR have not been determined. It is recommended that symptomatic patients undergo surgery rather than long-term medical therapy.
There is scant information about long-term therapy with drugs other than vasodilators in asymptomatic patients with severe AR and normal LV function. Thus, there are no data to support the long-term use of digoxin, diuretics, nitrates, or positive inotropic agents in asymptomatic patients and no data with regard to any drug in patients with mild or moderate AR.
188.8.131.52 Physical Activity and Exercise
There are no data suggesting that exercise, particularly strenuous periodic exercise, will contribute to or accelerate the progression of LV dysfunction in AR. Asymptomatic patients with normal LV systolic function may participate in all forms of normal daily physical activity, including mild forms of exercise and in some cases competitive athletics. Isometric exercise should be avoided. Recommendations regarding participation in competitive athletics were published by the Task Force on Acquired Valvular Heart Disease of the 36th Bethesda Conference (138). Before participation in athletics, exercise testing to at least the level of exercise required by the proposed activity is recommended so that the patient’s tolerance for this degree of exercise can be evaluated. This does not necessarily evaluate the long-term effects of strenuous exercise, which are unknown.
184.108.40.206 Serial Testing
The aim of serial evaluation of asymptomatic patients with chronic AR is to detect the onset of symptoms and objectively assess changes in LV size and function that can occur in the absence of symptoms. In general, the stability and chronicity of the regurgitant lesion and the LV response to volume load need to be established when the patient first presents to the physician, especially if AR is moderate to severe. If the chronic nature of the lesion is uncertain and the patient does not present initially with one of the indications for surgery, repeat physical examination and echocardiography should be performed within 2 to 3 months after the initial evaluation to ensure that a subacute process with rapid progression is not under way. Once the chronicity and stability of the process has been established, the frequency of clinical re-evaluation and repeat noninvasive testing depends on the severity of the valvular regurgitation, the degree of LV dilatation, the level of systolic function, and whether previous serial studies have revealed progressive changes in LV size or function (Fig. 4). In most patients, serial testing during the long-term follow-up period should include a detailed history, physical examination, and echocardiography. Serial chest X-rays and ECGs have less value but are helpful in selected patients.
Asymptomatic patients with mild AR, little or no LV dilatation, and normal LV systolic function can be seen on a yearly basis, with instructions to alert the physician if symptoms develop in the interim. Yearly echocardiography is not necessary unless there is clinical evidence that regurgitation has worsened. Routine echocardiography can be performed every 2 to 3 years in such patients.
Asymptomatic patients with normal systolic function but severe AR and significant LV dilatation (end-diastolic dimension greater than 60 mm) require more frequent and careful re-evaluation, with a history and physical examination every 6 months and echocardiography every 6 to 12 months, depending on the severity of dilatation and stability of measurements. If patients are stable, echocardiographic measurements are not required more frequently than every 12 months. In patients with more advanced LV dilatation (end-diastolic dimension greater than 70 mm or end-systolic dimension greater than 50 mm), for whom the risk of developing symptoms or LV dysfunction ranges between 10% and 20% per year (271,272), it is reasonable to perform serial echocardiograms as frequently as every 4 to 6 months. Serial chest X-rays and ECGs have less value but are helpful in selected patients.
Chronic AR may develop from disease processes that involve the proximal ascending aorta. In patients with aortic root dilatation, serial echocardiograms are indicated to evaluate aortic root size, as well as LV size and function. This is discussed in Section 3.2.4.
Repeat echocardiograms are also recommended when the patient has onset of symptoms, there is an equivocal history of changing symptoms or changing exercise tolerance, or there are clinical findings that suggest worsening regurgitation or progressive LV dilatation. Patients with echocardiographic evidence of progressive ventricular dilatation or declining systolic function have a greater likelihood of developing symptoms or LV dysfunction (271) and should have more frequent follow-up examinations (every 6 months) than those with stable LV function.
In some centers with expertise in nuclear cardiology, serial radionuclide ventriculograms to assess LV volume and function at rest may be an accurate and cost-effective alternative to serial echocardiograms. However, there is no justification for routine serial testing with both an echocardiogram and a radionuclide ventriculogram. Serial radionuclide ventriculograms are also recommended in patients with suboptimal echocardiograms, patients with suggestive but not definite echocardiographic evidence of LV systolic dysfunction, and patients for whom there is discordance between clinical assessment and echocardiographic data. In centers with specific expertise in cardiac magnetic resonance imaging, serial magnetic resonance imaging may be performed in place of radionuclide angiography for the indications listed above. In addition to accurate assessment of LV volume, mass, wall thickness, and systolic function (318–322), cardiac magnetic resonance imaging may be used to quantify the severity of valvular regurgitation (323–327).
Serial exercise testing is also not recommended routinely in asymptomatic patients with preserved systolic function; however, exercise testing may be invaluable to assess functional capacity and symptomatic responses in patients with equivocal changes in symptomatic status. Serial exercise imaging studies to assess LV functional reserve are not indicated in asymptomatic patients or those in whom symptoms develop.
220.127.116.11 Indications for Cardiac Catheterization
1. Cardiac catheterization with aortic root angiography and measurement of LV pressure is indicated for assessment of severity of regurgitation, LV function, or aortic root size when noninvasive tests are inconclusive or discordant with clinical findings in patients with AR. (Level of Evidence: B)
2. Coronary angiography is indicated before AVR in patients at risk for CAD. (Level of Evidence: C)
1. Cardiac catheterization with aortic root angiography and measurement of LV pressure is not indicated for assessment of LV function, aortic root size, or severity of regurgitation before AVR when noninvasive tests are adequate and concordant with clinical findings and coronary angiography is not needed. (Level of Evidence: C)
2. Cardiac catheterization with aortic root angiography and measurement of LV pressure is not indicated for assessment of LV function and severity of regurgitation in asymptomatic patients when noninvasive tests are adequate. (Level of Evidence: C)
Cardiac catheterization is not required in patients with chronic AR unless there are questions about the severity of AR, hemodynamic abnormalities, or LV systolic dysfunction that persist despite physical examination and noninvasive testing, or unless AVR is contemplated and there is a need to assess coronary anatomy. The indications for coronary arteriography are discussed in Section 10.2. In some patients undergoing left-heart catheterization for coronary angiography, additional aortic root angiography and hemodynamic measurements may provide useful supplementary data.
Hemodynamic and angiographic assessment of the severity of AR and LV function may be necessary in some patients being considered for surgery when there are conflicting data between clinical assessment and noninvasive tests. Less commonly, asymptomatic patients who are not being considered for surgery may also require invasive measurement of hemodynamics and/or determination of severity of AR when this information cannot be obtained accurately from noninvasive tests.
Hemodynamic measurements during exercise are occasionally helpful for determining the effect of AR on LV function or making decisions regarding medical or surgical therapy. In selected patients with severe AR, borderline or normal LV systolic function, and LV chamber enlargement that is approaching the threshold for surgery (defined below), measurement of cardiac output and LV filling pressures at rest and during exercise with a right-heart catheter may be valuable for identifying patients with severe hemodynamic abnormalities in whom surgery is warranted.
18.104.22.168 Indications for Aortic Valve Replacement or Aortic Valve Repair
The majority of patients with severe AR requiring surgery undergo valve replacement (see Section 7.2.). However, in several surgical centers, there is increasing experience in performing aortic valve replacement in selected patients (see Section 7.2.6.). In the discussion that follows, the term “AVR” applies to both aortic valve replacement and aortic valve repair, with the understanding that aortic valve repair should be considered only in those surgical centers that have developed the appropriate technical expertise, gained experience in patient selection, and demonstrated outcomes equivalent to those of valve replacement. The indications for valve replacement and repair do not differ.
In patients with pure, chronic AR, AVR should be considered only if AR is severe (Table 4) (27). Patients with only mild AR are not candidates for AVR, and if such patients have symptoms or LV dysfunction, other causes should be considered, such as CAD, hypertension, or cardiomyopathic processes. If the severity of AR is uncertain after a review of clinical and echocardiographic data, additional information may be needed, such as invasive hemodynamic and angiographic data. The following discussion applies only to those patients with pure, severe AR.
1. AVR is indicated for symptomatic patients with severe AR irrespective of LV systolic function. (Level of Evidence: B)
2. AVR is indicated for asymptomatic patients with chronic severe AR and LV systolic dysfunction (ejection fraction 0.50 or less) at rest. (Level of Evidence: B)
3. AVR is indicated for patients with chronic severe AR while undergoing CABG or surgery on the aorta or other heart valves. (Level of Evidence: C)
AVR is reasonable for asymptomatic patients with severe AR with normal LV systolic function (ejection fraction greater than 0.50) but with severe LV dilatation (end-diastolic dimension greater than 75 mm or end-systolic dimension greater than 55 mm).* (Level of Evidence: B)
1. AVR may be considered in patients with moderate AR while undergoing surgery on the ascending aorta. (Level of Evidence: C)
2. AVR may be considered in patients with moderate AR while undergoing CABG. (Level of Evidence: C)
3. AVR may be considered for asymptomatic patients with severe AR and normal LV systolic function at rest (ejection fraction greater than 0.50) when the degree of LV dilatation exceeds an end-diastolic dimension of 70 mm or end-systolic dimension of 50 mm, when there is evidence of progressive LV dilatation, declining exercise tolerance, or abnormal hemodynamic responses to exercise.* (Level of Evidence: C)
AVR is not indicated for asymptomatic patients with mild, moderate, or severe AR and normal LV systolic function at rest (ejection fraction greater than 0.50) when degree of dilatation is not moderate or severe (end-diastolic dimension less than 70 mm, end-systolic dimension less than 50 mm).* (Level of Evidence: B)
*Consider lower threshold values for patients of small stature of either gender.
22.214.171.124.1 Symptomatic Patients With Normal Left Ventricular Systolic Function
AVR is indicated in patients with normal LV systolic function (defined as ejection fraction greater than 0.50 at rest) who have NYHA functional class III or IV symptoms. Patients with Canadian Heart Association functional class II to IV angina pectoris should also be considered for surgery. In many patients with NYHA functional class II dyspnea, the cause of symptoms is often unclear, and clinical judgment is required. Patients with well-compensated AR often have chronic mild dyspnea or fatigue, and it may be difficult to differentiate the effects of deconditioning or aging from true cardiac symptoms. In such patients, exercise testing may be valuable. If the cause of these mild symptoms is uncertain and they are not severe enough to interfere with the patient’s lifestyle, a period of observation may be reasonable. However, new onset of mild dyspnea has different implications in severe AR, especially in patients with increasing LV chamber size or evidence of declining LV systolic function into the low normal range. Thus, even if patients have not achieved the threshold values of LV size and function recommended for surgery in asymptomatic patients, development of mild symptoms is an indication for AVR in a patient who is nearing these values.
126.96.36.199.2 Symptomatic Patients With Left Ventricular Dysfunction
Patients with NYHA functional class II, III, or IV symptoms and with mild to moderate LV systolic dysfunction (ejection fraction 0.25 to 0.50) should undergo AVR. Patients with NYHA functional class IV symptoms have worse postoperative survival rates and lower likelihood of recovery of systolic function than patients with less severe symptoms (245,250,252,254), but AVR will improve ventricular loading conditions and expedite subsequent management of LV dysfunction (238).
Severely symptomatic patients (NYHA functional class IV) with advanced LV dysfunction (ejection fraction less than 0.25 and/or end-systolic dimension greater than 60 mm) present difficult management issues. Some patients will manifest meaningful recovery of LV function after AVR, but many will have developed irreversible myocardial changes. The mortality associated with valve replacement approaches 10%, and postoperative mortality over the subsequent few years is high. Valve replacement should be considered more strongly in patients with NYHA functional class II and III symptoms, especially if
• symptoms and evidence of LV dysfunction are of recent onset;
• intensive short-term therapy with vasodilators and diuretics results in symptomatic improvement;
• intravenous positive inotropic agents result in substantial improvement in hemodynamics or systolic function.
However, even in patients with NYHA functional class IV symptoms and ejection fraction less than 0.25, the high risks associated with AVR and subsequent medical management of LV dysfunction are usually a better alternative than the higher risks of long-term medical management alone (328).
188.8.131.52.3 Asymptomatic Patients
AVR in asymptomatic patients remains a controversial topic, but it is generally agreed (233,329–335) that AVR is indicated in patients with LV systolic dysfunction. As noted previously, for the purposes of these guidelines, LV systolic dysfunction is defined as an ejection fraction below normal at rest. The lower limit of normal will be assumed to be 0.50, with the realization that this lower limit is technique dependent and may vary among institutions. The committee also realizes that there may be variability in any given measurement of LV dimension or ejection fraction. Therefore, the committee recommends that 2 consecutive measurements be obtained before one proceeds with a decision to recommend surgery in the asymptomatic patient. These consecutive measurements could be obtained with the same test repeated in a short time period (such as a second echocardiogram after an initial echocardiogram) or with a separate, independent test (e.g., radionuclide ventriculography, magnetic resonance imaging, or contrast left ventriculography after an initial echocardiogram).
AVR is also recommended in patients with severe LV dilatation (end-diastolic dimension greater than 75 mm or end-systolic dimension greater than 55 mm), even if ejection fraction is normal. The majority of patients with this degree of dilatation will have already developed systolic dysfunction because of afterload mismatch and will thus be candidates for valve replacement on the basis of the depressed ejection fraction. The elevated end-systolic dimension in this regard is often a surrogate for systolic dysfunction. The relatively small number of asymptomatic patients with preserved ejection fraction despite severe increases in end-systolic and end-diastolic chamber size should be considered for surgery, because they appear to represent a high-risk group with an increased incidence of sudden death (271,336), and the results of valve replacement in such patients have thus far been excellent (264). In contrast, postoperative mortality is considerable once patients with severe LV dilatation develop symptoms or LV systolic dysfunction (264). The recommendations regarding the risk of sudden death and postoperative outcome with severe LV dilatation were based on reports of sudden death in 2 of 3 patients with an LV end-diastolic dimension greater than 80 mm (271) and 2 patients with an LV end-diastolic volume index greater than 200 ml/m2(336). It should be recognized, however, that LV end-diastolic dimension, whether examined as a continuous or as a dichotomous variable (less than 80 vs. greater than 80 mm), has not been found to be predictive of postoperative survival or LV function, whereas ejection fraction is predictive. Conservatively managed patients with an end-diastolic dimension exceeding 70 mm likewise exhibit a favorable clinical outcome (276). These data do not strongly support the use of extreme LV enlargement as an indication for AVR, unless cardiac symptoms or systolic dysfunction is present (337). However, the committee recommends surgery before the left ventricle achieves an extreme degree of dilatation and recommends AVR for patients with LV end-diastolic dimension greater than 75 mm.
Anthropometric normalization of LV end-diastolic dimension (or volume) should be considered, but unfortunately, there is lack of agreement as to whether or not normalization based on body surface area or body mass index is predictive of outcome (288,338). Normalization of end-diastolic dimension for body surface area tends to mask the diagnosis of LV enlargement, especially in patients who are overweight (339). The use of height and a consideration of gender are likely to be more appropriate than body surface area (340).
Patients with severe AR in whom the degree of LV dilatation has not reached but is approaching these threshold values (e.g., LV end-diastolic dimension of 70 to 75 mm or end-systolic dimension of 50 to 55 mm) should be followed with frequent echocardiograms every 4 to 6 months, as noted previously (Fig. 4). In addition, AVR may be considered in such patients if there is evidence of declining exercise tolerance or abnormal hemodynamic responses to exercise, for example, an increase in pulmonary artery wedge pressure greater than 25 mm Hg with exercise.
Several patient subgroups develop LV systolic dysfunction with less marked LV dilatation than observed in the majority of patients with uncomplicated AR. These include patients with long-standing hypertension in whom the pressure-overloaded ventricle has reduced compliance and a limited potential to increase its chamber size; patients with concomitant CAD, in whom myocardial ischemia may develop with increasing myocardial wall stress, resulting in LV dysfunction; and patients with concomitant MS, in whom the left ventricle will not dilate to the same extent as in patients with pure AR (341). In such patients, it is particularly important that LV ejection fraction and not merely systolic dimension be monitored. Women also tend to develop symptoms and LV dysfunction with less LV dilatation than men (338); this appears to be related to body size, because these differences are not apparent when LV dimensions are corrected for body surface area. Hence, LV dimensions alone may be misleading in small patients of either gender, and the threshold values of end-diastolic and end-systolic dimension recommended above for AVR in asymptomatic patients (75 and 55 mm, respectively) may need to be reduced in such patients. There are no data with which to derive guidelines for LV dimensions corrected for body size, and clinical judgment is required.
A decrease in ejection fraction during exercise should not be used as the only indication for AVR in asymptomatic patients with normal LV systolic function at rest, because the exercise ejection fraction response is multifactorial, and the strength of evidence is limited. The ejection fraction response to exercise has not proved to have independent prognostic value in patients undergoing surgery (254). The change in ejection fraction with exercise is a relatively nonspecific response related to both severity of volume load (271,296,300,301) and exercise-induced changes in preload and peripheral resistance (280) that develop early in the natural history of AR. AVR should also not be recommended in asymptomatic patients with normal systolic function merely because of evidence of LV dilatation as long as the dilatation is not severe (end-diastolic dimension less than 75 mm or end-systolic dimension less than 55 mm).
Patients who demonstrate progression of LV dilatation or progressive decline in ejection fraction on serial studies represent a higher-risk group who require careful monitoring (271), but such patients often reach a new steady state and may do well for extended periods of time. Hence, AVR is not recommended until the threshold values noted above are reached or symptoms or LV systolic dysfunction develop. However, prompt referral to AVR once patients develop symptoms, subnormal ejection fraction, or progressive LV dilatation results in significantly better postoperative survival than if AVR is delayed until symptoms or LV systolic function becomes more severe (254,265,267).
The surgical options for treating AR are expanding, with growing experience in aortic homografts, pulmonary autografts, unstented tissue valves, and aortic valve repair. If these techniques are ultimately shown to improve long-term survival or reduce postoperative valve complications, it is conceivable that the thresholds for recommending AVR may be reduced. Until such data are available, the indications for surgery for AR should not vary with the operative technique to be used.
3.2.4 Concomitant Aortic Root Disease
In addition to causing acute AR, diseases of the proximal aorta may also contribute to chronic AR. Dilatation of the ascending aorta is among the most common causes of isolated AR (342). In such patients, the valvular regurgitation may be less important in decision making than the primary disease of the aorta, such as Marfan syndrome, dissection, or chronic dilatation of the aortic root related to hypertension or a bicuspid aortic valve (see Section 3.3). In such patients, if the AR is mild or the left ventricle is only mildly dilated, management should focus on treating the underlying aortic root disease. In many patients, however, AR may be severe and associated with severe LV dilatation or systolic dysfunction, in which case decisions regarding medical therapy and timing of the operation must consider both conditions. In general, AVR and aortic root reconstruction are indicated in patients with disease of the aortic root or proximal aorta and AR of any severity when the degree of dilatation of the aorta or aortic root reaches or exceeds 5.0 cm by echocardiography (343). However, some have recommended surgery at a lower level of dilatation (4.5 cm) or based on a rate of increase of 0.5 cm per year or greater in surgical centers with established expertise in repair of the aortic root and ascending aorta (344). Aortic root and ascending aorta dilation in patients with bicuspid aortic valves is discussed in greater detail in Section 3.3.
3.2.5 Evaluation of Patients After Aortic Valve Replacement
After AVR, close follow-up is necessary during the early and long-term postoperative course to evaluate prosthetic valve function and assess LV function, as discussed in Sections 9.3. to 9.3.3. An echocardiogram should be performed soon after surgery to assess the results of surgery on LV size and function and to serve as a baseline against which subsequent echocardiograms may be compared. This could be performed either before hospital discharge or preferably at the first outpatient re-evaluation. Within the first few weeks of surgery, there is little change in LV systolic function, and ejection fraction may even deteriorate compared with preoperative values because of the reduced preload (345), even though ejection fraction may increase over the subsequent several months. Thus, persistent or more severe systolic dysfunction early after AVR is a poor predictor of subsequent improvement in LV function in patients with preoperative LV dysfunction. A better predictor of subsequent LV systolic function is the reduction in LV end-diastolic dimension, which declines significantly within the first week or 2 after AVR (240,245,346). This is an excellent marker of the functional success of valve replacement, because 80% of the overall reduction in end-diastolic dimension observed during the long-term postoperative course occurs within the first 10 to 14 days after AVR (240,245,346), and the magnitude of reduction in end-diastolic dimension after surgery correlates with the magnitude of increase in ejection fraction (245).
After the initial postoperative re-evaluation, the patient should be seen and examined again at 6 and 12 months and then on a yearly basis if the clinical course is uncomplicated. If the patient is asymptomatic, the early postoperative echocardiogram demonstrates substantial reduction in LV end-diastolic dimension, and LV systolic function is normal, serial postoperative echocardiograms after the initial early postoperative study are usually not indicated. However, repeat echocardiography is warranted at any point at which there is evidence of a new murmur, questions of prosthetic valve integrity, or concerns about LV function. Patients with persistent LV dilatation on the initial postoperative echocardiogram should be treated as would any other patient with symptomatic or asymptomatic LV dysfunction, including treatment with ACE inhibitors and beta-adrenergic blocking agents. In such patients, repeat echocardiography to assess LV size and systolic function is warranted at the 6- and 12-month re-evaluations. If LV dysfunction persists beyond this time frame, repeat echocardiograms should be performed as clinically indicated. Management of patients after AVR is discussed in greater detail in Section 9.3.
3.2.6 Special Considerations in the Elderly
The vast majority of elderly patients with aortic valve disease have AS or combined AS and AR, and pure AR is uncommon (347). Elderly patients with AR generally fare less well than patients who are young or middle-aged. Patients older than 75 years are more likely to develop symptoms or LV dysfunction at earlier stages of LV dilatation, have more persistent ventricular dysfunction and heart failure symptoms after surgery, and have worse postoperative survival rates than their younger counterparts. Many such patients have concomitant CAD, which must be considered in the evaluation of symptoms, LV dysfunction, and indications for surgery. Because the goal of therapy is to improve the quality of life rather than longevity, symptoms are the most important guide to determining whether or not AVR should be performed. Nonetheless, asymptomatic or mildly symptomatic patients who develop LV dysfunction (as defined previously) should be considered for AVR if the risks of surgery are balanced in otherwise healthy patients against the expected improvement in long-term outcome.
3.3 Bicuspid Aortic Valve With Dilated Ascending Aorta
1. Patients with known bicuspid aortic valves should undergo an initial transthoracic echocardiogram to assess the diameters of the aortic root and ascending aorta. (Level of Evidence: B)
2. Cardiac magnetic resonance imaging or cardiac computed tomography is indicated in patients with bicuspid aortic valves when morphology of the aortic root or ascending aorta cannot be assessed accurately by echocardiography. (Level of Evidence: C)
3. Patients with bicuspid aortic valves and dilatation of the aortic root or ascending aorta (diameter greater than 4.0 cm*) should undergo serial evaluation of aortic root/ascending aorta size and morphology by echocardiography, cardiac magnetic resonance, or computed tomography on a yearly basis. (Level of Evidence: C)
4. Surgery to repair the aortic root or replace the ascending aorta is indicated in patients with bicuspid aortic valves if the diameter of the aortic root or ascending aorta is greater than 5.0 cm* or if the rate of increase in diameter is 0.5 cm per year or more. (Level of Evidence: C)
5. In patients with bicuspid valves undergoing AVR because of severe AS or AR (see Sections 3.1.7 and 184.108.40.206), repair of the aortic root or replacement of the ascending aorta is indicated if the diameter of the aortic root or ascending aorta is greater than 4.5 cm.* (Level of Evidence: C)
1. It is reasonable to give beta-adrenergic blocking agents to patients with bicuspid valves and dilated aortic roots (diameter greater than 4.0 cm*) who are not candidates for surgical correction and who do not have moderate to severe AR. (Level of Evidence: C)
2. Cardiac magnetic resonance imaging or cardiac computed tomography is reasonable in patients with bicuspid aortic valves when aortic root dilatation is detected by echocardiography to further quantify severity of dilatation and involvement of the ascending aorta. (Level of Evidence: B)
*Consider lower threshold values for patients of small stature of either gender.
There is growing awareness that many patients with bicuspid aortic valves have disorders of vascular connective tissue, involving loss of elastic tissue (348,349), which may result in dilatation of the aortic root or ascending aorta even in the absence of hemodynamically significant AS or AR (350–353). Aortic root or ascending aortic dilatation can progress with time in this condition (354). These patients have a risk of aortic dissection that is related to the severity of dilatation (349,355–357). Recommendations for athletic participation in patients with bicuspid valve disease and associated dilatation of the aortic root or ascending aorta from the 36th Bethesda Conference (138) are based on limited data but with the understanding that aortic dissection can occur in some patients with aortic root or ascending aorta diameters less than 50 mm (344,356,358). Therapy with beta-adrenergic blocking agents might be effective in slowing the progression of aortic dilatation, but the available data have been developed in patients with Marfan syndrome (359) and not in patients with bicuspid aortic valves.
Echocardiography remains the primary imaging technique for identifying those patients in whom the aortic root or ascending aorta is enlarged. In many cases, echocardiography, including transesophageal imaging, provides all of the necessary information required to make management decisions. More accurate quantification of the diameter of the aortic root and ascending aorta, as well as full assessment of the degree of enlargement, can be obtained with cardiac magnetic resonance imaging or computed tomography. These techniques also allow for an accurate depiction of the size and contour of the aorta in its arch, descending thoracic, and abdominal segments. When the findings on transthoracic echocardiography relative to the aortic root and ascending aorta are concordant with those of either cardiac magnetic resonance or computed tomographic imaging, then transthoracic echocardiography can be used for annual surveillance. The dimensions of the aortic root and ascending aorta show considerable variability in normal populations. Regression formulas and nomograms have been developed for adolescents and adults that account for age and body surface area (360). An upper limit of 2.1 cm per m2has been established at the level of the aortic sinuses. Dilatation is considered an increase in diameter above the norm for age and body surface area, and an aneurysm has been defined as a 50% increase over the normal diameter (361).
Surgery to repair the aortic root or replace the ascending aorta has been recommended for those patients with greatly enlarged aortic roots or ascending aortas (344,349,357,358). In recommending elective surgery for this condition, a number of factors must be considered, including the patient’s age, the relative size of the aorta and aortic root, the structure and function of the aortic valve, and the experience of the surgical team. Aortic valve-sparing operations are feasible in most patients with dilatation of the aortic root or ascending aorta who do not have significant AR or aortic valve calcification (362–364). It is recommended that patients with bicuspid valves should undergo elective repair of the aortic root or replacement of the ascending aorta if the diameter of these structures exceeds 5.0 cm. Such surgery should be performed by a surgical team with established expertise in these procedures. Others have recommended a value of 2.5 cm per m2or greater as the indication for surgery (365). If patients with bicuspid valves and associated aortic root enlargement undergo AVR because of severe AS or AR (Sections 3.1.7. and 220.127.116.11.), it is recommended that repair of the aortic root or replacement of the ascending aorta be performed if the diameter of these structures is greater than 4.5 cm (366).
3.4 Mitral Stenosis
3.4.1 Pathophysiology and Natural History
MS is an obstruction to LV inflow at the level of the MV as a result of a structural abnormality of the MV apparatus, which prevents proper opening during diastolic filling of the left ventricle. The predominant cause of MS is rheumatic carditis. Isolated MS occurs in 40% of all patients presenting with rheumatic heart disease, and a history of rheumatic fever can be elicited from approximately 60% of patients presenting with pure MS (367,368). The ratio of women to men presenting with isolated MS is 2:1 (367–369). Congenital malformation of the MV occurs rarely and is observed mainly in infants and children (370). Acquired causes of MV obstruction, other than rheumatic heart disease, are rare. These include left atrial myxoma, ball valve thrombus, mucopolysaccharidosis, and severe annular calcification.
In patients with MS due to rheumatic fever, the pathological process causes leaflet thickening and calcification, commissural fusion, chordal fusion, or a combination of these processes (370,371). The result is a funnel-shaped mitral apparatus in which the orifice of the mitral opening is decreased in size. Interchordal fusion obliterates the secondary orifices, and commissural fusion narrows the principal orifice (370,371).
The normal MV area is 4.0 to 5.0 cm2. Narrowing of the valve area to less than 2.5 cm2typically occurs before the development of symptoms (139). With a reduction in valve area by the rheumatic process, blood can flow from the left atrium to the left ventricle only if propelled by a pressure gradient. This diastolic transmitral gradient is the fundamental expression of MS (372) and results in elevation of left atrial pressure, which is reflected back into the pulmonary venous circulation. Decreased pulmonary venous compliance that results in part from an increased pulmonary endothelin-1 spillover rate may also contribute to increased pulmonary venous pressure (373). Increased pressure and distension of the pulmonary veins and capillaries can lead to pulmonary edema as pulmonary venous pressure exceeds that of plasma oncotic pressure. In patients with chronic MV obstruction, however, even when it is severe and pulmonary venous pressure is very high, pulmonary edema may not occur owing to a marked decrease in pulmonary microvascular permeability. The pulmonary arterioles may react with vasoconstriction, intimal hyperplasia, and medial hypertrophy, which lead to pulmonary arterial hypertension.
An MV area greater than 1.5 cm2usually does not produce symptoms at rest (374). However, if there is an increase in transmitral flow or a decrease in the diastolic filling period, there will be a rise in left atrial pressure and development of symptoms. From hydraulic considerations, at any given orifice size, the transmitral gradient is a function of the square of the transvalvular flow rate and is dependent on the diastolic filling period (139). Thus, the first symptoms of dyspnea in patients with mild MS are usually precipitated by exercise, emotional stress, infection, pregnancy, or atrial fibrillation with a rapid ventricular response (374). As the obstruction across the MV increases, decreasing effort tolerance occurs.
As the severity of stenosis increases, cardiac output becomes subnormal at rest (374) and fails to increase during exercise (375). The degree of pulmonary vascular disease is also an important determinant of symptoms in patients with MS (373,374,376). A second obstruction to flow develops from increased pulmonary arteriolar resistance (376,377), which may protect the lungs from pulmonary edema (376,377). In some patients, an additional reversible obstruction develops at the level of the pulmonary veins (378,379). The low cardiac output and increased pulmonary arteriolar resistance, which results from functional and structural changes (alveolar basement membrane thickening, adaptation of neuroreceptors, increased lymphatic drainage, and increased transpulmonary endothelin spillover rate), contribute to the ability of a patient with severe MS to remain minimally symptomatic for prolonged periods of time (374,376,377).
The natural history of patients with untreated MS has been defined from studies in the 1950s and 1960s (367–369). Mitral stenosis is a continuous, progressive, lifelong disease, usually consisting of a slow, stable course in the early years followed by a progressive acceleration later in life (367–369,380). In developed countries, there is a long latent period of 20 to 40 years from the occurrence of rheumatic fever to the onset of symptoms. Once symptoms develop, there is another period of almost a decade before symptoms become disabling (367). Overall, the 10-year survival of untreated patients presenting with MS is 50% to 60%, depending on symptoms at presentation (368,369). In the asymptomatic or minimally symptomatic patient, survival is greater than 80% at 10 years, with 60% of patients having no progression of symptoms (368,369,380). However, once significant limiting symptoms occur, there is a dismal 0% to 15% 10-year survival rate (367–369,380,381). Once there is severe pulmonary hypertension, mean survival drops to less than 3 years (382). The mortality of untreated patients with MS is due to progressive pulmonary and systemic congestion in 60% to 70%, systemic embolism in 20% to 30%, pulmonary embolism in 10%, and infection in 1% to 5% (369,370). In North America and Europe, this classic history of MS has been replaced by an even milder delayed course with the decline in incidence of rheumatic fever (380,383). The mean age of presentation is now in the fifth to sixth decade (380,383); more than one third of patients undergoing valvotomy are older than 65 years (384). In some geographic areas, MS progresses more rapidly, presumably due to either a more severe rheumatic insult or repeated episodes of rheumatic carditis due to new streptococcal infections, resulting in severe symptomatic MS in the late teens and early 20s (380). Serial hemodynamic and Doppler-echocardiographic studies have reported annual loss of MV area ranging from 0.09 to 0.32 cm2(385,386).
Although MS is best described as a disease continuum, and there is no single value that defines severity, for these guidelines, MS severity is based on a variety of hemodynamic and natural history data (Table 4) (27) using mean gradient, pulmonary artery systolic pressure, and valve area as follows: mild (area greater than 1.5 cm2, mean gradient less than 5 mm Hg, or pulmonary artery systolic pressure less than 30 mm Hg), moderate (area 1.0 to 1.5 cm2, mean gradient 5 to 10 mm Hg, or pulmonary artery systolic pressure 30 to 50 mm Hg), and severe (area less than 1.0 cm2, mean gradient greater than 10 mm Hg, or pulmonary artery systolic pressure greater than 50 mm Hg).
3.4.2 Indications for Echocardiography in Mitral Stenosis
1. Echocardiography should be performed in patients for the diagnosis of MS, assessment of hemodynamic severity (mean gradient, MV area, and pulmonary artery pressure), assessment of concomitant valvular lesions, and assessment of valve morphology (to determine suitability for percutaneous mitral balloon valvotomy). (Level of Evidence: B)
2. Echocardiography should be performed for re-evaluation in patients with known MS and changing symptoms or signs. (Level of Evidence: B)
3. Echocardiography should be performed for assessment of the hemodynamic response of the mean gradient and pulmonary artery pressure by exercise Doppler echocardiography in patients with MS when there is a discrepancy between resting Doppler echocardiographic findings, clinical findings, symptoms, and signs. (Level of Evidence: C)
4. Transesophageal echocardiography in MS should be performed to assess the presence or absence of left atrial thrombus and to further evaluate the severity of MR in patients considered for percutaneous mitral balloon valvotomy. (Level of Evidence: C)
5. Transesophageal echocardiography in MS should be performed to evaluate MV morphology and hemodynamics in patients when transthoracic echocardiography provides suboptimal data. (Level of Evidence: C)
Echocardiography is reasonable in the re-evaluation of asymptomatic patients with MS and stable clinical findings to assess pulmonary artery pressure (for those with severe MS, every year; moderate MS, every 1 to 2 years; and mild MS, every 3 to 5 years). (Level of Evidence: C)
Transesophageal echocardiography in the patient with MS is not indicated for routine evaluation of MV morphology and hemodynamics when complete transthoracic echocardiographic data are satisfactory. (Level of Evidence: C)
The diagnosis of MS should be made on the basis of the history, physical examination, chest X-ray, and ECG (Fig. 5).Patients may present with no symptoms but have an abnormal physical examination (380,383). Although some patients may present with fatigue, dyspnea, or frank pulmonary edema, in others, the initial manifestation of MS is the onset of atrial fibrillation or an embolic event (367). Rarely, patients may present with hemoptysis, hoarseness, or dysphagia. The characteristic auscultatory findings of rheumatic MS are accentuated first heart sound (S1), opening snap (OS), low-pitched middiastolic rumble, and a presystolic murmur. These findings, however, may also be present in patients with nonrheumatic MV obstruction (e.g., left atrial myxoma) and may be absent with severe pulmonary hypertension, low cardiac output, and a heavily calcified immobile MV. A shorter A2-OS interval and longer duration of diastolic rumble indicates more severe MS. An A2-OS interval of less than 0.08 seconds implies severe MS (387). Physical findings of pulmonary hypertension, such as a loud P2or right ventricular (RV) heave, also suggest severe MS.
The diagnostic tool of choice in the evaluation of a patient with MS is 2D and Doppler echocardiography (388–393). Echocardiography is able to identify restricted diastolic opening of the MV leaflets due to “doming” of the anterior leaflet and immobility of the posterior leaflet (388,390,392,393). Other entities that can simulate the clinical features of rheumatic MS, such as left atrial myxoma, mucopolysaccharidosis, nonrheumatic calcific MS, cor triatriatum, and a parachute MV, can be readily identified by 2D echocardiography. Planimetry of the orifice area may be possible from the short-axis view. Two-dimensional echocardiography can be used to assess the morphological appearance of the MV apparatus, including leaflet mobility and flexibility, leaflet thickness, leaflet calcification, subvalvular fusion, and the appearance of commissures (391,394–398). These features may be important when one considers the timing and type of intervention to be performed (394–400). Patients with mobile noncalcified leaflets, no commissural calcification, and little subvalvular fusion may be candidates for either balloon catheter or surgical commissurotomy/valvotomy (394–399). There are several methods used to assess suitability for valvotomy, including a Wilkins score (Table 17)(400), an echocardiographic grouping (based on valve flexibility, subvalvular fusion, and leaflet calcification) (397), and the absence or presence of commissural calcium (398). Chamber size and function and other structural valvular, myocardial, or pericardial abnormalities can be assessed with the 2D echocardiographic study.
Doppler echocardiography can be used to assess the hemodynamic severity of the obstruction (389,391,401). The mean transmitral gradient can be accurately and reproducibly measured from the continuous-wave Doppler signal across the MV with the modified Bernoulli equation (391,401). The MV area can be noninvasively derived from Doppler echocardiography with either the diastolic pressure half-time method (401–404) or the continuity equation (402). The half-time method may be inaccurate in patients with abnormalities of left atrial or LV compliance, those with associated AR, and those who have had mitral valvotomy (403,404). Doppler echocardiography may also be used to estimate pulmonary artery systolic pressure from the TR velocity signal (405) and to assess severity of concomitant MR or AR. Formal hemodynamic exercise testing can be done noninvasively with either a supine bicycle or upright treadmill with Doppler recordings of transmitral and tricuspid velocities (406–409). This allows measurement of both the transmitral gradient (407–409) and pulmonary artery systolic pressure (406,408) at rest and with exercise (410). The criteria for the assessment of the severity of MS are summarized in Table 4(27). These criteria are applicable when the heart rate is between 60 and 90 bpm.
In all patients with MS, an initial clinical history, physical examination, ECG, and chest X-ray should be performed. 2D and Doppler echocardiography should also be performed to confirm the diagnosis of MS and rule out other causes of MV obstruction and concomitant problems that would require further therapy, that is, myocardial or other valvular heart disease. The morphology of the MV apparatus and suitability for valvotomy should be assessed. The severity of MS should be determined using both the mean transmitral gradient and valve area from the Doppler echocardiogram, and pulmonary artery pressure should be estimated when possible. A transesophageal echocardiogram is not required unless a question about diagnosis remains after transthoracic echocardiography.
In the asymptomatic patient who has documented mild MS (valve area greater than 1.5 cm2and mean gradient less than 5 mm Hg), no further investigations are needed on the initial workup (Fig. 5). These patients usually remain stable for years (368,369,380). If there is more significant MS, a decision to proceed further should be based on the suitability of the patient for mitral valvotomy. In patients with pliable, noncalcified valves with no or little subvalvular fusion, no calcification in the commissures, and no left atrial thrombus, percutaneous mitral valvotomy can be performed with a low complication rate and may be indicated if symptoms develop. Because of the slowly progressive course of MS, patients may remain “asymptomatic” with severe stenosis merely by readjusting their lifestyles to a more sedentary level. Elevated pulmonary vascular resistance and/or low cardiac output may also play an adaptive role in preventing congestive symptoms from occurring in patients with severe MS (374,376,377). Elevation of pulmonary vascular resistance is an important physiological event in MS (377), and the level of pulmonary pressure is an indicator of the overall hemodynamic consequence. Patients with moderate pulmonary hypertension at rest (pulmonary artery systolic pressure greater than 50 mm Hg) and pliable MV leaflets may be considered for percutaneous mitral valvotomy even if they deny symptoms. In patients who lead a sedentary lifestyle, a hemodynamic exercise test with Doppler echocardiography is useful (406–409). Objective limitation of exercise tolerance with a rise in transmitral gradient greater than 15 mm Hg and a rise in pulmonary artery systolic pressure greater than 60 mm Hg may be an indication for percutaneous valvotomy if the MV morphology is suitable. There is a subset of asymptomatic patients with severe MS (valve area less than 1.0 cm2) and severe pulmonary hypertension (pulmonary artery systolic pressure greater than 75% of systemic pressure either at rest or with exercise). If these patients do not have a valve morphology favorable for percutaneous mitral balloon valvotomy or surgical valve repair, it is controversial whether MV replacement should be performed in the absence of symptoms to prevent RV failure, but surgery is generally recommended in such patients. However, the patient (and the family) should be involved in the decision regarding intervention.
3.4.3 Medical Therapy
18.104.22.168 Medical Therapy: General
In the patient with MS, the major problem is mechanical obstruction to inflow at the level of the MV, and no medical therapy will specifically relieve the fixed obstruction. The left ventricle is protected from a volume or pressure overload, and thus, no specific medical therapy is required in the asymptomatic patient in normal sinus rhythm who has mild MS. Because rheumatic fever is the primary cause of MS, prophylaxis against rheumatic fever is recommended. Infective endocarditis is uncommon but does occur in isolated MS (368,369), and appropriate endocarditis prophylaxis is also recommended.
In the patient who has more than a mild degree of MS, counseling on avoidance of unusual physical stresses is advised. Increased flow and a shortening of the diastolic filling period by tachycardia increase left atrial pressure against an obstructed MV. Agents with negative chronotropic properties, such as beta blockers or heart rate–regulating calcium channel blockers, may be of benefit in patients in sinus rhythm who have exertional symptoms if these symptoms occur with high heart rates (411,412). The greater efficacy of a beta blocker compared with a heart rate–regulating calcium channel blocker has been reported (413). Some patients with MS have increased bronchial reactivity that may improve with inhaled corticosteroids (414). Salt restriction and intermittent administration of a diuretic are useful if there is evidence of pulmonary vascular congestion. Digitalis does not benefit patients with MS in sinus rhythm unless there is LV or RV dysfunction (415).
Although MS is a slowly progressive condition, acute pulmonary edema can occur suddenly in asymptomatic patients with severe MS, especially with the onset of rapid atrial fibrillation, and this can be rapidly fatal. Thus, patients should be counseled to seek medical attention immediately if they experience a sudden marked increase in shortness of breath.
22.214.171.124 Medical Therapy: Atrial Fibrillation
Patients with MS are prone to developing atrial arrhythmias, particularly atrial fibrillation and atrial flutter. Thirty to forty percent of patients with symptomatic MS develop atrial fibrillation (367,368). Structural changes from the pressure and volume overload alter the electrophysiological properties of the left atrium (380), and the rheumatic process itself may lead to fibrosis of the internodal and interatrial tracts and damage to the sinoatrial node. There may be significant hemodynamic consequences resulting from the acute development of atrial fibrillation, primarily from the rapid ventricular rate, which shortens the diastolic filling period and causes elevation of left atrial pressure. Atrial fibrillation occurs more commonly in older patients (367) and is associated with a poorer prognosis, with a 10-year survival rate of 25% compared with 46% in patients who remain in sinus rhythm (369). The risk of arterial embolization, especially stroke, is significantly increased in patients with atrial fibrillation (367,368,416–418).
Treatment of an acute episode of rapid atrial fibrillation consists of anticoagulation with heparin and control of the heart rate response. Intravenous digoxin, heart rate–regulating calcium channel blockers, or beta blockers should be used to control ventricular response by slowing conduction through the atrioventricular node. Intravenous or oral amiodarone can also be used when beta blockers or heart rate-regulating calcium channel blockers cannot be used. If there is hemodynamic instability, electrical cardioversion should be undertaken urgently, with intravenous heparin before, during, and after the procedure. In selected patients, chemical cardioversion may also be attempted. Patients who have been in atrial fibrillation longer than 24 to 48 h without anticoagulation are at an increased risk for embolic events after cardioversion, but embolization may occur with less than 24 h of atrial fibrillation. The decision to proceed with elective cardioversion is dependent on multiple factors, including duration of atrial fibrillation, hemodynamic response to the onset of atrial fibrillation, a documented history of prior episodes of atrial fibrillation, and a history of prior embolic events. If the decision has been made to proceed with elective cardioversion in a patient who has had documented atrial fibrillation for longer than 24 to 48 h and who has not been on long-term anticoagulation, 1 of 2 approaches is recommended based on data from patients with nonrheumatic atrial fibrillation. The first is anticoagulation with warfarin for more than 3 weeks, followed by elective cardioversion (419). The second is anticoagulation with heparin and transesophageal echocardiography to look for left atrial thrombus. In the absence of left atrial thrombus, cardioversion is performed with intravenous heparin before, during, and after the procedure (420). It is important to continue long-term anticoagulation after cardioversion.
Recurrent paroxysmal atrial fibrillation may be treated for maintenance of sinus rhythm in selected patients with class IC antiarrhythmic drugs (in conjunction with negative dromotropic agent) or class III antiarrhythmic drugs; however, eventually, the atrial fibrillation becomes resistant to prevention or cardioversion (376), and control of ventricular response becomes the mainstay of therapy. Digoxin slows the heart rate response in patients with atrial fibrillation and MS (415). However, heart rate–regulating calcium channel blockers or beta blockers are more effective for preventing exercise-induced increases in heart rate. Patients with either paroxysmal or sustained atrial fibrillation should be treated with long-term anticoagulation with warfarin to prevent embolic events if they do not have a strong contraindication to anticoagulation (417,421). It is controversial whether percutaneous mitral valvotomy should be performed in patients with new-onset atrial fibrillation and moderate to severe MS who are otherwise asymptomatic.
Successful percutaneous balloon mitral commissurotomy may not prevent the development of atrial fibrillation. Advanced age and left atrial dimension appear to be the important predictors of development of atrial fibrillation (422).
126.96.36.199 Medical Therapy: Prevention of Systemic Embolization
1. Anticoagulation is indicated in patients with MS and atrial fibrillation (paroxysmal, persistent, or permanent). (Level of Evidence: B)
2. Anticoagulation is indicated in patients with MS and a prior embolic event, even in sinus rhythm. (Level of Evidence: B)
3. Anticoagulation is indicated in patients with MS with left atrial thrombus. (Level of Evidence: B)
1. Anticoagulation may be considered for asymptomatic patients with severe MS and left atrial dimension greater than or equal to 55 mm by echocardiography.* (Level of Evidence: B)
2. Anticoagulation may be considered for patients with severe MS, an enlarged left atrium, and spontaneous contrast on echocardiography. (Level of Evidence: C)
*This recommendation is based on a grade C level of evidence given by the American College of Chest Physicians Fourth Consensus Conference on Antithrombotic Therapy (423).
Systemic embolization may occur in 10% to 20% of patients with MS (367,368,416). The risk of embolization is related to age and the presence of atrial fibrillation (367,368,416–418). One third of embolic events occur within 1 month of the onset of atrial fibrillation, and two thirds occur within 1 year. The frequency of embolic events does not seem to be related to the severity of MS, cardiac output, size of the left atrium, or even the presence or absence of heart failure symptoms (368,417,424). An embolic event may thus be the initial manifestation of MS (367). In patients who have experienced an embolic event, the frequency of recurrence is as high as 15 to 40 events per 100 patient-months (417–421).
There are no randomized trials examining the efficacy of anticoagulation in preventing embolic events specifically in patients with MS. Retrospective studies have shown a 4- to 15-fold decrease in the incidence of embolic events with anticoagulation in these patients (417,421). This benefit applies to both systemic and pulmonary embolism. Most trials involved patients who had 1 embolus before the onset of anticoagulation therapy (421). However, large randomized trials have demonstrated a significant reduction in embolic events by treatment with anticoagulation in subsets of patients with atrial fibrillation not associated with MS (425,426). In these randomized trials, the subset of patients who benefited most from anticoagulation were those with the highest risk of embolic events (353,354). Patients with MS at the highest risk for future embolic events are those with prior embolic events and those with paroxysmal or persistent atrial fibrillation (367,368,416–418,421). Paroxysmal atrial fibrillation may be difficult to detect; ambulatory ECG monitoring is valuable in patients with palpitations. There are no data to support the concept that oral anticoagulation is beneficial in patients with MS who have not had atrial fibrillation or an embolic event. It is controversial whether patients without atrial fibrillation or an embolic event who might be at higher risk for future embolic events (i.e., those with severe MS or an enlarged left atrium) should be considered for long-term warfarin therapy (423,427).
Although embolic events are thought to originate from left atrial thrombi (417,418), the presence or absence of a left atrial thrombus does not appear to correlate with embolic events (367,418). Left atrial thrombi are found during surgery in 15% to 20% of patients with prior embolic events and a similar number of patients without embolic events (367,416). However, in clinical practice, anticoagulation is frequently used if obvious left atrial thrombi are detected.
It has been suggested that surgical commissurotomy reduces the incidence of future embolic events (381). There are no randomized trial data to support this hypothesis, and the retrospective studies that have been reported were performed before the availability of standardized anticoagulation regimens. Other retrospective studies have concluded that surgery does not decrease the incidence of systemic emboli (380,428,429). One prospective study has reported decreased risk for arterial embolism after mitral commissurotomy (430).
3.4.4 Recommendations Regarding Physical Activity and Exercise
Many patients with mild MS will remain asymptomatic even with strenuous exercise. In more severe MS, exercise can cause sudden marked increases in pulmonary venous pressure from the increase in heart rate and cardiac output, at times resulting in pulmonary edema (375,376). The long-term effects of repeated exertion-related increases in pulmonary venous and pulmonary artery pressures on the lung or right ventricle remain unknown. MS rarely causes sudden death (367–369). These factors must be considered when recommending physical activity and exercise for the patient with MS.
In the majority of patients with MS, recommendations for exercise are symptom limited. Patients should be encouraged to pursue a low-level aerobic exercise program for maintenance of cardiovascular fitness. Exertional symptoms of dyspnea are the limiting factors in terms of exercise tolerance. However, there is a subset of asymptomatic patients who wish to participate in competitive athletics who may deny symptoms. The 36th Bethesda Conference on Recommendations for Determining Eligibility for Competition in Athletes with Cardiovascular Abnormalities published guidelines for patients with MS who wish to engage in competitive athletics (138).
3.4.5 Serial Testing
Serial follow-up testing of a patient with MS should be based on whether the results of a test will dictate either a change in therapy or a recommendation for a procedure. Patients with MS usually have years without symptoms before the onset of deterioration (367,380). All patients should be informed that any change in symptoms warrants re-evaluation. In the asymptomatic patient, yearly re-evaluation is recommended (Fig. 5). At the time of the yearly evaluation, a history, physical examination, chest X-ray, and ECG should be obtained. Physical examination is useful to assess the progression of the severity of MS. A shortening of the A2-OS interval, longer duration of the middiastolic murmur, and the presence of findings of pulmonary hypertension indicates more severe MS. An echocardiogram is not recommended yearly unless there is a change in clinical status or the patient has severe MS. Ambulatory ECG monitoring (Holter or event recorder) to detect paroxysmal atrial fibrillation is indicated in patients with palpitations.
3.4.6 Evaluation of the Symptomatic Patient
Patients who develop symptoms should undergo evaluation with a history, physical examination, ECG, chest X-ray, and echocardiogram (Figs. 6 and 7).⇓⇓Two-dimensional and Doppler echocardiography are indicated to evaluate MV morphology, MV hemodynamics, and pulmonary artery pressure. Patients with NYHA functional class II symptoms and moderate or severe MS (MV area less than or equal to 1.5 cm2or mean gradient greater than 5 mm Hg) may be considered for mitral balloon valvotomy if they have suitable MV morphology and no left atrial thrombi. Patients who have NYHA functional class III or IV symptoms and evidence of severe MS have a poor prognosis if left untreated (367–369) and should be considered for intervention with either balloon valvotomy or surgery.
A subset of patients have significant limiting symptoms, yet clinical and Doppler echocardiographic evaluation do not indicate moderate or severe MS. In such patients, formal exercise testing or dobutamine stress may be useful to differentiate symptoms due to MS from other causes of symptoms. Exercise tolerance, heart rate and blood pressure response, transmitral gradient, and pulmonary artery pressure can be obtained at rest and during exercise. This can usually be accomplished with either supine bicycle or upright exercise testing with Doppler recording of TR and transmitral velocities (406–409). Right- and left-heart catheterization with exercise may be helpful and occasionally necessary (431). Patients who are symptomatic with a significant elevation of pulmonary artery pressure (greater than 60 mm Hg), mean transmitral gradient (greater than 15 mm Hg), or pulmonary artery wedge pressure (greater than 25 mm Hg) during exercise (375,407–409,432,433) have hemodynamically significant MS and should be considered for further intervention. Alternatively, patients who do not manifest elevation in either pulmonary artery, pulmonary artery wedge, or transmitral pressures coincident with development of exertional symptoms most likely would not benefit from intervention on the MV.
3.4.7 Indications for Invasive Hemodynamic Evaluation
1. Cardiac catheterization for hemodynamic evaluation should be performed for assessment of severity of MS when noninvasive tests are inconclusive or when there is discrepancy between noninvasive tests and clinical findings regarding severity of MS. (Level of Evidence: C)
2. Catheterization for hemodynamic evaluation including left ventriculography (to evaluate severity of MR) for patients with MS is indicated when there is a discrepancy between the Doppler-derived mean gradient and valve area. (Level of Evidence: C)
1. Cardiac catheterization is reasonable to assess the hemodynamic response of pulmonary artery and left atrial pressures to exercise when clinical symptoms and resting hemodynamics are discordant. (Level of Evidence: C)
2. Cardiac catheterization is reasonable in patients with MS to assess the cause of severe pulmonary arterial hypertension when out of proportion to severity of MS as determined by noninvasive testing. (Level of Evidence: C)
Diagnostic cardiac catheterization is not recommended to assess the MV hemodynamics when 2D and Doppler echocardiographic data are concordant with clinical findings. (Level of Evidence: C)
Hemodynamic measurements by cardiac catheterization can be used to determine the severity of MS. Direct measurements of left atrial and LV pressure determine the transmitral gradient, which is the fundamental expression of severity of MS (372). Because the severity of obstruction is dependent on both flow and gradient (376), the hydraulic Gorlin equation has been used in the catheterization laboratory to derive a calculated valve area (139). Pulmonary artery pressure and pulmonary vascular resistance can be measured to determine the effect of MS on the pulmonary circulation.
With the advent of Doppler echocardiography, cardiac catheterization is no longer required for assessment of hemodynamics in the majority of patients with isolated MS. Reliable measurements of the transmitral gradient may be obtained with the modified Bernoulli equation (389,391). The potential problems of angle dependence, pressure recovery, proximal acceleration, and inadequate velocity signals that occur in the evaluation of other valve lesions are not present with MS. There is often overestimation of the transmitral gradient when catheterization is performed with pulmonary artery wedge pressure as a substitute for left atrial pressure, even after correction for phase delay. Thus, the transmitral gradient derived by Doppler echocardiography may be more accurate than that obtained by cardiac catheterization with pulmonary artery wedge pressure (434).
MV area is derived from either the half-time method or the continuity equation by Doppler echocardiography. These measurements correlate well in most instances with valve areas from cardiac catheterization (401,402). The Doppler half-time method may be inaccurate if there are changes in compliance of the left atrium or left ventricle (402,403), especially after mitral balloon valvotomy, or if there is concomitant AR. There are limitations to MV area calculations derived from catheter hemodynamic measurements, because the Gorlin equation may not be valid under varying hemodynamic conditions, and the empirical coefficient of discharge may be inaccurate with different orifice shapes (379,404). Calculation of valve area by catheterization is also dependent on measurement of transmitral gradient and cardiac output. Gradients may be inaccurate when pulmonary artery wedge pressure is used, as may cardiac output derived by the thermodilution method. When there is concomitant MR, measures of forward flow by thermodilution or the Fick method will result in underestimation of the MV area, as discussed in Section 188.8.131.52.2. Thus, there may be inaccuracies with both Doppler and catheter-derived valve areas, and a single valve area should not be the sole measure of MS severity. Estimates of the severity of MS should be based on all data, including transmitral gradient, MV area, pulmonary artery wedge pressure, and pulmonary artery pressure.
In most instances, Doppler measurements of transmitral gradient, valve area, and pulmonary pressure will correlate well with each other. Catheterization is indicated to assess hemodynamics when there is a discrepancy between Doppler-derived hemodynamics and the clinical status of a symptomatic patient. Absolute left- and right-side pressure measurements should be obtained by catheterization when there is elevation of pulmonary artery pressure out of proportion to mean gradient and valve area. Invasive hemodynamic evaluation is also necessary to assess the severity and the hemodynamic cause of increased pulmonary vascular resistance, because pulmonary vasodilator therapy may be of benefit in such patients. Catheterization including left ventriculography (to evaluate the severity of MR) is indicated when there is a discrepancy between the Doppler-derived mean gradient and valve area. Aortic root angiography may be necessary to evaluate severity of AR. If symptoms appear to be out of proportion to noninvasive assessment of resting hemodynamics, right- and left-heart catheterization with exercise may be useful. Transseptal catheterization may rarely be required for direct measurement of left atrial pressure if there is doubt about the accuracy of pulmonary artery wedge pressure. Coronary angiography may be required in selected patients who may need intervention (see Section 10.2.).
3.4.8 Indications for Percutaneous Mitral Balloon Valvotomy
1. Percutaneous mitral balloon valvotomy is effective for symptomatic patients (NYHA functional class II, III, or IV), with moderate or severe MS* and valve morphology favorable for percutaneous mitral balloon valvotomy in the absence of left atrial thrombus or moderate to severe MR. (Level of Evidence: A)
2. Percutaneous mitral balloon valvotomy is effective for asymptomatic patients with moderate or severe MS* and valve morphology that is favorable for percutaneous mitral balloon valvotomy who have pulmonary hypertension (pulmonary artery systolic pressure greater than 50 mm Hg at rest or greater than 60 mm Hg with exercise) in the absence of left atrial thrombus or moderate to severe MR. (Level of Evidence: C)
Percutaneous mitral balloon valvotomy is reasonable for patients with moderate or severe MS* who have a nonpliable calcified valve, are in NYHA functional class III–IV, and are either not candidates for surgery or are at high risk for surgery. (Level of Evidence: C)
1. Percutaneous mitral balloon valvotomy may be considered for asymptomatic patients with moderate or severe MS* and valve morphology favorable for percutaneous mitral balloon valvotomy who have new onset of atrial fibrillation in the absence of left atrial thrombus or moderate to severe MR. (Level of Evidence: C)
2. Percutaneous mitral balloon valvotomy may be considered for symptomatic patients (NYHA functional class II, III, or IV) with MV area greater than 1.5 cm2if there is evidence of hemodynamically significant MS based on pulmonary artery systolic pressure greater than 60 mm Hg, pulmonary artery wedge pressure of 25 mm Hg or more, or mean MV gradient greater than 15 mm Hg during exercise. (Level of Evidence: C)
3. Percutaneous mitral balloon valvotomy may be considered as an alternative to surgery for patients with moderate or severe MS who have a nonpliable calcified valve and are in NYHA class III–IV. (Level of Evidence: C)
1. Percutaneous mitral balloon valvotomy is not indicated for patients with mild MS. (Level of Evidence: C)
2. Percutaneous mitral balloon valvotomy should not be performed in patients with moderate to severe MR or left atrial thrombus. (Level of Evidence: C)
The concept of mitral commissurotomy was first proposed by Brunton in 1902, and the first successful surgical mitral commissurotomy was performed in the 1920s. By the late 1940s and 1950s, both transatrial and transventricular closed surgical commissurotomy were accepted clinical procedures. With the development of cardiopulmonary bypass, open mitral commissurotomy and replacement of the MV became the surgical procedures of choice for the treatment of MS. Percutaneous mitral balloon valvotomy emerged in the mid 1980s. This procedure, in which 1 or more large balloons is inflated across the MV by a catheter-based approach, has become the preferred procedure in selected patients compared with surgical approaches.
The mechanism of improvement from surgical commissurotomy or percutaneous valvotomy is related to the successful opening of commissures that were fused by the rheumatic process. This results in a decrease in gradient and an increase in the calculated MV area, with resulting improvement in clinical symptomatology. The extent of hemodynamic and clinical improvement is dependent on the magnitude of decrease of transmitral gradient and increase in valve area. Patients with pliable, noncalcified valves and minimal fusion of the subvalvular apparatus achieve the best immediate and long-term results when a substantial increase in the valve area can be achieved.
Closed surgical commissurotomy with either a transatrial or transventricular approach was popularized in the 1950s and 1960s. Early and long-term postoperative follow-up studies showed that patients had a significant improvement in symptoms and survival compared with those treated medically (435–437). Closed commissurotomy remains the surgical technique of choice in many developing countries, but open commissurotomy is the accepted surgical procedure in most institutions in the United States (438–441), because it allows direct inspection of the MV apparatus and, under direct vision, division of the commissures, splitting of fused chordae tendineae and papillary muscles, and debridement of calcium deposits. Amputation of the left atrial appendage is recommended to reduce the likelihood of postoperative thromboembolic events (442). The results of the operation are dependent on the morphology of the MV apparatus and the surgeon’s skill and experience. In patients with marked deformity of the MV apparatus, a decision for MV replacement can be made at the time of operation. The risk of surgery is between 1% and 3%, depending on the concomitant medical status of the patient (439–441). Although there is an inherent bias in the large reported surgical series, the 5-year reoperation rate is 4% to 7%, and the 5-year complication-free survival rate ranges from 80% to 90%.
Percutaneous mitral balloon valvotomy was first performed in the early 1980s and became a clinically approved technique in 1994. In the past decade, there have been major advances in techniques and equipment, as well as changes in patient selection. A double-balloon technique was the initial procedure used by most investigators. Today, an hourglass-shaped single balloon (Inoue balloon) is used by most centers performing the technique. Percutaneous mechanical mitral commissurotomy with a metallic valvotome has been introduced, and the results appear to be similar. The advantage of this technique is that multiple uses of the metallic device after sterilization are feasible and reduce the cost of treatment (443); however, it is not widely available, and there is limited experience with this technique. The balloon valvotomy procedure itself is technically challenging and involves a steep learning curve. There is a higher success rate and lower complication rate in experienced, high-volume centers (444). Thus, the results of the procedure are highly dependent on the experience of the operators involved, which must be considered when making recommendations for proceeding with this technique.
The immediate results of percutaneous mitral valvotomy are similar to those of mitral commissurotomy (444–453). The mean valve area usually doubles (from 1.0 to 2.0 cm2), with a 50% to 60% reduction in transmitral gradient. Overall, 80% to 95% of patients may have a successful procedure, which is defined as a MV area greater than 1.5 cm2and a decrease in left atrial pressure to less than 18 mm Hg in the absence of complications. The most common acute complications reported in large series include severe MR, which occurs in 2% to 10%, and a residual atrial septal defect. A large atrial septal defect (greater than 1.5:1 left-to-right shunt) occurs in fewer than 12% of patients with the double-balloon technique and fewer than 5% with the Inoue balloon technique. Smaller atrial septal defects may be detected by transesophageal echocardiography in larger numbers of patients. Less frequent complications include perforation of the left ventricle (0.5% to 4.0%), embolic events (0.5% to 3%), and myocardial infarction (0.3% to 0.5%). The mortality rate with balloon valvotomy in larger series has ranged from 1% to 2% (444–447,453); however, with increasing experience with the procedure, percutaneous mitral valvotomy can be done in selected patients with a mortality rate of less than 1% (448). Simultaneous echocardiography may be useful in directing balloon placement and assessing hemodynamics.
Follow-up information after percutaneous balloon valvotomy is limited. Event-free survival (freedom from death, repeat valvotomy, or MV replacement) overall is 50% to 65% over 3 to 7 years, with an event-free survival of 80% to 90% in patients with favorable MV morphology (398,446,448–455). More than 90% of patients free of events remain in NYHA functional class I or II after percutaneous mitral valvotomy. Randomized trials have compared percutaneous balloon valvotomy with both closed and open surgical commissurotomy (456–461). These trials, summarized in Table 18,consisted primarily of younger patients (aged 10 to 30 years) with pliable MV leaflets. There was no significant difference in acute hemodynamic results or complication rate between percutaneous mitral valvotomy and surgery, and early follow-up data indicate no difference in hemodynamics, clinical improvement, or exercise time. However, longer-term follow-up studies at 3 to 7 years (459,460) indicate more favorable hemodynamic and symptomatic results with percutaneous balloon valvotomy than with closed commissurotomy. Of the 2 studies that compared percutaneous balloon valvotomy with open commissurotomy, one reported equivalent results (460), and the other showed more favorable results with open commissurotomy (461). This latter study included older patients with higher MV scores.
The immediate results, acute complications, and follow-up results of percutaneous balloon valvotomy are dependent on multiple factors. It is of utmost importance that this procedure be performed in centers with skilled and experienced operators. Other factors include age, NYHA functional class, stenosis severity, LV end-diastolic pressure, cardiac output, and pulmonary artery wedge pressure (446,448,449,453). The underlying MV morphology is the factor of greatest importance in determining outcome (394–400,446,449,450,453,454,462), and immediate postvalvotomy hemodynamics are predictive of long-term clinical outcome (448,450,453). Patients with valvular calcification, thickened fibrotic leaflets with decreased mobility, and subvalvular fusion have a higher incidence of acute complications and a higher rate of recurrent stenosis on follow-up (Table 19).Because the success of the procedure is dependent on the ability to split fused commissures, the presence of marked fusion and severe calcification of commissures is associated with an increased complication rate and higher incidence of recurrent symptoms (396–398). Alternatively, in patients with noncalcified pliable valves, mild subvalvular fusion, and no calcium in the commissures, the procedure can be performed with a high success rate (greater than 90%), low complication rate (less than 3%), and sustained improvement in 80% to 90% over a 3- to 7-year follow-up period (397,398,400,446,448,450,453,454).
Relative contraindications to percutaneous balloon valvotomy include the presence of a left atrial thrombus and significant (3+ to 4+) MR. Transesophageal echocardiography is recommended before the procedure to determine the presence of left atrial thrombus, specifically examining the left atrial appendage. If a thrombus is found, 3 months of anticoagulation with warfarin may result in resolution of the thrombus. A prognostic model for predicting the resolution of left atrial thrombi in candidates for percutaneous mitral commissurotomy has been suggested. Combined clinical functional class and echocardiographic left atrial thrombus are predictive of the outcome of oral anticoagulation for thrombus resolution (463).
In centers with skilled, experienced operators, percutaneous balloon valvotomy should be considered the initial procedure of choice for symptomatic patients with moderate to severe MS who have a favorable valve morphology in the absence of significant MR or left atrial thrombus. Echocardiographic parameters that can predict the risks of developing severe MR after percutaneous mitral valvotomy by the Inoue technique have been reported (464), and the overall echocardiographic assessment (397,398,400) identifies patients with less favorable long-term outcome (Tables 17 and 19). In asymptomatic patients with a favorable valve morphology, percutaneous mitral valvotomy may be considered if there is evidence of a hemodynamic effect on left atrial pressure or pulmonary circulation (pulmonary artery systolic pressure greater than 50 mm Hg at rest or greater than 60 mm Hg with exercise); the strength of evidence for this recommendation is low because there are no data comparing the results of percutaneous balloon valvotomy and those of medical therapy in such asymptomatic patients. It is controversial whether severely symptomatic patients with less favorable valve morphology should undergo this catheter-based procedure (465) (Fig. 7; Table 19). Although there is a higher acute complication rate and a lower event-free survival rate (approximately 50% at 5 years in these patients compared with 80% to 90% in patients with favorable valve morphology), this must be weighed against the average in-hospital mortality of surgical MV replacement of 6% (164,165), which is as high as 16% in low-volume centers (166), and the expected long-term outcome. In many cases, MV replacement is preferable for patients with severe valvular calcification and deformity.
Patients who are being considered for an intervention should undergo evaluation with a history, physical examination, and 2D and Doppler echocardiographic examination. The appearance and mobility of the MV apparatus and commissures should be evaluated by 2D echocardiography, and the transmitral gradient, MV area, and pulmonary artery pressure should be obtained from the Doppler examination. If there is a discrepancy between symptoms and hemodynamics, a formal hemodynamic exercise test may be performed. Patients thought to be candidates for percutaneous mitral valvotomy should undergo transesophageal echocardiography to rule out left atrial thrombus and to examine the severity of MR. If a left atrial thrombus is present, a repeat transesophageal echocardiogram can be performed after several months of anticoagulation. Percutaneous mitral balloon valvotomy may be safely performed if there has been resolution of the thrombus. If there is a suspicion that the severity of MR is 3+ or 4+ based on the physical examination or echocardiogram, a left ventriculogram should be performed. Mitral balloon valvotomy should not be performed in patients who have grade 3+ or 4+ MR. Percutaneous mitral balloon valvotomy should be performed only by skilled operators at institutions with extensive experience in performing the technique (444,447). Thus, the decision to proceed with percutaneous balloon valvotomy or surgical commissurotomy is dependent on the experience of the operator and institution. Because of the less invasive nature of percutaneous balloon valvotomy compared with surgical intervention, appropriate patients without symptoms or those with NYHA functional class II symptoms may be considered for catheter-based therapy (Figs. 5 and 6).
3.4.9 Indications for Surgery for Mitral Stenosis
1. MV surgery (repair if possible) is indicated in patients with symptomatic (NYHA functional class III–IV) moderate or severe MS* when 1) percutaneous mitral balloon valvotomy is unavailable, 2) percutaneous mitral balloon valvotomy is contraindicated because of left atrial thrombus despite anticoagulation or because concomitant moderate to severe MR is present, or 3) the valve morphology is not favorable for percutaneous mitral balloon valvotomy in a patient with acceptable operative risk. (Level of Evidence: B)
2. Symptomatic patients with moderate to severe MS* who also have moderate to severe MR should receive MV replacement, unless valve repair is possible at the time of surgery. (Level of Evidence: C)
MV replacement is reasonable for patients with severe MS* and severe pulmonary hypertension (pulmonary artery systolic pressure greater than 60) with NYHA functional class I–II symptoms who are not considered candidates for percutaneous mitral balloon valvotomy or surgical MV repair. (Level of Evidence: C)
MV repair may be considered for asymptomatic patients with moderate or severe MS* who have had recurrent embolic events while receiving adequate anticoagulation and who have valve morphology favorable for repair. (Level of Evidence: C)
1. MV repair for MS is not indicated for patients with mild MS. (Level of Evidence: C)
2. Closed commissurotomy should not be performed in patients undergoing MV repair; open commissurotomy is the preferred approach. (Level of Evidence: C)
MV replacement is an accepted surgical procedure for patients with severe MS who are not candidates for surgical commissurotomy or percutaneous mitral valvotomy. The perioperative mortality of MV replacement is dependent on multiple factors, including functional status, age, LV function, cardiac output, concomitant medical problems, and concomitant CAD. In the young, healthy person, MV replacement can be performed with a risk of less than 5%; however, in the older patient with concomitant medical problems or pulmonary hypertension at systemic levels, the perioperative mortality of MV replacement may be as high as 10% to 20% (166,167). MV replacement with preservation of subvalvular apparatus aids in maintaining LV function (466), but this can be particularly difficult in patients with rheumatic MS. Alternative approaches to ventricular preservation exist, such as artificial chordal reconstruction before MV replacement (467,468). Complications of MV replacement include valve thrombosis, valve dehiscence, valve infection, valve malfunction, and embolic events. These are discussed in Section 7.3. There is also the known risk of long-term anticoagulation in patients receiving mechanical prostheses.
If there is significant calcification, fibrosis, and subvalvular fusion of the MV apparatus, commissurotomy or percutaneous balloon valvotomy is less likely to be successful, and MV replacement will be necessary. Given the risk of MV replacement and the potential long-term complications of a prosthetic valve, there are stricter indications for MV operation in these patients with calcified fibrotic valves. In the patient with NYHA functional class III symptoms due to severe MS or combined MS/MR, MV replacement results in excellent symptomatic improvement. Postponement of surgery until the patient reaches the functional class IV symptomatic state should be avoided, because operative mortality is high and the long-term outcome is suboptimal. However, if the patient presents in NYHA functional class IV heart failure, surgery should not be denied, because the outlook without surgical intervention is grave. It is controversial whether asymptomatic or mildly symptomatic patients with severe MS (valve area less than 1 cm2) and severe pulmonary hypertension (pulmonary artery systolic pressure greater than 60 to 80 mm Hg) should undergo MV replacement to prevent RV failure, but surgery is generally recommended in such patients. It is recognized that patients with such severe pulmonary hypertension are rarely asymptomatic.
3.4.10 Management of Patients After Valvotomy or Commissurotomy
Symptomatic improvement occurs almost immediately after successful percutaneous balloon valvotomy or surgical commissurotomy, although objective measurement of maximum oxygen consumption may continue to improve over several months postoperatively owing to slowly progressive improvement in skeletal muscle metabolism (469). Hemodynamic measurements before and after either percutaneous valvotomy or surgical commissurotomy have confirmed a decrease in left atrial pressure, pulmonary artery pressure, and pulmonary arteriolar resistance and an improvement in cardiac output (470–473). In patients with significant right heart failure after catheter-based or surgical relief of MV obstruction, inhaled nitric oxide, intravenous prostacyclin, or an endothelin antagonist may be useful in reducing pulmonary vascular resistance and pulmonary hypertension (474). Gradual regression of pulmonary hypertension over months has been demonstrated (470–472).
Recurrent symptoms after successful surgical commissurotomy have been reported to occur in as many as 60% of patients after 9 years (405,435,475); however, recurrent stenosis accounts for symptoms in fewer than 20% of patients (475). In patients with an adequate initial result, progressive MR and development of other valvular or coronary problems are more frequently responsible for recurrent symptoms (475). Thus, in patients presenting with symptoms late after commissurotomy, a comprehensive evaluation is required to look for other causes. Patients undergoing percutaneous mitral valvotomy with an unfavorable MV morphology have a higher incidence of recurrent symptoms at 1- to 2-year follow-up due to either an initial inadequate result or restenosis (476).
The management of patients after successful percutaneous balloon valvotomy or surgical commissurotomy is similar to that of the asymptomatic patient with MS. A baseline echocardiogram should be performed after the procedure to obtain a baseline measurement of postoperative hemodynamics and to exclude significant complications such as MR, LV dysfunction, or atrial septal defect (in the case of percutaneous valvotomy). This echocardiogram should be performed at least 72 h after the procedure, because acute changes in atrial and ventricular compliance immediately after the procedure affect the reliability of the half-time in calculation of valve area (402,403). Patients with severe MR or a large atrial septal defect should be considered for early surgery; however, the majority of small left-to-right shunts at the atrial level will close spontaneously over the course of 6 months. In patients with a history of atrial fibrillation, warfarin should be restarted 1 to 2 days after the procedure.
A history, physical examination, chest X-ray, and ECG should be obtained at yearly intervals in the patient who remains asymptomatic or minimally symptomatic. Prophylaxis against infective endocarditis (Section 2.3.1) and recurrence of rheumatic fever (Section 184.108.40.206; Table 11) (45) should be followed. If the patient is in atrial fibrillation or has a history of atrial fibrillation, anticoagulation is recommended, as would be the case for all patients with MS. With recurrent symptoms, extensive 2D and Doppler echocardiography should be performed to evaluate the MV hemodynamics and pulmonary artery pressure and to rule out significant MR or a left-to-right shunt. As with all patients with MS, exercise hemodynamics may be indicated in the patient with a discrepancy in clinical and hemodynamic findings.
Repeat percutaneous balloon valvotomy can be performed in the patient in whom there is restenosis after either a prior surgical commissurotomy or a balloon valvotomy (378,477). The results of these procedures are adequate in many patients but may be less satisfactory than the overall results of initial valvotomy, because there is usually more valve deformity, calcification, and fibrosis than with the initial procedure (395,477,478). MV replacement should be considered in those patients with recurrent severe symptoms and severe deformity of the mitral apparatus.
3.4.11 Special Considerations
220.127.116.11 Pregnant Patients
MS often affects young women who are in their childbearing years. The increased intravascular volume, increased cardiac output, and tachycardia associated with pregnancy may raise complex issues in the patient with MS and are reviewed in Section 5.5.1. Percutaneous mitral valvuloplasty can be performed with few or no complications to the mother or the fetus and excellent clinical and hemodynamic results (479).
18.104.22.168 Older Patients
An increasing number of older patients now present with symptomatic MS, most likely due to a change in the natural history of the disease (383,384). Older patients are more likely to have heavy calcification and fibrosis of the MV leaflets, with significant subvalvular fusion. In patients older than 65 years, the success rate of percutaneous valvotomy is lower (less than 50%) than in prior reports of younger patients. Procedural mortality is 3%, and there is an increased risk of complications, including pericardial tamponade in 5% and thromboembolism in 3%; however, in selected patients with favorable valve morphology, the procedure may be done safely with good intermediate-term results (384). The long-term clinical improvement is considerably less and mortality is higher in older than younger patients (480).
3.5 Mitral Valve Prolapse
3.5.1 Pathophysiology and Natural History
MVP refers to a systolic billowing of 1 or both mitral leaflets into the left atrium with or without MR. Utilizing current echocardiographic criteria for diagnosing MVP (valve prolapse of 2 mm or more above the mitral annulus in the long-axis parasternal view and other views ), the prevalence of this entity is 1% to 2.5% of the population (482). MVP occurs as a clinical entity with or without thickening (5 mm or greater, measured during diastasis) and with or without MR.
Primary MVP can be familial or nonfamilial. There is interchordal hooding due to leaflet redundancy that includes both the rough and clear zones of the involved leaflets (483). The basic microscopic feature of primary MVP is marked proliferation of the spongiosa, the delicate myxomatous connective tissue between the atrialis (a thick layer of collagen and elastic tissue that forms the atrial aspect of the leaflet) and the fibrosa or ventricularis (dense layer of collagen that forms the basic support of the leaflet). Myxomatous proliferation of the acid mucopolysaccharide–containing spongiosa tissue causes focal interruption of the fibrosa. Secondary effects of the primary MVP syndrome include fibrosis of the surface of the MV leaflets, thinning and/or elongation of the chordae tendineae, and ventricular friction lesions. Fibrin deposits often form at the MV–left atrial angle.
Familial MVP is transmitted as an autosomal trait (484,485), and several chromosomal loci have been identified (486–488). Primary MVP occurs with increased frequency in patients with Marfan syndrome and other connective tissue diseases (483,489–491). It has been speculated that the primary MVP syndrome represents a generalized disease of connective tissue. The increased incidence of MVP in Von Willebrand’s disease and other coagulopathies, primary hypomastia, and various connective tissue diseases has been used to support the concept that increased incidence of MVP is a result of defective embryogenesis of cell lines of mesenchymal origin (492). Thoracic skeletal abnormalities such as straight thoracic spine and pectus excavatum are commonly associated with MVP.
The auscultatory findings in MVP, when present, may consist of a click or multiple clicks that move within systole with changes in LV dimensions and/or a late systolic or holosystolic murmur of MR. There may be left atrial dilatation and LV enlargement, depending on the presence and severity of MR. Involvement of other valves may occur. Tricuspid valve prolapse may occur in 40% of patients with MVP (485). Pulmonic and aortic valve prolapses occur in 2% to 10% of patients with MVP (483). There is an increased incidence of associated secundum atrial septal defect and/or left-sided atrioventricular bypass tracts and supraventricular arrhythmias.
The natural history of asymptomatic MVP is heterogeneous and can vary from benign and normal life expectancy to adverse with significant morbidity or mortality. The spectrum of MR ranges from absent to severe. The most frequent predictor of cardiovascular mortality is moderate to severe MR and, less frequently, an LV ejection fraction less than 0.50 (493). Echocardiographic evidence of thickened MV leaflets (5 mm or greater) is also a predictor of complications related to MVP (Table 20)(494–499). In most patients, the MVP syndrome is associated with a benign prognosis (500,501). The age-adjusted survival rate for both men and women with MVP is similar to that of individuals without this entity (485).
The gradual progression of MR in patients with MVP may result in the progressive dilatation of the left atrium and ventricle. Left atrial dilatation may result in atrial fibrillation, and moderate to severe MR may eventually result in LV dysfunction and congestive heart failure (502). Pulmonary hypertension may occur, with associated RV dysfunction. In some patients, after an initially prolonged asymptomatic interval, the entire process may enter an accelerated phase as a result of left atrial and ventricular dysfunction and atrial fibrillation. In some instances, spontaneous rupture of MV chordae will occur (502). Infective endocarditis is a serious complication of MVP, which is the leading predisposing cardiovascular diagnosis in most series of patients reported with endocarditis (490,502,503). Because the absolute incidence of endocarditis is extremely low for the entire population with MVP, there is much controversy about the risk of endocarditis in MVP (504).
Fibrin emboli are responsible in patients with visual symptoms consistent with involvement of the ophthalmic or posterior cerebral circulation (505). Several studies have indicated an increased likelihood of cerebrovascular accidents in patients under age 45 years who have MVP beyond what would have been expected in a similar population without MVP (506).
Sudden death is a rare complication of MVP, occurring in fewer than 2% of known cases during long-term follow-up (495,500–511), with annual mortality rates less than 1% per year. The likely cause is a ventricular tachyarrhythmia, given the finding of increased incidence of complex ventricular ectopy on ambulatory ECG recordings in patients with MVP who had sudden death (512,513). Although infrequent, the highest incidence of sudden death has been reported in the familial form of MVP; some patients have also been noted to have QT prolongation (502,514).
3.5.2 Evaluation and Management of the Asymptomatic Patient
Echocardiography is indicated for the diagnosis of MVP and assessment of MR, leaflet morphology, and ventricular compensation in asymptomatic patients with physical signs of MVP. (Level of Evidence: B)
1. Echocardiography can effectively exclude MVP in asymptomatic patients who have been diagnosed without clinical evidence to support the diagnosis. (Level of Evidence: C)
2. Echocardiography can be effective for risk stratification in asymptomatic patients with physical signs of MVP or known MVP. (Level of Evidence: C)
1. Echocardiography is not indicated to exclude MVP in asymptomatic patients with ill-defined symptoms in the absence of a constellation of clinical symptoms or physical findings suggestive of MVP or a positive family history. (Level of Evidence: B)
2. Routine repetition of echocardiography is not indicated for the asymptomatic patient who has MVP and no MR or MVP and mild MR with no changes in clinical signs or symptoms. (Level of Evidence: C)
The primary diagnostic evaluation of the patient with MVP is the physical examination (502,515). The principal auscultatory feature of this syndrome is the midsystolic click, a high-pitched sound of short duration. One or more clicks may vary considerably in intensity and timing in systole according to LV loading conditions and contractility. Clicks result from sudden tensing of the MV apparatus as the leaflets prolapse into the left atrium during systole. The midsystolic click may be followed by a late systolic murmur that is usually medium to high-pitched and loudest at the cardiac apex. Occasionally the murmur has a musical or honking quality. The character and intensity of the murmur also vary under certain conditions, from brief and almost inaudible to holosystolic and loud. Dynamic auscultation is often useful for establishing the diagnosis of MVP syndrome (515). Changes in LV end-diastolic volume result in changes in the timing of the midsystolic click(s) and murmur. When end-diastolic volume is decreased (such as with standing), MVP occurs earlier in systole and the click-murmur complex occurs shortly after the first heart sound. In contrast, any maneuver that augments the volume of blood in the ventricle reduces myocardial contractility or increases LV afterload (such as squatting) lengthens the time from onset of systole to occurrence of MVP and the click-murmur complex moves toward the second heart sound. MVP can be present in the absence of these classic auscultatory findings and the clicks may be intermittent and variable.
Although the ECG may provide some information in patients with MVP, it is often normal. Nonspecific ST-T wave changes, T-wave inversions, prominent Q waves, and prolongation of the QT interval also occur. Continuous ambulatory ECG recordings or event monitors may be useful for documenting arrhythmias in patients with palpitations. They are not indicated as a routine test for asymptomatic patients. Most of the arrhythmias detected are not life threatening and patients often complain of palpitations when the ambulatory ECG recording shows no abnormality.
Two-dimensional and Doppler echocardiography is the most useful noninvasive test for defining MVP. Valve prolapse of 2 mm or more above the mitral annulus in the long-axis parasternal view and other views, and especially when the leaflet coaptation occurs on the atrial side of the annular plane, indicates a high likelihood of MVP. There is disagreement concerning the reliability of echocardiographic appearance of anterior leaflet billowing when observed only in the apical 4-chamber view (496,516). Leaflet thickness of 5 mm or more indicates abnormal leaflet thickness and its added presence makes MVP even more certain. Leaflet redundancy is often associated with an enlarged mitral annulus and elongated chordae tendineae (502). The absence or presence of MR is an important consideration and MVP is more likely when MR is detected as a high velocity eccentric jet in late systole (517).
Reassurance is a major part of the management of patients with MVP. Patients with mild or no symptoms and findings of milder forms of prolapse should be reassured of the benign prognosis. A normal lifestyle and regular exercise is encouraged (502, 515).
Antibiotic prophylaxis, for the prevention of endocarditis during procedures associated with bacteremia, is recommended for most patients with a definite diagnosis of MVP, particularly if there is associated MR (518). The committee recommends that patients without MR but who have leaflet thickening, elongated chordae, left atrial enlargement or LV dilatation should receive endocarditis prophylaxis (494–499) (see Section 2.3.1).
3.5.3 Evaluation and Management of the Symptomatic Patient
1. Aspirin therapy (75 to 325 mg per day) is recommended for symptomatic patients with MVP who experience cerebral transient ischemic attacks. (Level of Evidence: C)
2. In patients with MVP and atrial fibrillation, warfarin therapy is recommended for patients aged greater than 65 or those with hypertension, MR murmur, or a history of heart failure. (Level of Evidence: C)
3. Aspirin therapy (75 to 325 mg per day) is recommended for patients with MVP and atrial fibrillation who are less than 65 years old and have no history of MR, hypertension, or heart failure. (Level of Evidence: C)
4. In patients with MVP and a history of stroke, warfarin therapy is recommended for patients with MR, atrial fibrillation or left atrial thrombus. (Level of Evidence: C)
1. In patients with MVP and a history of stroke, who do not have MR, atrial fibrillation or left artrial thrombus, warfarin therapy is reasonable for patients with echocardiographic evidence of thickening (5mm or greater) and/or redundancy of the valve leaflets. (Level of Evidence: C)
2. In patients with MVP and a history of stroke, aspirin therapy is reasonable for patients who do not have MR, atrial fibrillation, left atrial thrombus, or echocardiographic evidence of thickening (5 mm or greater) or redundancy of the valve leaflets. (Level of Evidence: C)
3. Warfarin therapy is reasonable for patients with MVP with transient ischemic attacks despite aspirin therapy. (Level of Evidence: C)
4. Aspirin therapy (75 to 325 mg per day) can be beneficial for patients with MVP and a history of stroke who have contraindications to anticoagulants. (Level of Evidence: B)
Aspirin therapy (75 to 325 mg per day) may be considered for patients in sinus rhythm with echocardiographic evidence of high-risk MVP. (Level of Evidence: C)
Some patients consult their physicians about 1 or more of the common symptoms that occur with this syndrome: palpitations, often reported at a time when continuous ambulatory ECG recordings show no arrhythmias; atypical chest pain that rarely resembles classic angina pectoris; dyspnea and fatigue, when objective exercise testing often fails to show any impairment in exercise tolerance; and neuropsychiatric complaints, with many patients having panic attacks and similar syndromes (502). Bankier and Littman report that a significant number of patients with agoraphobia also have MVP; that 45% of patients with panic disorder have MVP; and that significant predictors for palpitations in these patients are depression, poor self-rated health, alcohol intoxication in women, and heavy coffee drinking and physical inactivity in men (519).
Transient cerebral ischemic episodes occur with increased incidence in patients with MVP, and some patients develop stroke syndromes. Reports of amaurosis fugax, homonymous field loss, and retinal artery occlusion have been described; occasionally, the visual loss persists (506,520–522).
The roles of cardiac auscultation and echocardiography in the assessment of symptomatic patients with MVP are the same as for patients without symptoms. The indications for antibiotic prophylaxis to prevent endocarditis are also unchanged.
Patients with MVP and palpitations associated with mild tachyarrhythmias or increased adrenergic symptoms and those with chest pain, anxiety, or fatigue often respond to therapy with beta blockers (523). In many cases, however, the cessation of stimulants such as caffeine, alcohol, and cigarettes may be sufficient to control symptoms. In patients with recurrent palpitations, continuous or event-activated ambulatory ECG recordings may reveal the presence or absence of arrhythmias at the time of symptoms and indicate appropriate treatment of existing arrhythmias. The indications for electrophysiological testing are similar to those in the general population (e.g., aborted sudden death, recurrent syncope of unknown cause, and symptomatic or sustained ventricular tachycardia) (524).
Orthostatic symptoms due to postural hypotension and tachycardia are best treated with volume expansion, preferably by liberalizing fluid and salt intake. Mineralocorticoid therapy or clonidine may be needed in severe cases, and it may be beneficial to have the patient wear support stockings.
Daily aspirin therapy (75 to 325 mg per day) is recommended for MVP patients with documented transient focal neurological events who are in sinus rhythm with no atrial thrombi. Such patients also should avoid cigarettes and oral contraceptives. The American Stroke Association guidelines (524a) recommend aspirin for patients with MVP who have experienced an ischemic stroke (class IIa, level of evidence C), based on the evidence of efficacy of antiplatelet agents for general stroke patients. No randomized trials have addressed the efficacy of selected antithrombotic therapies for the specific subgroup of stroke patients with MVP. In the current guidelines, the committee recommends aspirin for those post-stroke patients with MVP who have no evidence of MR, atrial fibrillation, left atrial thrombus, or echocardiographic evidence of thickening (5 mm or greater) or redundancy of the valve leaflets. However, long-term anticoagulation therapy with warfarin is recommended (class I) for post-stroke patients with MVP who have MR, atrial fibrillation, or left atrial thrombus. In the absence of these indications, warfarin is also recommended (class IIa) in post-stroke patients with MVP who have echocardiographic evidence of thickening (5 mm or greater) or redundancy of the valve leaflets and in MVP patients who experience recurrent transient ischemic attacks while taking aspirin. In each of these situations, the international normalized ratio (INR) should be maintained between 2.0 and 3.0). In MVP patients with atrial fibrillation, warfarin therapy is indicated in patients aged greater than 65 years and in those with MR, hypertension, or a history of heart failure (INR 2.0 to 3.0). Aspirin therapy is satisfactory in patients with atrial fibrillation who are younger than 65 years old, have no MR, and have no history of hypertension or heart failure (525,526). Daily aspirin therapy is often recommended for patients with high-risk echocardiographic characteristics.
A normal lifestyle and regular exercise are encouraged for most patients with MVP, especially those who are asymptomatic (511,526). Whether exercise-induced ischemia develops in some patients with MVP remains controversial (527,528). Restriction from competitive sports is recommended when moderate LV enlargement, LV dysfunction, uncontrolled tachyarrhythmias, long-QT interval, unexplained syncope, prior resuscitation from cardiac arrest, or aortic root enlargement is present individually or in combination (502). A familial occurrence of MVP should be explained to the patient and is particularly important in those with associated disease who are at greater risk for complications. There is no contraindication to pregnancy based on the diagnosis of MVP alone.
Asymptomatic patients with MVP and no significant MR can be evaluated clinically every 3 to 5 years. Serial echocardiography is not necessary in most patients and is recommended only in patients who have high-risk characteristics on the initial echocardiogram and in those who develop symptoms consistent with cardiovascular disease or who have a change in physical findings that suggests development of significant MR. Patients who have high-risk characteristics, including those with moderate to severe MR, should be followed up once a year.
Patients with severe MR with symptoms or impaired LV systolic function require cardiac catheterization and evaluation for MV surgery (see Section 22.214.171.124). The thickened, redundant MV can often be repaired rather than replaced with a low operative mortality and excellent short- and long-term results (529,530). Follow-up studies also suggest lower thrombotic and endocarditis risk with valve repair than with prosthetic valves.
3.5.4 Surgical Considerations
Management of MVP may require valve surgery, particularly in those patients who develop a flail mitral leaflet due to rupture of chordae tendineae or their marked elongation. Most such valves can be repaired successfully by surgeons experienced in MV repair, especially when the posterior leaflet of the MV is predominantly affected. MV repair for MR due to MVP is associated with excellent long-term survival and remains superior to MV replacement beyond 10 years and up to 20 years after surgery (529,530). Anterior leaflet MV repair is associated with a higher risk for reoperation than posterior leaflet repair. As noted in Section 126.96.36.199, cardiologists are strongly encouraged to refer patients who are candidates for complex MV repair to surgical centers experienced in performing MV repair. Residual MR is associated with a higher risk for reoperation (530). Symptoms of heart failure, severity of MR, presence or absence of atrial fibrillation, LV systolic function, LV end-diastolic and end-systolic volumes, and pulmonary artery pressure (rest and exercise) all influence the decision to recommend MV surgery. Recommendations for surgery in patients with MVP and MR are the same as for those with other forms of nonischemic severe MR. For further detail, please review Section 7.3. on MV surgery.
3.6 Mitral Regurgitation
The common causes of organic MR include MVP syndrome, rheumatic heart disease, CAD, infective endocarditis, certain drugs, and collagen vascular disease. MR may also occur secondary to a dilated annulus from dilatation of the left ventricle. In some cases, such as ruptured chordae tendineae, ruptured papillary muscle, or infective endocarditis, MR may be acute and severe. Alternatively, MR may worsen gradually over a prolonged period of time. These 2 ends of the spectrum have quite different clinical presentations.
3.6.2 Acute Severe Mitral Regurgitation
In acute severe MR, a sudden volume overload is imposed on the left atrium and left ventricle. Acute volume overload increases LV preload, allowing for a modest increase in total LV stroke volume (531). However, in the absence of compensatory eccentric hypertrophy (which has had no time to develop), forward stroke volume and cardiac output are reduced. At the same time, the unprepared left atrium and left ventricle cannot accommodate the regurgitant volume, which causes large v waves in the left atrium and results in pulmonary congestion. In this phase of the disease, the patient has both reduced forward output (even shock) and simultaneous pulmonary congestion. In severe MR, the hemodynamic overload often cannot be tolerated, and MV repair or replacement must often be performed urgently.
The patient with acute severe MR is almost always severely symptomatic. Physical examination of the precordium may be misleading, because a normal-sized left ventricle does not produce a hyperdynamic apical impulse. The systolic murmur of MR may not be holosystolic and may even be absent. A third heart sound or early diastolic flow rumble may be the only abnormal physical finding present. Transthoracic echocardiography may demonstrate the disruption of the MV and help provide semiquantitative information on lesion severity; however, transthoracic echocardiography may underestimate lesion severity by inadequate imaging of the color flow jet. Thus, if there is hyperdynamic systolic function of the left ventricle on a transthoracic echocardiogram in a patient with acute heart failure, the suspicion of severe MR should be raised. Because transesophageal echocardiography can more accurately assess the color flow jet (532), transesophageal imaging should be performed if MV morphology and regurgitant severity are still in question after transthoracic echocardiography. Transesophageal echocardiography is also helpful in demonstrating the anatomic cause of acute severe MR and directing successful surgical repair.
In the hemodynamically stable patient, if CAD is suspected or there are risk factors for CAD (see Section 10.2), coronary arteriography is necessary before surgery because myocardial revascularization should be performed during MV surgery in those patients with concomitant CAD (533,534).
188.8.131.52 Medical Therapy
In acute severe MR, medical therapy has a limited role and is aimed primarily to stabilize hemodynamics in preparation for surgery. The goal of nonsurgical therapy is to diminish the amount of MR, in turn increasing forward output and reducing pulmonary congestion. In the normotensive patient, administration of nitroprusside may effectively accomplish all 3 goals. Nitroprusside increases forward output not only by preferentially increasing aortic flow but also by partially restoring MV competence as LV size diminishes (535,536). In the patient rendered hypotensive because of a severe reduction in forward output, nitroprusside should not be administered alone, but combination therapy with an inotropic agent (such as dobutamine) and nitroprusside is of benefit in some patients. In such patients, aortic balloon counterpulsation increases forward output and mean arterial pressure while diminishing regurgitant volume and LV filling pressure and can be used to stabilize the patient while they are prepared for surgery. If infective endocarditis is the cause of acute MR, identification and treatment of the infectious organism are essential.
3.6.3 Chronic Asymptomatic Mitral Regurgitation
184.108.40.206 Pathophysiology and Natural History
Patients with mild to moderate MR may remain asymptomatic with little or no hemodynamic compromise for many years; however, MR from a primary MV abnormality tends to progress over time with an increase in volume overload due to an increase in the effective orifice area. Progression of the MR is variable and determined by progression of lesions or mitral annulus size (537).
Once the MR has become severe, there has been time for development of eccentric cardiac hypertrophy in which new sarcomeres are laid down in series, which increases the length of individual myocardial fibers (228,531). The resulting increase in LV end-diastolic volume is compensatory because it permits an increase in total stroke volume, which allows for restoration of forward cardiac output (538). At the same time, the increase in LV and left atrial size allows accommodation of the regurgitant volume at a lower filling pressure, and the symptoms of pulmonary congestion abate. In this phase of compensated MR, the patient may be entirely asymptomatic, even during vigorous exercise. It should be noted that in the compensatory phase, augmented preload and reduced or normal afterload (provided by the unloading of the left ventricle into the left atrium) facilitate LV ejection, which results in a large total stroke volume and a normal forward stroke volume.
The compensated phase of MR is variable but may last for many years. However, the prolonged burden of volume overload may eventually result in LV dysfunction. In this phase, contractile dysfunction impairs ejection, and end-systolic volume increases. There may be further LV dilatation and increased LV filling pressure. These hemodynamic events result in reduced forward output and pulmonary congestion. However, the still favorable loading conditions often maintain ejection fraction in the low normal range (0.50 to 0.60) despite the presence of significant muscle dysfunction (531,539,540). Correction of MR should be performed before the advanced phases of LV decompensation.
Numerous studies indicate that patients with chronic severe MR have a high likelihood of developing symptoms or LV dysfunction over the course of 6 to 10 years (518,526,541,542). However, the incidence of sudden death in asymptomatic patients with normal LV function varies widely among these studies.
The natural history of severe MR due to a flail posterior leaflet has been documented (518). At 10 years, 90% of patients are dead or require MV operation. The mortality rate in patients with severe MR caused by flail leaflets is 6% to 7% per year. However, patients at risk of death are predominantly those with LV ejection fractions less than 0.60 or with NYHA functional class III–IV symptoms, and less so those who are asymptomatic and have normal LV function (518,543). Severe symptoms also predict a poor outcome after MV repair or replacement (543).
In evaluating the patient with chronic MR, the history is invaluable. A well-established estimation of baseline exercise tolerance is important in gauging the subtle onset of symptoms at subsequent evaluations. Physical examination should demonstrate displacement of the LV apical impulse, which indicates that MR is severe and chronic, producing cardiac enlargement. A third heart sound or early diastolic flow rumble is usually present and does not necessarily indicate LV dysfunction. Findings consistent with pulmonary hypertension are worrisome because they indicate advanced disease with worsened prognosis (544). An ECG and chest X-ray are useful in establishing rhythm and for assessment of the pulmonary vascularity and pulmonary congestion.
220.127.116.11 Indications for Transthoracic Echocardiography
1. Transthoracic echocardiography is indicated for baseline evaluation of LV size and function, RV and left atrial size, pulmonary artery pressure, and severity of MR (Table 4) in any patient suspected of having MR. (Level of Evidence: C)
2. Transthoracic echocardiography is indicated for delineation of the mechanism of MR. (Level of Evidence: B)
3. Transthoracic echocardiography is indicated for annual or semiannual surveillance of LV function (estimated by ejection fraction and end-systolic dimension) in asymptomatic patients with moderate to severe MR. (Level of Evidence: C)
4. Transthoracic echocardiography is indicated in patients with MR to evaluate the MV apparatus and LV function after a change in signs or symptoms. (Level of Evidence: C)
5. Transthoracic echocardiography is indicated to evaluate LV size and function and MV hemodynamics in the initial evaluation after MV replacement or MV repair. (Level of Evidence: C)
Exercise Doppler echocardiography is reasonable in asymptomatic patients with severe MR to assess exercise tolerance and the effects of exercise on pulmonary artery pressure and MR severity. (Level of Evidence: C)
Transthoracic echocardiography is not indicated for routine follow-up evaluation of asymptomatic patients with mild MR and normal LV size and systolic function. (Level of Evidence: C)
An initial comprehensive 2D, Doppler echocardiogram is indispensable in the management of the patient with MR. The echocardiogram provides a baseline estimation of LV and left atrial size, an estimation of LV ejection fraction, and approximation of the severity of regurgitation (2). Quantification of the severity of MR (Table 4) (27) is strongly recommended (27,541,545,546). In the majority of patients, an estimate of pulmonary artery pressure can be obtained from the TR peak velocity (547). Changes from these baseline values are subsequently used to guide the timing of MV surgery. The blood pressure at the time of each study should be documented, because the afterload on the ventricle will affect the measured severity of the MR.
The initial transthoracic echocardiogram should disclose the anatomic cause of the MR. A central color flow jet of MR with a structurally normal MV apparatus suggests the presence of functional MR, which may be due to annular dilatation from LV dilatation or tethering of the posterior leaflet because of regional LV dysfunction in patients with ischemic heart disease. An eccentric color flow jet of MR with abnormalities of the MV apparatus indicates organic MR. In patients with organic MR, the echocardiogram should assess the presence of calcium in the annulus or leaflets, the redundancy of the valve leaflets, and the MV leaflet involved (anterior leaflet, posterior leaflet, or bileaflet). These factors will help determine the feasibility of valve repair if surgery is contemplated. The system proposed by Carpentier (548) allows the echocardiographer to focus on the anatomic and physiologic characteristics of the valve that aid the surgeon in planning the repair. The valve dysfunction is described on the basis of the motion of the free edge of the leaflet relative to the plane of the annulus: type I, normal; type II, increased, as in MVP; type IIIA, restricted during systole and diastole, and type IIIB, restricted during systole.
The diagnosis of severe MR should be made by correlating the findings on physical examination with the findings from a comprehensive 2D, Doppler echocardiogram. Multiple parameters from the Doppler examination should be used to diagnose severe MR (Table 4) (27), including the color flow jet width and area, the intensity of the continuous-wave Doppler signal, the pulmonary venous flow contour, the peak early mitral inflow velocity, and quantitative measures of effective orifice area and regurgitation volume (2). In addition, there should be enlargement of the left ventricle and left atrium in chronic severe MR. Abnormalities of the MV apparatus are often present if there is severe MR, but ischemic LV dysfunction may also result in severe MR. If a discrepancy is present, or if the patient has poor windows on transthoracic echocardiography, then further evaluation of the severity of MR is required, including cardiac catheterization, magnetic resonance imaging, or transesophageal echocardiography.
18.104.22.168 Indications for Transesophageal Echocardiography (See also Section 8.1.4.)
1. Preoperative or intraoperative transesophageal echocardiography is indicated to establish the anatomic basis for severe MR in patients in whom surgery is recommended to assess feasibility of repair and to guide repair. (Level of Evidence: B)
2. Transesophageal echocardiography is indicated for evaluation of MR patients in whom transthoracic echocardiography provides nondiagnostic information regarding severity of MR, mechanism of MR, and/or status of LV function. (Level of Evidence: B)
Preoperative transesophageal echocardiography is reasonable in asymptomatic patients with severe MR who are considered for surgery to assess feasibility of repair. (Level of Evidence: C)
Transesophageal echocardiography is not indicated for routine follow-up or surveillance of asymptomatic patients with native valve MR. (Level of Evidence: C)
22.214.171.124 Serial Testing
The aim of serial follow-up of the patient with MR is to subjectively assess changes in symptomatic status and objectively assess changes in LV function and exercise tolerance that can occur in the absence of symptoms. Asymptomatic patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension can be followed on a yearly basis with instructions to alert the physician if symptoms develop in the interim. Yearly echocardiography is not necessary unless there is clinical evidence that MR has worsened. In patients with moderate MR, clinical evaluation including echocardiography should be performed annually and sooner if symptoms occur.
Asymptomatic patients with severe MR should be followed up with history, physical examination, and echocardiography every 6 to 12 months to assess symptoms or transition to asymptomatic LV dysfunction. Exercise stress testing may be used to add objective evidence regarding symptoms and changes in exercise tolerance. Exercise testing is especially important if a good history of the patient’s exercise capacity cannot be obtained. Measurement of pulmonary artery pressure and assessment of severity of MR during exercise may be helpful.
Interpretation of LV ejection fraction in the patient with MR is made difficult because the loading conditions present in MR facilitate ejection and increase ejection fraction, the standard guide to LV function. Nonetheless, several studies have indicated that the preoperative ejection fraction is an important predictor of postoperative survival in patients with chronic MR (539,544,549–551). Ejection fraction in a patient with MR with normal LV function is usually greater than or equal to 0.60. Consistent with this concept, postoperative ventricular function is lower and survival is reduced in patients with a preoperative ejection fraction less than 0.60 compared with patients with higher ejection fractions (550,551).
Alternatively or in concert, echocardiographic LV end-systolic dimension (or volume) can be used in the timing of MV surgery. End-systolic dimension, which may be less load dependent than ejection fraction (552), should be less than 40 mm preoperatively to ensure normal postoperative LV function (538,551–553). If patients become symptomatic, they should undergo MV surgery even if LV function is normal.
126.96.36.199 Guidelines for Physical Activity and Exercise
Recommendations regarding participation in competitive athletics were published by the Task Force on Acquired Valvular Heart Disease of the 36th Bethesda Conference (138). Asymptomatic patients with MR of any severity who are in sinus rhythm and who have normal LV and left atrial dimensions and normal pulmonary artery pressure may exercise without restriction (138). However, those with definite LV enlargement (greater than or equal to 60 mm), pulmonary hypertension, or any degree of LV systolic dysfunction at rest should not participate in any competitive sports.
188.8.131.52 Medical Therapy
In the asymptomatic patient with chronic MR, there is no generally accepted medical therapy. Although intuitively, the use of vasodilators may appear to be logical for the same reasons that they are effective in acute MR, there are no large, long-term studies to indicate that they are beneficial. Furthermore, because MR with normal ejection fraction is a disease in which afterload is not increased (230,538,554,555), drugs that reduce afterload might produce a physiological state of chronic low afterload with which there is very little experience. There has not been a consistent improvement in LV volumes and severity of MR in the small studies that have examined the effect of ACE inhibitors (312,556–558). The beneficial effect seen in some studies may be more related to blockade of tissue angiotensin rather than the vasodilatory effect of the drug (559). Thus, in the absence of systemic hypertension, there is no known indication for the use of vasodilating drugs or ACE inhibitors in asymptomatic patients with MR and preserved LV function.
However, in patients with functional or ischemic MR (resulting from dilated or ischemic cardiomyopathy), there is reason to believe that preload reduction may be beneficial (535). If LV systolic dysfunction is present, primary treatment of the LV systolic dysfunction with drugs such as ACE inhibitors or beta blockers (particularly carvedilol) and biventricular pacing have all been shown to reduce the severity of functional MR (560–563).
In patients with MR who develop symptoms but have preserved LV function, surgery is the most appropriate therapy. If atrial fibrillation develops, heart rate should be controlled with rate-lowering calcium channel blockers, beta blockers, digoxin, or, rarely, amiodarone. In patients with severe MR and chronic atrial fibrillation, a Maze procedure may be added to an MV repair (see Section 184.108.40.206.4), because this will reduce the risk of postoperative stroke. Although the risk of embolism with the combination of MR and atrial fibrillation was formerly considered similar to that of MS and atrial fibrillation, subsequent studies suggest that embolic risk may be less in MR (564,565). Nonetheless, it is recommended that the INR be maintained at 2 to 3 in this population.
220.127.116.11 Indications for Cardiac Catheterization
1. Left ventriculography and hemodynamic measurements are indicated when noninvasive tests are inconclusive regarding severity of MR, LV function, or the need for surgery. (Level of Evidence: C)
2. Hemodynamic measurements are indicated when pulmonary artery pressure is out of proportion to the severity of MR as assessed by noninvasive testing. (Level of Evidence: C)
3. Left ventriculography and hemodynamic measurements are indicated when there is a discrepancy between clinical and noninvasive findings regarding severity of MR. (Level of Evidence: C)
4. Coronary angiography is indicated before MV repair or MV replacement in patients at risk for CAD. (Level of Evidence: C)
1. Left ventriculography and hemodynamic measurements are not indicated in patients with MR in whom valve surgery is not contemplated. (Level of Evidence: C)
Cardiac catheterization, with or without exercise, is necessary when there is a discrepancy between clinical and noninvasive findings. Catheterization is also performed when surgery is contemplated in cases in which there is still some doubt about the severity of MR after noninvasive testing or when there is a need to assess extent and severity of CAD preoperatively. In patients with MR who have risk factors for CAD (e.g., advanced age, hypercholesterolemia, or hypertension) or when there is a suspicion that MR is ischemic in origin (either because of known myocardial infarction or suspected ischemia), coronary angiography should be performed before surgery.
Patients should usually not undergo valve surgery unless the degree of MR is severe. If there is a discrepancy regarding the severity of MR between the physical examination or elements of the comprehensive 2D, Doppler examination, then transesophageal echocardiography, magnetic resonance imaging, or left ventriculography should be performed. Although the standard semiquantitative approach to determining the severity of MR from ventriculography has its own limitations (566), ventriculography does provide an additional method to assess LV dilatation and function and gauge the severity of MR. Exercise hemodynamics may provide additional information that is helpful in decision making.
During the catheterization procedure, a right-heart catheterization should be performed if the severity of MR is uncertain to obtain right-sided pressures to quantify the increase in left atrial pressure (pulmonary artery wedge pressure) and pulmonary artery pressure. The presence or absence of a large v wave has little diagnostic impact when combined with data from the rest of the catheterization (567).
3.6.4 Indications for Surgery
18.104.22.168 Types of Surgery
Three different MV operations are currently used for correction of MR: 1) MV repair; 2) MV replacement with preservation of part or all of the mitral apparatus; and 3) MV replacement with removal of the mitral apparatus. Each procedure has its advantages and disadvantages, and therefore, the indications for each procedure are somewhat different.
In most cases, MV repair is the operation of choice when the valve is suitable for repair and appropriate surgical skill and expertise are available. This procedure preserves the patient’s native valve without a prosthesis and therefore avoids the risk of chronic anticoagulation (except in patients in atrial fibrillation) or prosthetic valve failure late after surgery. Additionally, preservation of the mitral apparatus leads to better postoperative LV function and survival than in cases in which the apparatus is disrupted (545,568–573). Improved postoperative function occurs with repair because the mitral apparatus is an integral part of the left ventricle that is essential for maintenance of normal shape, volume, and function of the left ventricle (574). However, MV repair is technically more demanding than MV replacement, may require longer extracorporeal circulation time, and may occasionally fail. Valve morphology and surgical expertise are of critical importance for the success of valve repair (see below).
The reoperation rate after MV repair is similar to the reoperation rate after MV replacement (530). There is a 7% to 10% reoperation rate at 10 years in patients undergoing MV repair, usually for severe recurrent MR (530,575–578). Approximately 70% of the recurrent MR is thought to be due to the initial procedure and 30% to progressive valve disease (575). The reoperation rate is lower in those patients who had the initial operation for posterior leaflet abnormalities than in those who had bileaflet or anterior leaflet abnormalities (518,577).
The advantage of MV replacement with preservation of the chordal apparatus is that this operation ensures postoperative MV competence, preserves LV function, and enhances postoperative survival compared with MV replacement, in which the apparatus is disrupted (570,579–582). The disadvantage is the use of a prosthetic valve, with the risks of deterioration inherent in tissue valves or the need for anticoagulation inherent in mechanical valves.
MV replacement in which the MV apparatus is resected should almost never be performed. It should only be performed in those circumstances in which the native valve and apparatus are so distorted by the preoperative pathology (rheumatic disease, for example) that the mitral apparatus cannot be spared. As noted previously (Section 3.4.9), artificial chordal reconstruction does extend the opportunities for repair in some such patients with rheumatic MR (467,468).
The advantages of MV repair make it applicable across the full spectrum of MR, including the 2 extremes of the spectrum. Valve repair might be possible in patients with far-advanced symptomatic MR and depressed LV function because it preserves LV function at the preoperative level (572); MV replacement with disruption of the apparatus in such patients could lead to worsened or even fatal LV dysfunction after surgery. At the other extreme, in the relatively asymptomatic patient with well-preserved LV function, repair of a severely regurgitant valve might be contemplated to avoid the onset of ventricular dysfunction from longstanding volume overload (583). However, failed MV repair would result in the need for a prosthetic valve; this would represent a clear complication, because it would impose the risks of a prosthesis on a patient who did not previously require it. Hence, “prophylactic” surgery in an asymptomatic patient with MR and normal LV function requires a high likelihood of successful repair.
22.214.171.124 Indications for Mitral Valve Operation
1. MV surgery is recommended for the symptomatic patient with acute severe MR.* (Level of Evidence: B)
2. MV surgery is beneficial for patients with chronic severe MR* and NYHA functional class II, III, or IV symptoms in the absence of severe LV dysfunction (severe LV dysfunction is defined as ejection fraction less than 0.30) and/or end-systolic dimension greater than 55 mm. (Level of Evidence: B)
3. MV surgery is beneficial for asymptomatic patients with chronic severe MR* and mild to moderate LV dysfunction, ejection fraction 0.30 to 0.60, and/or end-systolic dimension greater than or equal to 40 mm. (Level of Evidence: B)
4. MV repair is recommended over MV replacement in the majority of patients with severe chronic MR* who require surgery, and patients should be referred to surgical centers experienced in MV repair. (Level of Evidence: C)
1. MV repair is reasonable in experienced surgical centers for asymptomatic patients with chronic severe MR* with preserved LV function (ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) in whom the likelihood of successful repair without residual MR is greater than 90%. (Level of Evidence: B)
2. MV surgery is reasonable for asymptomatic patients with chronic severe MR,* preserved LV function, and new onset of atrial fibrillation. (Level of Evidence: C)
3. MV surgery is reasonable for asymptomatic patients with chronic severe MR,* preserved LV function, and pulmonary hypertension (pulmonary artery systolic pressure greater than 50 mm Hg at rest or greater than 60 mm Hg with exercise). (Level of Evidence: C)
4. MV surgery is reasonable for patients with chronic severe MR* due to a primary abnormality of the mitral apparatus and NYHA functional class III-IV symptoms and severe LV dysfunction (ejection fraction less than 0.30 and/or end-systolic dimension greater than 55 mm) in whom MV repair is highly likely. (Level of Evidence: C)
MV repair may be considered for patients with chronic severe secondary MR* due to severe LV dysfunction (ejection fraction less than 0.30) who have persistent NYHA functional class III-IV symptoms despite optimal therapy for heart failure, including biventricular pacing. (Level of Evidence: C)
1. MV surgery is not indicated for asymptomatic patients with MR and preserved LV function (ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) in whom significant doubt about the feasibility of repair exists. (Level of Evidence: C)
2. Isolated MV surgery is not indicated for patients with mild or moderate MR. (Level of Evidence: C)
In many cases, the type of operation, MV repair versus replacement, is important in timing surgery. In fact, although the type of surgery to be performed is never actually established until the operation, many situations lend themselves to preoperative prediction of the operation that can be performed. This prediction is based on the skill and experience of the surgeon in performing repair and on the location and type of MV disease that caused the MR. Nonrheumatic posterior leaflet prolapse due to degenerative MV disease or a ruptured chordae tendineae can usually be repaired using a resection of the portion of the valve and an annuloplasty (584,585). Involvement of the anterior leaflet or both anterior and posterior leaflets diminishes the likelihood of repair because the operation requires other interventions, such as chordal shortening, chordal transfer, and innovative anatomic repairs (586–591). Consequently, the skill and experience of the surgeon are probably the most important determinants of the eventual operation that will be performed. In general, rheumatic involvement of the MV and calcification of the MV leaflets or annulus diminish the likelihood of repair, even in experienced hands (592).
The number of patients undergoing MV repair for MR has increased steadily over the past decade in the United States and Canada in relation to the number undergoing MV replacement. However, among isolated MV procedures reported in the STS National Cardiac Database from 1999 to 2000 (593), the frequency of repair was only 35.7% (3027 of a total of 8486 procedures), which suggests that MV repair is underutilized. The STS National Database also indicates an operative mortality rate of under 2% in patients undergoing isolated MV repair in 2004, which compares favorably to the greater than 6% operative mortality rate for patients undergoing isolated MV replacement (165). Considering the beneficial effect of MV repair on survival and LV function, cardiologists are strongly encouraged to refer patients who are candidates for MV repair to surgical centers experienced in performing MV repair.
126.96.36.199.1 Symptomatic Patients With Normal Left Ventricular Function
Patients with symptoms of congestive heart failure despite normal LV function on echocardiography (ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) require surgery. Surgery should be performed in patients with mild symptoms and severe MR (Fig. 8),especially if it appears that MV repair rather than replacement can be performed. The feasibility of repair is dependent on several factors, including valve anatomy and surgical expertise. Successful surgical repair improves symptoms, preserves LV function, and avoids the problems of a prosthetic valve. When repair is not feasible, MV replacement with chordal preservation should relieve symptoms and maintain LV function.
188.8.131.52.2 Asymptomatic or Symptomatic Patients With Left Ventricular Dysfunction
Preoperative variables that are predictive of postoperative survival, symptomatic improvement, and postoperative LV function are summarized in Table 21(538,539,544,549–552). The timing of surgery for asymptomatic patients is controversial, but most would now agree that MV surgery is indicated with the appearance of echocardiographic indicators of LV dysfunction. These include LV ejection fraction less than or equal to 0.60 and/or LV end-systolic dimension greater than or equal to 40 mm (Fig. 8). Surgery performed at this time will likely prevent further deterioration in LV function and improve longevity. This is true whether repair or replacement is performed (551), although repair is clearly preferred. It must be emphasized that, unlike with the timing of AVR for AR, LV ejection fraction should not be allowed to fall into the lower limit of the normal range in patients with chronic MR (551,594–596). The data regarding postoperative survival are much stronger with LV ejection fraction than with end-systolic dimension (544,549–551), whereas both ejection fraction and end-systolic dimension strongly influence postoperative LV function and heart failure (538,539,544,551,552). MV surgery should also be recommended for symptomatic patients with evidence of LV systolic dysfunction (ejection fraction less than or equal to 0.60, and/or end-systolic dimension greater than or equal to 40 mm).
Determining the surgical candidacy of the symptomatic patient with MR and far-advanced LV dysfunction is a common clinical dilemma. The question that often arises is whether the patient with MR has such advanced LV dysfunction that he or she is no longer a candidate for surgery. Often such cases present difficulty in distinguishing primary cardiomyopathy with secondary MR from primary MR with secondary myocardial dysfunction. In the latter case, if MV repair appears likely, surgery should still be contemplated (Fig. 8). Even though such a patient is likely to have persistent LV dysfunction, surgery is likely to improve symptoms and prevent further deterioration of LV function (328). If MV replacement is necessary in such patients, it should be performed only if the chordal apparatus can be preserved. The modification of MV geometry by an “undersized” annular ring in patients with severe LV dysfunction and significant functional MR may be beneficial in a subset of patients with primary myocardial disease (597–602), although the impact on outcomes compared with aggressive medical therapy, including beta blockers and cardiac resynchronization therapy (560–563), has not been studied in a prospective randomized trial.
184.108.40.206.3 Asymptomatic Patients with Normal Left Ventricular Function
As noted previously, repair of a severely regurgitant valve may be contemplated in an asymptomatic patient with severe MR and normal LV function to preserve LV size and function and prevent the sequelae of chronic severe MR (541). Although there are no randomized data with which to recommend this approach to all patients, the committee recognizes that some experienced centers are moving in thi