consenso valvopatias 2006

doi:10.1016/j.jacc.2006.05.030 2006;48;598-675 J. Am. Coll. Cardiol.

Nishimura, Richard L. Page and Barbara Riegel Jonathan L. Halperin, Loren F. Hiratzka, Sharon A. Hunt, Bruce W. Lytle, Rick

Adams, Jeffrey L. Anderson, Elliott M. Antman, David P. Faxon, Valentin Fuster,M. Shah, Jack S. Shanewise, Sidney C. Smith, Jr, Alice K. Jacobs, Cynthia D.

A. Nishimura, Patrick T. O’Gara, Robert A. O’Rourke, Catherine M. Otto, PravinDavid P. Faxon, Michael D. Freed, William H. Gaasch, Bruce Whitney Lytle, Rick

Robert O. Bonow, Blase A. Carabello, Kanu Chatterjee, Antonio C. de Leon, Jr, Society of Thoracic Surgeons

by the Society for Cardiovascular Angiography and Interventions and theCollaboration With the Society of Cardiovascular Anesthesiologists Endorsed

Developed inManagement of Patients With Valvular Heart Disease) Guidelines (Writing Committee to Revise the 1998 Guidelines for the

College of Cardiology/American Heart Association Task Force on PracticeValvular Heart Disease: Executive Summary: A Report of the American

ACC/AHA 2006 Practice Guidelines for the Management of Patients With

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CC/AHA PRACTICE GUIDELINES—EXECUTIVE SUMMARY

CC/AHA 2006 Practice Guidelinesor the Management of Patients Withalvular Heart Disease: Executive SummaryReport of the American College of Cardiology/Americaneart Association Task Force on Practice Guidelines

Writing Committee to Revise the 1998 Guidelinesor the Management of Patients With Valvular Heart Disease)

eveloped in Collaboration With the Society of Cardiovascular Anesthesiologistsndorsed by the Society for Cardiovascular Angiography and Interventions and

ublished by Elsevier Inc. doi:10.1016/j.jacc.2006.05.030

he Society of Thoracic Surgeons

WRITING COMMITTEE MEMBERS

Robert O. Bonow, MD, FACC, FAHA, Chair

BRPRC

lase A. Carabello, MD, FACC, FAHAanu Chatterjee, MB, FACCntonio C. de Leon, JR, MD, FACC, FAHAavid P. Faxon, MD, FACC, FAHAichael D. Freed, MD, FACC, FAHA

Jack S. Shanew

Alice K. Jacobs, MD, FAC

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ruce Whitney Lytle, MD, FACCick A. Nishimura, MD, FACC, FAHAatrick T. O’Gara, MD, FACC, FAHAobert A. O’Rourke, MD, MACC, FAHAatherine M. Otto, MD, FACC, FAHA

illiam H. Gaasch, MD, FACC, FAHA Pravin M. Shah, MD, MACC, FAHA
ise, MD*
Society of Cardiovascular Anesthesiologists Representative

TASK FORCE MEMBERS

Sidney C. Smith, JR, MD, FACC, FAHA, Chair
C, FAHA, Vice-Chair
ynthia D. Adams, MSN, APRN-BC, FAHAeffrey L. Anderson, MD, FACC, FAHAlliott M. Antman, MD, FACC, FAHA†avid P. Faxon, MD, FACC, FAHA‡alentin Fuster, MD, PHD, FACC, FAHA‡

oren F. Hiratzka, MD, FACC, FAHA‡haron A. Hunt, MD, FACC, FAHAruce W. Lytle, MD, FACC, FAHAick Nishimura, MD, FACC, FAHAichard L. Page, MD, FACC, FAHA

onathan L. Halperin, MD, FACC, FAHA Barbara Riegel, DNSC, RN, FAHA

Immediate Past Chair; ‡Former Task Force member during this writing effort

TABLE OF CONTENTSreamble....................................................................................600

This document was approved by the American College of Cardiology Foundationoard of Trustees in May 2006 and by the American Heart Association Sciencedvisory and Coordinating Committee in May 2006.When citing this document, the American College of Cardiology Foundation requests

hat the following citation format be used: Bonow RO, Carabello BA, Chatterjee K, deeon AC Jr., Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’GaraT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. ACC/AHA 2006 practiceuidelines for the management of patients with valvular heart disease: executive summary:report of the American College of Cardiology/American Heart Association Task Forcen Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the

. Introduction ....................................................................601

I. General Principles...........................................................602

This article has been copublished in the August 1, 2006 issue of Circulation.Copies: This document is available on the World Wide Web sites of the American

ollege of Cardiology (www.acc.org) and the American Heart Association (www.y.americanheart.org). Single copies of this document are available by calling 1-800-

53-4636 or writing the American College of Cardiology Foundation, Resourceenter, at 9111 Old Georgetown Road, Bethesda, MD 20814-1699. To purchaseulk reprints, fax: 212-633-3820 or E-mail: [email protected]: Multiple copies, modification, alteration, enhancement, and/or distribu-

ion of this document are not permitted without the express permission of the Americaneart Association. Please direct requests to [email protected].

by on October 16, 2006 c.org

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599JACC Vol. 48, No. 3, 2006 Bonow et al.August 1, 2006:598–675 ACC/AHA Practice Guidelines

A. Evaluation of the Patient With a CardiacMurmur ....................................................................6021. Electrocardiography and Chest

Roentgenography ..............................................6022. Echocardiography..............................................6023. Cardiac Catheterization ....................................6044. Exercise Testing ................................................6045. Approach to the Patient ...................................604

B. Valve Disease Severity Table ...................................605C. Endocarditis and Rheumatic Fever

Prophylaxis ...............................................................6061. Endocarditis Prophylaxis...................................6062. Rheumatic Fever Prophylaxis ...........................606

II. Specific Valve Lesions ....................................................607A. Aortic Stenosis .........................................................607

1. Grading the Degree of Stenosis .......................6072. Natural History .................................................6073. Management of the Asymptomatic Patient .....607

a. Echocardiography (Imaging, Spectral,and Color Doppler) in Aortic Stenosis .......607

b. Exercise Testing...........................................608c. Serial Evaluations.........................................608d. Medical Therapy ..........................................608e. Physical Activity and Exercise .....................609

4. Indications for Cardiac Catheterization ...........6095. Low-Flow/Low-Gradient Aortic Stenosis .......6096. Indications for Aortic Valve Replacement .......610

a. Symptomatic Patients ..................................610b. Asymptomatic Patients ................................610c. Patients Undergoing Coronary Artery

Bypass or Other Cardiac Surgery ................6117. Aortic Balloon Valvotomy ................................6128. Medical Therapy for the Inoperable Patient....6129. Special Considerations in the Elderly ..............612

B. Aortic Regurgitation ................................................6121. Acute Aortic Regurgitation ..............................612

a. Diagnosis......................................................612b. Treatment.....................................................613

2. Chronic Aortic Regurgitation...........................613a. Natural History ............................................613b. Diagnosis and Initial Evaluation .................614c. Medical Therapy ..........................................614d. Physical Activity and Exercise .....................616e. Serial Testing ...............................................616f. Indications for Cardiac Catheterization ......617g. Indications for Aortic Valve

Replacement or Repair ................................6173. Concomitant Aortic Root Disease ...................6184. Evaluation of Patients After Aortic Valve

Replacement ......................................................6195. Special Considerations in the Elderly ..............619

C. Bicuspid Aortic Valve With Dilated AscendingAorta.........................................................................619

D. Mitral Stenosis .........................................................6201. Natural History .................................................6202. Indications for Echocardiography in

Mitral Stenosis ..................................................6213. Medical Therapy ...............................................622

a. Medical Therapy: General ...........................622
b. Medical Therapy: Atrial Fibrillation ...........623

c. Medical Therapy: Prevention ofSystemic Embolization.................................623

4. Recommendations Regarding PhysicalActivity and Exercise ........................................624

5. Serial Testing ....................................................6246. Evaluation of the Symptomatic Patient............6247. Indications for Invasive Hemodynamic

Evaluation .........................................................6268. Indications for Percutaneous Mitral Balloon

Valvotomy .........................................................6269. Indications for Surgery for Mitral Stenosis ......627

10. Management of Patients After Valvotomyor Commissurotomy .........................................628

E. Mitral Valve Prolapse...............................................6281. Natural History .................................................6282. Evaluation and Management of the

Asymptomatic Patient.......................................6283. Evaluation and Management of the Symptomatic

Patient ...............................................................6294. Surgical Considerations.....................................630

F. Mitral Regurgitation ................................................6301. Acute Severe Mitral Regurgitation...................630

a. Diagnosis......................................................630b. Medical Therapy ..........................................630

2. Chronic Asymptomatic Mitral Regurgitation ..631a. Natural History ............................................631b. Indications for Transthoracic

Echocardiography.........................................631c. Indications for Transesophageal

Echocardiography.........................................632d. Serial Testing ...............................................632e. Guidelines for Physical Activity and

Exercise ........................................................632f. Medical Therapy ..........................................632g. Indications for Cardiac Catheterization ......633

3. Indications for Surgery......................................633a. Types of Surgery ..........................................633b. Indications for Mitral Valve Operation.......633

4. Ischemic Mitral Regurgitation..........................6365. Evaluation of Patients After Mitral Valve

Replacement or Repair......................................6366. Special Considerations in the Elderly ..............636

G. Multiple Valve Disease ............................................637H. Tricuspid Valve Disease...........................................637

1. Diagnosis ...........................................................6372. Management......................................................637

I. Drug-Related Valvular Heart Disease .....................637J. Radiation Heart Disease ..........................................638

V. Evaluation and Management of InfectiveEndocarditis ....................................................................638A. Antimicrobial Therapy.............................................638B. Indications for Echocardiography in Suspected

or Known Endocarditis ............................................6381. Transthoracic Echocardiography in

Endocarditis ......................................................6392. Transesophageal Echocardiography in

Endocarditis ......................................................639C. Indications for Surgery in Patients With Acute

Infective Endocarditis ..............................................639



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600 Bonow et al. JACC Vol. 48, No. 3, 2006ACC/AHA Practice Guidelines August 1, 2006:598–675

1. Surgery for Native Valve Endocarditis .............6402. Surgery for Prosthetic Valve Endocarditis .......640

. Management of Valvular Disease in Pregnancy ............641A. Physiological Changes of Pregnancy .......................641B. Echocardiography.....................................................641C. Management Guidelines ..........................................641

1. Mitral Stenosis ..................................................6412. Mitral Regurgitation .........................................6423. Aortic Stenosis ..................................................6424. Aortic Regurgitation .........................................6425. Pulmonic Stenosis .............................................6426. Tricuspid Valve Disease....................................6427. Marfan Syndrome .............................................642

D. Endocarditis Prophylaxis..........................................642E. Cardiac Valve Surgery..............................................643F. Anticoagulation During Pregnancy .........................643

1. Warfarin ............................................................6432. Unfractionated Heparin ....................................6433. Low-Molecular-Weight Heparins ....................6434. Selection of Anticoagulation Regimen in

Pregnant Patients With MechanicalProsthetic Valves ...............................................643

I. Management of Congenital Valvular Heart Diseasein Adolescents and Young Adults..................................644A. Aortic Stenosis .........................................................645

1. Evaluation of Asymptomatic Adolescentsor Young Adults With Aortic Stenosis............645

2. Indications for Aortic Balloon Valvotomyin Adolescents and Young Adults ....................646

B. Aortic Regurgitation ................................................646C. Mitral Regurgitation ................................................647D. Mitral Stenosis .........................................................647E. Tricuspid Valve Disease...........................................648

1. Evaluation of Tricuspid Valve Disease inAdolescents and Young Adults.........................648

2. Indications for Intervention in TricuspidRegurgitation.....................................................649

F. Pulmonic Stenosis ....................................................6491. Evaluation of Pulmonic Stenosis in

Adolescents and Young Adults.........................6492. Indications for Balloon Valvotomy in

Pulmonic Stenosis .............................................650G. Pulmonary Regurgitation .........................................650

II. Surgical Considerations ..................................................650A. Aortic Valve Surgery ................................................650

1. Antithrombotic Therapy for Patients WithAortic Mechanical Heart Valves.......................650

2. Stented and Nonstented Heterografts ..............650a. Aortic Valve Replacement With Stented

Heterografts .................................................650b. Aortic Valve Replacement With Stentless

Heterografts .................................................6513. Aortic Valve Homografts..................................6514. Pulmonic Valve Autotransplantation................6515. Aortic Valve Repair ..........................................6516. Major Criteria for Aortic Valve Selection........651

B. Mitral Valve Surgery ................................................6521. Mitral Valve Repair ..........................................652

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b. Rheumatic Heart Disease ............................652c. Ischemic Mitral Valve Disease ....................653d. Mitral Valve Endocarditis............................653

2. Selection of Mitral Valve Prostheses(Mechanical or Bioprostheses)..........................653

3. Choice of Mitral Valve Operation ...................653C. Tricuspid Valve Surgery...........................................653D. Valve Selection for Women of Child-Bearing

Age ...........................................................................654

III. Intraoperative Assessment ..............................................654

X. Management of Patients With Prosthetic Heart Valves....654A. Antithrombotic Therapy ..........................................654

1. Mechanical Valves.............................................6552. Biological Valves ...............................................6563. Embolic Events During Adequate

Antithrombotic Therapy ...................................6564. Excessive Anticoagulation.................................6565. Bridging Therapy in Patients With Mechanical

Valves Who Require Interruption of WarfarinTherapy for Noncardiac Surgery, InvasiveProcedures, or Dental Care ..............................656

6. Antithrombotic Therapy in Patients WhoNeed Cardiac Catheterization/Angiography......................................................657

7. Thrombosis of Prosthetic Heart Valves ...........657B. Follow-Up Visits ......................................................658

1. First Outpatient Postoperative Visit.................6582. Follow-Up Visits in Patients Without

Complications ...................................................6593. Follow-Up Visits in Patients With

Complications ...................................................659

. Evaluation and Treatment of Coronary Artery Diseasein Patients with Valvular Heart Disease ........................659A. Probability of Coronary Artery Disease in

Patients With Valvular Heart Disease.....................659B. Diagnosis of Coronary Artery Disease ....................660C. Treatment of Coronary Artery Disease at the

Time of Aortic Valve Replacement .........................660D. Aortic Valve Replacement in Patients

Undergoing Coronary Artery Bypass Surgery .........661E. Management of Concomitant Mitral Valve

Disease and Coronary Artery Disease .....................661

REAMBLE

t is important that the medical profession play a significantole in critically evaluating the use of diagnostic procedures andherapies as they are introduced in the detection, management,r prevention of disease states. Rigorous and expert analysis ofhe available data documenting the absolute and relativeenefits and risks of those procedures and therapies canroduce helpful guidelines that improve the effectiveness ofare, optimize patient outcomes, and favorably affect the overallost of care by focusing resources on the most effective strategies.

The American College of Cardiology (ACC) and themerican Heart Association (AHA) have jointly engaged in

he production of such guidelines in the area of cardiovascular
isease since 1980. This effort is directed by the ACC/AHA


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ask Force on Practice Guidelines, whose charge is to develop,pdate, or revise practice guidelines for important cardiovas-ular diseases and procedures. Writing committees are chargedith the task of performing an assessment of the evidence and

cting as an independent group of authors to develop or updateritten recommendations for clinical practice.Experts in the subject under consideration are selected

rom both organizations to examine subject-specific datand write guidelines. The process includes additional rep-esentatives from other medical practitioner and specialtyroups where appropriate. Writing committees are specifi-ally charged to perform a formal literature review, weighhe strength of evidence for or against a particular treatmentr procedure, and include estimates of expected healthutcomes where data exist. Patient-specific modifiers, co-orbidities, and issues of patient preference that might

nfluence the choice of particular tests or therapies areonsidered, as well as frequency of follow-up. When avail-ble, information from studies on cost will be considered;owever, review of data on efficacy and clinical outcomesill be the primary basis for preparing recommendation in

hese guidelines.The ACC/AHA Task Force on Practice Guidelinesakes every effort to avoid any actual, potential, or per-

eived conflicts of interest that might arise as a result of anutside relationship or personal interest of a member of theriting committee. Specifically, all members of the writing

ommittee and peer reviewers of the document are asked torovide disclosure statements of all such relationships thatight be perceived as real or potential conflicts of interest.riting committee members are also strongly encouraged

o declare a previous relationship with industry that mighte perceived as relevant to guideline development. If ariting committee member develops a new relationshipith industry during his or her tenure, he or she is required

o notify guideline staff in writing. The continued partici-ation of the writing committee member will be reviewed.hese statements are reviewed by the parent task force,

eported orally to all members of the writing panel at eacheeting, and updated and reviewed by the writing commit-

ee as changes occur. Please refer to the methodologyanual for ACC/AHA guideline writing committees for

urther description of the relationships with industry policy,vailable on ACC and AHA World Wide Web siteshttp://www.acc.org/clinical/manual/manual_introltr.htmnd http://circ.ahajournals.org/manual/). Relationshipsith industry pertinent to these guidelines are listed inppendixes 1 and 2 of the full-text Guidelines for membersf the writing committee and peer reviewers, respectively.These practice guidelines are intended to assist healthcare

roviders in clinical decision making by describing a rangef generally acceptable approaches for the diagnosis, man-gement, and prevention of specific diseases or conditions.hese guidelines attempt to define practices that meet theeeds of most patients in most circumstances. These guide-

ine recommendations reflect a consensus of expert opinion acontent.onlinejacDownloaded from

fter a thorough review of the available, current scientificvidence and are intended to improve patient care. If theseuidelines are used as the basis for regulatory/payer deci-ions, the ultimate goal is quality of care and serving theatient’s best interests. The ultimate judgment regardingare of a particular patient must be made by the healthcarerovider and patient in light of all of the circumstancesresented by that patient. There are circumstances in whicheviations from these guidelines are appropriate.The “ACC/AHA 2006 Practice Guidelines for the Man-

gement of Patients With Valvular Heart Disease” waspproved for publication by the ACC Foundation (ACCF)oard of trustees in May 2006 and the AHA Sciencedvisory and Coordinating Committee in May 2006. The

xecutive summary and recommendations are published inhe August 1, 2006 issue of the Journal of the Americanollege of Cardiology and the August 1, 2006 issue ofirculation. The full-text guideline is e-published in the

ame issues of each journal and is posted on the Worldide Web sites of the ACC (www.acc.org) and the AHA

www.americanheart.org). The guidelines will be reviewednnually by the ACC/AHA Task Force on Practice Guide-ines and will be considered current unless they are updated,evised, or sunsetted and withdrawn from distribution.opies of the full text and the executive summary are

vailable from both organizations.Sidney C. Smith, Jr., MD, FACC, FAHA,

Chair, ACC/AHA Task Force on Practice Guidelines

. INTRODUCTION

his guideline focuses primarily on valvular heart disease inhe adult, with a separate section dealing with specificecommendations for valve disorders in adolescents andoung adults. The diagnosis and management of infants andoung children with congenital valvular abnormalities areignificantly different from those of the adolescent or adultnd are beyond the scope of these guidelines.

The committee emphasizes the fact that many factorsltimately determine the most appropriate treatment ofndividual patients with valvular heart disease within a givenommunity. These include the availability of diagnosticquipment and expert diagnosticians, the expertise of inter-entional cardiologists and surgeons, and notably, theishes of well-informed patients. Therefore, deviation from

hese guidelines may be appropriate in some circumstances.hese guidelines are written with the assumption that aiagnostic test can be performed and interpreted with skill

evels consistent with previously reported ACC training andompetency statements and ACC/AHA guidelines, thatnterventional cardiological and surgical procedures can beerformed by highly trained practitioners within acceptableafety standards, and that the resources necessary to performhese diagnostic procedures and provide this care are readily
vailable. This is not true in all geographic areas, which

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urther underscores the committee’s position that its recom-endations are guidelines and not rigid requirements.All of the recommendations in this guideline revision

ere converted from the tabular format used in the 1998uideline to a listing of recommendations that has beenritten in full sentences to express a complete thought, such

hat a recommendation, even if separated and presentedpart from the rest of the document, would still convey theull intent of the recommendation. It is hoped that this willncrease the readers’ comprehension of the guidelines. Also,he level of evidence, either A, B, or C, for each recom-endation is now provided. See Figure 1 for further details

n the classification and level of evidence schema.

I. GENERAL PRINCIPLES

. Evaluation of the Patient With a Cardiac Murmur

ardiac auscultation remains the most widely used methodf screening for valvular heart disease. The production ofurmurs is due to 3 main factors: 1) high blood flow rate

hrough normal or abnormal orifices, 2) forward flowhrough a narrowed or irregular orifice into a dilated vesselr chamber, and 3) backward or regurgitant flow through anncompetent valve.

A heart murmur may have no pathological significancer may be an important clue to the presence of valvular,ongenital, or other structural abnormalities of the heart.

ost systolic heart murmurs do not signify cardiacisease, and many are related to physiological increases inlood flow velocity. In other instances, a heart murmuray be an important clue to the diagnosis of undetected

ardiac disease that may be important even when asymp-omatic or that may define the reason for cardiac symp-oms. In these situations, various noninvasive or invasiveardiac tests may be necessary to establish a firm diagno-is and form the basis for rational treatment of annderlying disorder. Echocardiography is particularlyseful in this regard, as discussed in the “ACC/AHA/SE 2003 Guidelines for the Clinical Application ofchocardiography” (1). Diastolic murmurs virtually al-ays represent pathological conditions and require fur-

her cardiac evaluation, as do most continuous murmurs.ontinuous “innocent” murmurs include venous hums

nd mammary souffles.

. Electrocardiography and Chest Roentgenography

lthough echocardiography usually provides more spe-ific and often quantitative information about the signif-cance of a heart murmur and may be the only testeeded, the electrocardiogram (ECG) and chest X-rayre readily available and may have been obtained previ-usly. The absence of ventricular hypertrophy, atrialnlargement, arrhythmias, conduction abnormalities,rior myocardial infarction, and evidence of active isch-
mia on the ECG provides useful negative information at e

relatively low cost. Abnormal ECG findings in a patientith a heart murmur, such as ventricular hypertrophy orprior infarction, should lead to a more extensive

valuation that includes echocardiography.Chest roentgenograms often yield qualitative information

n cardiac chamber size, pulmonary blood flow, pulmonarynd systemic venous pressure, and cardiac calcification inatients with cardiac murmurs. When abnormal findings areresent on chest X-ray, echocardiography should be per-ormed.

. Echocardiography

lass I

. Echocardiography is recommended for asymptomaticpatients with diastolic murmurs, continuous murmurs,holosystolic murmurs, late systolic murmurs, murmursassociated with ejection clicks or murmurs that radiateto the neck or back. (Level of Evidence: C)

. Echocardiography is recommended for patients withheart murmurs and symptoms or signs of heart failure,myocardial ischemia/infarction, syncope, thrombo-embolism, infective endocarditis, or other clinicalevidence of structural heart disease. (Level of Evi-dence: C)

. Echocardiography is recommended for asymptomaticpatients who have grade 3 or louder midpeakingsystolic murmurs. (Level of Evidence: C)

lass IIa

. Echocardiography can be useful for the evaluation ofasymptomatic patients with murmurs associated withother abnormal cardiac physical findings or murmursassociated with an abnormal ECG or chest X-ray.(Level of Evidence: C)

. Echocardiography can be useful for patients whosesymptoms and/or signs are likely noncardiac in originbut in whom a cardiac basis cannot be excluded bystandard evaluation. (Level of Evidence: C)

lass III

Echocardiography is not recommended for patientswho have a grade 2 or softer midsystolic murmuridentified as innocent or functional by an experiencedobserver. (Level of Evidence: C)

chocardiography with color flow and spectral Dopplervaluation is an important noninvasive method for assessinghe significance of cardiac murmurs. Information regardingalve morphology and function, chamber size, wall thick-ess, ventricular function, pulmonary and hepatic vein flow,nd estimates of pulmonary artery pressures can be readilyntegrated.

Although echocardiography can provide important infor-ation, such testing is not necessary for all patients with

ardiac murmurs and usually adds little but expense in the
valuation of asymptomatic younger patients with short


Figure 1. Applying classification of recommendations and level of evidence. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, historyof diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Manyimportant clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particulartest or therapy is useful or effective. †In 2003 the ACC/AHA Task Force on Practice Guidelines provided a list of suggested phrases to use when writing recommendations. All recommendations in thisguideline have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above setsof recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individualrecommendation level. 603JACC

Vol.48,No.3,2006Bonow

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August1,2006:598–675ACC/AHA

PracticeGuidelines

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rade 1 to 2 midsystolic murmurs and otherwise normalhysical findings. At the other end of the spectrum areatients with heart murmurs for whom transthoracic echo-ardiography proves inadequate. Depending on the specificlinical circumstances, transesophageal echocardiographyTEE), cardiac magnetic resonance, or cardiac catheteriza-ion may be indicated for better characterization of thealvular lesion.

It is important to note that Doppler ultrasound devicesre very sensitive and may detect trace or mild valvularegurgitation through structurally normal tricuspid andulmonic valves in a large percentage of young, healthyubjects and through normal left-sided valves (particularlyhe mitral valve [MV]) in a variable but lower percentage ofatients (2–6).General recommendations for performing echocardiog-

aphy in patients with heart murmurs are provided. Ofourse, individual exceptions to these indications may exist.

. Cardiac Catheterization

ardiac catheterization can provide important informationbout the presence and severity of valvular obstruction,alvular regurgitation, and intracardiac shunting. It is notecessary in most patients with cardiac murmurs andormal or diagnostic echocardiograms, but it providesdditional information for some patients in whom there is aiscrepancy between the echocardiographic and clinicalndings. Indications for cardiac catheterization for hemo-ynamic assessment of specific valve lesions are given inection III, “Specific Valve Lesions.” Specific indicationsor coronary angiography to screen for the presence oforonary artery disease (CAD) are given in Section X-B.

. Exercise Testing

xercise testing can provide valuable information in patientsith valvular heart disease, especially in those whose symp-

oms are difficult to assess. It can be combined withchocardiography, radionuclide angiography, and cardiacatheterization. It has a proven track record of safety, evenmong asymptomatic patients with severe aortic stenosisAS). Exercise testing has generally been underutilized inhis patient population and should constitute an importantomponent of the evaluation process.

. Approach to the Patient

he evaluation of the patient with a heart murmur may varyreatly depending on the timing of the murmur in theardiac cycle, its location and radiation, and its response toarious physiological maneuvers. Also of importance is theresence or absence of cardiac and noncardiac symptomsnd other findings on physical examination that suggest theurmur is clinically significant.Echocardiography is indicated for patients with diastolic

r continuous heart murmurs not due to a cervical venous
um or a mammary souffle during pregnancy, for those with p

olosystolic or late systolic murmurs, for those with mid-ystolic murmurs of grade 3 or greater intensity, and forhose with softer systolic murmurs in whom dynamicardiac auscultation suggests a definite diagnosis (e.g.,ypertrophic cardiomyopathy). Echocardiography is also

ndicated in certain patients with grade 1 or 2 midsystolicurmurs, including patients with symptoms or signs con-

istent with infective endocarditis, thromboembolism, heartailure, myocardial ischemia/infarction, or syncope.

It must be re-emphasized that trivial, minimal, or phys-ological valvular regurgitation, especially affecting the mi-ral, tricuspid, or pulmonic valves, is detected by color flowmaging techniques in many otherwise normal patients,ncluding many patients who have no heart murmur at all2,5,6). This observation must be considered when theesults of echocardiography are used to guide decisions insymptomatic patients in whom echocardiography was usedo assess the significance of an isolated murmur.

Characteristics of innocent murmurs in asymptomaticdults that have no functional significance include theollowing:

grade 1 to 2 intensity at the left sternal bordera systolic ejection patternnormal intensity and splitting of the second heartsoundno other abnormal sounds or murmursno evidence of ventricular hypertrophy or dilatationand the absence of increased murmur intensity withthe Valsalva maneuver or with standing from a squat-ting position.

Throughout these guidelines, treatment recommenda-ions will often derive from specific echocardiographiceasurements of left ventricular (LV) size and systolic

unction. Accuracy and reproducibility are critical, particu-arly when applied to surgical recommendations for asymp-omatic patients with mitral regurgitation (MR) or aorticegurgitation (AR). Serial measurements over time, oreassessment with a different imaging technology (radionu-lide ventriculography or cardiac magnetic resonance), areften helpful for counseling individual patients. Lastly,lthough handheld echocardiography can be used forcreening purposes, it is important to note that its accuracys highly dependent on the experience of the user. Therecise role of handheld echocardiography for the assess-ent of patients with valvular heart disease has not been

lucidated.As valuable as echocardiography may be, the basic car-

iovascular physical examination is still the most appropri-te method of screening for cardiac disease and will establishany clinical diagnoses. Echocardiography should not re-

lace the cardiovascular examination but can be useful inetermining the cause and severity of valvular lesions,
articularly in older and/or symptomatic patients.


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. Valve Disease Severity Tablelassification of the severity of valve disease in adults is listed inable 1. The classification for regurgitant lesions is adapted from

he recommendations of the American Society of Echocardiog-

able 1. Classification of the Severity of Valve Disease in Adults

. Left-Sided Valve Disease

Indicator Mild

et velocity (m per second) Less than 3.0ean gradient (mm Hg)* Less than 25

alve area (cm2) Greater than 1.5alve area index (cm2 per m2)

M

ean gradient (mm Hg)* Less thaulmonary artery systolic pressure (mm Hg) Less thaalve area (cm2) Greater

Mild

ualitativeAngiographic grade 1�Color Doppler jet width Central jet, width less than

25% of LVOTDoppler vena contracta width (cm) Less than 0.3uantitative (cath or echo)Regurgitant volume (ml per beat) Less than 30Regurgitant fraction (%) Less than 30Regurgitant orifice area (cm2) Less than 0.10

dditional essential criteriaLeft ventricular size

Mild

ualitativeAngiographic grade 1�Color Doppler jet area Small, central jet (less than

4 cm2 or less than 20%LA area)

Doppler vena contracta width (cm) Less than 0.3uantitative (cath or echo)Regurgitant volume (ml per beat) Less than 30Regurgitant fraction (%) Less than 30Regurgitant orifice area (cm2) Less than 0.20

dditional essential criteriaLeft atrial sizeLeft ventricular size

B. Right-Sided Valve Disease

evere tricuspid stenosis: Valveevere tricuspid regurgitation: Venaevere pulmonic stenosis: Jet ve

Hgevere pulmonic regurgitation: Color

Dense

Valve gradients are flow dependent and when used as estimates of severity of valve steodified from the Journal of the American Society of Echocardiography, 16, Zoghbi W

wo-dimensional and Doppler echocardiography, 777–802, Copyright 2003, with permissioath, catheterization; echo, echocardiography; LA, left atrial/atrium; LVOT, left ventricula


aphy (7). For full recommendations of the American Society ofchocardiography, please refer to the original document. Subse-uent sections of the current guidelines refer to the criteria inable 1 to define severe valvular stenosis or regurgitation.

Aortic Stenosis

Moderate Severe

3.0–4.0 Greater than 4.025–40 Greater than 40

1.0–1.5 Less than 1.0Less than 0.6

Mitral Stenosis

Moderate Severe

5–10 Greater than 1030–50 Greater than 50

1.5 1.0–1.5 Less than 1.0

Aortic Regurgitation

Moderate Severe

2� 3–4�Greater than mild but no signs

of severe ARCentral jet, width greater than

65% LVOT0.3–0.6 Greater than 0.6

30–59 Greater than or equal to 6030–49 Greater than or equal to 50

0.10–0.29 Greater than or equal to 0.30

Increased

Mitral Regurgitation

Moderate Severe

2� 3–4�of MR greater than

ld present but noteria for severe MR

Vena contracta width greater than 0.7 cm withlarge central MR jet (area greater than 40%of LA area) or with a wall-impinging jet ofany size, swirling in LA

.69 Greater than or equal to 0.70

9 Greater than or equal to 609 Greater than or equal to 50.39 Greater than or equal to 0.40

EnlargedEnlarged

Characteristic

less than 1.0 cm2

acta width greater than 0.7 cm and systolic flow reversal in hepatic veinsgreater than 4 m per second or maximum gradient greater than 60 mm

lls outflow tractinuous wave Doppler signal with a steep deceleration slope

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. Endocarditis and Rheumatic Fever Prophylaxis

he following information is based on recommendationsade by the AHA in 1997 (8). These recommendations are

urrently under revision and subject to change. Recommen-ations for prophylaxis against and treatment of nonvalvularardiac device–related infections have been published pre-iously (9).

. Endocarditis Prophylaxis

lass I

rophylaxis against infective endocarditis is recom-ended for the following patients:

Patients with prosthetic heart valves and patients with ahistory of infective endocarditis. (Level of Evidence: C)Patients who have complex cyanotic congenital heartdisease (e.g., single-ventricle states, transposition ofthe great arteries, tetralogy of Fallot). (Level of Evi-dence: C)Patients with surgically constructed systemic-pulmonaryshunts or conduits. (Level of Evidence: C)Patients with congenital cardiac valve malformations,particularly those with bicuspid aortic valves, and pa-tients with acquired valvular dysfunction (e.g., rheumaticheart disease). (Level of Evidence: C)Patients who have undergone valve repair. (Level ofEvidence: C)Patients who have hypertrophic cardiomyopathy whenthere is latent or resting obstruction. (Level of Evi-dence: C)Patients with MV prolapse (MVP) and auscultatoryevidence of valvular regurgitation and/or thickenedleaflets on echocardiography.* (Level of Evidence: C)

lass IIIrophylaxis against infective endocarditis is not recom-ended for the following patients:

Patients with isolated secundum atrial septal defect.(Level of Evidence: C)Patients 6 or more months after successful surgical orpercutaneous repair of atrial septal defect, ventricularseptal defect, or patent ductus arteriosus. (Level ofEvidence: C)Patients with MVP without MR or thickened leafletson echocardiography.* (Level of Evidence: C)Patients with physiological, functional, or innocentheart murmurs, including patients with aortic valvesclerosis as defined by focal areas of increased echo-genicity and thickening of the leaflets without restric-tion of motion and a peak velocity less than 2.0 m persecond. (Level of Evidence: C)Patients with echocardiographic evidence of physio-logic MR in the absence of a murmur and with
structurally normal valves. (Level of Evidence: C) r

Patients with echocardiographic evidence of physio-logical tricuspid regurgitation (TR) and/or pulmonaryregurgitation in the absence of a murmur and withstructurally normal valves. (Level of Evidence: C)

Patients with MVP without regurgitation require addi-ional clinical judgment. Indications for antibiotic prophy-axis in MVP are discussed in Section III-E-2. Patients

ho do not have MR but who do have echocardiographicvidence of thickening and/or redundancy of the valveeaflets, and especially men 45 years of age or older, maye at increased risk for infective endocarditis (10). Addi-ionally, approximately one third of patients with MVP

ithout MR at rest may have exercise-induced MR (11).ome patients may exhibit MR at rest on one occasion andot on another. There are no data available to address this

atter issue, and at present, the decision must be left tolinical judgment, taking into account the nature of thenvasive procedure, the previous history of endocarditis,nd the presence or absence of valve thickening and/oredundancy.

. Rheumatic Fever Prophylaxis

lass I

Patients who have had rheumatic fever with or with-out carditis (including patients with MS) shouldreceive prophylaxis for recurrent rheumatic fever.(Level of Evidence: B)

heumatic fever is an important cause of valvular heartisease worldwide. In the United States (and Westernurope), cases of acute rheumatic fever have been uncom-on since the 1970s. However, starting in 1987, an increase

n cases has been observed. The enhanced understanding ofhe causative organism, group A beta hemolytic streptococ-us, has resulted in the development of kits that allow rapidetection of group A streptococci with specificity greaterhan 95% and more rapid identification of their presence inpper respiratory infection. Because the test has a lowensitivity, a negative test requires throat culture confirma-ion. Rheumatic fever prevention and treatment guidelinesave been established previously by the AHA (12). Promptecognition and treatment comprise primary rheumaticever prevention.

Patients who have had an episode of rheumatic fever aret high risk of developing recurrent episodes of acuteheumatic fever. Patients who develop carditis are especiallyrone to similar episodes with subsequent attacks. Second-ry prevention of rheumatic fever recurrence is thus of greatmportance. Continuous antimicrobial prophylaxis has beenhown to be effective. Anyone who has had rheumatic feverith or without carditis, including patients with mitral

tenosis (MS) should receive prophylaxis for recurrent
heumatic fever (12).


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II. SPECIFIC VALVE LESIONS

. Aortic Stenosis

he most common cause of AS in adults is calcification ofnormal trileaflet or congenital bicuspid valve (13,14).alcific AS is an active disease process characterized by lipid

ccumulation, inflammation, and calcification, with manyimilarities to atherosclerosis (15–19). Rheumatic AS due tousion of the commissures with scarring and eventualalcification of the cusps is less common and is invariablyccompanied by MV disease.

. Grading the Degree of Stenosis

or these guidelines, we graded AS severity on the basis ofvariety of hemodynamic and natural history data (Table 1)

7,20), using definitions of aortic jet velocity, mean pressureradient, and valve area as follows:

Mild (area 1.5 cm2, mean gradient less than 25 mmHg, or jet velocity less than 3.0 m per second)Moderate (area 1.0 to 1.5 cm2, mean gradient 25– 40mm Hg, or jet velocity 3.0 – 4.0 m per second)Severe (area less than 1.0 cm2, mean gradient greaterthan 40 mm Hg or jet velocity greater than 4.0 m persecond).

hen stenosis is severe and cardiac output is normal, theean transvalvular pressure gradient is generally greater

han 40 mm Hg. However, when cardiac output is low,evere stenosis may be present with a lower transvalvularradient and velocity, as discussed below. Some patientsith severe AS remain asymptomatic, whereas others withnly moderate stenosis develop symptoms. Therapeuticecisions, particularly those related to corrective surgery, areased largely on the presence or absence of symptoms.hus, the absolute valve area (or transvalvular pressureradient) is not the primary determinant of the need forortic valve replacement (AVR).

. Natural History

he natural history of AS in the adult consists of arolonged latent period during which morbidity and mor-ality are very low. The rate of progression of the stenoticesion has been estimated in a variety of invasive andoninvasive studies (21). Once even moderate stenosis isresent (jet velocity greater than 3.0 m per second; Table 1),he average rate of progression is an increase in jet velocityf 0.3 m per second per year, an increase in mean pressureradient of 7 mm Hg per year, and a decrease in valve areaf 0.1 cm2 per year (22–27); however, there is markedndividual variability in the rate of hemodynamic progres-ion. Although it appears that the progression of AS can beore rapid in patients with degenerative calcific disease

han in those with congenital or rheumatic disease (27–29),t is not possible to predict the rate of progression in an
ndividual patient. For this reason, regular clinical follow-up

s mandatory in all patients with asymptomatic mild tooderate AS. In addition, progression to AS may occur in

atients with aortic sclerosis, defined as valve thickeningithout obstruction to LV outflow (30).Aortic sclerosis is present in approximately 25% of adults

ver 65 years of age and is associated with clinical factorsuch as age, sex, hypertension, smoking, serum low-densityipoprotein and lipoprotein(a) levels, and diabetes mellitus31). Aortic sclerosis on echocardiography in subjects with-ut known coronary disease is also associated with adverselinical outcome, with an approximately 50% increased riskf myocardial infarction and cardiovascular death comparedith subjects with a normal aortic valve (32–34). Theechanism of this association is unclear and is likely related

o subclinical atherosclerosis, endothelial dysfunction, orystemic inflammation rather than valve hemodynamics.

Eventually, symptoms of angina, syncope, or heart failureevelop after a long latent period, and the outlook changesramatically. After the onset of symptoms, average survivals 2 to 3 years (35–39), with a high risk of sudden death.hus, the development of symptoms identifies a criticaloint in the natural history of AS. It is important tomphasize that symptoms may be subtle and often are notlicited by the physician in taking a routine clinical history.

Sudden death is known to occur in patients with severeS and, in older retrospective studies, has been reported toccur without prior symptoms (35,40–42). However, inrospective echocardiographic studies, sudden death inreviously asymptomatic patients is rare (20,27,38,43–45),stimated at less than 1% per year when patients withnown AS are followed up prospectively.

. Management of the Asymptomatic Patient

symptomatic patients with AS have outcomes similar toge-matched normal adults; however, disease progressionith symptom onset is common (20,27,38,43–47). Patientsith asymptomatic AS require frequent monitoring forevelopment of symptoms and progressive disease.

. Echocardiography (Imaging, Spectral, and Color Dopp-er) in Aortic Stenosis

lass I

. Echocardiography is recommended for the diagnosisand assessment of AS severity. (Level of Evidence: B)

. Echocardiography is recommended in patients withAS for the assessment of LV wall thickness, size, andfunction. (Level of Evidence: B)

. Echocardiography is recommended for re-evaluationof patients with known AS and changing symptomsor signs. (Level of Evidence: B)

. Echocardiography is recommended for the assess-ment of changes in hemodynamic severity and LVfunction in patients with known AS during preg-
nancy. (Level of Evidence: B)


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. Transthoracic echocardiography is recommended forre-evaluation of asymptomatic patients: every year forsevere AS; every 1–2 years for moderate AS; and every3–5 years for mild AS. (Level of Evidence: B)

chocardiography is indicated when there is a systolicurmur that is grade 3/6 or greater, when there is a single

2, or if there are symptoms that might be due to AS. The-dimensional (2D) echocardiogram is valuable for evalua-ion of valve anatomy and function and to determine the LVesponse to pressure overload. In nearly all patients, theeverity of the stenotic lesion can be defined with Dopplerchocardiographic measurements of maximum jet velocity,ean transvalvular pressure gradient, and continuity equa-

ion valve area, as discussed in the “ACC/AHA/ASE 2004uidelines for the Clinical Application of Echocardiogra-

hy” (1). Doppler evaluation of AS severity requires atten-ion to technical details, with the most common error beingnderestimation of disease severity due to a nonparallelntercept angle between the ultrasound beam and high-elocity jet through the narrowed valve. When measurementf LV outflow tract diameter is problematic, the ratio ofutflow tract velocity to aortic jet velocity can be substitutedor valve area, because this ratio is, in effect, indexed forody size. A ratio of 0.9 to 1.0 is normal, with a ratio lesshan 0.25 indicating severe stenosis. Echocardiography islso used to assess LV size and function, degree of hyper-rophy, and presence of other associated valvular disease.

. Exercise Testing

lass IIb

Exercise testing in asymptomatic patients with ASmay be considered to elicit exercise-induced symp-toms and abnormal blood pressure responses. (Levelof Evidence: B)

lass III

Exercise testing should not be performed in symp-tomatic patients with AS. (Level of Evidence: B)

xercise testing in adults with AS has poor diagnosticccuracy for evaluation of concurrent CAD. Presumably,his is due to the presence of an abnormal baseline ECG,V hypertrophy, and limited coronary flow reserve. Elec-

rocardiographic ST depression during exercise occurs in0% of adults with asymptomatic AS and has no knownrognostic significance.Exercise testing should not be performed in symptomatic

atients because of the high risk of complications; however,n asymptomatic patients, exercise testing is relatively safend may provide information that is not uncovered duringhe initial clinical evaluation (20,46–52). When the medicalistory is unclear, exercise testing can identify a limitedxercise capacity, abnormal blood pressure responses, orven exercise-induced symptoms (46,47,52). An abnormal
emodynamic response (e.g., hypotension or failure to o

ncrease blood pressure with exercise) in a patient withevere AS is considered a poor prognostic finding (46,53).inally, in selected patients, the observations made duringxercise may provide a basis for advice about physical activity.xercise testing in asymptomatic patients should be performednly under the supervision of an experienced physician, withlose monitoring of blood pressure and the ECG.

. Serial Evaluations

he frequency of follow-up visits to the physician de-ends on the severity of AS and on the presence ofomorbid conditions. An essential component of eachisit is patient education about the expected diseaseourse and symptoms of AS. Patients should be advisedo promptly report the development of any change inxercise tolerance, exertional chest discomfort, dyspnea,ightheadedness, or syncope.

Serial echocardiography is an important part of anntegrated approach that includes a detailed history,hysical examination, and, in some patients, a carefullyonitored exercise test. Because the rate of progression

aries considerably, clinicians often perform an annualchocardiogram on patients known to have moderate toevere AS. Serial echocardiograms are helpful to assesshanges in stenosis severity, LV hypertrophy, and LVunction. Therefore, in patients with severe AS, anchocardiogram every year may be appropriate. In pa-ients with moderate AS, serial studies performed every 1o 2 years are satisfactory, and in patients with mild AS,erial studies can be performed every 3 to 5 years.chocardiograms should be performed more frequently if

here is a change in signs or symptoms.

. Medical Therapy

ntibiotic prophylaxis is indicated in all patients with ASor prevention of infective endocarditis and, in those withheumatic AS, for prevention of recurrent rheumaticever. Patients with associated systemic arterial hyperten-ion should be treated cautiously with appropriate anti-ypertensive agents. With these exceptions, there is nopecific medical therapy for patients who have not yeteveloped symptoms. Patients who develop symptomsequire surgery, not medical therapy.

There are no medical treatments proven to prevent orelay the disease process in the aortic valve leaflets;owever, the association of AS with clinical factorsimilar to those associated with atherosclerosis and theechanisms of disease at the tissue level (15–19,30 –

4,54 –58) and small retrospective studies of the effect ofipid-lowering therapy (59 – 64) have led to the hypoth-sis that intervention may be possible to slow or preventisease progression in the valve leaflet (56,65). Yet, arospective, randomized, placebo-controlled trial in pa-ients with calcific aortic valve disease failed to demon-trate a benefit of atorvastatin in reducing the progression
f aortic valve stenosis over a 3-year period (66). It is


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oteworthy that the patients in this study had high levelsf aortic valve calcification by computed tomography andvidence of moderate to severe AS at baseline. Thus,urther trials in patients with less severe aortic valvealcification, with longer follow-up periods, are needed.n the meanwhile, evaluation and modification of cardiacisk factors is important in patients with aortic valveisease to prevent concurrent CAD.

. Physical Activity and Exercise

ecommendations for physical activity are based on thelinical examination, with special emphasis on the hemody-amic severity of the stenotic lesion. Recommendations onarticipation in competitive sports have been published byhe Task Force on Acquired Valvular Heart Disease of the6th Bethesda Conference (67). Physical activity is notestricted in asymptomatic patients with mild AS; theseatients can participate in competitive sports. Patients withoderate to severe AS should avoid competitive sports that

nvolve high dynamic and static muscular demands. Otherorms of exercise can be performed safely, but it is advisableo evaluate such patients with an exercise test before theyegin an exercise or athletic program.

. Indications for Cardiac Catheterization

lass I

. Coronary angiography is recommended before AVRin patients with AS at risk for CAD (see SectionX-B). (Level of Evidence: B)

. Cardiac catheterization for hemodynamic measure-ments is recommended for assessment of severity ofAS in symptomatic patients when noninvasive testsare inconclusive or when there is a discrepancybetween noninvasive tests and clinical findings re-garding severity of AS. (Level of Evidence: C)

. Coronary angiography is recommended before AVRin patients with AS for whom a pulmonary autograft(Ross procedure) is contemplated and if the origin ofthe coronary arteries was not identified by noninva-sive technique. (Level of Evidence: C)

lass III

. Cardiac catheterization for hemodynamic measure-ments is not recommended for the assessment ofseverity of AS before AVR when noninvasive tests areadequate and concordant with clinical findings.(Level of Evidence: C)

. Cardiac catheterization for hemodynamic measure-ments is not recommended for the assessment of LVfunction and severity of AS in asymptomatic patients.(Level of Evidence: C)

n preparation for AVR, coronary angiography is indicatedn patients suspected of having CAD, as discussed inection X-B. If the clinical and echocardiographic data are
ypical of severe isolated AS, coronary angiography may be 0

ll that is needed before AVR. A complete left- andight-heart catheterization may be necessary to assess theemodynamic severity of the AS if there is a discrepancyetween clinical and echocardiographic data.The pressure gradient across a stenotic valve is related to

he valve orifice area and the transvalvular flow (68). Thus,n the presence of depressed cardiac output, relatively lowressure gradients may be obtained in patients with severeS. On the other hand, during exercise or other high-flow

tates, significant pressure gradients can be measured ininimally stenotic valves. For these reasons, complete

ssessment of AS requires measurement of transvalvularow, determination of the mean transvalvular pressureradient, and calculation of the effective valve area. Atten-ion to detail with accurate measurements of pressure andow is important, especially in patients with low cardiacutput or a low transvalvular pressure gradient.

. Low-Flow/Low-Gradient Aortic Stenosis

lass IIa

. Dobutamine stress echocardiography is reasonable toevaluate patients with low-flow/low-gradient AS andLV dysfunction. (Level of Evidence: B)

. Cardiac catheterization for hemodynamic measure-ments with infusion of dobutamine can be useful forevaluation of patients with low-flow/low-gradient ASand LV dysfunction. (Level of Evidence: C)

atients with severe AS and low cardiac output oftenresent with a relatively low transvalvular pressure gradienti.e., mean gradient less than 30 mm Hg). Such patients cane difficult to distinguish from those with low cardiac outputnd only mild to moderate AS. In the latter group, primaryontractile dysfunction is responsible for the decreasedjection fraction and low stroke volume; the problem isurther complicated by reduced valve opening forces thatontribute to limited valve mobility and apparent stenosis.n both situations, the low-flow state and low-pressureradient contribute to a calculated effective valve area thatan meet criteria for severe AS. Alternate measures of ASeverity have been proposed as being less flow dependenthan gradients or valve area. These include valve resistancend stroke work loss. However, all of these measures areow dependent, have not been shown to predict clinicalutcome, and have not gained widespread clinical use (69).In selected patients with low-flow/low-gradient AS and

V dysfunction, it may be useful to determine the transval-ular pressure gradient and to calculate valve area during aaseline state and again during exercise or low-dose phar-acological (i.e., dobutamine infusion) stress, with the goal

f determining whether stenosis is severe or only moderaten severity (51,70–76). Such studies can be performed inither the echocardiography or the cardiac catheterizationaboratory. If a dobutamine infusion produces an incrementn stroke volume and an increase in valve area greater than
.2 cm2 and little change in gradient, it is likely that the


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aseline evaluation overestimated the severity of stenosis. Inontrast, patients with severe AS will have a fixed valve areaith an increase in stroke volume and an increase inradient. These patients are likely to respond favorably tourgery. Patients in whom stroke volume fails to increaseith dobutamine (less than 20% increase) appear to have aery poor prognosis with either medical or surgical therapy1,77).

Dobutamine stress testing in patients with AS should beerformed only in centers with experience in pharmacolog-cal stress testing and with a cardiologist in attendance.

. Indications for Aortic Valve Replacement

lass I

. AVR is indicated for symptomatic patients withsevere AS.* (Level of Evidence: B)

. AVR is indicated for patients with severe AS* under-going coronary artery bypass graft surgery (CABG).(Level of Evidence: C)

. AVR is indicated for patients with severe AS* under-going surgery on the aorta or other heart valves.(Level of Evidence: C)

. AVR is recommended for patients with severe AS*and LV systolic dysfunction (ejection fraction lessthan 0.50). (Level of Evidence: C)

lass IIa

AVR is reasonable for patients with moderate AS*undergoing CABG or surgery on the aorta or otherheart valves (see Section X-D). (Level of Evidence: B)

lass IIb

. AVR may be considered for asymptomatic patientswith severe AS* and abnormal response to exercise(e.g., development of symptoms or asymptomatichypotension). (Level of Evidence: C)

. AVR may be considered for adults with severe asymp-tomatic AS* if there is a high likelihood of rapidprogression (age, calcification, and CAD) or if sur-gery might be delayed at the time of symptom onset.(Level of Evidence: C)

. AVR may be considered in patients undergoingCABG who have mild AS* when there is evidence,such as moderate to severe valve calcification, thatprogression may be rapid. (Level of Evidence: C)

. AVR may be considered for asymptomatic patientswith extremely severe AS (aortic valve area less than0.6 cm2, mean gradient greater than 60 mm Hg, andjet velocity greater than 5.0 m per second) when thepatient’s expected operative mortality is 1.0% or less.(Level of Evidence: C)

lass III

AVR is not useful for the prevention of sudden death
in asymptomatic patients with AS who have none of p

the findings listed under the Class IIa/IIb recom-mendations. (Level of Evidence: B)

See Table 1 (7).

n adults with severe, symptomatic, calcific AS, AVR is thenly effective treatment. Younger patients with congenitalr rheumatic AS may be candidates for valvotomy (seeection VI-A-2). Although there is some lack of agreementbout the optimal timing of surgery in asymptomatic pa-ients, it is possible to develop rational guidelines for mostatients. A proposed management strategy for patients withevere AS is shown in Figure 2 (78). Particular consider-tion should be given to the natural history of asymptomaticatients and to operative risks and outcomes after surgery.ee also Section VII-A.

. Symptomatic Patients

n symptomatic patients with AS, AVR improves symptomsnd improves survival (36,79–83). These salutary results ofurgery are partly dependent on LV function. The depressedjection fraction in many patients in this latter group isaused by excessive afterload (afterload mismatch) (84), andV function improves after AVR in such patients. If LVysfunction is not caused by afterload mismatch, survival istill improved, but improvement in LV function and reso-ution of symptoms might not be complete after AVR79,82,85–87). Therefore, in the absence of serious comor-id conditions, AVR is indicated in virtually all symptom-tic patients with severe AS. Because of the risk of suddeneath, AVR should be performed promptly after the onsetf symptoms. Age is not a contraindication to surgery, witheveral series showing outcomes similar to age-matchedormal subjects in the very elderly. The operative risks cane estimated with readily available and well-validated onlineisk calculators from the Society of Thoracic Surgeonswww.sts.org), the European System for Cardiac Operativeisk Evaluation (www.euroscore.org) (88–90), and Ambler

t al (91).

. Asymptomatic Patients

lthough AVR is associated with low perioperative mor-idity and mortality in many centers, the average perioper-tive mortality in the Society of Thoracic Surgeons (STS)atabase is 3.0% to 4.0% for isolated AVR and 5.5% to 6.8%or AVR plus CABG (92,93). These rates are 33% higher inenters with low volume than in centers with the highesturgical volume (94). A review of Medicare data (95),nvolving 684 US hospitals and more than 142 000 patients,ndicates that the average in-hospital mortality for AVR inatients over the age of 65 years is 8.8% (13.0% in

ow-volume centers and 6.0% in high-volume centers). Inddition, despite improved longevity of current-generationioprosthetic valves (96,97), AVR in young patients subjectshem to the risks of structural valve deterioration of bio-
rostheses (96,98–102) and the appreciable morbidity and

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ortality of mechanical valves (100,102–106). Thus, theombined risk of surgery in older patients and the lateomplications of a prosthesis in younger patients needs to bealanced against the possibility of preventing sudden death,hich, as noted above, occurs at a rate of less than 1.0% perear.

Despite these considerations, some difference of opinionersists among clinicians regarding the indications for AVRn asymptomatic patients with severe AS, because therobability of remaining free of cardiac symptoms withouturgery is less than 50% at 5 years (20,27,45). Studiesuggest that patients at risk of rapid disease progression andmpending symptom onset can be identified on the basis oflinical and echocardiographic parameters. The rate ofemodynamic progression is faster in patients with asymp-omatic severe (27) or mild to moderate (29) AS whenatient age is over 50 years and severe valve calcification oroncurrent CAD is present. Adverse clinical outcomes areore likely in patients with a more rapid rate of hemody-

amic progression, defined as an annual increase in aortic jetelocity greater than 0.3 m per second per year or a decreasen valve area greater than 0.1 cm2 per year (20,27). Theresence of LV hypertrophy by ECG and smaller aortic

igure 2. Management strategy for patients with severe aortic stenosis. Pry age, symptoms, and coronary risk factors. Cardiac catheterization and angnd echocardiography. Modified from CM Otto. Valvular aortic stenosis: d78). AVA indicates aortic valve area; BP, blood pressure; CABG, coronaryaximal velocity across aortic valve by Doppler echocardiography.

alve area by Doppler echocardiography predict the devel- Ccontent.onlinejacDownloaded from

pment of symptoms (20,45). In addition, serum levels of-type natriuretic peptide may provide important prognos-

ic information (107). In situations in which there is delayetween symptom onset and surgical intervention, patientsre at high risk of adverse outcomes during the waitingeriod. These higher-risk patients might warrant morerequent echocardiography or earlier consideration of valveeplacement.

. Patients Undergoing Coronary Artery Bypass or Otherardiac Surgery

atients with severe AS, with or without symptoms, whore undergoing CABG should undergo AVR at the timef the revascularization procedure. Similarly, patientsith severe AS undergoing surgery on other valves (such

s MV repair) or the aortic root should also undergoVR as part of the surgical procedure. In patients withoderate AS, it is generally accepted practice to performVR at the time of CABG (108 –112). However, there

re no data to support a policy of AVR for mild AS at theime of CABG, with the exception of those patients withoderate to severe valvular calcification (29,108,109,

12–114). Recommendations for AVR at the time of

ative coronary angiography should be performed routinely as determinedphy may also be helpful when there is discordance between clinical findings

severity and timing of intervention. J Am Coll Cardiol 2006;47:2141–51y bypass graft surgery; echo, echocardiography; LV, left ventricular; Vmax,

eoperiograisease

ABG are discussed in Section X-D. by on October 16, 2006 c.org


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. Aortic Balloon Valvotomy

lass IIb

. Aortic balloon valvotomy might be reasonable as abridge to surgery in hemodynamically unstable adultpatients with AS who are at high risk for AVR. (Levelof Evidence: C)

. Aortic balloon valvotomy might be reasonable forpalliation in adult patients with AS in whom AVRcannot be performed because of serious comorbidconditions. (Level of Evidence: C)

lass III

Aortic balloon valvotomy is not recommended as analternative to AVR in adult patients with AS; certainyounger adults without valve calcification may be anexception (see Section VI-A-2). (Level of Evidence: B)

ercutaneous balloon aortic valvotomy has an importantole in treating adolescents and young adults with AS (seeection VI-A-2) but a very limited role in older adults.mmediate hemodynamic results include a moderate reduc-ion in the transvalvular pressure gradient, but the postval-otomy valve area rarely exceeds 1.0 cm2. Although earlyymptomatic improvement often occurs, serious acute com-lications develop with a frequency greater than 10% (115–18), and restenosis and clinical deterioration occur withinto 12 months in most patients (116,119–122). Therefore,

n adults with AS, balloon valvotomy is not a substitute forVR (122–125).The indications for palliative valvotomy in patients in

hom AVR cannot be recommended because of seriousomorbid conditions are even less well established. Mostsymptomatic patients with severe AS who require urgentoncardiac surgery can undergo surgery at a reasonably lowisk with monitoring of anesthesia and attention to fluidalance (126–130). Balloon aortic valvotomy is not recom-ended for these patients. If preoperative correction of AS

s needed, they should be considered for AVR.

. Medical Therapy for the Inoperable Patient

omorbid conditions (e.g., malignancy) or, on occasion,atient preferences might preclude AVR for severe AS.nder such circumstances, there is no therapy that prolongs

ife, and only limited medical therapies are available tolleviate symptoms. Patients with evidence of pulmonaryongestion can benefit from cautious treatment with digi-alis, diuretics, and angiotensin-converting enzyme (ACE)nhibitors. In patients with acute pulmonary edema due toS, nitroprusside infusion may be used to reduce congestion

nd improve LV performance. Such therapy should beerformed in an intensive care unit under the guidance ofnvasive hemodynamic monitoring (131). Atrial fibrillationas an adverse effect on atrial pump function and ventricularate; if prompt cardioversion is unsuccessful, pharmacolog-
cal control of the ventricular rate is essential. a

. Special Considerations in the Elderly

ecause there is no effective medical therapy and balloonalvotomy is not an acceptable alternative to surgery, AVRust be considered in all elderly patients who have symp-

oms caused by AS. AVR is technically possible at any age132), but the decision to proceed with such surgeryepends on many factors, including the patient’s wishes andxpectations. Older patients with symptoms due to severeS, normal coronary arteries, and preserved LV function

an expect a better outcome than those with CAD or LVysfunction (133). Deconditioned and debilitated patientsften do not return to an active existence, and the presencef the other comorbid disorders could have a major impactn outcome.In addition to the confounding effects of CAD and the

otential for stroke, other considerations are peculiar tolder patients. For example, a narrow LV outflow tract andsmall aortic annulus sometimes present in elderly women

ould require enlargement of the annulus. Heavy calcifica-ion of the valve, annulus, and aortic root may requireebridement. Likewise, excessive or inappropriate hypertro-hy associated with AS can increase the risk of perioperativeorbidity and mortality, and preoperative recognition of

lderly patients with marked LV hypertrophy followed byppropriate perioperative management can reduce this riskubstantially. There is no perfect method for weighing all ofhe relevant factors and identifying specifically high- andow-risk elderly patients, but this risk can be estimated welln individual patients (88–91,134).

. Aortic Regurgitation

. Acute Aortic Regurgitation

n acute severe AR, the sudden large regurgitant volume ismposed on a left ventricle of normal size that has not hadime to accommodate to the volume overload. With anbrupt increase in end-diastolic volume, the ventricle oper-tes on the steep portion of a normal diastolic pressure-olume relationship, and LV end-diastolic and left atrialressures may increase rapidly and dramatically. The Frank-tarling mechanism is used, but the inability of the ventricleo develop compensatory chamber dilatation acutely resultsn a decrease in forward stroke volume. Although tachycar-ia develops as a compensatory mechanism to maintainardiac output, this is often insufficient. Hence, patientsrequently present with pulmonary edema and/or cardio-enic shock. Patients may also present with signs andymptoms of myocardial ischemia.

. Diagnosis

any of the characteristic physical findings of chronic ARre modified or absent when valvular regurgitation is acute,hich can lead to underestimation of its severity. Echocar-iography is indispensable in confirming the presence andeverity of the valvular regurgitation, determining its cause,
nd determining whether there is rapid equilibration of


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ortic and LV diastolic pressure. Evidence for rapid pressurequilibration includes a short AR diastolic half-time (lesshan 300 ms), a short mitral deceleration time (less than 150s), or premature closure of the MV.Acute AR caused by aortic root dissection is a surgical

mergency that requires particularly prompt identificationnd management. TEE is indicated when aortic dissections suspected (135–137). In some settings, computed tomo-raphic imaging or magnetic resonance imaging should beerformed if this will lead to a more rapid diagnosis thanan be achieved by TEE (135,136,138). Cardiac catheter-zation, aortography, and coronary angiography are rarelyequired, are associated with increased risk, and might delayrgent surgery unnecessarily (136,139–142). Angiographyhould be considered only when the diagnosis cannot beetermined by noninvasive imaging and when patients havenown CAD, especially those with previous CABG (seeection X-B).

. Treatment

eath due to pulmonary edema, ventricular arrhythmias,lectromechanical dissociation, or circulatory collapse is com-on in acute severe AR, even with intensive medical manage-ent. Urgent surgical intervention is recommended. Nitro-

russide, and possibly inotropic agents such as dopamine orobutamine to augment forward flow and reduce LV end-iastolic pressure, may be helpful to manage the patientemporarily before operation. Intra-aortic balloon counterpul-ation is contraindicated. Although beta blockers are oftensed in treating aortic dissection, these agents should be usedery cautiously, if at all, in the setting of acute AR because theyill block the compensatory tachycardia. In patients with acute

evere AR resulting from infective endocarditis, surgery shouldot be delayed, especially if there is hypotension, pulmonarydema, or evidence of low output.

. Chronic Aortic Regurgitation

R represents a condition of combined volume overload andressure overload (143). As the disease progresses, recruitmentf preload reserve and compensatory hypertrophy permit theentricle to maintain normal ejection performance despite thelevated afterload. The majority of patients remain asymptom-tic throughout this compensated phase, which may last forecades. In many patients, however, the balance betweenfterload excess, preload reserve, and hypertrophy cannot beaintained indefinitely, and afterload mismatch (144) or

epressed contractility ultimately results in a reduction injection fraction, first into the low-normal range and thenelow normal. Patients often develop dyspnea at this point inhe natural history, and diminished coronary flow reserve mayesult in exertional angina. However, this transition may beuch more insidious, and it is possible for patients to remain

symptomatic until severe LV dysfunction has developed.For purposes of the subsequent discussion, patients with

ormal LV systolic function will be defined as those with
ormal LV ejection fraction at rest. It is recognized that other i

ndices of LV function may not be “normal” in chronic severeR and that the hemodynamic abnormalities noted above maye considerable. It is also recognized that the transition to LVystolic dysfunction represents a continuum and that there iso single hemodynamic measurement that represents thebsolute boundary between normal LV systolic function andV systolic dysfunction.LV systolic dysfunction (defined as an ejection fraction

elow normal at rest) is initially a reversible phenomenonelated predominantly to afterload excess, and full recoveryf LV size and function is possible with AVR (145–152).

ith time, depressed myocardial contractility predominatesver excessive loading as the cause of progressive systolicysfunction. This can progress to the extent that the fullenefit of surgical correction of AR, in terms of recovery ofV function and improved survival, can no longer bechieved (150,153–159).

. Natural History

symptomatic Patients With Normal Left Ventricular Function

The current recommendations are derived from 9 pub-ished series (160–169) involving a total of 593 asymptom-tic patients with initially normal LV systolic function withmean follow-up period of 6.6 years. The rate of progres-

ion to symptoms or LV systolic dysfunction averaged 4.3%er year. Sudden death occurred in 7 of the 593 patients, anverage mortality rate of less than 0.2% per year. Seven ofhe 9 studies reported the rate of development of asymp-omatic LV dysfunction, defined as an ejection fraction atest below normal (161–165,167,168); 37 of a total of 535atients developed depressed systolic function at rest with-ut symptoms during a mean 5.9-year follow-up period, aate of 1.2% per year.

Despite the low likelihood of patients developing asymp-omatic LV dysfunction, it should also be emphasized thatore than one fourth of patients who die or develop systolic

ysfunction do so before the onset of warning symptoms161–163,167). Thus, thorough questioning of patientsegarding symptomatic status is not sufficient in the serialvaluation of asymptomatic patients, and quantitative eval-ation of LV function is also indispensable.

symptomatic Patients With Depressed Systolic Function

he limited data in asymptomatic patients with depressedV ejection fraction indicate that the majority develop

ymptoms that warrant AVR within 2 to 3 years (170–172).he average rate of symptom onset in such patients isreater than 25% per year.

ymptomatic Patients

here are no contemporary large-scale studies of the naturalistory of symptomatic patients with chronic AR becausehe onset of angina or significant dyspnea is usually an
ndication for valve replacement. Data emanating from the


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resurgical era indicate that patients with dyspnea, angina, orvert heart failure have a poor outcome with mortality rates ofreater than 10% per year in patients with angina pectoris andreater than 20% per year in those with heart failure (173–75). Similar poor outcomes have been reported in theurrent era in symptomatic patients who do not undergoVR, even among those with preserved LV systolic func-

ion (166,176,177).

. Diagnosis and Initial Evaluation

lass I

. Echocardiography is indicated to confirm the pres-ence and severity of acute or chronic AR. (Level ofEvidence: B)

. Echocardiography is indicated for diagnosis and assess-ment of the cause of chronic AR (including valvemorphology and aortic root size and morphology) andfor assessment of LV hypertrophy, dimension (or vol-ume), and systolic function. (Level of Evidence: B)

. Echocardiography is indicated in patients with anenlarged aortic root to assess regurgitation and theseverity of aortic dilatation. (Level of Evidence: B)

. Echocardiography is indicated for the periodic re-evaluation of LV size and function in asymptomaticpatients with severe AR. (Level of Evidence: B)

. Radionuclide angiography or magnetic resonanceimaging is indicated for the initial and serial assess-ment of LV volume and function at rest in patientswith AR and suboptimal echocardiograms. (Level ofEvidence: B)

. Echocardiography is indicated to re-evaluate mild,moderate, or severe AR in patients with new orchanging symptoms. (Level of Evidence: B)

lass IIa

. Exercise stress testing for chronic AR is reasonablefor assessment of functional capacity and symptom-atic response in patients with a history of equivocalsymptoms. (Level of Evidence: B)

. Exercise stress testing for patients with chronic AR isreasonable for the evaluation of symptoms and func-tional capacity before participation in athletic activ-ities. (Level of Evidence: C)

. Magnetic resonance imaging is reasonable for theestimation of AR severity in patients with unsatisfac-tory echocardiograms. (Level of Evidence: B)

lass IIb

Exercise stress testing in patients with radionuclideangiography may be considered for assessment of LVfunction in asymptomatic or symptomatic patientswith chronic AR. (Level of Evidence: B)

chocardiography is indicated 1) to confirm the diagno-is of AR if there is an equivocal diagnosis based on
hysical examination; 2) to assess the cause of AR and to

ssess valve morphology; 3) to provide a semiquantitativestimate of the severity of AR; 4) to assess LV dimension,ass, and systolic function; and 5) to assess aortic root

ize. In asymptomatic patients with preserved systolicunction, these initial measurements represent the base-ine information with which future serial measurementsan be compared. In addition to semiquantitative assess-ent of the severity of AR by color flow jet area andidth by Doppler echocardiography, quantitative mea-

urement of regurgitant volume, regurgitant fraction, andegurgitant orifice area can be performed in experiencedaboratories (Table 1). Indirect measures of severity ofR are helpful, using the rate of decline in regurgitant

radient measured by the slope of diastolic flow velocity,he degree of reversal in pulse wave velocity in theescending aorta, and the magnitude of LV outflow tractelocity (1,178,179).

For purposes of the subsequent discussion of managementf patients with AR, severe AR is defined as clinical andoppler evidence of severe regurgitation (Table 1) in addition

o LV cavity dilatation. If the patient is asymptomatic andeads an active lifestyle, and the echocardiogram is of gooduality, no other testing is necessary. If the patient has severeR and is sedentary or has equivocal symptoms, exercise

esting is helpful to assess functional capacity, symptomaticesponses, and hemodynamic effects of exercise (Fig. 3). If thechocardiogram is of insufficient quality to assess LV function,adionuclide angiography or cardiac magnetic resonancehould be used in asymptomatic patients to measure LVjection fraction at rest and to estimate LV volumes. Inatients who are symptomatic on initial evaluation, it iseasonable to proceed directly to TEE or cardiac catheteriza-ion and angiography if the echocardiogram is of insufficientuality to assess LV function or severity of AR.

The exercise ejection fraction and the change in ejectionraction from rest to exercise are often abnormal, even insymptomatic patients (160,162–164,67,172,180–186). How-ver, the predictive nature of this response in asymptomaticatients with normal LV systolic function and without severeV dilatation has not been fully demonstrated.

. Medical Therapy

lass I

Vasodilator therapy is indicated for chronic therapyin patients with severe AR who have symptoms or LVdysfunction when surgery is not recommended be-cause of additional cardiac or noncardiac factors.(Level of Evidence: B)

lass IIa

Vasodilator therapy is reasonable for short-term ther-apy to improve the hemodynamic profile of patients
with severe heart failure symptoms and severe LV


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dysfunction before proceeding with AVR. (Level ofEvidence: C)

lass IIb

Vasodilator therapy may be considered for long-termtherapy in asymptomatic patients with severe ARwho have LV dilatation but normal systolic function.(Level of Evidence: B)

lass III

. Vasodilator therapy is not indicated for long-termtherapy in asymptomatic patients with mild to mod-erate AR and normal LV systolic function. (Level ofEvidence: B)

. Vasodilator therapy is not indicated for long-termtherapy in asymptomatic patients with LV systolicdysfunction who are otherwise candidates for AVR.

igure 3. Management strategy for patients with chronic severe aortic reguetermined by age, symptoms, and coronary risk factors. Cardiac catheterilinical findings and echocardiography. “Stable” refers to stable echocardiogadionuclide ventriculography (RVG) or magnetic resonance imaging (MRnd systolic function. AVR indicates aortic valve replacement; DD, endimension.

(Level of Evidence: C) r


. Vasodilator therapy is not indicated for long-termtherapy in symptomatic patients with either normalLV function or mild to moderate LV systolic dys-function who are otherwise candidates for AVR.(Level of Evidence: C)

herapy with vasodilating agents is designed to improveorward stroke volume and reduce regurgitant volume.hese effects should translate into reductions in LV end-iastolic volume, wall stress, and afterload, resulting inreservation of LV systolic function and reduction in LVass. Reduced end-diastolic volume and increased ejection

raction have been observed in small numbers of patientseceiving long-term oral therapy with hydralazine andifedipine for periods of 1 to 2 years (187,188); withifedipine, these effects are associated with a reduction inV mass (164,188). Less consistent results have been

tion. Preoperative coronary angiography should be performed routinely asand angiography may also be helpful when there is discordance between

c measurements. In some centers, serial follow-up may be performed withther than echocardiography (Echo) to assess left ventricular (LV) volumeolic dimension; EF, ejection fraction; eval, evaluation; SD, end-systolic

rgitazationraphiI) ra

eported with ACE inhibitors, depending on the degree of



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eduction in arterial pressure and end-diastolic volume189–191). Reduced blood pressure with enalapril anduinapril has been associated with decreases in end-diastolicolume and mass but no change in ejection fraction190,191).

Whether vasodilator therapy can prolong the compensatedhase of asymptomatic patients who have volume-loaded leftentricles but normal systolic function has been investigated innly 2 studies. The first compared long-acting nifedipineersus digoxin in a prospective randomized trial (164). Over a-year period, fewer patients randomized to nifedipine re-uired AVR because of symptoms or development of LVysfunction (ejection fraction less than 0.50). This studynrolled a relatively small number of patients (143 patients);here were relatively few end points (20 patients in the digoxinroup and 6 in the nifedipine group underwent AVR); andhere was no placebo control group. A second study comparedlacebo, long-acting nifedipine, and enalapril in 95 consecutiveatients, who were followed for 7 years (169). Neither nifed-pine nor enalapril reduced the development of symptoms orV dysfunction warranting AVR compared with placebo.oreover, neither drug significantly altered LV dimension,

jection fraction, or mass over the course of time comparedith placebo. Thus, definitive recommendations regarding the

ndications for long-acting nifedipine or ACE inhibitors can-ot be made at this time.Vasodilator therapy is not recommended for asymptom-

tic patients with mild or moderate AR and normal LVunction in the absence of systemic hypertension, becausehese patients have an excellent outcome with no therapy. Inatients with severe AR, vasodilator therapy is not anlternative to surgery in asymptomatic patients with LVystolic dysfunction. Symptomatic patients should be con-idered surgical candidates rather than candidates for long-erm medical therapy unless AVR is not recommendedecause of additional cardiac or noncardiac factors.

. Physical Activity and Exercise

symptomatic patients with normal LV systolic functionay participate in all forms of normal daily physical activity,

ncluding mild forms of exercise and in some cases compet-tive athletics. Isometric exercise should be avoided. Rec-mmendations regarding participation in competitive ath-etics were published by the Task Force on Acquiredalvular Heart Disease of the 36th Bethesda Conference

67). Before participation in athletics, exercise testing to ateast the level of exercise required by the proposed activity isecommended so that the patient’s tolerance for this degreef exercise can be evaluated. This does not necessarilyvaluate the long-term effects of strenuous exercise, whichre unknown.

. Serial Testing

n general, the stability and chronicity of the regurgitantesion and the LV response to volume load need to be
stablished when the patient first presents to the physician, e

specially if AR is moderate to severe. If the chronic naturef the lesion is uncertain and the patient does not presentnitially with one of the indications for surgery, repeathysical examination and echocardiography should be per-ormed within 2 to 3 months after the initial evaluation tonsure that a subacute process with rapid progression is notnder way. Once the chronicity and stability of the processave been established, the frequency of clinical re-evaluationnd repeat noninvasive testing depends on the severity ofhe valvular regurgitation, the degree of LV dilatation, theevel of systolic function, and whether previous serial studiesave revealed progressive changes in LV size or functionFig. 3).

Asymptomatic patients with mild AR, little or no LVilatation, and normal LV systolic function can be seen onyearly basis with instructions to alert the physician if

ymptoms develop in the interim. Yearly echocardiographys not necessary unless there is clinical evidence that regur-itation has worsened. Routine echocardiography can beerformed every 2 to 3 years in such patients.Asymptomatic patients with normal systolic function but

evere AR and significant LV dilatation (end-diastolicimension greater than 60 mm) require more frequent andareful re-evaluation, with a history and physical examina-ion every 6 months and echocardiography every 6 to 12onths, depending on the severity of dilatation and stability

f measurements. If patients are stable, echocardiographiceasurements are not required more frequently than every

2 months. In patients with more advanced LV dilatationend-diastolic dimension greater than 70 mm or end-ystolic dimension greater than 50 mm), for whom the riskf developing symptoms or LV dysfunction ranges between0% and 20% per year (163,164), it is reasonable to performerial echocardiograms as frequently as every 4 to 6 months.erial chest X-rays and ECGs have less value but are helpful

n selected patients.Chronic AR may develop from disease processes that

nvolve the proximal ascending aorta. In patients with aorticoot dilatation, serial echocardiograms are indicated tovaluate aortic root size, as well as LV size and function.his is discussed in Section III-B-3.Repeat echocardiograms are also recommended when the

atient has onset of symptoms, there is an equivocal historyf changing symptoms or exercise tolerance, or there arelinical findings that suggest worsening regurgitation orrogressive LV dilatation. Patients with echocardiographicvidence of progressive LV dilatation or declining systolicunction have a greater likelihood of developing symptomsr LV dysfunction (163) and should have more frequentollow-up examinations (every 6 months) than those withtable LV function.

Serial exercise testing is also not recommended routinelyn asymptomatic patients with preserved systolic function;owever, exercise testing may be invaluable to assess func-ional capacity and symptomatic responses in patients with
quivocal changes in symptomatic status. Serial exercise


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lass I

. Cardiac catheterization with aortic root angiographyand measurement of LV pressure is indicated forassessment of severity of regurgitation, LV function,or aortic root size when noninvasive tests are incon-clusive or discordant with clinical findings in patientswith AR. (Level of Evidence: B)

. Coronary angiography is indicated before AVR inpatients at risk for CAD. (Level of Evidence: C)

lass III

. Cardiac catheterization with aortic root angiographyand measurement of LV pressure is not indicated forassessment of LV function, aortic root size, or sever-ity of regurgitation before AVR when noninvasivetests are adequate and concordant with clinical find-ings and coronary angiography is not needed. (Levelof Evidence: C)

. Cardiac catheterization with aortic root angiographyand measurement of LV pressure is not indicated forassessment of LV function and severity of regurgita-tion in asymptomatic patients when noninvasive testsare adequate. (Level of Evidence: C)

ardiac catheterization is not required in patients withhronic AR unless there are questions about the severity ofR, hemodynamic abnormalities, or LV systolic dysfunc-

ion that persist despite physical examination and noninva-ive testing, or unless AVR is contemplated and there is aeed to assess coronary anatomy. The indications fororonary arteriography are discussed in Section X-B.

Hemodynamic and angiographic assessment of the sever-ty of AR and LV function may be necessary in someatients being considered for surgery when there are con-icting data between clinical assessment and noninvasiveests. Hemodynamic measurements during exercise are oc-asionally helpful for determining the effect of AR on LVunction or making decisions regarding medical or surgicalherapy.

. Indications for Aortic Valve Replacement or Repair

he majority of patients with severe AR requiring surgeryndergo valve replacement (see Section VII-A). However,n several surgical centers, there is increasing experience inerforming aortic valve repair in selected patients. In theiscussion that follows, the term “AVR” applies to bothortic valve replacement and aortic valve repair, with thenderstanding that aortic valve repair should be considerednly in those surgical centers that have developed theppropriate technical expertise, gained experience in patient
election, and demonstrated outcomes equivalent to those of o

alve replacement. The indications for valve replacementnd repair do not differ.

In patients with pure, chronic AR, AVR should beonsidered only if AR is severe (Table 1). Patients with onlyild AR are not candidates for AVR, and if such patients

ave symptoms or LV dysfunction, other causes should beonsidered, such as CAD, hypertension, or cardiomyopathicrocesses. The following discussion applies only to patientsith pure, severe AR.

lass I

. AVR is indicated for symptomatic patients withsevere AR irrespective of LV systolic function. (Levelof Evidence: B)

. AVR is indicated for asymptomatic patients withchronic severe AR and LV systolic dysfunction (ejectionfraction 0.50 or less) at rest. (Level of Evidence: B)

. AVR is indicated for patients with chronic severe ARwhile undergoing CABG or surgery on the aorta orother heart valves. (Level of Evidence: C)

lass IIa

AVR is reasonable for asymptomatic patients withsevere AR with normal LV systolic function (ejectionfraction greater than 0.50) but with severe LV dila-tation (end-diastolic dimension greater than 75 mmor end-systolic dimension greater than 55 mm).*(Level of Evidence: B)

lass IIb

. AVR may be considered in patients with moderateAR while undergoing surgery on the ascending aorta.(Level of Evidence: C)

. AVR may be considered in patients with moderateAR while undergoing CABG. (Level of Evidence: C)

. AVR may be considered for asymptomatic patients withsevere AR and normal LV systolic function at rest(ejection fraction greater than 0.50) when the degree ofLV dilatation exceeds an end-diastolic dimension of 70mm or end-systolic dimension of 50 mm, when there isevidence of progressive LV dilatation, declining exercisetolerance, or abnormal hemodynamic responses to ex-ercise.* (Level of Evidence: C)

lass III

AVR is not indicated for asymptomatic patients withmild, moderate, or severe AR and normal LV systolicfunction at rest (ejection fraction greater than 0.50)when the degree of dilatation is not moderate orsevere (end-diastolic dimension less than 70 mm,end-systolic dimension less than 50 mm).* (Level ofEvidence: B)

Consider lower threshold values for patients of small stature
f either gender.


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ymptomatic Patients With Normal Left Ventricular Systolicunction

VR is indicated in patients with normal LV systolicunction (ejection fraction greater than 0.50 at rest) whoave symptoms. In selected patients, exercise testing may bealuable in determining symptomatic status. If the cause ofhese mild symptoms is uncertain and they are not severenough to interfere with the patient’s lifestyle, a period ofbservation may be reasonable. However, new onset of mildyspnea has different implications in severe AR, especially ifhere is increasing LV chamber size or declining LV systolicunction. Thus, even if patients have not achieved thehreshold values of LV size and function recommended forurgery in asymptomatic patients, development of mildymptoms is an indication for AVR in a patient who isearing these values.

ymptomatic Patients With Left Ventricular Dysfunction

ymptomatic patients with mild to moderate LV systolicysfunction (ejection fraction 0.25 to 0.50) should undergoVR. Patients with New York Heart Association (NYHA)

unctional class IV symptoms have worse postoperative survivalates and lower likelihood of recovery of systolic function thanatients with less severe symptoms (151,153,155,157), butVR will improve ventricular loading conditions and expedite

ubsequent management of LV dysfunction (192).

symptomatic Patients

VR in asymptomatic patients remains a controversialopic, but it is generally agreed (144,193–199) that AVR isndicated in patients with LV systolic dysfunction. Theommittee recognizes that there may be variability in anyiven measurement of LV dimension or ejection fraction.herefore, the committee recommends that 2 consecutiveeasurements be obtained before one proceeds with a

ecision to recommend surgery in the asymptomatic pa-ient. These consecutive measurements could be obtainedith the same test repeated in a short time period (such assecond echocardiogram after an initial echocardiogram) orith a separate, independent test (e.g., radionuclide ven-

riculography, magnetic resonance imaging, or contrast leftentriculography after an initial echocardiogram).

AVR is also recommended in patients with severe LVilatation (end-diastolic dimension greater than 75 mm ornd-systolic dimension greater than 55 mm), even if ejec-ion fraction is normal. The relatively small number ofsymptomatic patients with preserved ejection fraction de-pite severe increases in end-systolic and end-diastolichamber size should be considered for surgery, because theyppear to represent a high-risk group with an increasedncidence of sudden death (163,200), and the results of valveeplacement in such patients have thus far been excellent201). In contrast, postoperative mortality is considerable
nce patients with severe LV dilatation develop symptoms c

r LV systolic dysfunction (201). These data do not stronglyupport the use of extreme LV enlargement as an indicationor AVR, unless cardiac symptoms or systolic dysfunction isresent (202). However, the committee recommends sur-ery before the left ventricle achieves an extreme degree ofilatation and recommends AVR for patients with LVnd-diastolic dimension greater than 75 mm.

Patients with severe AR in whom the degree of LVilatation has not reached but is approaching these thresh-ld values (e.g., LV end-diastolic dimension of 70 to 75 mmr end-systolic dimension of 50 to 55 mm) should beollowed with frequent echocardiograms every 4 to 6onths, as noted previously (Fig. 3). In addition, AVR may

e considered in such patients if there is evidence ofeclining exercise tolerance or abnormal hemodynamicesponses to exercise, for example, an increase in pulmonaryrtery wedge pressure greater than 25 mm Hg with exercise.

Anthropometric normalization of LV end-diastolicimension (or volume) should be considered, but unfor-unately, there is lack of agreement as to whether or notormalization based on body surface area or body mass

ndex is predictive of outcome (177,203). Normalizationf end-diastolic dimension for body surface area tends toask the diagnosis of LV enlargement, especially in

atients who are overweight (204). The use of height andconsideration of gender are likely to be more appropri-

te than body surface area (205). LV dimensions aloneay be misleading in small patients of either gender, and

he threshold values of end-diastolic and end-systolicimension recommended above for AVR in asymptom-tic patients (75 and 55 mm, respectively) may need to beeduced in such patients. In such patients, it is particu-arly important that LV ejection fraction and not merelyystolic dimension be monitored.

. Concomitant Aortic Root Disease

n addition to causing acute AR, diseases of the proximalorta may also contribute to chronic AR (206). In suchatients, the valvular regurgitation may be less importantn decision making than the primary disease of the aorta,uch as Marfan syndrome, dissection, or chronic dilata-ion of the aortic root related to hypertension or aicuspid aortic valve (see Section III-C). In general, AVRnd aortic root reconstruction are indicated in patientsith disease of the aortic root or proximal aorta and ARf any severity when the degree of dilatation of the aortar aortic root reaches or exceeds 5.0 cm by echocardiog-aphy (207). However, some have recommended surgeryt a lower level of dilatation (4.5 cm) or based on a ratef increase of 0.5 cm per year or greater in surgical centersith established expertise in repair of the aortic root and

scending aorta (208). Aortic root and ascending aortailation in patients with bicuspid aortic valves is dis-
ussed in greater detail in Section III-C.


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. Evaluation of Patients After Aortic Valve Replacement

fter AVR, close follow-up is necessary during the earlynd long-term postoperative course to evaluate prostheticalve function and assess LV function (see Section IX-B).n echocardiogram should be performed soon after surgery

o assess the results of surgery on LV size and function ando serve as a baseline against which subsequent echocardio-rams may be compared. Within the first few weeks ofurgery, there is little change in LV systolic function, andjection fraction may even deteriorate compared with pre-perative values because of the reduced preload (209), evenhough ejection fraction may increase over the subsequenteveral months. Thus, persistent or more severe systolicysfunction early after AVR is a poor predictor of subse-uent improvement in LV function in patients with preop-rative LV dysfunction. A better predictor of subsequentV systolic function is the reduction in LV end-diastolicimension, which declines significantly within the first weekr 2 after AVR (151,210,211). This is an excellent markerf the functional success of valve replacement, because 80%f the overall reduction in end-diastolic dimension observeduring the long-term postoperative course occurs within therst 10 to 14 days after AVR (151,210,211), and theagnitude of reduction in end-diastolic dimension after

urgery correlates with the magnitude of increase in ejectionraction (151).

Patients with persistent LV dilatation on the initialostoperative echocardiogram should be treated as wouldny other patient with symptomatic or asymptomatic LVysfunction, including treatment with ACE inhibitors andeta-adrenergic blocking agents. In such patients, repeatchocardiography to assess LV size and systolic function isarranted at the 6- and 12-month re-evaluations. If LVysfunction persists beyond this time frame, repeat echo-ardiograms should be performed as clinically indicated.


he vast majority of elderly patients with aortic valve diseaseave AS or combined AS and AR, and pure AR isncommon (212). Patients older than 75 years are moreikely to develop symptoms or LV dysfunction at earliertages of LV dilatation, have more persistent LV dysfunc-ion and heart failure symptoms after surgery, and haveorse postoperative survival rates than their younger coun-

erparts. Many such patients have concomitant CAD,hich must be considered in the evaluation of symptoms,V dysfunction, and indications for surgery.

. Bicuspid Aortic Valve With Dilated Ascending Aorta

lass I

. Patients with known bicuspid aortic valves shouldundergo an initial transthoracic echocardiogram toassess the diameters of the aortic root and ascending
aorta. (Level of Evidence: B) w

. Cardiac magnetic resonance imaging or cardiac com-puted tomography is indicated in patients with bicus-pid aortic valves when morphology of the aortic rootor ascending aorta cannot be assessed accurately byechocardiography. (Level of Evidence: C)

. Patients with bicuspid aortic valves and dilatation ofthe aortic root or ascending aorta (diameter greaterthan 4.0 cm*) should undergo serial evaluation ofaortic root/ascending aorta size and morphology byechocardiography, cardiac magnetic resonance, orcomputed tomography on a yearly basis. (Level ofEvidence: C)

. Surgery to repair the aortic root or replace theascending aorta is indicated in patients with bicuspidaortic valves if the diameter of the aortic root orascending aorta is greater than 5.0 cm* or if the rateof increase in diameter is 0.5 cm per year or more.(Level of Evidence: C)

. In patients with bicuspid valves undergoing AVRbecause of severe AS or AR (see Sections III-A-6 andIII-B-2-g), repair of the aortic root or replacement ofthe ascending aorta is indicated if the diameter of theaortic root or ascending aorta is greater than 4.5 cm.*(Level of Evidence: C)

lass IIa

. It is reasonable to give beta-adrenergic blockingagents to patients with bicuspid valves and dilatedaortic roots (diameter greater than 4.0 cm*) who arenot candidates for surgical correction and who do nothave moderate to severe AR. (Level of Evidence: C)

. Cardiac magnetic resonance imaging or cardiac com-puted tomography is reasonable in patients with bicus-pid aortic valves when aortic root dilatation is detectedby echocardiography to further quantify severity ofdilatation and involvement of the ascending aorta.(Level of Evidence: B)

Consider lower threshold values for patients of small staturef either gender.

Many patients with bicuspid aortic valves have disordersf vascular connective tissue that involve loss of elastic tissue213,214), which may result in dilatation of the aortic rootr ascending aorta even in the absence of hemodynamicallyignificant AS or AR (215–218). Aortic root or ascendingortic dilatation can progress with time in this condition,nd the risk of aortic dissection is related to the severity ofilatation (214,219–221). Recommendations for athleticarticipation in patients with bicuspid valve disease andssociated dilatation of the aortic root or ascending aortarom the 36th Bethesda Conference (67) are based onimited data but with the understanding that aortic dissec-ion can occur in some patients with aortic root or ascendingorta diameters less than 50 mm (208,220,222). Therapy
ith beta-adrenergic blocking agents might be effective in


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lowing the progression of aortic dilatation, but the availableata have been developed in patients with Marfan syndrome223) and not in patients with bicuspid aortic valves.

The dimensions of the aortic root and ascending aortahow considerable variability in normal populations. Re-ression formulas and nomograms have been developed fordolescents and adults that account for age and body surfacerea (224). An upper limit of 2.1 cm per m2 has beenstablished at the level of the aortic sinuses. Dilatation isonsidered an increase in diameter above the norm for agend body surface area, and an aneurysm has been defined as50% increase over the normal diameter (225).In recommending elective surgery for this condition, a

umber of factors must be considered, including the pa-ient’s age, the relative size of the aorta and aortic root, thetructure and function of the aortic valve, and the experiencef the surgical team (208,214,221,222). Aortic valve–paring operations are feasible in most patients with dilata-ion of the aortic root or ascending aorta who do not haveignificant AR or aortic valve calcification (226–228). Pa-ients with bicuspid valves should undergo elective repair ofhe aortic root or replacement of the ascending aorta if theiameter of these structures exceeds 5.0 cm. Such surgeryhould be performed by a surgical team with establishedxpertise in these procedures. Others have recommended aalue of 2.5 cm per m2 or greater as the indication forurgery (229). If patients with bicuspid valves and associatedortic root enlargement undergo AVR because of severe ASr AR (Sections III-A-6 and III-B-2-g), it is recommendedhat repair of the aortic root or replacement of the ascendingorta be performed if the diameter of these structures isreater than 4.5 cm (230).

. Mitral Stenosis

n patients with MS from rheumatic fever, the pathologicalrocess causes leaflet thickening and calcification, commis-ural fusion, chordal fusion, or a combination of theserocesses (231,232). The normal MV area is 4.0 to 5.0 cm2.arrowing of the valve area to less than 2.5 cm2 typically

ccurs before the development of symptoms (68). With aeduction in valve area by the rheumatic process, blood canow from the left atrium to the left ventricle only ifropelled by a pressure gradient, and the transmitral gradi-nt is the fundamental expression of MS (233). Theesulting elevation of left atrial pressure is reflected back intohe pulmonary venous circulation. Decreased pulmonaryenous compliance that results in part from an increasedulmonary endothelin-1 spillover rate may also contributeo increased pulmonary venous pressure (234). Increasedressure and distension of the pulmonary veins and capil-

aries can lead to pulmonary edema as pulmonary venousressure exceeds that of plasma oncotic pressure. In patientsith chronic MV obstruction, however, even when it is

evere and pulmonary venous pressure is very high, pulmo-ary edema may not occur owing to a marked decrease in
ulmonary microvascular permeability. The pulmonary ar- g

erioles may react with vasoconstriction, intimal hyperplasia,nd medial hypertrophy, which lead to pulmonary arterialypertension.

. Natural History

n MV area greater than 1.5 cm2 usually does not produceymptoms at rest; however, if there is an increase inransmitral flow or a decrease in the diastolic filling period,here will be a rise in left atrial pressure and development ofymptoms. From hydraulic considerations, at any givenrifice size, the transmitral gradient is a function of thequare of the transvalvular flow rate and is dependent on theiastolic filling period (68). Thus, the first symptoms ofyspnea in patients with mild MS are usually precipitated byxercise, emotional stress, infection, pregnancy, or atrialbrillation with a rapid ventricular response. As the obstruc-ion across the MV increases, decreasing effort toleranceccurs. As the severity of stenosis increases, cardiac outputecomes subnormal at rest and fails to increase duringxercise.

The natural history of patients with untreated MS haseen defined from studies in the 1950s and 1960s (235–37). MS is a continuous, progressive, lifelong disease,sually consisting of a slow, stable course in the early yearsollowed by a progressive acceleration later in life (235–238).

nce symptoms develop, there is another period of almostdecade before symptoms become disabling (235). In the

symptomatic or minimally symptomatic patient, survival isreater than 80% at 10 years, with 60% of patients having norogression of symptoms, but once significant limitingymptoms occur, there is a dismal 0% to 15% 10-yearurvival rate (235–239). When severe pulmonary hyperten-ion develops, mean survival drops to less than 3 years (240).he mortality rate of untreated patients with MS is due torogressive pulmonary and systemic congestion in 60% to0%, systemic embolism in 20% to 30%, pulmonary embo-ism in 10%, and infection in 1% to 5% (231,237). In Northmerica and Europe, this classic history of MS has been

eplaced by an even milder, delayed course with the declinen incidence of rheumatic fever (238,241). The mean age ofresentation is now in the fifth to sixth decade (238,241);ore than one third of patients undergoing valvotomy are

lder than 65 years (242). In some geographic areas, MSrogresses more rapidly, presumably owing to either a moreevere rheumatic insult or repeated episodes of rheumaticarditis due to new streptococcal infections, which results inevere symptomatic MS in the late teens and early 20s (238).

Although MS is best described as a disease continuum,nd there is no single value that defines severity, for theseuidelines, MS severity is based on a variety of hemody-amic and natural history data (Table 1) using meanradient, pulmonary artery systolic pressure, and valve areas follows: mild (area greater than 1.5 cm2, mean gradientess than 5 mm Hg, or pulmonary artery systolic pressureess than 30 mm Hg), moderate (area 1.0 to 1.5 cm2, mean
radient 5 to 10 mm Hg, or pulmonary artery systolic


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ressure 30 to 50 mm Hg), and severe (area less than 1.0m2, mean gradient greater than 10 mm Hg, or pulmonaryrtery systolic pressure greater than 50 mm Hg).

. Indications for Echocardiography in Mitral Stenosis

lass I

. Echocardiography should be performed in patientsfor the diagnosis of MS, assessment of hemodynamicseverity (mean gradient, MV area, and pulmonaryartery pressure), assessment of concomitant valvularlesions, and assessment of valve morphology (todetermine suitability for percutaneous mitral balloonvalvotomy). (Level of Evidence: B)

. Echocardiography should be performed for re-evaluation in patients with known MS and changingsymptoms or signs. (Level of Evidence: B)

. Echocardiography should be performed for assess-ment of the hemodynamic response of the meangradient and pulmonary artery pressure by exerciseDoppler echocardiography in patients with MS whenthere is a discrepancy between resting Doppler echo-cardiographic findings, clinical findings, symptoms,and signs. (Level of Evidence: C)

. TEE in MS should be performed to assess thepresence or absence of left atrial thrombus and tofurther evaluate the severity of MR in patients con-sidered for percutaneous mitral balloon valvotomy.(Level of Evidence: C)

. TEE in MS should be performed to evaluate MVmorphology and hemodynamics in patients when trans-thoracic echocardiography provides suboptimal data.(Level of Evidence: C)

lass IIa

Echocardiography is reasonable in the re-evaluationof asymptomatic patients with MS and stable clinicalfindings to assess pulmonary artery pressure (forthose with severe MS, every year; moderate MS,every 1 to 2 years; and mild MS, every 3 to 5 years).(Level of Evidence: C)

lass III

TEE in the patient with MS is not indicated forroutine evaluation of MV morphology and hemody-namics when complete transthoracic echocardio-graphic data are satisfactory. (Level of Evidence: C)

he diagnostic tool of choice in the evaluation of a patientith MS is 2D and Doppler echocardiography. Echocardi-graphy is able to identify restricted diastolic opening of theV leaflets due to “doming” of the anterior leaflet and

mmobility of the posterior leaflet. Planimetry of the orificerea may be possible from the short-axis view. 2-D echo-ardiography can be used to assess the morphologicalppearance of the MV apparatus, including leaflet mobility
nd flexibility, leaflet thickness, leaflet calcification, subval- 7

ular fusion, and the appearance of commissures (243–245).hese features may be important when one considers the

iming and type of intervention to be performed. Patients withobile noncalcified leaflets, no commissural calcification, and

ittle subvalvular fusion may be candidates for either balloonatheter or surgical commissurotomy/valvotomy. There areeveral methods used to assess suitability for valvotomy,ncluding a Wilkins score (246), an echocardiographicrouping (based on valve flexibility, subvalvular fusion, andeaflet calcification) (244), and the absence or presence ofommisural calcium (245).

The mean transmitral gradient can be accurately andeproducibly measured from the continuous-wave Dopplerignal across the MV with the modified Bernoulli equation247,248). The MV area can be noninvasively derived fromoppler echocardiography with either the diastolic pressure

alf-time method (248–251) or the continuity equation249). Doppler echocardiography may also be used tostimate pulmonary artery systolic pressure from the TRelocity signal (252) and to assess severity of concomitant

R or AR. Formal hemodynamic exercise testing can beone noninvasively with either a supine bicycle or uprightreadmill with Doppler recordings of transmitral and tricus-id velocities to assess both the transmitral gradient andulmonary artery systolic pressure at rest and with exercise253–257). The criteria for assessment of the severity of MSre summarized in Table 1 and are applicable when theeart rate is between 60 and 90 bpm.In the asymptomatic patient who has documented mild MS

valve area greater than 1.5 cm2 and mean gradient less than 5m Hg), no further investigations are needed on the initialorkup (Fig. 4). These patients usually remain stable for years.

f there is more significant MS, a decision to proceed furtherhould be based on the suitability of the patient for mitralalvotomy. In patients with pliable, noncalcified valves with nor little subvalvular fusion, no calcification in the commissures,nd no left atrial thrombus, percutaneous mitral valvotomy cane performed with a low complication rate and may bendicated if symptoms develop. Because of the slowly progres-ive course of MS, patients may remain “asymptomatic” withevere stenosis merely by readjusting their lifestyles to a moreedentary level. Patients with moderate pulmonary hyperten-ion at rest (pulmonary artery systolic pressure greater than 50m Hg) and pliable MV leaflets may be considered for

ercutaneous mitral valvotomy even if they deny having symp-oms. In patients who lead a sedentary lifestyle, a hemody-amic exercise test with Doppler echocardiography is useful, asoted above. Objective limitation of exercise tolerance with aise in transmitral gradient greater than 15 mm Hg and a risen pulmonary artery systolic pressure greater than 60 mm Hg

ay be an indication for percutaneous valvotomy if the MVorphology is suitable. In asymptomatic patients with severeS (valve area less than 1.0 cm2) and severe pulmonary

ypertension (pulmonary artery systolic pressure greater than
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. Medical Therapy

. Medical Therapy: General

ecause rheumatic fever is the primary cause of MS, prophy-axis against rheumatic fever is recommended. Infective endo-

igure 4. Management strategy for patients with mitral stenosis. *The wriitral valve area (MVA) and that the mean transmitral gradients, pulmonar

hould also be taken into consideration. †There is controversy as to wheulmonary hypertension (pulmonary artery pressure greater than 60 mm Halve replacement to prevent right ventricular failure. ‡Assuming no other chest X-ray; ECG, electrocardiogram; echo, echocardiography; LA, left a

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ppropriate endocarditis prophylaxis is also recommended. Inatients with more than a mild degree of MS, counseling onvoidance of unusual physical stresses is advised. Agents withegative chronotropic properties, such as beta blockers or heartate-regulating calcium channel blockers, may be of benefit inatients in sinus rhythm who have exertional symptoms ifhese symptoms occur with high heart rates. Salt restrictionnd intermittent administration of a diuretic are useful if theres evidence of pulmonary vascular congestion.

Although MS is a slowly progressive condition, acute

ommittee recognizes that there may be variability in the measurement ofry wedge pressure (PAWP), and pulmonary artery systolic pressure (PASP)atients with severe mitral stenosis (MVA less than 1.0 cm2) and severe

hould undergo percutaneous mitral balloon valvotomy (PMBV) or mitralor pulmonary hypertension is present. AF indicates atrial fibrillation; CXR,MR, mitral regurgitation; 2D, 2-dimensional.

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atients with severe MS, especially with the onset of rapidtrial fibrillation, and this can be rapidly fatal. Thus,atients should be counseled to seek medical attentionmmediately if they experience a sudden marked increase inhortness of breath.

. Medical Therapy: Atrial Fibrillation

hirty to forty percent of patients with symptomatic MSevelop atrial fibrillation (235,236). There may be signifi-ant hemodynamic consequences that result from the acuteevelopment of atrial fibrillation, primarily from the rapidentricular rate, which shortens the diastolic filling periodnd causes elevation of left atrial pressure. Atrial fibrillationccurs more commonly in older patients (235) and isssociated with a poorer prognosis, with a 10-year survivalate of 25% compared with 46% in patients who remain ininus rhythm (237). The risk of arterial embolization,specially stroke, is significantly increased in patients withtrial fibrillation.

Treatment of an acute episode of rapid atrial fibrillationonsists of anticoagulation with heparin and control of theeart rate response. Intravenous digoxin, heart rate-regulatingalcium channel blockers, or beta blockers should be used toontrol ventricular response. Intravenous or oral amiodaronean also be used when beta blockers or heart rate-regulatingalcium channel blockers cannot be used. If there is hemody-amic instability, electrical cardioversion should be undertakenrgently, with intravenous heparin before, during, and after therocedure. In selected patients, chemical cardioversion maylso be attempted. Patients who have been in atrial fibrillationonger than 24 to 48 hours without anticoagulation are at anncreased risk for embolic events after cardioversion, butmbolization may occur with less than 24 hours of atrialbrillation. The decision to proceed with elective cardioversion

s dependent on multiple factors, including duration of atrialbrillation, hemodynamic response to the onset of atrialbrillation, a documented history of prior episodes of atrialbrillation, and a history of prior embolic events. If theecision has been made to proceed with elective cardioversion

n a patient who has had documented atrial fibrillation foronger than 24 to 48 hours and who has not been undergoingong-term anticoagulation, 1 of 2 approaches is recommended,ased on data from patients with nonrheumatic atrial fibrilla-ion. The first is anticoagulation with warfarin for more than 3eeks, followed by elective cardioversion (258). The second is

nticoagulation with heparin and TEE to look for left atrialhrombus. In the absence of left atrial thrombus, cardioversions performed with intravenous heparin before, during, and afterhe procedure (259). It is important to continue long-termnticoagulation after cardioversion.

Recurrent paroxysmal atrial fibrillation may be treatedn selected patients with class IC antiarrhythmic drugs (inonjunction with a negative dromotropic agent) or classII antiarrhythmic drugs for maintenance of sinushythm. However, eventually, atrial fibrillation becomes
esistant to prevention or cardioversion, and control of t

entricular response becomes the mainstay of therapy.atients with either paroxysmal or sustained atrial fibril-

ation should be treated with long-term anticoagulationith warfarin to prevent embolic events. It is controver-

ial whether percutaneous mitral valvotomy should beerformed in patients with new-onset atrial fibrillationnd moderate to severe MS who are otherwisesymptomatic.

. Medical Therapy: Prevention of Systemic Embolization

lass I

. Anticoagulation is indicated in patients with MS andatrial fibrillation (paroxysmal, persistent, or perma-nent). (Level of Evidence: B)

. Anticoagulation is indicated in patients with MS anda prior embolic event, even in sinus rhythm. (Level ofEvidence: B)

. Anticoagulation is indicated in patients with MSwith left atrial thrombus. (Level of Evidence: B)

lass IIb

. Anticoagulation may be considered for asymptomaticpatients with severe MS and left atrial dimensiongreater than or equal to 55 mm by echocardiography.*(Level of Evidence: B)

. Anticoagulation may be considered for patients withsevere MS, an enlarged left atrium, and spontaneouscontrast on echocardiography. (Level of Evidence: C)

This recommendation is based on a grade C level of evidenceiven by the American College of Chest Physicians Fourthonsensus Conference on Antithrombotic Therapy (260).

Systemic embolization may occur in 10% to 20% ofatients with MS (235,236), with increasing risk related toge and atrial fibrillation (235,236,261). One third ofmbolic events occur within 1 month of the onset of atrialbrillation, and two thirds occur within 1 year. An embolicvent may thus be the initial manifestation of MS.

There are no randomized trials examining the efficacyf anticoagulation in preventing embolic events specifi-ally in patients with MS, but retrospective studies havehown a 4- to 15-fold decrease in the incidence ofmbolic events with anticoagulation in these patients262,263). Most studies involved patients who had 1mbolus before the onset of anticoagulation therapy.owever, large randomized trials have demonstrated a

ignificant reduction in embolic events by treatment withnticoagulation in patients with atrial fibrillation notssociated with MS (264,265), and the subset of patientsho benefited most from anticoagulation were those with

he highest risk of embolic events. Patients with MS athe highest risk for future embolic events are those withrior embolic events and those with paroxysmal orersistent atrial fibrillation. There are no data to support
he concept that oral anticoagulation is beneficial in


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atients with MS who have not had atrial fibrillation orn embolic event. It is controversial whether patientsithout atrial fibrillation or an embolic event who mighte at higher risk for future embolic events (i.e., those withevere MS or an enlarged left atrium) should be consid-red for long-term warfarin therapy.

. Recommendations Regarding Physical Activity andxercise

n the majority of patients with MS, exertional symptomsre the limiting factor in terms of exercise tolerance. The6th Bethesda Conference on Recommendations for De-ermining Eligibility for Competition in Athletes withardiovascular Abnormalities published guidelines for

symptomatic patients with MS who wish to engage inompetitive athletics (67).

igure 5. Management strategy for patients with mitral stenosis and mieasurement of mitral valve area (MVA) and that the mean transmitral gra

ressure (PASP) should also be taken into consideration. †There is controveevere pulmonary hypertension (PH; PASP greater than 60 mm Hg) should u
MVR) to prevent right ventricular failure. CXR indicates chest X-ray; ECG, electro
VG, mean mitral valve pressure gradient; NYHA, New York Heart Association


. Serial Testing

n the asymptomatic patient, yearly re-evaluation is recom-ended (Fig. 4). At the time of the yearly evaluation, a

istory, physical examination, chest X-ray, and ECG shoulde obtained. An echocardiogram is not recommended yearlynless there is a change in clinical status or the patient hasevere MS. Ambulatory ECG monitoring (Holter or eventecorder) to detect paroxysmal atrial fibrillation is indicatedn patients with palpitations.

. Evaluation of the Symptomatic Patient

atients who develop symptoms should undergo evaluationith a history, physical examination, ECG, chest X-ray, and

chocardiogram (Figs. 5 and 6). 2-D and Doppler echocar-iography is indicated to evaluate MV morphology, MV

ptoms. *The committee recognizes that there may be variability in the, pulmonary artery wedge pressure (PAWP), and pulmonary artery systolicto whether patients with severe mitral stenosis (MVA less than 1.0 cm2) andpercutaneous mitral balloon valvotomy (PMBV) or mitral valve replacement

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emodynamics, and pulmonary artery pressure. Patientsith NYHA functional class II symptoms and moderate or

evere MS (MV area less than or equal to 1.5 cm2 or meanradient greater than 5 mm Hg) may be considered for mitralalloon valvotomy if they have suitable MV morphology ando left atrial thrombi. Patients who have NYHA functionallass III or IV symptoms and evidence of severe MS have aoor prognosis if left untreated and should be considered forntervention with either balloon valvotomy or surgery.

Formal exercise testing or dobutamine stress testing may

igure 6. Management strategy for patients with mitral stenosis and modeariability in the measurement of mitral valve area (MVA) and that theulmonary artery systolic pressure (PASP) should also be taken into conorphology should undergo percutaneous mitral balloon valvotomy (PM

lectrocardiogram; echo, echocardiography; LA, left atrial; MR, mitral replacement; NYHA, New York Heart Association; 2D, 2-dimensional.

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auses. Exercise tolerance, heart rate and blood pressureesponse, transmitral gradient, and pulmonary artery pres-ure can be obtained at rest and during exercise. This cansually be accomplished with either supine bicycle or up-ight exercise with Doppler recording of TR and transmitralelocities. Right- and left-heart catheterization with exer-ise may be helpful and occasionally necessary. Patients whore symptomatic with a significant elevation of pulmonaryrtery pressure (greater than 60 mm Hg), mean transmitralradient (greater than 15 mm Hg), or pulmonary artery

o severe symptoms. *The writing committee recognizes that there may ben transmitral gradient, pulmonary artery wedge pressure (PAWP), andation. †It is controversial as to which patients with less favorable valve

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ave hemodynamically significant MS and should be con-idered for further intervention.

. Indications for Invasive Hemodynamic Evaluation

lass I

. Cardiac catheterization for hemodynamic evaluationshould be performed for assessment of severity of MSwhen noninvasive tests are inconclusive or whenthere is discrepancy between noninvasive tests andclinical findings regarding severity of MS. (Level ofEvidence: C)

. Catheterization for hemodynamic evaluation includ-ing left ventriculography (to evaluate severity of MR)for patients with MS is indicated when there is adiscrepancy between the Doppler-derived mean gra-dient and valve area. (Level of Evidence: C)

lass IIa

. Cardiac catheterization is reasonable to assess the he-modynamic response of pulmonary artery and left atrialpressures to exercise when clinical symptoms and rest-ing hemodynamics are discordant. (Level of Evidence: C)

. Cardiac catheterization is reasonable in patients withMS to assess the cause of severe pulmonary arterialhypertension when out of proportion to severity ofMS as determined by noninvasive testing. (Level ofEvidence: C)

lass III

Diagnostic cardiac catheterization is not recommendedto assess the MV hemodynamics when 2D and Dopplerechocardiographic data are concordant with clinicalfindings. (Level of Evidence: C)

ith the advent of Doppler echocardiography, cardiacatheterization is no longer required for assessment ofemodynamics in the majority of patients with isolated MS.here is often overestimation of the transmitral gradienthen catheterization is performed with pulmonary arteryedge pressure as a substitute for left atrial pressure, even

fter correction for phase delay. Thus, the transmitralradient derived by Doppler echocardiography may be moreccurate than that obtained by cardiac catheterization withulmonary artery wedge pressure (266).In most instances, Doppler measurements of transmitral

radient, valve area, and pulmonary pressure will correlateell with each other. Catheterization is indicated to assessemodynamics when there is a discrepancy betweenoppler-derived hemodynamics and the clinical status of a

ymptomatic patient. Absolute left- and right-side pressureeasurements should be obtained by catheterization when

here is elevation of pulmonary artery pressure out ofroportion to mean gradient and valve area. Catheterizationncluding left ventriculography (to evaluate the severity of

R) is indicated when there is a discrepancy between the
oppler-derived mean gradient and valve area. If symptoms

ppear to be out of proportion to noninvasive assessment ofesting hemodynamics, right- and left-heart catheterizationith exercise may be useful. Coronary angiography may be

equired in selected patients who may need intervention (seeection X-B).

. Indications for Percutaneous Mitral Balloon Valvotomy

lass I

. Percutaneous mitral balloon valvotomy is effective forsymptomatic patients (NYHA functional class II, III,or IV), with moderate or severe MS* and valve mor-phology favorable for percutaneous mitral balloon val-votomy in the absence of left atrial thrombus or mod-erate to severe MR. (Level of Evidence: A)

. Percutaneous mitral balloon valvotomy is effective forasymptomatic patients with moderate or severe MS*and valve morphology that is favorable for percutaneousmitral balloon valvotomy who have pulmonary hyper-tension (pulmonary artery systolic pressure greaterthan 50 mm Hg at rest or greater than 60 mm Hgwith exercise) in the absence of left atrial thrombus ormoderate to severe MR. (Level of Evidence: C)

lass IIa

Percutaneous mitral balloon valvotomy is reasonablefor patients with moderate or severe MS* who have anonpliable calcified valve, are in NYHA functionalclass III–IV, and are either not candidates for surgeryor are at high risk for surgery. (Level of Evidence: C)

lass IIb

. Percutaneous mitral balloon valvotomy may be con-sidered for asymptomatic patients with moderate orsevere MS* and valve morphology favorable for percu-taneous mitral balloon valvotomy who have new onsetof atrial fibrillation in the absence of left atrial throm-bus or moderate to severe MR. (Level of Evidence: C)

. Percutaneous mitral balloon valvotomy may be con-sidered for symptomatic patients (NYHA functionalclass II, III, or IV) with MV area greater than 1.5 cm2

if there is evidence of hemodynamically significantMS based on pulmonary artery systolic pressuregreater than 60 mm Hg, pulmonary artery wedgepressure of 25 mm Hg or more, or mean MV gradientgreater than 15 mm Hg during exercise. (Level ofEvidence: C)

. Percutaneous mitral balloon valvotomy may be con-sidered as an alternative to surgery for patients withmoderate or severe MS who have a nonpliable calci-fied valve and are in NYHA class III–IV. (Level ofEvidence: C)

lass III

. Percutaneous mitral balloon valvotomy is not indicated
for patients with mild MS. (Level of Evidence: C)


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. Percutaneous mitral balloon valvotomy should not beperformed in patients with moderate to severe MR orleft atrial thrombus. (Level of Evidence: C)

See Table 1 (7).

The immediate results of percutaneous mitral valvotomy areimilar to those of mitral commissurotomy (267–276). Theean valve area usually doubles (from 1.0 to 2.0 cm2), with a

0% to 60% reduction in transmitral gradient. Overall, 80% to5% of patients may have a successful procedure, which isefined as an MV area greater than 1.5 cm2 and a decrease in

eft atrial pressure to less than 18 mm Hg in the absence ofomplications. The most common acute complications re-orted in large series include severe MR, which occurs in 2% to0%, and a residual atrial septal defect.

Event-free survival after percutaneous balloon valvotomyfreedom from death, repeat valvotomy, or MV replace-ent) overall is 50% to 65% over 3 to 7 years, with an

vent-free survival of 80% to 90% in patients with favorableV morphology (245,269,271–278). More than 90% of

atients free of events remain in NYHA functional class I orI after percutaneous mitral valvotomy. Randomized trialsave compared percutaneous balloon valvotomy with bothlosed and open surgical commissurotomy (279–284).here was no significant difference in acute hemodynamic

esults or complication rate between percutaneous mitralalvotomy and surgery, and early follow-up data indicate noifference in hemodynamics, clinical improvement, or exer-ise time. However, longer-term follow-up studies at 3 to 7ears (282,283) indicate more favorable hemodynamic andymptomatic results with percutaneous balloon valvotomyhan with closed commissurotomy.

The immediate results, acute complications, and follow-upesults of percutaneous balloon valvotomy are dependent onultiple factors. It is of utmost importance that this procedure

e performed in centers with skilled and experienced operators.ther factors include age, NYHA functional class, stenosis

everity, LV end-diastolic pressure, cardiac output, and pul-onary artery wedge pressure (269,271,272,276). The under-

ying MV morphology is the factor of greatest importance inetermining outcome (243–246,269,272,273,276,277,285–88), and immediate postvalvotomy hemodynamics are pre-ictive of long-term clinical outcome (271,273,276). Patientsith valvular calcification, thickened fibrotic leaflets withecreased mobility, and subvalvular fusion have a higher

ncidence of acute complications and a higher rate of recurrenttenosis on follow-up.

Patients who are being considered for an interventionhould undergo evaluation with a history, physical examina-ion, and 2D and Doppler echocardiographic examination.he appearance and mobility of the MV apparatus and

ommissures should be evaluated by 2D echocardiography, andhe transmitral gradient, MV area, and pulmonary arteryressure should be obtained from the Doppler examination. Ifhere is a discrepancy between symptoms and hemodynamics,
formal hemodynamic exercise test may be performed.

Relative contraindications to percutaneous balloon val-otomy include the presence of a left atrial thrombus andignificant (3� to 4�) MR. Patients thought to be candi-ates for percutaneous mitral valvotomy should undergoEE to rule out left atrial thrombus and to examine the

everity of MR. Percutaneous mitral balloon valvotomyhould be performed only by skilled operators at institutionsith extensive experience in performing the technique

267,270). Thus, the decision to proceed with percutaneousalloon valvotomy or surgical commissurotomy is depen-ent on the experience of the operator and institution.ecause of the less invasive nature of percutaneous balloonalvotomy compared with surgical intervention, appropriateatients without symptoms or those with NYHA functionallass II symptoms may be considered for catheter-basedherapy (Figs. 4 and 5).

. Indications for Surgery for Mitral Stenosis

lass I

. MV surgery (repair if possible) is indicated in pa-tients with symptomatic (NYHA functional classIII–IV) moderate or severe MS* when 1) percutane-ous mitral balloon valvotomy is unavailable, 2) per-cutaneous mitral balloon valvotomy is contraindi-cated because of left atrial thrombus despiteanticoagulation or because concomitant moderate tosevere MR is present, or 3) the valve morphology isnot favorable for percutaneous mitral balloon valvot-omy in a patient with acceptable operative risk. (Levelof Evidence: B)

. Symptomatic patients with moderate to severe MS*who also have moderate to severe MR should receiveMV replacement, unless valve repair is possible at thetime of surgery. (Level of Evidence: C)

lass IIa

MV replacement is reasonable for patients with se-vere MS* and severe pulmonary hypertension (pul-monary artery systolic pressure greater than 60 mmHg) with NYHA functional class I–II symptoms whoare not considered candidates for percutaneous mitralballoon valvotomy or surgical MV repair. (Level ofEvidence: C)

lass IIb

MV repair may be considered for asymptomatic pa-tients with moderate or severe MS* who have hadrecurrent embolic events while receiving adequateanticoagulation and who have valve morphology fa-vorable for repair. (Level of Evidence: C)

lass III

. MV repair for MS is not indicated for patients with
mild MS. (Level of Evidence: C)


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. Closed commissurotomy should not be performed inpatients undergoing MV repair; open commissurot-omy is the preferred approach. (Level of Evidence: C)

See Table 1 (7).

f there is significant calcification, fibrosis, and subvalvularusion of the MV apparatus, commissurotomy or percuta-eous balloon valvotomy is less likely to be successful, andV replacement will be necessary. Given the risk of MV

eplacement and the potential long-term complications of arosthetic valve, there are stricter indications for MVperation in these patients with calcified fibrotic valves. Inhe patient with NYHA functional class III symptoms dueo severe MS or combined MS/MR, MV replacementesults in excellent symptomatic improvement. Postpone-ent of surgery until the patient reaches the functional class

V symptomatic state should be avoided, because operativeortality is high and the long-term outcome is suboptimal.owever, if the patient presents in NYHA functional class

V heart failure, surgery should not be denied, because theutlook without surgical intervention is grave. It is contro-ersial whether asymptomatic or mildly symptomatic pa-ients with severe MS (valve area less than 1 cm2) and severeulmonary hypertension (pulmonary artery systolic pressurereater than 60 to 80 mm Hg) should undergo MVeplacement to prevent RV failure, but surgery is generallyecommended in such patients. It is recognized that patientsith such severe pulmonary hypertension are rarely asymp-

omatic.

0. Management of Patients After Valvotomy or Com-issurotomy

baseline echocardiogram should be performed after therocedure to obtain a baseline measurement of postopera-ive hemodynamics and to exclude significant complicationsuch as MR, LV dysfunction, or atrial septal defect (in thease of percutaneous valvotomy). This echocardiogramhould be performed at least 72 h after the procedure,ecause acute changes in atrial and ventricular compliancemmediately after the procedure affect the reliability of thealf-time in calculation of valve area (249,250). Patientsith severe MR or a large atrial septal defect should be

onsidered for early surgery; however, the majority of smalleft-to-right shunts at the atrial level will close spontane-usly over the course of 6 months.Repeat percutaneous balloon valvotomy can be performed

n the patient in whom there is restenosis after either a priorurgical commissurotomy or balloon valvotomy (289,290).he results of these procedures are adequate in manyatients but may be less satisfactory than the overall resultsf initial valvotomy because there is usually more valveeformity, calcification, and fibrosis than with the initial
rocedure (286,290,291).

. Mitral Valve Prolapse

tilizing current echocardiographic criteria for diagnosingVP (valve prolapse of 2 mm or more above the mitral

nnulus in the long-axis parasternal view and other views292), the prevalence of this entity is 1% to 2.5% of theopulation (293). MVP occurs as a clinical entity with orithout thickening (5 mm or greater, measured duringiastasis) and with or without MR.The basic microscopic feature of primary MVP is marked

roliferation of the spongiosa, the delicate myxomatousonnective tissue between the atrialis (a thick layer ofollagen and elastic tissue that forms the atrial aspect of theeaflet) and the fibrosa or ventricularis (dense layer ofollagen that forms the basic support of the leaflet). Myx-matous proliferation of the acid mucopolysaccharide–ontaining spongiosa tissue causes focal interruption of thebrosa. Secondary effects of the primary MVP syndrome

nclude fibrosis of the surface of the MV leaflets, thinningnd/or elongation of the chordae tendineae, and ventricularriction lesions.

. Natural History

he natural history of asymptomatic MVP is heterogeneousnd can vary from benign with normal life expectancy todverse with significant morbidity or mortality. The mostrequent predictor of cardiovascular mortality is moderate toevere MR and, less frequently, an LV ejection fraction lesshan 0.50 (294). Echocardiographic evidence of thickened

V leaflets (5 mm or greater) is also a predictor ofomplications related to MVP (295–299). In most patients,

VP is associated with a benign prognosis (300,301), withn age-adjusted survival rate for both men and womenimilar to that of individuals without this entity (302).

In some patients, after an initially prolonged asymptomaticnterval, the entire process may enter an accelerated phase as aesult of left atrial and ventricular dysfunction and atrialbrillation. In some instances, spontaneous rupture of MVhordae will occur. Infective endocarditis is a serious compli-ation of MVP, which is the leading predisposing cardiovas-ular diagnosis in most series of patients reported with endo-arditis. Several studies have indicated an increased likelihoodf cerebrovascular accidents in patients under 45 years of ageho have MVP beyond what would have been expected in a

imilar population without MVP (303).Sudden death is a rare complication of MVP, occurring in

ewer than 2% of known cases during long-term follow-up296,303–309). Annual mortality rates are less than 1% per year.

. Evaluation and Management of the Asymptomaticatient

lass I

Echocardiography is indicated for the diagnosis of
MVP and assessment of MR, leaflet morphology, and


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lass IIa

. Echocardiography can effectively exclude MVP inasymptomatic patients who have been diagnosedwithout clinical evidence to support the diagnosis.(Level of Evidence: C)

. Echocardiography can be effective for risk stratifica-tion in asymptomatic patients with physical signs ofMVP or known MVP. (Level of Evidence: C)

lass III

. Echocardiography is not indicated to exclude MVP inasymptomatic patients with ill-defined symptoms inthe absence of a constellation of clinical symptoms orphysical findings suggestive of MVP or a positivefamily history. (Level of Evidence: B)

. Routine repetition of echocardiography is not indi-cated for the asymptomatic patient who has MVPand no MR or MVP and mild MR with no changesin clinical signs or symptoms. (Level of Evidence: C)

The primary diagnostic evaluation of the patient withVP is the physical examination (307,310). However,VP can be present in the absence of the classic ausculta-

ory findings, and systolic clicks may be intermittent andariable.

2D and Doppler echocardiography is the most usefuloninvasive tests for defining MVP. Valve prolapse of 2m or more above the mitral annulus in the long-axis

arasternal view and other views, especially when theeaflet coaptation occurs on the atrial side of the annularlane, indicates a high likelihood of MVP. There isisagreement concerning the reliability of the echocar-iographic appearance of anterior leaflet billowing whenbserved only in the apical 4-chamber view (297,311).eaflet thickness of 5 mm or more indicates abnormal

eaflet thickness, and its added presence makes MVPven more certain. Leaflet redundancy is often associatedith an enlarged mitral annulus and elongated chordae

endineae (307). The absence or presence of MR is anmportant consideration, and MVP is more likely when

R is detected as a high-velocity eccentric jet in lateystole (312).

Antibiotic prophylaxis, for the prevention of endocarditisuring procedures associated with bacteremia, is recom-ended for most patients with a definite diagnosis of MVP,

articularly if there is associated MR (313). The committeeecommends that patients without MR who have leaflethickening, elongated chordae, left atrial enlargement, or LVilatation receive endocarditis prophylaxis (295–299,314)
see Section II-C-1). m

. Evaluation and Management of the Symptomaticatient

lass I

. Aspirin therapy (75 to 325 mg per day) is recom-mended for symptomatic patients with MVP whoexperience cerebral transient ischemic attacks. (Levelof Evidence: C)

. In patients with MVP and atrial fibrillation, warfarintherapy is recommended for patients aged greaterthan 65 or those with hypertension, MR murmur, ora history of heart failure. (Level of Evidence: C)

. Aspirin therapy (75 to 325 mg per day) is recom-mended for patients with MVP and atrial fibrillationwho are less than 65 years old and have no history ofMR, hypertension, or heart failure. (Level of Evi-dence: C)

. In patients with MVP and a history of stroke,warfarin therapy is recommended for patients withMR, atrial fibrillation or left atrial thrombus. (Levelof Evidence: C)

lass IIa

. In patients with MVP and a history of stroke, who donot have MR, atrial fibrillation or left atrial throm-bus, warfarin therapy is reasonable for patients withechocardiographic evidence of thickening (5 mm orgreater) and/or redundancy of the valve leaflets.(Level of Evidence: C)

. In patients with MVP and a history of stroke, aspirintherapy is reasonable for patients who do not have MR,atrial fibrillation, left atrial thrombus, or echocardio-graphic evidence of thickening (5mm or greater) orredundancy of the valve leaflets. (Level of Evidence: C)

. Warfarin therapy is reasonable for patients withMVP with transient ischemic attacks despite aspirintherapy. (Level of Evidence: C)

. Aspirin therapy (75 to 325 mg per day) can bebeneficial for patients with MVP and a history ofstroke who have contraindications to anticoagulants.(Level of Evidence: B)

lass IIb

Aspirin therapy (75 to 325 mg per day) may beconsidered for patients in sinus rhythm with echo-cardiographic evidence of high-risk MVP. (Level ofEvidence: C)

atients with MVP and palpitations associated with mildachyarrhythmias or increased adrenergic symptoms andhose with chest pain, anxiety, or fatigue often respond toherapy with beta blockers (315). In many cases, however,he cessation of stimulants such as caffeine, alcohol, andigarettes may be sufficient to control symptoms.

Daily aspirin therapy (75 to 325 mg per day) is recom-
ended for MVP patients with documented transient focal


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eurological events who are in sinus rhythm with no atrialhrombi. Such patients also should avoid cigarettes and oralontraceptives. The American Stroke Association guidelines315a) recommend aspirin for patients with MVP who havexperienced an ischemic stroke (class IIa, level of evidence C),ased on the evidence of efficacy of antiplatelet agents foreneral stroke patients. No randomized trials have addressedhe efficacy of selected antithrombotic therapies for the specificubgroup of stroke patients with MVP. In the current guide-ines, the committee recommends aspirin for those post-strokeatients with MVP who have no evidence of MR, atrialbrillation, left artrial thrombus, or echocardiographic evidencef thickening (5mm or greater) or redundancy of the valveeaflets. However, long-term anticoagulation therapy witharfarin is recommended (class I) for post-stroke patients withVP who have MR, atrial fibrillation, or left atrial thrombus.

n the absence of these indications, warfarin is also recom-ended (class IIa) in post-stroke patients with MVP who have

chocardiographic evidence of thickening (5 mm or greater) oredundancy of the valve leaflets and in MVP patients whoxperience recurrent transient ischemic attacks while takingspirin. In each of these situations, the international normal-zed ratio (INR) should be maintained between 2.0o 3.0).

In MVP patients with atrial fibrillation, warfarin therapy isndicated in patients aged greater than 65 years and in thoseith MR, hypertension, or a history of heart failure (INR 2.0

o 3.0). Aspirin therapy is satisfactory in patients with atrialbrillation who are younger than 65 years old, have no MR,nd have no history of hypertension or heart failure (316,317).aily aspirin therapy is often recommended for patients with

igh-risk echocardiographic characteristics.A normal lifestyle and regular exercise are encouraged forost patients with MVP, especially those who are asymp-

omatic (309,317). Restriction from competitive sports isecommended when moderate LV enlargement, LV dys-unction, uncontrolled tachyarrhythmias, long-QT interval,nexplained syncope, prior resuscitation from cardiac arrest,r aortic root enlargement is present individually or inombination (307).

Asymptomatic patients with MVP and no significantR can be evaluated clinically every 3 to 5 years. Serial

chocardiography is not necessary in most patients and isecommended only in patients who have high-risk charac-eristics on the initial echocardiogram and in those whoevelop symptoms consistent with cardiovascular disease orho have a change in physical findings that suggestsevelopment of significant MR. Patients who have high-isk characteristics, including those with moderate to severe

R, should be followed up once a year.Patients with severe MR with symptoms or impaired LV

ystolic function require cardiac catheterization and evalua-ion for MV surgery (see Section III-F-3-b). The thick-ned, redundant MV can often be repaired rather thaneplaced, with a low operative mortality and excellent short-
nd long-term results (318,319). i

. Surgical Considerations

anagement of MVP may require surgery, particularly inhose patients who develop a flail leaflet due to rupture ofhordae tendineae or their marked elongation. Most suchalves can be repaired successfully by surgeons experiencedn MV repair, especially when the posterior leaflet of the

V is predominantly affected. MV repair for MR due toVP is associated with excellent long-term survival and

emains superior to MV replacement beyond 10 years andp to 20 years after surgery (318,319). Anterior leaflet repairs associated with a higher risk for reoperation than poste-ior leaflet repair. As noted in Section III-F-3-b, cardiolo-ists are strongly encouraged to refer patients who areandidates for complex MV repair to surgical centers expe-ienced in performing MV repair. Residual MR is associ-ted with a higher risk for reoperation (319). Recommen-ations for surgery in patients with MVP and MR are theame as for those with other forms of nonischemic severe

R (see Section VII-B-1-c).

. Mitral Regurgitation

. Acute Severe Mitral Regurgitation

. Diagnosis

he patient with acute severe MR is almost always severelyymptomatic. Physical examination of the precordium maye misleading, because a normal-sized left ventricle does notroduce a hyperdynamic apical impulse. The systolic mur-ur of MR may not be holosystolic and may even be absent.ransthoracic echocardiography may demonstrate the dis-

uption of the MV and provide semiquantitative informa-ion on lesion severity; however, transthoracic echocardiog-aphy may underestimate lesion severity by inadequatemaging of the color flow jet, and TEE should be performedf MV morphology and regurgitant severity are still inuestion after transthoracic echocardiography. TEE is alsoelpful in demonstrating the anatomic cause of acute severeR and directing successful surgical repair.

. Medical Therapy

n acute severe MR, medical therapy has a limited role ands aimed primarily to stabilize hemodynamics in preparationor surgery. In the normotensive patient, nitroprusside mayffectively diminish the amount of MR, which in turnncreases forward output and reduces pulmonary congestion.n the hypotensive patient, nitroprusside should not bedministered alone, but combination therapy with an ino-ropic agent (such as dobutamine) and nitroprusside is ofenefit in some patients. In such patients, aortic balloonounterpulsation increases forward output and mean arterialressure while diminishing regurgitant volume and LVlling pressure and can be used to stabilize the patient whilehey are prepared for surgery. If infective endocarditis is theause of acute MR, identification and treatment of the
nfectious organism are essential.


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. Chronic Asymptomatic Mitral Regurgitation

. Natural History

atients with mild to moderate MR may remain asymp-omatic with little or no hemodynamic compromise forany years; however, MR from a primary MV abnormality

ends to progress over time with an increase in volumeverload due to an increase in the effective orifice area.rogression of the MR is variable and is determined byrogression of lesions or mitral annulus size (320).The compensated phase of MR is variable but may last

or many years, but the prolonged burden of volumeverload may eventually result in LV dysfunction. In thishase, contractile dysfunction impairs ejection, and end-ystolic volume increases. There may be further LV dilata-ion and increased LV filling pressure. These hemodynamicvents result in reduced forward output and pulmonaryongestion. However, the still favorable loading conditionsften maintain ejection fraction in the low-normal range0.50 to 0.60) despite the presence of significant muscleysfunction (321–323). Correction of MR should be per-ormed before the advanced phases of LV decompensation.

Numerous studies indicate that patients with chronicevere MR have a high likelihood of developing symptomsr LV dysfunction over the course of 6 to 10 years313,317,324,325). However, the incidence of sudden deathn asymptomatic patients with normal LV function variesidely among these studies.The natural history of severe MR due to a flail posterior

eaflet has been documented (313). At 10 years, 90% ofatients are dead or require MV operation. The mortalityate in patients with severe MR caused by flail leaflets is 6%o 7% per year. However, patients at risk of death areredominantly those with LV ejection fractions less than.60 or with NYHA functional class III–IV symptoms, andess so those who are asymptomatic and have normal LVunction (313,326). Severe symptoms also predict a poorutcome after MV repair or replacement (326).

. Indications for Transthoracic Echocardiography

lass I

. Transthoracic echocardiography is indicated forbaseline evaluation of LV size and function, RV andleft atrial size, pulmonary artery pressure, and sever-ity of MR (Table 1) in any patient suspected ofhaving MR. (Level of Evidence: C)

. Transthoracic echocardiography is indicated for de-lineation of the mechanism of MR. (Level of Evi-dence: B)

. Transthoracic echocardiography is indicated for an-nual or semiannual surveillance of LV function (es-timated by ejection fraction and end-systolic dimen-sion) in asymptomatic patients with moderate to
severe MR. (Level of Evidence: C) e

. Transthoracic echocardiography is indicated in pa-tients with MR to evaluate the MV apparatus and LVfunction after a change in signs or symptoms. (Levelof Evidence: C)

. Transthoracic echocardiography is indicated to eval-uate LV size and function and MV hemodynamics inthe initial evaluation after MV replacement or MVrepair. (Level of Evidence: C)

lass IIa

Exercise Doppler echocardiography is reasonable inasymptomatic patients with severe MR to assessexercise tolerance and the effects of exercise onpulmonary artery pressure and MR severity. (Level ofEvidence: C)

lass III

Transthoracic echocardiography is not indicated forroutine follow-up evaluation of asymptomatic pa-tients with mild MR and normal LV size and systolicfunction. (Level of Evidence: C)

n initial comprehensive 2D Doppler echocardiogram pro-ides a baseline estimation of LV and left atrial size, anstimation of LV ejection fraction, and approximation ofhe severity of MR (1). Quantification of the severity of MRTable 1) is strongly recommended (7,324,327,328). In theajority of patients, an estimate of pulmonary artery pres-

ure can be obtained from the TR peak velocity. Changesrom these baseline values are used subsequently to guidehe timing of MV surgery.

The initial transthoracic echocardiogram should disclose thenatomic cause of the MR. A central color flow jet of MR withstructurally normal MV apparatus suggests the presence of

unctional MR, which may be due to annular dilatation fromV dilatation or tethering of the posterior leaflet because of

egional LV dysfunction in patients with ischemic heartisease. An eccentric color flow jet of MR with abnormalitiesf the MV apparatus indicates organic MR. In patients withrganic MR, the echocardiogram should assess the presence ofalcium in the annulus or leaflets, the redundancy of the valveeaflets, and the MV leaflet involved (anterior leaflet, posterioreaflet, or bileaflet). These factors will help determine theeasibility of valve repair if surgery is contemplated. The systemroposed by Carpentier (329) identifies the anatomic andhysiologic characteristics of the valve that aid the surgeon inlanning MV repair. The valve dysfunction is described on theasis of the motion of the free edge of the leaflet relative to thelane of the annulus: type I, normal; type II, increased, as inVP; type IIIA, restricted during systole and diastole, and

ype IIIB, restricted during systole.Multiple parameters from the Doppler examination should

e used to diagnose severe MR (Table 1), including the colorow jet width and area, the intensity of the continuous-waveoppler signal, the pulmonary venous flow contour, the peak

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ffective orifice area and regurgitation volume (1). In addition,here should be enlargement of the left ventricle and left atriumn chronic severe MR. Abnormalities of the MV apparatus areften present if there is severe MR, but ischemic LV dysfunc-ion may also result in severe MR. If a discrepancy is present,r if the patient has poor windows on transthoracic echocar-iography, then further evaluation of the severity of MR isequired, including cardiac catheterization, magnetic resonancemaging, or TEE.

. Indications for Transesophageal Echocardiography

lass I

. Preoperative or intraoperative TEE is indicated toestablish the anatomic basis for severe MR in pa-tients in whom surgery is recommended to assessfeasibility of repair and to guide repair. (Level ofEvidence: B)

. TEE is indicated for evaluation of MR patients inwhom transthoracic echocardiography provides nondi-agnostic information regarding severity of MR, mech-anism of MR, and/or status of LV function. (Level ofEvidence: B)

lass IIa

Preoperative TEE is reasonable in asymptomaticpatients with severe MR who are considered forsurgery to assess feasibility of repair. (Level of Evi-dence: C)

lass III

TEE is not indicated for routine follow-up or surveil-lance of asymptomatic patients with native valve MR.(Level of Evidence: C)

. Serial Testing

symptomatic patients with mild MR and no evidence ofV enlargement, LV dysfunction, or pulmonary hyperten-

ion can be followed on a yearly basis with instructions tolert the physician if symptoms develop in the interim.early echocardiography is not necessary unless there is

linical evidence that MR has worsened. In patients withoderate MR, clinical evaluation including echocardiogra-

hy should be performed annually and sooner if symptomsccur.In asymptomatic patients with severe MR, clinical eval-

ation and echocardiography should be performed every 6o 12 months to assess symptoms or transition to asymp-omatic LV dysfunction. Exercise stress testing may be usedo add objective evidence regarding symptoms and changesn exercise tolerance. Exercise testing is especially importantf a good history of the patient’s exercise capacity cannot bebtained. Measurement of pulmonary artery pressure andssessment of severity of MR during exercise may be
elpful. w

Although interpretation of LV ejection fraction in pa-ients with severe MR is difficult because the loadingonditions facilitate ejection, several studies indicate thathe preoperative ejection fraction is an important predictorf postoperative survival in patients with chronic MR321,330–333). Ejection fraction in a patient with MR withormal LV function is usually greater than or equal to 0.60.onsistent with this concept, postoperative ventricular

unction is lower and survival is reduced in patients with areoperative ejection fraction less than 0.60 compared withatients with higher ejection fractions (332,333).Alternatively or in concert, LV end-systolic dimension

or volume), which may be less load dependent than ejectionraction, can be used in timing of MV surgery. End-systolicimension should be less than 40 mm preoperatively tonsure normal postoperative LV function (333–336).

If patients become symptomatic, they should undergoV surgery even if LV function appears to be normal.

. Guidelines for Physical Activity and Exercise

ecommendations regarding participation in competitivethletics were published by the Task Force on Acquiredalvular Heart Disease of the 36th Bethesda Conference

67). Asymptomatic patients with MR of any severity whore in sinus rhythm and who have normal LV and left atrialimensions and normal pulmonary artery pressure mayxercise without restriction (67). However, those withefinite LV enlargement (greater than or equal to 60 mm),ulmonary hypertension, or any degree of LV systolicysfunction at rest should not participate in any competitiveports.

. Medical Therapy

n asymptomatic patients with chronic MR, there is noenerally accepted medical therapy. Although the use ofasodilators may appear to be logical for the same reasonshat they are effective in acute MR, there are no largeong-term studies to indicate that they are beneficial. Thus,n the absence of systemic hypertension, there is no knownndication for the use of vasodilating drugs or ACE inhib-tors in asymptomatic patients with MR and preserved LVunction.

However, in patients with functional or ischemic MRresulting from dilated or ischemic cardiomyopathy), theres reason to believe that preload reduction may be beneficial337). If LV systolic dysfunction is present, primary treat-ent of the LV systolic dysfunction with drugs such asCE inhibitors or beta blockers (particularly carvedilol) andiventricular pacing have all been shown to reduce theeverity of functional MR (338–341).

In patients with MR who develop symptoms but havereserved LV function, surgery is the most appropriateherapy. If atrial fibrillation develops, heart rate should beontrolled with rate-lowering calcium channel blockers,eta blockers, digoxin, or, rarely, amiodarone. In patients
ith severe MR and chronic atrial fibrillation, a Maze


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rocedure may be added to an MV repair (see Atrialibrillation in Section III-F-3-b), because this will reduce

he risk of postoperative stroke. Patients with MR and atrialbrillation should receive chronic anticoagulation, with theNR maintained at 2.0 to 3.0.


lass I

. Left ventriculography and hemodynamic measurementsare indicated when noninvasive tests are inconclusiveregarding severity of MR, LV function, or the need forsurgery. (Level of Evidence: C)

. Hemodynamic measurements are indicated whenpulmonary artery pressure is out of proportion to theseverity of MR as assessed by noninvasive testing.(Level of Evidence: C)

. Left ventriculography and hemodynamic measure-ments are indicated when there is a discrepancybetween clinical and noninvasive findings regardingseverity of MR. (Level of Evidence: C)

. Coronary angiography is indicated before MV repairor MV replacement in patients at risk for CAD.(Level of Evidence: C)

lass III

Left ventriculography and hemodynamic measure-ments are not indicated in patients with MR inwhom valve surgery is not contemplated. (Level ofEvidence: C)

Cardiac catheterization, with or without exercise, isecessary when there is a discrepancy between clinical andoninvasive findings. Although the standard semiquantita-ive approach to determining the severity of MR fromentriculography has its own limitations (342), ventriculog-aphy does provide an additional method to assess LVilatation and function and gauge the severity of MR.xercise hemodynamics may provide additional information

hat is helpful in decision making. In patients who have riskactors for CAD (e.g., advanced age, hypercholesterolemia,r hypertension), or when there is a suspicion that MR isschemic in origin (either because of known myocardialnfarction or suspected ischemia), coronary angiographyhould be performed before surgery.

. Indications for Surgery

. Types of Surgery

n most cases, MV repair is the operation of choice whenhe valve is suitable for repair and appropriate surgicalkill and expertise are available. This procedure preserveshe patient’s native valve without a prosthesis and there-ore avoids the risk of chronic anticoagulation (except inatients in atrial fibrillation) or prosthetic valve failure

ate after surgery. Additionally, preservation of the mitral
pparatus leads to better postoperative LV function and

urvival than in cases in which the apparatus is disrupted327,343–348). Valve morphology and surgical expertisere of critical importance for the success of MV repairsee below).

The reoperation rate after MV repair is similar to thatfter MV replacement (319). There is a 7% to 10%eoperation rate at 10 years in patients undergoing MVepair, usually for severe recurrent MR (319,349–352).pproximately 70% of the recurrent MR is thought to beue to the initial procedure and 30% to progressive valveisease (349).If MV replacement is required, MV replacement with

reservation of the chordal apparatus enhances postop-rative mitral competence, preserves LV function, andncreases postoperative survival compared with MV re-lacement in which the apparatus is disrupted (345,353–56). This latter form of MV replacement is neverecommended and should only be performed in thoseircumstances in which the native valve and apparatus areo distorted by the preoperative pathology (rheumaticisease, for example) that the mitral apparatus cannot bepared. Artificial chordal reconstruction does extend thepportunities for repair in some such patients (357,358).The advantages of MV repair make it applicable across

he full spectrum of MR, including the 2 extremes of thepectrum. Valve repair might be possible in patients withar-advanced symptomatic MR and depressed LV func-ion, because it preserves LV function at the preoperativeevel (347). At the other extreme, in the relativelysymptomatic patient with well-preserved LV function,epair of a severely regurgitant valve might be contem-lated to avoid the onset of LV dysfunction from

ong-standing volume overload. However, failed MVepair that results in the need for a prosthetic valve in ansymptomatic patient would represent a clear complica-ion of surgery. Hence, “prophylactic” surgery in ansymptomatic patient with MR and normal LV functionequires a very high likelihood of successful repair.

. Indications for Mitral Valve Operation

lass I

. MV surgery is recommended for the symptomaticpatient with acute severe MR.* (Level of Evidence: B)

. MV surgery is beneficial for patients with chronicsevere MR* and NYHA functional class II, III, or IVsymptoms in the absence of severe LV dysfunction(severe LV dysfunction is defined as ejection fractionless than 0.30) and/or end-systolic dimension greaterthan 55 mm. (Level of Evidence: B)

. MV surgery is beneficial for asymptomatic patientswith chronic severe MR* and mild to moderate LVdysfunction, ejection fraction 0.30 to 0.60, and/orend-systolic dimension greater than or equal to 40
mm. (Level of Evidence: B)


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. MV repair is recommended over MV replacementin the majority of patients with severe chronic MR*who require surgery, and patients should be re-ferred to surgical centers experienced in MV repair.(Level of Evidence: C)

lass IIa

. MV repair is reasonable in experienced surgical cen-ters for asymptomatic patients with chronic severeMR* with preserved LV function (ejection fractiongreater than 0.60 and end-systolic dimension lessthan 40 mm) in whom the likelihood of successfulrepair without residual MR is greater than 90%.(Level of Evidence: B)

. MV surgery is reasonable for asymptomatic pa-tients with chronic severe MR,* preserved LVfunction, and new onset of atrial fibrillation. (Levelof Evidence: C)

. MV surgery is reasonable for asymptomatic pa-tients with chronic severe MR,* preserved LVfunction, and pulmonary hypertension (pulmonaryartery systolic pressure greater than 50 mm Hg atrest or greater than 60 mm Hg with exercise).(Level of Evidence: C)

. MV surgery is reasonable for patients with chronicsevere MR* due to a primary abnormality of themitral apparatus and NYHA functional class III–IVsymptoms and severe LV dysfunction (ejection frac-tion less than 0.30 and/or end-systolic dimensiongreater than 55 mm) in whom MV repair is highlylikely. (Level of Evidence: C)

lass IIb

MV repair may be considered for patients withchronic severe secondary MR* due to severe LVdysfunction (ejection fraction less than 0.30) whohave persistent NYHA functional class III–IV symp-toms despite optimal therapy for heart failure, in-cluding biventricular pacing. (Level of Evidence: C)

lass III

. MV surgery is not indicated for asymptomatic pa-tients with MR and preserved LV function (ejectionfraction greater than 0.60 and end-systolic dimensionless than 40 mm) in whom significant doubt aboutthe feasibility of repair exists. (Level of Evidence: C)

. Isolated MV surgery is not indicated for patients withmild or moderate MR. (Level of Evidence: C)

See Table 1 (7).

The prediction of successful MV repair is important iniming surgery. This prediction is based on the skill andxperience of the surgeon in performing repair, on the
ause of the MR, and on MV morphology. The skill and w

xperience of the surgeon are probably the most impor-ant determinants of the eventual success of MV repair.

The number of patients undergoing MV repair for MRas increased steadily over the past decade in the Unitedtates and Canada in relation to the number undergoingV replacement. However, among isolated MV procedures

eported in the STS National Cardiac Database from 1999o 2000 (359), the frequency of repair was only 35.7% (3027f a total of 8486 procedures), which suggests that MVepair is underutilized. Current data indicate that therequency of MV repair is increasing yearly (93). The STSational database also indicates an operative mortality rate of

ess than 2% in patients undergoing isolated MV repair in004, which compares favorably to the more than 6% operativeortality rate for patients undergoing isolated MV replace-ent (93). In light of the beneficial effect of MV repair on

urvival and LV function, cardiologists are strongly encouragedo refer patients who are candidates for MV repair to surgicalenters experienced in performing MV repair.

ymptomatic Patients With Normal Left Ventricular Function

atients with symptoms of congestive heart failure despiteormal LV systolic function (ejection fraction greater than.60 and end-systolic dimension less than 40 mm) requireurgery. Surgery should be performed in patients with evenild symptoms and severe MR (Fig. 7), especially if it

ppears that MV repair rather than replacement can beerformed.

symptomatic and Symptomatic Patients with Left Ventricularysfunction

he timing of surgery for asymptomatic patients is contro-ersial, but most would now agree that MV surgery isndicated with the appearance of echocardiographic indica-ors of LV dysfunction. These include LV ejection fractioness than or equal to 0.60 and/or LV end-systolic dimensionreater than or equal to 40 mm (Fig. 7). MV surgery shouldlso be recommended for symptomatic patients with evi-ence of LV systolic dysfunction (ejection fraction less thanr equal to 0.60 and/or end-systolic dimension greater thanr equal to 40 mm).Determining the surgical candidacy of the symptomatic

atient with MR and far-advanced LV dysfunction is aommon clinical dilemma. The question that often arises ishether the patient with MR with advanced LV dysfunc-

ion is no longer a candidate for surgery. Although it isifficult, one must distinguish primary cardiomyopathy withecondary “functional” MR from primary MR with second-ry myocardial dysfunction. In the latter case, surgeryhould still be contemplated if MV repair appears likelyFig. 7). In patients with severe LV dysfunction andignificant functional MR, the modification of MV geom-try by an “undersized” annular ring may be beneficial360–365), although the impact on outcomes compared
ith aggressive medical therapy, including beta blockers and


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ardiac resynchronization therapy (338–341), has not beentudied in a prospective randomized trial.

symptomatic Patients With Normal Left Ventricular Function

s noted previously, repair of a severely regurgitant valveay be contemplated in an asymptomatic patient with

evere MR and normal LV function to preserve LV size andunction and prevent the sequelae of chronic severe MR324). Although there are no randomized data with whicho recommend this approach to all patients, the committeeecognizes that some experienced centers are moving in thisirection for patients for whom the likelihood of successful

igure 7. Management strategy for patients with chronic severe mitral reguith normal left ventricular (LV) function if performed by an experiencedF indicates atrial fibrillation; Echo, echocardiography; EF, ejection fractitral valve replacement.

epair is high. Natural history studies indicate uniformly tcontent.onlinejacDownloaded from

hat asymptomatic patients with severe MR and normal LVunction have a high likelihood of developing symptomsnd/or LV dysfunction that warrants surgery over the coursef 6 to 10 years (313,317,324,325). Two recent studies havelso addressed the risk of sudden death in asymptomaticatients with severe MR and normal LV function (324,325).n a long-term retrospective study in which severity of MR wasuantified by Doppler echocardiography (324), 198 patientsith an effective orifice area greater than 40 mm2 had a 4%er year risk of cardiac death during a mean follow-uperiod of 2.7 years. However, in the second study of 132atients followed up prospectively for 5 years, during which

ion. *Mitral valve (MV) repair may be performed in asymptomatic patientsal team and if the likelihood of successful MV repair is greater than 90%.SD, end-systolic dimension; eval, evaluation; HT, hypertension; MVR,

rgitatsurgicion; E

he indications for surgery were symptoms, development of by on October 16, 2006 c.org


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V dysfunction (ejection fraction less than 0.60), LVilatation (LV end-systolic dimension greater than 45 mm),trial fibrillation, or pulmonary hypertension, there was onlycardiac death in an asymptomatic patient, but this patientad refused surgery which was indicated by development ofV dilatation (325).MV repair is often recommended in hemodynamically

table patients with newly acquired severe MR, such asight occur with ruptured chordae. Surgery is also recom-ended in asymptomatic patients with chronic MR with

ecent onset of atrial fibrillation in whom there is a highikelihood of successful valve repair (see below).

Surgery for asymptomatic patients with severe MR andormal LV function should only be considered if there is areater than 90% likelihood of successful valve repair in aenter experienced in this procedure. As noted above, cardiol-gists are strongly encouraged to refer patients who areandidates for MV repair to surgical centers experienced inerforming MV repair.

trial Fibrillation

he development of atrial fibrillation is independentlyssociated with a high risk of cardiac death or heart failure366), and preoperative atrial fibrillation is an independentredictor of reduced long-term survival after MV surgery forhronic MR (333,366–368). Hence, many clinicians con-ider the recent onset of atrial fibrillation to be an indicationn and of itself for surgery, if there is a high likelihood ofalve repair (Fig. 7) (356,369). In patients presenting for

V operation with chronic atrial fibrillation, a concomitantaze procedure may prevent future thromboembolic events

y restoring normal sinus rhythm (370–376). The decisiono proceed with a Maze procedure should be based on thege and health of the patient, as well as the surgicalxpertise, because this procedure may add to the morbidityf the operation.

. Ischemic Mitral Regurgitation

he outlook for the patient with ischemic MR is substan-ially worse than that for regurgitation from other causes377,378). A worse prognosis accrues from the fact thatschemic MR is usually caused by LV dysfunction resultingrom myocardial infarction. Furthermore, the MV itself issually anatomically normal, and MR is secondary to papillaryuscle displacement and tethering of the mitral leaflet(s).he mechanism of MR in chronic ischemic disease is localV remodeling (apical and posterior displacement of pap-

llary muscles), which leads to excess valvular tenting andoss of systolic annular contraction (379–386). The indica-ion for MV operation in the patient who undergoes CABGith mild to moderate MR is still unclear, but there are data

o indicate benefit of MV repair in such patients (387–390).atients with ischemic heart disease who have MR have aorse prognosis than those without MR (391–394). CABG

lone may improve LV function and reduce ischemic MR in rcontent.onlinejacDownloaded from

elected patients (392,395), especially those with transientevere MR due to ischemia, in whom myocardial revascu-arization can eliminate episodes of severe MR. However,ABG alone is usually insufficient and leaves many patientsith significant residual MR, and these patients wouldenefit from concomitant MV repair at the time of theABG (386–390,396–405). Mitral annuloplasty aloneith a downsized annuloplasty ring is often effective at

elieving MR (400,401,404).In severe MR secondary to acute myocardial infarction,

ypotension and pulmonary edema often occur. Severe MRccurs in 6% to 7% of patients with cardiogenic shock (406).he cause of the MR should be established, because theR may be due to a ruptured papillary muscle, papillaryuscle displacement with leaflet tethering, or annular dila-

ation from severe LV dilatation. Those patients with ancute rupture of the papillary muscle should undergo surgeryn an emergency basis, with either valve repair or MVeplacement (407). In those patients with papillary muscleysfunction, treatment should initially consist of hemody-amic stabilization, usually with insertion of an intra-aorticalloon pump. Surgery should be considered for thoseatients who do not improve with aggressive medicalherapy. Correction of acute severe ischemic MR usuallyequires valve surgery in addition to revascularization. Theest operation for ischemic MR is controversial (408,409),ut MV repair with an annuloplasty ring is the bestpproach in most instances (387,390,396–405).

. Evaluation of Patients After Mitral Valve Replace-ent or Repair

fter MV surgery, follow-up is necessary to detect lateurgical failure and assess LV function, as discussed inection IX-B. For patients in whom a bioprosthesis haseen inserted, the specter of eventual deterioration is alwaysresent and must be anticipated. If a mechanical valve haseen inserted, anticoagulation is required, and chronicurveillance of prothrombin time and INR is necessary.fter valve repair, follow-up to assess the effectiveness of the

epair is indicated early, especially because most repairailures are detected soon after surgery.


perative mortality increases and survival is reduced inatients with MR older than 75 years of age, especially ifV replacement must be performed or if the patient has

oncomitant CAD or other valve lesions (92,95,327,410–13). Operative mortality in the elderly is low in experi-nced centers (414), but the overall operative mortality for

V replacement in this age group in the United Statesxceeds 14% (95,412,413) and is particularly high (greaterhan 20%) in low-volume centers (95). Although the risksre reduced if MV repair is performed rather than MVeplacement, the majority of patients in this age groupequire concomitant CABG (413). The average operative
isk for combined MV repair plus CABG in the United


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tates is 8% (93), which will undoubtedly be higher in thelder population. These risks are worth taking in patientsith significant symptoms. However, under most circum-

tances, asymptomatic patients or patients with mild symp-oms should be treated medically.

. Multiple Valve Disease

emarkably few data exist to objectively guide the manage-ent of mixed valve disease. The large number of combined

emodynamic disturbances (and their varied severity) yieldslarge number of potential combinations to consider, and

ew data exist for any specific category. Hence, each caseust be considered individually, and management must be

ased on understanding the potential derangements inemodynamics and LV function and the probable benefit ofedical versus surgical therapy. The committee has devel-

ped no specific recommendations in this section. Specificombined valve lesions are discussed in the full text of theseuidelines.

. Tricuspid Valve Disease

. Diagnosis

he physical examination is the initial key to diagnosis ofricuspid valve disease. Echocardiography is valuable inssessing tricuspid valve structure and motion, measuringnnular size, and identifying other cardiac abnormalitieshat might influence tricuspid valve function. Dopplerchocardiography provides estimation of the severity of TR415), RV systolic pressure, and the tricuspid valve diastolicradient. Because clinically insignificant TR is detected byolor Doppler imaging in many normal persons, clinicalorrelation and judgment must accompany the echocardio-raphic results. Systolic pulmonary artery pressures greaterhan 55 mm Hg are likely to cause TR with anatomicallyormal tricuspid valves, whereas TR occurring with systoliculmonary artery pressures less than 40 mm Hg is likely toeflect a structural abnormality of the valve apparatus.ystolic pulmonary artery pressure estimation combinedith information about annular circumference will further

mprove the accuracy of clinical assessment.

. Management

lass I

Tricuspid valve repair is beneficial for severe TR inpatients with MV disease requiring MV surgery.(Level of Evidence: B)

lass IIa

. Tricuspid valve replacement or annuloplasty is rea-sonable for severe primary TR when symptomatic.(Level of Evidence: C)

. Tricuspid valve replacement is reasonable for severe TR
secondary to diseased/abnormal tricuspid valve leaflets r

not amenable to annuloplasty or repair. (Level of Evi-dence: C)

lass IIb

Tricuspid annuloplasty may be considered for lessthan severe TR in patients undergoing MV surgerywhen there is pulmonary hypertension or tricuspidannular dilatation. (Level of Evidence: C)

lass III

. Tricuspid valve replacement or annuloplasty is notindicated in asymptomatic patients with TR whosepulmonary artery systolic pressure is less than 60mm Hg in the presence of a normal MV. (Level ofEvidence: C)

. Tricuspid valve replacement or annuloplasty is notindicated in patients with mild primary TR. (Level ofEvidence: C)

Surgery for TR commonly occurs at the time of MVurgery. TR associated with dilatation of the tricuspidnnulus should be repaired (416,417) because tricuspidilatation is an ongoing process that may progress to severeR if left untreated. Patients with severe TR of any causeave a poor long-term outcome because of RV dysfunctionnd/or systemic venous congestion (418). Tricuspid valvend chordal reconstruction can be attempted in some casesf TR resulting from endocarditis and trauma (419–421).n recent years, annuloplasty has become an establishedurgical approach to significant TR (416,417,422–424).

When the valve leaflets themselves are diseased, abnor-al, or destroyed, valve replacement with a low-profileechanical valve or bioprosthesis is often necessary (425). A

iological prosthesis is preferred because of the high rate ofhromboembolic complications with mechanical prosthesesn the tricuspid position.

. Drug-Related Valvular Heart Disease

n addition to the common causes of the valvular lesionsescribed in the preceding sections, there are a number ofncommon causes related to systemic diseases (e.g., rheuma-oid arthritis, systemic lupus erythematosus, anti-phospholipidntibody syndrome, and ankylosing spondylitis), drugs (e.g.,rgotamine, methysergide, anorexiant medications, and per-olide), and toxins. It is beyond the scope of these guidelines toiscuss the specific pathology and natural history of valveisease stemming from each of these many causes. In general,he evaluation and management strategies for patients withalve disease related to these disorders are directed bothoward the underlying systemic process when appropriatend to the diagnosis and treatment of the associated valvularisease according to the guidelines developed for each of thealve lesions, as described in Section III.

The sympathomimetic appetite-suppressant drug fen-uramine and its pure d-enantiomer, dexfenfluramine, were
emoved from the market in September 1997 after several


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eports of unusual left-sided valvular heart disease (AR andR) linked to these agents (426–430). To date, an excess

revalence of valvular heart disease has not been reported foributramine, a serotonin and norepinephrine reuptake in-ibitor, or for phentermine when used as monotherapy forbesity (431,432). There are now several reports of aarcinoid-like valvulopathy in Parkinson’s disease patientsreated with pergolide, a dopamine-receptor agonist (433–35).

. Radiation Heart Disease

ediastinal radiation may produce cardiac valve abnormal-ties that usually become evident at least 5 years after theadiation injury. The assessment and treatment of theseatients can be difficult, in part because these valve lesionsccur within a context of multiple cardiac and noncardiacbnormalities produced by radiation. Radiation-inducedalvular lesions stem from calcification of valve leaflets andhe fibrous skeleton of the heart. Mixed aortic valve diseaseith AS and AR is the most common lesion, but MR andR may also occur.Valve dysfunction is often part of a presenting picture of

ongestive heart failure and dyspnea, but the relative con-ributions of valve dysfunction and restrictive cardiomyop-thy may be difficult to separate. In addition, recurrentleural effusions are often prominent, and radiation-inducedulmonary dysfunction can occur. Thus, dyspnea is usuallymultifactorial problem in these patients. For patients with

adiation heart disease, surgery for any cardiac lesion shoulde approached with caution (436). Patients with this con-ition should be evaluated in centers with experience in itsanagement (437).

V. EVALUATION AND MANAGEMENT OF INFECTIVENDOCARDITIS

lass I

Patients at risk for infective endocarditis who haveunexplained fever for more than 48 h should have atleast 2 sets of blood cultures obtained from differentsites. (Level of Evidence: B)

lass III

Patients with known valve disease or a valve prosthe-sis should not receive antibiotics before blood cul-tures are obtained for unexplained fever. (Level ofEvidence: C)

he diagnosis of infective endocarditis in a patient with aathological murmur or a valvular prosthesis and unex-lained fever lasting more than 72 h should include anssessment for vascular and immunologic phenomena, 3 tosets of blood cultures, and a transthoracic echocardiogram.definitive diagnosis may be made with positive blood

ultures and/or characteristic echocardiographic findings.
he role of echocardiography has emerged with visualiza- t

ion of vegetation by transthoracic echocardiography inpproximately 60% to 75% of patients and by TEE in morehan 95% of patients (438). When the echocardiogram isechnically inadequate, is nondiagnostic, or is negative fornfective endocarditis, TEE should be obtained. The mod-fied Duke criteria (439) define major and minor criteria fornfective endocarditis.

. Antimicrobial Therapy

ntimicrobial therapy in endocarditis is guided by identifi-ation of the causative organism. The majority (80%) ofases of endocarditis are due to streptococcal and staphylo-occal organisms. The latter species is also the most fre-uent organism in endocarditis resulting from intravenousrug abuse. Eighty percent of tricuspid valve infection is bytaphylococcus aureus. This organism is also a frequent causef infective endocarditis in patients with insulin-dependentiabetes mellitus. With prosthetic valve endocarditis, a widepectrum of organisms can be responsible within the firstear of operation. However, in “early” prosthetic valvendocarditis, usually defined as endocarditis during the first

months after surgery, Staphylococcus epidermidis is theredominant offending organism. Late-onset prostheticalve endocarditis follows the profile of native valve endo-arditis, that is, streptococci (viridans) and staphylococci. En-erococcus faecalis and E. faecium account for 90% of entero-occal endocarditis, which is usually associated withalignancy or manipulation of the genitourinary or gastro-

ntestinal tract. Gram-positive and Gram-negative bacillire relatively uncommon causes of endocarditis. In recentears, the HACEK group of organisms (Haemophilus,ctinobacillus, Cardiobacterium, Eikenella, and Kingella species)as become an important cause of endocarditis. These organ-

sms cause large vegetations (greater than 1 cm), large-vesselmbolism, and congestive heart failure. They should be con-idered along with fungal endocarditis when large vegetationsre noted. Fungi, especially Candida, are important causes ofndocarditis in patients with prosthetic valves, compromisedmmune systems, and intravenous drug abuse. The AHAecommendations for antimicrobial regimens were updated in005 (440), and complete treatment regimens are provided inhat document which can be found at http://www.mericanheart.org/presenter.jhtml?identifier�2158.

Culture-negative endocarditis most frequently (62%) re-ults from prior antibiotic treatment before blood culturesre drawn. Other reasons for negative blood cultures includenfections due to Candida; Aspergillus; other fastidious,low-growing organisms such as Q-fever and Bartonellarganisms; and noninfective endocarditis such as Libman-acks endocarditis in patients with systemic lupus erythem-tosus.

. Indications for Echocardiography in Suspected ornown Endocarditis

chocardiography is useful for detection and characteriza-
ion of the hemodynamic and pathological consequences

http://www.americanheart.org/presenter.jhtml?identifier=2158

http://www.americanheart.org/presenter.jhtml?identifier=2158


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f infection, including valvular vegetations; valvular re-urgitation; ventricular dysfunction; and associated le-ions such as abscesses, shunts, and ruptured chordae.he indications for transthoracic and TEE are discussed

n the “ACC/AHA/ASE 2004 Guidelines for the Clin-cal Application of Echocardiography” (1) and the 2005HA endocarditis guidelines (440). Transesophageal

maging is more sensitive in detecting vegetations thanransthoracic imaging (438,440,441), particularly in pa-ients with prosthetic valves, and in determining the pres-nce and severity of important complications such as ab-cesses and perforations. In patients with prosthetic valves,t is reasonable to proceed directly to TEE as the first-lineiagnostic test when endocarditis is suspected. Echocardi-graphy can be useful in the case of culture-negativendocarditis (442) or the diagnosis of a persistent bactere-ia the source of which remains unidentified after appro-

riate evaluation (1).

. Transthoracic Echocardiography in Endocarditis

lass I

. Transthoracic echocardiography to detect valvularvegetations with or without positive blood cultures isrecommended for the diagnosis of infective endocar-ditis. (Level of Evidence: B)

. Transthoracic echocardiography is recommended tocharacterize the hemodynamic severity of valvularlesions in known infective endocarditis. (Level ofEvidence: B)

. Transthoracic echocardiography is recommended forassessment of complications of infective endocarditis(e.g., abscesses, perforation, and shunts). (Level ofEvidence: B)

. Transthoracic echocardiography is recommended forreassessment of high-risk patients (e.g., those with avirulent organism, clinical deterioration, persistentor recurrent fever, new murmur, or persistent bacte-remia). (Level of Evidence: C)

lass IIa

Transthoracic echocardiography is reasonable to di-agnose infective endocarditis of a prosthetic valve inthe presence of persistent fever without bacteremia ora new murmur. (Level of Evidence: C)

lass IIb

Transthoracic echocardiography may be consideredfor the re-evaluation of prosthetic valve endocarditisduring antibiotic therapy in the absence of clinicaldeterioration. (Level of Evidence: C)

lass III

Transthoracic echocardiography is not indicated tore-evaluate uncomplicated (including no regurgita-
tion on baseline echocardiogram) native valve endo- p

carditis during antibiotic treatment in the absence ofclinical deterioration, new physical findings, or per-sistent fever. (Level of Evidence: C)

. Transesophageal Echocardiography in Endocarditis

lass I

. TEE is recommended to assess the severity of valvu-lar lesions in symptomatic patients with infectiveendocarditis, if transthoracic echocardiography isnondiagnostic. (Level of Evidence: C)

. TEE is recommended to diagnose infective endocar-ditis in patients with valvular heart disease andpositive blood cultures, if transthoracic echocardiog-raphy is nondiagnostic. (Level of Evidence: C)

. TEE is recommended to diagnose complications ofinfective endocarditis with potential impact on prog-nosis and management (e.g., abscesses, perforation,and shunts). (Level of Evidence: C)

. TEE is recommended as first-line diagnostic study todiagnose prosthetic valve endocarditis and assess forcomplications. (Level of Evidence: C)

. TEE is recommended for preoperative evaluation inpatients with known infective endocarditis, unlessthe need for surgery is evident on transthoracicimaging and unless preoperative imaging will delaysurgery in urgent cases. (Level of Evidence: C)

. Intraoperative TEE is recommended for patientsundergoing valve surgery for infective endocarditis.(Level of Evidence: C)

lass IIa

TEE is reasonable to diagnose possible infectiveendocarditis in patients with persistent staphylococ-cal bacteremia without a known source. (Level ofEvidence: C)

lass IIb

TEE might be considered to detect infective endo-carditis in patients with nosocomial staphylococcalbacteremia. (Level of Evidence: C)

. Indications for Surgery in Patients With Acutenfective Endocarditis

urgery is indicated in patients with life-threatening con-estive heart failure or cardiogenic shock due to surgicallyreatable valvular heart disease with or without provennfective endocarditis if the patient has reasonable prospectsf recovery with satisfactory quality of life after the opera-ion (378,440,443–453). Surgery should not be delayed inhe setting of acute infective endocarditis when congestiveeart failure intervenes. Surgery is not indicated if compli-ations (severe embolic cerebral damage) or comorbid con-itions make the prospect of recovery remote.The indications for surgery for infective endocarditis in

atients with stable hemodynamics are less clear. Consulta- by on October 16, 2006 c.org


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ion with a cardiovascular surgeon is recommended in aatient with complicated endocarditis so that the surgicaleam is aware of the patient who may suddenly need surgery.urgery is recommended in patients with annular or aorticbscesses, heart block, recurrent emboli on appropriatentibiotic therapy, infections resistant to antibiotic therapy,nd fungal endocarditis. Prosthetic valve endocarditis andative valve endocarditis caused by S. aureus are almostlways surgical diseases. Early surgery in MV endocarditisaused by virulent organisms (such as S. aureus or fungi) mayake repair possible. Echocardiography, especially with

ransesophageal imaging, identifies vegetations and providesize estimation in many instances. Patients with a vegetationiameter greater than 10 mm have a significantly higher

ncidence of embolization than those with a vegetationiameter less than or equal to 10 mm (438), and this riskppears to be higher in patients with MV endocarditis thann those with aortic valve endocarditis. However, surgery onhe basis of vegetation size alone is controversial.

Patients with prosthetic valves who receive warfarinnticoagulation and develop endocarditis should have theirarfarin discontinued and replaced with heparin. This

ecommendation is less related to the possibility of hemor-hagic complications of endocarditis (454) than to theossibility of urgent surgery. Likewise, aspirin, if part of theedical regimen, should also be discontinued. If neurolog-

cal symptoms develop, anticoagulation should be discon-inued until an intracranial hemorrhagic event is excluded byagnetic resonance imaging or computed tomographic

canning.

. Surgery for Native Valve Endocarditis

lass I

. Surgery of the native valve is indicated in patientswith acute infective endocarditis who present withvalve stenosis or regurgitation resulting in heartfailure. (Level of Evidence: B)

. Surgery of the native valve is indicated in patientswith acute infective endocarditis who present withAR or MR with hemodynamic evidence of elevatedLV end-diastolic or left atrial pressures (e.g., prema-ture closure of MV with AR, rapid decelerating MRsignal by continuous-wave Doppler [v-wave cutoffsign], or moderate or severe pulmonary hyperten-sion). (Level of Evidence: B)

. Surgery of the native valve is indicated in patientswith infective endocarditis caused by fungal or otherhighly resistant organisms. (Level of Evidence: B)

. Surgery of the native valve is indicated in patientswith infective endocarditis complicated by heartblock, annular or aortic abscess, or destructive pen-etrating lesions (e.g., sinus of Valsalva to right
atrium, right ventricle, or left atrium fistula; mitral

leaflet perforation with aortic valve endocarditis; orinfection in annulus fibrosa). (Level of Evidence: B)

lass IIa

Surgery of the native valve is reasonable in patientswith infective endocarditis who present with recur-rent emboli and persistent vegetations despite appro-priate antibiotic therapy. (Level of Evidence: C)

lass IIb

Surgery of the native valve may be considered inpatients with infective endocarditis who present withmobile vegetations in excess of 10 mm with orwithout emboli. (Level of Evidence: C)

. Surgery for Prosthetic Valve Endocarditis

lass I

. Consultation with a cardiac surgeon is indicated forpatients with infective endocarditis of a prostheticvalve. (Level of Evidence: C)

. Surgery is indicated for patients with infective endo-carditis of a prosthetic valve who present with heartfailure. (Level of Evidence: B)

. Surgery is indicated for patients with infective endo-carditis of a prosthetic valve who present with dehis-cence evidenced by cine fluoroscopy or echocardiog-raphy. (Level of Evidence: B)

. Surgery is indicated for patients with infective endo-carditis of a prosthetic valve who present with evi-dence of increasing obstruction or worsening regur-gitation. (Level of Evidence: C)

. Surgery is indicated for patients with infective endo-carditis of a prosthetic valve who present with com-plications (e.g., abscess formation). (Level of Evi-dence: C)

lass IIa

. Surgery is reasonable for patients with infectiveendocarditis of a prosthetic valve who present withevidence of persistent bacteremia or recurrent embolidespite appropriate antibiotic treatment. (Level ofEvidence: C)

. Surgery is reasonable for patients with infectiveendocarditis of a prosthetic valve who present withrelapsing infection. (Level of Evidence: C)

lass III

Routine surgery is not indicated for patients withuncomplicated infective endocarditis of a prostheticvalve caused by first infection with a sensitive organ-
ism. (Level of Evidence: C)


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. MANAGEMENT OF VALVULAR DISEASE INREGNANCY

. Physiological Changes of Pregnancy

he evaluation and management of valvular heart disease inhe pregnant patient requires an understanding of theormal physiological changes associated with gestation,

abor, delivery, and the early postpartum period. On aver-ge, there is a 50% increase in circulating blood volumeuring pregnancy that is accompanied by a commensurate

ncrease in cardiac output that usually peaks between theidportion of the second and third trimesters. Because of

he effects of uterine circulation and endogenous hormones,ystemic vascular resistance falls with a disproportionatelyreater lowering of diastolic blood pressure and a wide pulseressure. Inferior vena caval obstruction from a gravid uterusn the supine position can result in an abrupt decrease inardiac preload, which leads to hypotension.

There is an abrupt increase in cardiac output during labornd delivery related in part to the associated anxiety andain. Uterine contractions can lead to marked increases inoth systolic and diastolic blood pressure. After delivery,here is an initial surge in preload related to the autotrans-usion of uterine blood into the systemic circulation and toaval decompression (455).

Pregnancy is also associated with a hypercoagulable stateue to relative decreases in protein S activity, stasis, andenous hypertension (456). Estrogens can interfere withollagen deposition within the media of the medium andarge muscular arteries. Circulating elastase can break up thelastic lamellae and weaken the aortic media during preg-ancy. Weakening of the vascular wall may in turn predis-ose to dissection with or without an underlying connectiveissue disorder (457). Relaxin, an insulin-like growth factorormone, is detectable in serum during pregnancy andauses a decrease in collagen synthesis and may predisposeo aortic dissection during pregnancy (458).

The increased blood volume and enhanced cardiac outputssociated with normal pregnancy can accentuate the mur-urs associated with stenotic heart valve lesions (e.g., MS

nd AS). On the other hand, murmurs of AR, MR, andentricular septal defect can actually attenuate or becomenaudible as systemic vascular resistance is lowered (459).

. Echocardiography

ormal pregnancy is accompanied by echocardiographicvidence of mild ventricular chamber enlargement. Pul-onic and tricuspid valvular regurgitation, as assessed byoppler interrogation, is the rule rather than the exception

460). Most women will demonstrate Doppler evidence ofphysiological” MR in the absence of structural valve dis-ase. Atrioventricular valve regurgitation may result fromhe annular dilatation that accompanies ventricular enlarge-ent. Appreciation of these echocardiographic and Doppler

ndings in normal individuals is an important foundation tcontent.onlinejacDownloaded from

or the noninvasive evaluation of subjects with suspectedalvular disease. The use of ultrasound during pregnancyoses no risk to the mother or fetus.

. Management Guidelines

linical experience has identified several cardiac conditionsn which the physiological changes of pregnancy are poorlyolerated. For some conditions, such as cyanotic heartisease, Eisenmenger syndrome, or severe pulmonary hy-ertension, pregnancy should be discouraged. Valvular heart

esions associated with high maternal and fetal risk duringregnancy include severe AS with or without symptoms,R or AR with NYHA functional class III or IV symp-

oms, MS with NYHA functional class II to IV symptoms,echanical valves that require chronic anticoagulation, AR

ssociated with Marfan syndrome, bicuspid aortic valvesith aortic root dilatation, and any condition that results inV systolic dysfunction or pulmonary hypertension (461–64). Outcomes data are limited for pregnant patients withalvular heart disease, except for those with MS.

Individual counseling usually requires a multidisciplinarypproach and should include information regarding contra-eption, maternal and fetal risks of pregnancy, and expectedong-term outcomes. However, many patients with valvulareart disease can be successfully managed throughout preg-ancy and during labor and delivery with conservativeedical measures designed to optimize intravascular volume

nd systemic loading conditions. Simple interventions suchs bed rest and avoidance of the supine position should note overlooked. Whenever possible, symptomatic or severealvular lesions should be addressed and rectified beforeonception and pregnancy. Contemporaneous managementith a dedicated obstetric team accustomed to working withigh-risk patients is encouraged.

. Mitral Stenosis

oung pregnant women with a previous history of acuteheumatic fever and carditis should continue to receiveenicillin prophylaxis as indicated in the nonpregnant state.atients with mild to moderate MS can almost always beanaged with judicious use of diuretics and beta blockade.iuretics are given to relieve pulmonary and excess systemic

enous congestion, but care must be taken to avoid vigorousolume depletion to protect against uteroplacental hypoper-usion. Beta blockers are chiefly indicated to treat or preventachycardia to optimize diastolic filling. Although the non-elective beta blocker propranolol has been in use forecades, some authorities recommend a cardioselective betalocker such as metoprolol or atenolol to prevent theotential deleterious effects of epinephrine blockade onyometrial activity.Patients with severe MS who are symptomatic before

onception will not predictably tolerate the hemodynamicurden of pregnancy and should be considered for percuta-eous balloon mitral valvotomy before conception, provided
he valve is anatomically suitable. Patients with severe MS


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ho develop NYHA functional class III–IV symptomsuring pregnancy should undergo percutaneous balloonalvotomy (465). Percutaneous mitral balloon valvotomyhould only be performed in experienced centers and onlyfter aggressive medical measures have been exhausted.


VP is the most common cause of MR in pregnantomen. MR can usually be managed medically, although on

are occasions, MV surgery is required because of rupturedhordae and acute, severe worsening of MR. Medicalanagement includes diuretics for the rare patient with

ulmonary congestion. Vasodilator therapy is indicated onlyn the presence of concomitant systemic hypertension. ACEnhibitors are considered unsafe and are contraindicatedecause of their multiple adverse effects on fetal develop-ent. When MV surgery is required, repair is always

referred.

. Aortic Stenosis

atients with mild AS and normal LV systolic function cane managed conservatively throughout the entire pregnancy.atients with moderate to severe obstruction (Table 1) orymptoms should be advised to delay conception until relieff AS can be obtained. Women with severe AS who becomeregnant but who remain asymptomatic or have mildymptoms may often be managed conservatively duringregnancy with bed rest, oxygen, and beta blockers. Inomen with severe AS who develop symptoms, consider-

tion may have to be given to either percutaneous aorticalloon valvotomy (466,467) or surgery (depending on thenatomic findings) before labor and delivery. These proce-ures are fraught with danger to both the mother and fetus,lthough successful outcomes have been reported. Aorticoot dilatation in patients with bicuspid aortic valves mayredispose to spontaneous aortic dissection, usually in thehird trimester.


solated AR, like MR, can usually be managed medicallyith a combination of diuretics and, if necessary, vasodilator

herapy (468). ACE inhibitors are considered unsafe and areontraindicated because of their multiple adverse effects onetal development. Women with symptoms or signs of LVailure should be closely monitored throughout labor andelivery with strict attention to volume status and bloodressure. Surgery for AR during pregnancy should beontemplated only for control of refractory NYHA func-ional class III or IV symptoms. The recommendations forVR based on LV size that apply to nonpregnant patients

hould not be used for pregnant patients.

. Pulmonic Stenosis

solated pulmonic stenosis is rarely a significant impediment
o a successful pregnancy. This lesion can be approached o

ith percutaneous valvotomy under echocardiographicuidance when necessary.


ricuspid valve disease may be congenital (Ebstein’s anom-ly, tricuspid atresia) or acquired (endocarditis, myxomatouseplacement/proliferation, carcinoid). The approach to theatient with tricuspid valve involvement as part of a moreomplex congenital heart disease syndrome is predicated onhe features of the associated lesions. Isolated TR shouldot pose a significant problem during pregnancy, althoughare should be taken to prevent diuretic-induced hypoper-usion.

. Marfan Syndrome

pontaneous aortic dissection or rupture is the most fearedardiovascular complication associated with pregnancy inhe Marfan syndrome (457,469,470). Dissection can occurt any point along the aorta but most commonly originatesn the ascending portion. Enlargement of the aortic root toreater than 4.0 cm identifies a particularly high-risk group,lthough a normal dimension is by no means a guaranteegainst this catastrophic complication. Aortic root enlarge-ent may or may not be accompanied by AR. MVP withR is also frequently detected.Any woman with Marfan syndrome should be counseled

gainst pregnancy, because aortic rupture or dissection canccur in any root size. All patients with Marfan syndromehould have a screening transthoracic echocardiogram withssessment of aortic root dimensions. Enlargement greaterhan 4.5 cm is generally considered an indication for electiveepair before conception. If any degree of aortic rootnlargement (greater than 4.0 cm) is first detected duringregnancy, some authorities recommend termination of theregnancy with prompt aortic repair, although this isontroversial. Less controversial is the recommendation forrompt repair if serial imaging studies demonstrate progres-ive dilatation over time. Dissection and rupture are mostikely to occur during the third trimester or near the time ofelivery. The use of prophylactic beta blockade throughouthe pregnancy is strongly recommended. Successful surgicalorrection does not confer a normal risk during subsequentregnancy. Special care must be taken during labor andelivery to provide adequate analgesia to prevent wideurges in blood pressure. Obstetric techniques to shorten theecond stage of labor are appropriate. General anesthesiand caesarean section may allow more optimal hemody-amic control.

. Endocarditis Prophylaxis

he Committee on Rheumatic Fever, Endocarditis, andawasaki Disease of the AHA does not recommend routine

ntibiotic prophylaxis in patients with valvular heart diseasendergoing uncomplicated vaginal delivery or caesareanection unless infection is suspected (8). Antibiotics are
ptional for high-risk patients with prosthetic heart valves,


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previous history of endocarditis, complex congenital heartisease, or a surgically constructed systemic-pulmonaryonduit. Many practitioners routinely provide antibiotics.

. Cardiac Valve Surgery

ardiac valve surgery is a difficult and complex undertakingn the pregnant patient. Even under ideal conditions, theres a high incidence of fetal distress, growth retardation, orastage (471–475). If possible, it is always preferable toelay surgery until the time the fetus is viable and aaesarean section can be performed as part of a concomitantrocedure (476,477). Surgery should be pursued only in theetting of medically refractory cardiac symptoms (pulmo-ary congestion), especially if a low-output syndrome inter-enes.

For suitable valve lesions, repair is always preferred overeplacement, and percutaneous mitral balloon valvotomy isreferred over MV replacement in patients with MS. Ifalve replacement is necessary, the choice of a heart valveubstitute can be problematic.

. Anticoagulation During Pregnancy

. Warfarin

arfarin crosses the placenta and has been associated withn increased incidence of spontaneous abortion, prematu-ity, stillbirth, and fetal bleeding. The true incidence ofarfarin embryopathy has been difficult to ascertain. It has

anged from less than 5% to as high as 67% (478–481), andn estimate of 4% to 10% seems reasonable (482,483).owever, the risk of clinically important embryopathy may

e lower if the dose of warfarin is less than or equal to 5 mger day.Warfarin is probably safe during the first 6 weeks of

estation, but there is a risk of embryopathy if warfarin isaken between 6 and 12 weeks of gestation. For womenequiring long-term warfarin therapy who are attemptingregnancy, it is wise to perform frequent pregnancy testsith the substitution of unfractionated heparin (UFH) or

ow-molecular-weight heparin (LMWH) for warfarin whenregnancy is achieved. Warfarin is also relatively safe duringhe second and third trimesters of pregnancy but must beiscontinued and switched to a heparin compound severaleeks before delivery.

. Unfractionated Heparin

eparin does not cross the placenta and does not have theotential to cause fetal bleeding or teratogenicity. Thus,eparin is generally considered safer than warfarin duringregnancy in terms of the development of embryopathy482,484). However, bleeding at the uteroplacental junctions possible, and numerous case series and patient registriesttest to a high incidence of thromboembolic complications12% to 24%), including fatal valve thrombosis, in high-riskregnant women managed with subcutaneous UFH or
MWH (482,485–487). When heparin is used during the

rst trimester, the risks of maternal thromboembolism andaternal death are more than doubled.During pregnancy, the activated partial thromboplastin

ime (aPTT) response to heparin is often attenuated becausef increased levels of factor VIII and fibrinogen. Adjusted-ose subcutaneous UFH can cause a persistent anticoagu-

ant effect at the time of delivery, which can complicate itsse before labor.

. Low-Molecular-Weight Heparins

MWHs have potential advantages over UFH duringregnancy (488) because they 1) cause less heparin-inducedhrombocytopenia; 2) have a longer plasma half-life and aore predictable dose response than UFH; 3) have greater

ase of administration, with lack of need for laboratoryonitoring and the potential for once-daily dosing admin-

stration; 4) are likely associated with a lower risk ofeparin-induced osteoporosis; and 5) appear to have a lowisk of bleeding complications. They do not cross thelacenta and are likely safe for the fetus.As the pregnancy progresses (and most women gain

eight), the potential volume of distribution for LMWHhanges. It is thus necessary to measure plasma anti-Xaevels 4 to 6 hours after the morning dose and adjust theose of LMWH to achieve an anti-Xa level of approxi-ately 0.7 to 1.2 units per ml.The use of LMWH during pregnancy remains contro-

ersial because of an early warning by the manufacturer andhe Food and Drug Administration in July 2001 regardingafety concerns in this situation. In 2004, labeling approvedy the Food and Drug Administration indicated specificallyhat use of LMWH for thromboprophylaxis in pregnantomen with mechanical prosthetic heart valves has not been

tudied adequately.

. Selection of Anticoagulation Regimen in Pregnantatients With Mechanical Prosthetic Valves

lass I

. All pregnant patients with mechanical prostheticvalves must receive continuous therapeutic anticoag-ulation with frequent monitoring (see Section IX-A).(Level of Evidence: B)

. For women requiring long-term warfarin therapywho are attempting pregnancy, pregnancy testsshould be monitored with discussions about subse-quent anticoagulation therapy, so that anticoagula-tion can be continued uninterrupted when pregnancyis achieved. (Level of Evidence: C)

. Pregnant patients with mechanical prosthetic valveswho elect to stop warfarin between weeks 6 and 12 ofgestation should receive continuous intravenousUFH, dose-adjusted UFH, or dose-adjusted subcu-taneous LMWH. (Level of Evidence: C)

. For pregnant patients with mechanical prosthetic
valves, up to 36 weeks of gestation, the therapeutic


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choice of continuous intravenous or dose-adjusted sub-cutaneous UFH, dose-adjusted LMWH, or warfarinshould be discussed fully. If continuous intravenousUFH is used, the fetal risk is lower, but the maternalrisks of prosthetic valve thrombosis, systemic emboli-zation, infection, osteoporosis, and heparin-inducedthrombocytopenia are relatively higher. (Level of Ev-idence: C)

. In pregnant patients with mechanical prostheticvalves who receive dose-adjusted LMWH, theLMWH should be administered twice daily subcuta-neously to maintain the anti-Xa level between 0.7and 1.2 U per ml 4 h after administration. (Level ofEvidence: C)

. In pregnant patients with mechanical prosthetic valveswho receive dose-adjusted UFH, the aPTT should be atleast twice control. (Level of Evidence: C)

. In pregnant patients with mechanical prostheticvalves who receive warfarin, the INR goal should be3.0 (range 2.5 to 3.5). (Level of Evidence: C)

. In pregnant patients with mechanical prostheticvalves, warfarin should be discontinued and contin-uous intravenous UFH given starting 2 to 3 weeksbefore planned delivery. (Level of Evidence: C)

lass IIa

. In patients with mechanical prosthetic valves, it isreasonable to avoid warfarin between weeks 6 and 12of gestation owing to the high risk of fetal defects.(Level of Evidence: C)

. In patients with mechanical prosthetic valves, it isreasonable to resume UFH 4 to 6 h after delivery andbegin oral warfarin in the absence of significantbleeding. (Level of Evidence: C)

. In patients with mechanical prosthetic valves, it isreasonable to give low-dose aspirin (75 to 100 mg perday) in the second and third trimesters of pregnancyin addition to anticoagulation with warfarin or hep-arin. (Level of Evidence: C)

lass III

. LMWH should not be administered to pregnantpatients with mechanical prosthetic valves unlessanti-Xa levels are monitored 4 to 6 h after adminis-tration. (Level of Evidence: C)

. Dipyridamole should not be used instead of aspirin asan alternative antiplatelet agent in pregnant patientswith mechanical prosthetic valves because of itsharmful effects on the fetus. (Level of Evidence: B)

n April 2004, labeling approved by the Food and Drugdministration stated that pregnancy alone conferred an

ncreased risk for thromboembolism and an even higher riskith thrombotic disease and certain high-risk pregnancy

onditions. Although not adequately studied, women with
echanical prosthetic heart valves may be at higher risk for i

hromboembolism during pregnancy regardless of the anti-oagulant used, and when pregnant, they have a higher ratef fetal loss from stillbirth, spontaneous abortion, andremature delivery.In patients receiving UFH, therapy requires aggressiveonitoring and appropriate dose adjustment. A minimum

arget aPTT ratio of 1.5 times the control is likely to benadequate. A target aPTT ratio of at least twice the controlhould be attained.

There are still insufficient grounds to make definitiveecommendations about optimal antithrombotic therapy inregnant patients with mechanical heart valves, becauseroperly designed studies have not been performed. Sub-tantial concern remains about the fetal safety of warfarin,he efficacy of subcutaneous UFH and of LMWH inreventing thromboembolic complications, and the risks ofaternal bleeding with various regimens.The American College of Chest Physicians Conference

n Antithrombotic and Thrombolytic Therapy (489,490)oncluded that it is reasonable to use one of the following 3egimens: 1) either LMWH or UFH between 6 and 12eeks and close to term only, with warfarin used at other

imes; 2) aggressive dose-adjusted UFH throughout preg-ancy; or 3) aggressive adjusted-dose LMWH throughoutregnancy. Before any of these approaches is used, it isrucial to explain the risks in detail to the patient. If warfarins used, the dose should be adjusted to attain a target INRf 3.0 (range 2.5 to 3.5). If subcutaneous UFH is used, ithould be initiated in high doses (17 500 to 20 000 U every2 h) and adjusted to prolong a 6-h postinjection aPTT oft least twice the control. Adjusted-dose LMWH appears toe a reasonable substitute for UFH, but further informations required about dosing during pregnancy; if LMWH issed during pregnancy, it has been recommended thatMWH be administered twice daily and dosed to achieventi-Xa levels of 0.7 to 1.2 U per ml 4 to 6 h after injection489,491).

The addition of aspirin 75 to 100 mg can be consideredn an attempt to further reduce the risk of thrombosis, withhe recognition that it can increase the risk of bleeding485). Dipyridamole should not be considered as an alter-ative antiplatelet agent because of its harmful effects on theetus. Neither warfarin nor heparin is contraindicated inostpartum mothers who breast-feed (484).

I. MANAGEMENT OF CONGENITAL VALVULAR HEARTISEASE IN ADOLESCENTS AND YOUNG ADULTS

he management of valvular abnormalities associated withomplex congenital heart disease is beyond the scope ofhese guidelines. Rather, this section concerns isolated valvenvolvement when it is the primary anatomic abnormality.

In evaluating valvular stenosis in children, severity issually reported as the peak ventricular-to-peak great arteryystolic gradient at cardiac catheterization or maximum
nstantaneous or mean gradient by Doppler echocardiogra-


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hy rather than valve area. With the development ofoppler echocardiographic assessment of valvular obstruc-

ion, many pediatric cardiologists have continued to rely onradients calculated from peak velocity for the semilunaralves rather than on mean gradient or valve area. The peakradient measured by Doppler velocity (based on maximumnstantaneous velocity) is almost always higher than theeak ventricular–to–peak great vessel gradient measured atatheterization. The difference between Doppler peak in-tantaneous and catheterization peak-to-peak gradients isreater with AS than with pulmonic stenosis and hasesulted in most cardiologists using mean gradients, espe-ially in patients with AS. Significant valvular regurgitationay exacerbate the differences. In contrast to children and

dolescents, valve area is used by many centers in evaluationf the young adult.

. Aortic Stenosis

dolescents and young adults with isolated AS almostlways have congenital fusion of 1 or more commissures thatesults in a bicuspid or unicuspid valve. Although therevalence of bicuspid and unicuspid valves may be as highs 1% to 2%, only 1 of 50 children born with thesebnormalities will actually have significant obstruction oregurgitation by adolescence. For purposes of these guide-ines, adolescents and young adults are defined as patientsith minimally calcified valves who are less than 30 yearsld. Some adults with minimally calcified valves who areore than 30 years old may also benefit under these

uidelines.As the aortic annulus and aortic valve must grow in

arallel with somatic growth throughout childhood, the ratef progression of AS during childhood and adolescentrowth can be different from that in the adult with acquiredS (see Section III-A).

. Evaluation of Asymptomatic Adolescents or Youngdults With Aortic Stenosis

lass I

. An ECG is recommended yearly in the asymptomaticadolescent or young adult with AS who has a Dopplermean gradient greater than 30 mm Hg or a peakvelocity greater than 3.5 m per second (peak gradientgreater than 50 mm Hg) and every 2 years if theechocardiographic Doppler mean gradient is less thanor equal to 30 mm Hg or the peak velocity is less thanor equal to 3.5 m per second (peak gradient less than orequal to 50 mm Hg). (Level of Evidence C)

. Doppler echocardiography is recommended yearly inthe asymptomatic adolescent or young adult with ASwho has a Doppler mean gradient greater than 30mm Hg or a peak velocity greater than 3.5 m persecond (peak gradient greater than 50 mm Hg) andevery 2 years if the Doppler gradient is less than or
equal to 30 mm Hg or the peak jet velocity is less a

than or equal to 3.5 m per second (peak gradient lessthan or equal to 50 mm Hg). (Level of Evidence C)

. Cardiac catheterization for the evaluation of AS is aneffective diagnostic tool in the asymptomatic adoles-cent or young adult when results of Doppler echo-cardiography are equivocal regarding severity of ASor when there is a discrepancy between clinical andnoninvasive findings regarding severity of AS. (Levelof Evidence: C)

. Cardiac catheterization is indicated in the adoles-cent or young adult with AS who has symptoms ofangina, syncope, or dyspnea on exertion if theDoppler mean gradient is greater than 30 mm Hgor the peak velocity is greater than 3.5 m persecond (peak gradient greater than 50 mm Hg).(Level of Evidence C)

. Cardiac catheterization is indicated in the asymp-tomatic adolescent or young adult with AS whodevelops T-wave inversion at rest over the left pre-cordium if the Doppler mean gradient is greater than30 mm Hg or the peak velocity is greater than 3.5 mper second (peak gradient greater than 50 mm Hg).(Level of Evidence C)

lass IIa

. Graded exercise testing is a reasonable diagnosticevaluation in the adolescent or young adult with ASwho has a Doppler mean gradient greater than 30mm Hg or a peak velocity greater than 3.5 m persecond (peak gradient greater than 50 mm Hg) if thepatient is interested in athletic participation, or if theclinical findings and Doppler findings are disparate.(Level of Evidence: C)

. Cardiac catheterization for the evaluation of AS is areasonable diagnostic tool in the asymptomatic ado-lescent or young adult who has a Doppler meangradient greater than 40 mm Hg or a peak velocitygreater than 4 m per second (peak gradient greaterthan 64 mm Hg). (Level of Evidence C)

. Cardiac catheterization for the evaluation of AS isreasonable in the adolescent or young adult who has aDoppler mean gradient greater than 30 mm Hg or apeak velocity greater than 3.5 m per second (peakgradient greater than 50 mm Hg) if the patient isinterested in athletic participation or becoming preg-nant, or if the clinical findings and Doppler echocar-diographic findings are disparate. (Level of Evidence C)

he diagnosis of AS can usually be made clinically, witheverity estimated by ECG and Doppler echocardiographictudies. Diagnostic cardiac catheterization is occasionallyequired if there is a discrepancy among clinical evaluation,CG, and/or Doppler echocardiographic findings. Exercise

esting may be useful, especially in those interested in
thletic participation. Diagnostic cardiac catheterization


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ay be helpful if the clinical findings and the Dopplerchocardiographic assessment are disparate.

. Indications for Aortic Balloon Valvotomy in Adoles-ents and Young Adults

lass I

. Aortic balloon valvotomy is indicated in the adoles-cent or young adult patient with AS who has symptomsof angina, syncope, or dyspnea on exertion and acatheterization peak LV-to-peak aortic gradient greaterthan or equal to 50 mm Hg without a heavily calcifiedvalve. (Level of Evidence: C)*

. Aortic balloon valvotomy is indicated for the asymp-tomatic adolescent or young adult patient with AS whohas a catheterization peak LV-to-peak aortic gradientgreater than 60 mm Hg. (Level of Evidence: C)*

. Aortic balloon valvotomy is indicated in the asymp-tomatic adolescent or young adult patient with ASwho develops ST or T-wave changes over the leftprecordium on ECG at rest or with exercise and whohas a catheterization peak LV-to-aortic gradientgreater than 50 mm Hg. (Level of Evidence: C)*

lass IIa

. Aortic balloon valvotomy is reasonable in the asymp-tomatic adolescent or young adult patient with ASwhen catheterization peak LV-to-peak aortic gradi-ent is greater than 50 mm Hg and the patient wantsto play competitive sports or desires to becomepregnant. (Level of Evidence: C)*

. In the adolescent or young adult patient with AS, aorticballoon valvotomy is probably recommended over valvesurgery when balloon valvotomy is possible. Patientsshould be referred to a center with expertise in balloonvalvotomy. (Level of Evidence: C)*

lass III

Aortic balloon valvotomy should not be performedwhen the asymptomatic adolescent or young adultpatient with AS has a catheterization peak LV-to-peak aortic gradient less than 40 mm Hg withoutsymptoms or ECG changes. (Level of Evidence: C)*

Gradients are usually obtained with patients sedated. Ifeneral anesthesia is used, the gradients may be somewhat

ower.

Balloon valvotomy is an efficacious treatment in childrennd adolescents with AS due to fusion of commissures,hereas it is rarely recommended in older adults with

alcific valves, because even short-term palliation is uncom-on. There are insufficient published data to establish an

ge cutoff. Until more information becomes available, rec-mmendations for balloon valvotomy should be limited todolescents and young adults. Because balloon valvotomy
as resulted in good midterm palliation with little morbidity

nd little or no short- or intermediate-term mortality inhildren, adolescents, and young adults, the indications forntervention are considerably more liberal than those inlder adults, in whom intervention usually involves AVR.urgical valvotomy is of historical interest and is now rarelysed except in situations in which interventional cardiolo-ists are not available.

Children and young adults with peak Doppler gradientsf 64 mm Hg or more or mean gradients greater than 40m Hg and those with symptoms may be considered for

ardiac catheterization and possible balloon dilation. Pa-ients with lower gradients (50 mm Hg peak or 30 mm Hgean) are sometimes referred for catheterization if they are

nterested in participating in athletics, are contemplatingregnancy, or have developed ST-T-wave changes over the

eft precordium at rest or with exercise. In those childrenho have had a balloon valvuloplasty when younger, a

epeat attempt is usually tried before surgical valve replace-ent using the above criteria if significant AR is not

resent.When balloon aortic valvotomy is ineffective or signifi-

ant AR is present, surgical valve repair or replacement maye necessary. Because degeneration of homograft or bio-rosthetic valves is usually accelerated in the young (seeections VII-A and VII-B), AVR is usually performed withmechanical valve. Recently, there has been a renewed

nterest in valve repair or the Ross operation (81,492–495).he most common complications of the Ross procedure areR, usually secondary to neoaortic root dilation, and RVutflow tract obstruction, with intervention necessary inoughly 10% of patients within 7 to 10 years. The indica-ions for surgery with the Ross operation or heterograftomograft do not differ from those for mechanical valveeplacement.


lass I

. An adolescent or young adult with chronic severeAR* with onset of symptoms of angina, syncope, ordyspnea on exertion should receive aortic valve repairor replacement. (Level of Evidence: C)

. Asymptomatic adolescent or young adult patientswith chronic severe AR* with LV systolic dysfunction(ejection fraction less than 0.50) on serial studies 1 to3 months apart should receive aortic valve repair orreplacement. (Level of Evidence: C)

. Asymptomatic adolescent or young adult patientswith chronic severe AR* with progressive LV enlarge-ment (end-diastolic dimension greater than 4 stan-dard deviations above normal) should receive aorticvalve repair or replacement. (Level of Evidence: C)

. Coronary angiography is recommended before AVRin adolescent or young adult patients with AR inwhom a pulmonary autograft (Ross operation) is
contemplated when the origin of the coronary arter-


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ies has not been identified by noninvasive techniques.(Level of Evidence: C)

lass IIb

. An asymptomatic adolescent with chronic severe AR*with moderate AS (peak LV–to–peak aortic gradientgreater than 40 mm Hg at cardiac catheterization)may be considered for aortic valve repair or replace-ment. (Level of Evidence: C)

. An asymptomatic adolescent with chronic severe AR*with onset of ST depression or T-wave inversion overthe left precordium on ECG at rest may be consid-ered for aortic valve repair or replacement. (Level ofEvidence: C)

See Table 1 (7).

AR is an uncommon isolated congenital lesion, al-hough it may occasionally develop in adolescents andoung adults with a bicuspid aortic valve, discrete sub-ortic obstruction, or prolapse of 1 aortic cusp into aentricular septal defect. It is commonly the consequencef attempts to relieve stenosis of the valve by eitheralloon dilation or surgical valvulotomy, or after the Rossrocedure. The indications for surgery with severe iso-

ated AR or mixed aortic valve disease are similar to thoseor adults, that is, symptoms, LV dysfunction (ejectionraction less than 0.50), or severely increased LV end-iastolic or end-systolic diameter, taking into accountariations in body size. As noted above, surgery hassually involved mechanical or biological valve replace-ent (see SectionVII-A), but the Ross operation or

ortic valve repair are viable alternatives in some centers.ndications for surgery in patients with AR and dilatedortic roots or ascending aortas are the same as those forlder adult patients (see Sections III-B-3 and III-C).


lass I

. MV surgery is indicated in the symptomatic adoles-cent or young adult with severe congenital MR* withNYHA functional class III or IV symptoms. (Level ofEvidence: C)

. MV surgery is indicated in the asymptomatic adoles-cent or young adult with severe congenital MR* andLV systolic dysfunction (ejection fraction less than orequal to 0.60). (Level of Evidence: C)

lass IIa

MV repair is reasonable in experienced surgical cen-ters in the asymptomatic adolescent or young adultwith severe congenital MR* with preserved LV sys-
tolic function if the likelihood of successful repair

without residual MR is greater than 90%. (Level ofEvidence: B)

lass IIb

The effectiveness of MV surgery is not well estab-lished in asymptomatic adolescent or young adultpatients with severe congenital MR* and preservedLV systolic function in whom valve replacement ishighly likely. (Level of Evidence: C)

See Table 1 (7).

MR caused by myxomatous MV disease and MVP is aommon congenital lesion. MR also develops commonly inhildren with primum atrioventricular septal defects, whichay involve an isolated ostium primum atrial septal defect;

entricular septal defect in the inlet (posterior) septum; abnor-alities of the mitral or tricuspid valve, including clefts; or a

ombination of these disorders. Repair of the defects in earlyhildhood is now commonplace, with low mortality andorbidity. The most common long-term sequela of surgery isR, which can be mild, moderate, or severe.The pathophysiology, diagnosis, and therapy of residualR in atrioventricular septal defects, rheumatic fever, orVP are similar to those discussed for the adult with MR

Section III-F). When patients with MR develop symptomsr deteriorating LV systolic function, surgery should beerformed. MV repair is usually possible in MR aftertrioventricular septal defect repair or MR secondary to

VP. Rarely, MV replacement with a mechanical oriological valve is necessary.

. Mitral Stenosis

lass I

MV surgery is indicated in adolescent or young adultpatients with congenital MS who have symptoms(NYHA functional class III or IV) and mean MVgradient greater than 10 mm Hg on Doppler echo-cardiography.* (Level of Evidence: C)

lass IIa

. MV surgery is reasonable in adolescent or youngadult patients with congenital MS who have mildsymptoms (NYHA functional class II) and mean MVgradient greater than 10 mm Hg on Doppler echo-cardiography.* (Level of Evidence: C)

. MV surgery is reasonable in the asymptomatic ado-lescent or young adult with congenital MS withpulmonary artery systolic pressure 50 mm Hg orgreater and a mean MV gradient greater than or equalto 10 mm Hg.* (Level of Evidence: C)

lass IIb

The effectiveness of MV surgery is not well estab-lished in the asymptomatic adolescent or young adult
with congenital MS and new-onset atrial fibrillation


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or multiple systemic emboli while receiving adequateanticoagulation.* (Level of Evidence: C)

See Table 1 (7).

In developed countries, MS in adolescents and youngdults is often congenital in origin. In developing areas ofhe world, MS is more likely to result from rheumatic fever.ongenital MS may be associated with a wide variety ofther congenital cardiac malformations of the left side of theeart, including bicuspid aortic valve and AS, supravalvaritral ring, and coarctation of the aorta.The clinical, electrocardiographic, and radiologic features

f congenital MS are similar to those of acquired MS indults. The echocardiogram is essential in evaluating the

V apparatus and papillary muscles and may provideonsiderable insight into the feasibility of successful valveepair. The information obtained from transthoracic imag-ng is usually sufficient in adolescents and young adults, butEE is sometimes necessary.Medical management including beta blockers and diuret-

cs may be of some utility with mild MS. It is important torevent and treat common complications such as pulmonarynfections, endocarditis, and atrial fibrillation. Surgical in-ervention may be necessary in severe cases. The surgicalanagement of congenital MS has improved considerablyith the improved appreciation of the mechanism of MV

unction and the improved ability to visualize the valvefforded by TEE. In those patients with a parachute MV,reation of fenestrations among the fused chordae mayncrease effective orifice area and improve symptoms dra-

atically. MV replacement may occasionally be necessaryut is especially problematic in those with a hypoplasticitral annulus, in whom an annulus-enlarging operationay be necessary. Recently, balloon dilation of congenitalS has been attempted (496), but its utility is limited in

atients with significant stenosis of the subvalvular appara-us. This is one of the most difficult and dangerous thera-eutic catheterization procedures and should be undertakennly in centers with operators who have established experi-nce and skill in this interventional procedure. In adolescentnd young adult patients with rheumatic MS, the results ofalloon dilation are similar to those in older adults (seeection III-D-8).


cquired disease of the tricuspid valve is very uncommon indolescents and young adults and is usually related torauma, bacterial endocarditis in intravenous drug abusers,nd small ventricular septal defects. Most cases of tricuspidalve disease are congenital, with Ebstein’s anomaly of thericuspid valve being the most common.

There is wide variation in the severity of valve leafletbnormalities in Ebstein’s anomaly. An interatrial commu-ication, usually in the form of a patent foramen ovale, is
resent in most cases. If TR elevates right atrial pressure

bove left atrial pressure, right-to-left shunting can occur,ith resulting hypoxemia. One or more accessory conduc-

ion pathways are quite common, with a risk of paroxysmaltrial tachycardia of approximately 25%. Patients withbstein’s anomaly may be asymptomatic with no cyanosis

nd no atrial arrhythmias, but they often are cyanotic owingo right-to-left shunting (497), which is associated withxercise intolerance. RV dysfunction may eventually lead toight-sided heart failure, frequently exacerbated by an atrialrrhythmia such as atrial tachycardia, atrial flutter, or atrialbrillation. Exercise testing may be useful in determiningymptom status and degree of exercise-induced arterialesaturation.Predictors of poor outcome include NYHA functional

lass III or IV symptoms, cardiothoracic ratio greater than5%, atrial fibrillation, severity of cyanosis, and magnitudef TR. However, patients with Ebstein’s anomaly who reachate adolescence and adulthood often have an excellentutcome (498).

. Evaluation of Tricuspid Valve Disease in Adolescentsnd Young Adults

lass I

. An ECG is indicated for the initial evaluation ofadolescent and young adult patients with TR, andserially every 1 to 3 years, depending on severity.(Level of Evidence: C)

. Chest X-ray is indicated for the initial evaluation ofadolescent and young adult patients with TR, andserially every 1 to 3 years, depending on severity.(Level of Evidence: C)

. Doppler echocardiography is indicated for the initialevaluation of adolescent and young adult patientswith TR, and serially every 1 to 3 years, depending onseverity. (Level of Evidence: C)

. Pulse oximetry at rest and/or during exercise isindicated for the initial evaluation of adolescent andyoung adult patients with TR if an atrial communi-cation is present, and serially every 1 to 3 years,depending on severity. (Level of Evidence: C)

lass IIa

. If there is a symptomatic atrial arrhythmia, an elec-trophysiology study can be useful for the initialevaluation of adolescent and young adult patientswith TR. (Level of Evidence: C)

. Exercise testing is reasonable for the initial evalua-tion of adolescent and young adult patients with TR,and serially every 1 to 3 years. (Level of Evidence: C)

lass IIb

Holter monitoring may be considered for the initialevaluation of asymptomatic adolescent and youngadult patients with TR, and serially every 1 to 3 years.
(Level of Evidence: C)


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. Indications for Intervention in Tricuspid Regurgitation

lass I

. Surgery for severe TR is recommended for adolescentand young adult patients with deteriorating exercisecapacity (NYHA functional class III or IV). (Level ofEvidence: C)

. Surgery for severe TR is recommended for adolescentand young adult patients with progressive cyanosisand arterial saturation less than 80% at rest or withexercise. (Level of Evidence: C)

. Interventional catheterization closure of the atrialcommunication is recommended for the adolescentor young adult with TR who is hypoxemic at rest andwith exercise intolerance due to increasing hypoxemiawith exercise, when the tricuspid valve appears diffi-cult to repair surgically. (Level of Evidence: C)

lass IIa

. Surgery for severe TR is reasonable in adolescent andyoung adult patients with NYHA functional class IIsymptoms if the valve appears to be repairable. (Levelof Evidence: C)

. Surgery for severe TR is reasonable in adolescent andyoung adult patients with atrial fibrillation. (Level ofEvidence: C)

lass IIb

. Surgery for severe TR may be considered in asymp-tomatic adolescent and young adult patients withincreasing heart size and a cardiothoracic ratio ofmore than 65%. (Level of Evidence: C)

. Surgery for severe TR may be considered in asymp-tomatic adolescent and young adult patients withstable heart size and an arterial saturation of less than85% when the tricuspid valve appears repairable.(Level of Evidence: C)

. In adolescent and young adult patients with TR whoare mildly cyanotic at rest but who become veryhypoxemic with exercise, closure of the atrial com-munication by interventional catheterization may beconsidered when the valve does not appear amenableto repair. (Level of Evidence: C)

. If surgery for Ebstein’s anomaly is planned in ado-lescent and young adult patients (tricuspid valverepair or replacement), a preoperative electrophysio-logical study may be considered to identify accessorypathways. If present, these may be considered formapping and ablation either preoperatively or at thetime of surgery. (Level of Evidence: C)

urgical management of Ebstein’s anomaly remains chal-enging (499). For adolescents and young adults, tricuspidalve repair may be performed, especially when there is aobile anterior leaflet free of tethering to the ventricular

eptum. If TR is mild and hypoxemia at rest or exercise iscontent.onlinejacDownloaded from

roblematic, closure of the atrial septal defect in theatheterization laboratory has been successful in eliminatinghe hypoxemia. Occasionally, the tricuspid valve is noteparable, and valve replacement with a bioprosthesis or aechanical valve may be necessary (500).

. Pulmonic Stenosis

ecause the pulmonary valve is the least likely valve to beffected by acquired heart disease, virtually all cases ofulmonary valve stenosis are congenital in origin. Mostatients with stenosis have a conical or dome-shapedulmonary valve formed by fusion of the valve leaflets.ccasionally, the valve may be thickened and dysplastic,ith the stenosis caused by inability of the valve leaflets to

eparate sufficiently during ventricular systole.Symptoms are unusual in children or adolescents with

ulmonary valve stenosis even when severe. Adults withong-standing severe obstruction may have dyspnea andatigue secondary to an inability to increase cardiac outputdequately with exercise. Exertional syncope or light-eadedness may occur in severe pulmonic stenosis withystemic or suprasystemic RV pressures, with decreasedreload or dehydration, or with a low systemic vascularesistance state (such as pregnancy). Eventually, with long-tanding untreated severe obstruction, TR and RV failureay occur. At any age, if the foramen ovale is patent, RV

ompliance may be reduced sufficiently to elevate right atrialressure, which allows right-to-left shunting and cyanosis.

. Evaluation of Pulmonic Stenosis in Adolescents andoung Adults

lass I

. An ECG is recommended for the initial evaluation ofpulmonic stenosis in adolescent and young adultpatients, and serially every 5 to 10 years for follow-upexaminations. (Level of Evidence: C)

. Transthoracic Doppler echocardiography is recom-mended for the initial evaluation of pulmonic steno-sis in adolescent and young adult patients, andserially every 5 to 10 years for follow-up examina-tions. (Level of Evidence: C)

. Cardiac catheterization is recommended in the ado-lescent or young adult with pulmonic stenosis forevaluation of the valvular gradient if the Dopplerpeak jet velocity is greater than 3 m per second(estimated peak gradient greater than 36 mm Hg) andballoon dilation can be performed if indicated. (Levelof Evidence: C)

lass III

Diagnostic cardiac catheterization is not recom-mended for the initial diagnostic evaluation of pul-monic stenosis in adolescent and young adult pa-
tients. (Level of Evidence: C)


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. Indications for Balloon Valvotomy in Pulmonic Stenosis

lass I

. Balloon valvotomy is recommended in adolescentand young adult patients with pulmonic stenosis whohave exertional dyspnea, angina, syncope, or presyn-cope and an RV-to-pulmonary artery peak-to-peakgradient greater than 30 mm Hg at catheterization.(Level of Evidence: C)

. Balloon valvotomy is recommended in asymptomaticadolescent and young adult patients with pulmonicstenosis and an RV-to-pulmonary artery peak-to-peak gradient greater than 40 mm Hg at catheteriza-tion. (Level of Evidence: C)

lass IIb

Balloon valvotomy may be reasonable in asymptom-atic adolescent and young adult patients with pul-monic stenosis and an RV-to-pulmonary artery peak-to-peak gradient 30 to 39 mm Hg at catheterization.(Level of Evidence: C)

lass III

Balloon valvotomy is not recommended in asymp-tomatic adolescent and young adult patients withpulmonic stenosis and an RV-to–pulmonary arterypeak-to-peak gradient less than 30 mm Hg at cath-eterization. (Level of Evidence: C)

The clinical course of children and young adults withulmonary valve stenosis has been well described. Theecond Natural History of Congenital Heart Defects study501) reported that the probability of 25-year survival was6%. Fewer than 20% of patients managed medicallyequired a valvotomy, and only 4% of the patients who hadndergone surgery required a second operation. Foratients who had an initial transpulmonary gradient lesshan 25 mm Hg, 96% were free of cardiac operation over25-year period.Infective endocarditis was uncommon. Only 1 case de-

eloped in the 592 patients followed up for a median of 18ears, an incidence of 0.94 per 10 000 patient-years.

Surgical relief of severe obstruction by valvotomy with aransventricular or transpulmonary artery approach predateshe introduction of cardiopulmonary bypass. Balloon val-otomy has now become the procedure of choice in thenited States for the typically domed, thickened valve

502–504). Although long-term follow-up of pulmonaryalloon valvotomy is not yet available, the early and mid-erm results (up to 10 years) (505) suggest that the long-erm results will be similar to surgical valvotomy, with littler no recurrence over a 22- to 30-year period.In those with severe or long-standing valvular obstruc-

ion, infundibular hypertrophy may cause secondary ob-truction when the pulmonary valve is successfully dilated.
his frequently regresses over time without treatment. a

ome have advocated transient pharmacological beta block-de, but there is insufficient information to determinehether this is effective or necessary.

. Pulmonary Regurgitation

ulmonic valve regurgitation is unusual as an isolatedongenital defect, but it is an almost unavoidable result ofither surgical or balloon valvuloplasty of valvular pulmonictenosis or surgical repair of tetralogy of Fallot. Amongatients with pulmonic stenosis who undergo surgical valvot-my, 87% have pulmonary regurgitation by Doppler echocar-iography (501), although it was audible in only 58%.Most physicians would perform pulmonary valve replace-ent in patients with NYHA class II or III symptoms and

evere pulmonary regurgitation, but the indications insymptomatic patients on the basis of regurgitant fraction,V end-diastolic or end-systolic volume, or RV ejection

raction remain unclear.

II. SURGICAL CONSIDERATIONS

. Aortic Valve Surgery

he types of operations available to treat aortic valveysfunction include AVR with a mechanical or biopros-hetic valve, AVR with an allograft (homograft) valve,ulmonic valve autotransplantation (Ross operation)81,492,493,495,506), aortic valve repair, and left ventricleo–descending aorta shunt. Each has specific advantagesnd disadvantages. Cardiopulmonary bypass is used in aorticalve operations, and these procedures are usually performedhrough a median sternotomy incision, although partialternotomy (minimally invasive incisions) is gaining accep-ance. See Sections III-A-6 and III-B-2-g for indicationsor AVR or repair in patients with AS and AR.

. Antithrombotic Therapy for Patients With Aorticechanical Heart Valves

fter mechanical AVR, the goal of antithrombotic therapys usually to achieve an INR of 2.5 to 3.5 for the first 3

onths after surgery and 2.0 to 3.0 beyond that time (seeection IX-A). Low-dose aspirin (75 to 100 mg per day) islso indicated in addition to warfarin (485), as discussed inection IX-A-1. At that level of anticoagulation, the risk ofignificant hemorrhage appears to be 1% to 2% per year.

. Stented and Nonstented Heterografts

. Aortic Valve Replacement With Stented Heterografts

he first-generation stented heterografts (porcine hetero-rafts) exhibited a freedom from structural valve deteriora-ion of approximately 40% by 18 postoperative years. How-ver, the rate of structural valve deterioration is age-related96,507–519), being increased for younger patients, and inatients less than 40 years of age, approximately half of allorcine valves fail by 10 years. Bovine pericardial valves
ppear to have a lower rate of structural valve deterioration,


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ith 15-year data indicating that 77% of valves in survivingatients of all ages are functioning without explantation,nd among patients undergoing primary AVR at an agereater than 65 years, fewer than 10% underwent valvexplantation by 15 postoperative years (96,515). The re-orted rate of structural valve deterioration for second-eneration porcine valves appears so far to be equivalent tohat of stented bovine valves.

. Aortic Valve Replacement With Stentless Heterografts

he major goal of stentless heterografts is to achievenhanced hemodynamic efficiency relative to stented valves520–525). The long-term importance of hemodynamicfficiency of prosthetic heart valves is currently a subject ofnvestigation and disagreement. The argument favoring these of stentless valves is that stented valves of any kind aret least partially stenotic (particularly in small sizes) and thatven small postoperative gradients may lead to incompleteV mass regression postoperatively (522,524–526), whichill, in turn, lead to impaired long-term survival and

ymptom status.Stentless heterografts have the disadvantages that their

mplantation is more complex than that for stented valvesnd their long-term outcomes are unknown. There is a lowncidence (7% to 10%) of early mild AR in some series522,523,525), which may progress with time. Observa-ional studies with 8- to 10-year follow-up (527) appear tohow a low risk of structural valve deterioration withtentless heterografts.

. Aortic Valve Homografts

t had been hoped that aortic valve homografts wouldutlast heterografts, particularly in young patients, but toate, long-term data do not support this view. One possibledvantage of homografts is in the avoidance of early endo-arditis and in the treatment of aortic valve endocarditis528–531), particularly complex aortic root endocarditis.he risk of thromboembolism is very low after homograft

mplantation, and hemodynamic efficiency is excellent evenn small sizes. The biggest disadvantage of homografts ishat reoperation after homograft AVR is more difficult thaneoperation after placement of standard prostheses, becausehe entire homograft may become severely calcified.

. Pulmonic Valve Autotransplantation

ulmonic valve autotransplantation (Ross operation) haseen performed in small numbers, and long-term follow-uptudies have been inconsistent, which makes analysis ofong-term advantages and disadvantages difficult. Thenown advantages of the procedure are that the autograftay grow in children, warfarin is not required, there is a low

ncidence of thromboembolism, the autograft is a hemody-amically efficient valve, and the incidence of endocarditis is

ow (81,492,493,495,506,532). The disadvantage of pul-onic autotransplantation is that the operation is much
ore complex than standard AVR and in most series has

een associated with at least some increase in in-hospitalortality. There is also an incidence of early aortic valve

ailure based on technical considerations or dilatation of theortic root, and the homograft used to replace the pulmonicalve is also subject to failure, sometimes early, within a fewears of operation (506). Deterioration of the pulmonaryomograft often offsets potential advantages of the au-ograft.

. Aortic Valve Repair

ultiple strategies for aortic valve repair have been ex-lored, some successfully. In particular, repair of insufficienticuspid aortic valves in the adult has been increasinglyuccessful at limited numbers of centers (533–535). Amonghe advantages of this strategy are the lack of need fornticoagulation, a low thromboembolic risk, a low endocar-itis risk, a hemodynamically efficient valve, and a straight-orward reoperation, if needed. The disadvantages are lackf uniform applicability, lack of widespread experience withurgical techniques, and the need for reoperation. Long-erm data are limited, but the risk of reoperation appears toe about 15% by 10 postoperative years.Much progress has been made in the repair of aortic

alves rendered insufficient by aortic root pathology228,536–541). When an aortic root aneurysm exists, theperation to restore competence to the aortic valve involvesesecting the aorta and resuspending the valve in associationith a Dacron graft that is used to replace the aorta.dvantages of this strategy include avoidance of warfarin, a

ow thromboembolic risk, a very efficient valve, and whatppears to be a low risk of prosthetic valve endocarditis. Theisadvantages are, again, limited applicability in the settingf intrinsic leaflet pathology and the high level of surgicalxpertise and experience required.

. Major Criteria for Aortic Valve Selection

lass I

. A mechanical prosthesis is recommended for AVR inpatients with a mechanical valve in the mitral ortricuspid position. (Level of Evidence: C)

. A bioprosthesis is recommended for AVR in patientsof any age who will not take warfarin or who havemajor medical contraindications to warfarin therapy.(Level of Evidence: C)

lass IIa

. Patient preference is a reasonable consideration inthe selection of aortic valve operation and valveprosthesis. A mechanical prosthesis is reasonable forAVR in patients under 65 years of age who do nothave a contraindication to anticoagulation. A bio-prosthesis is reasonable for AVR in patients under 65years of age who elect to receive this valve for lifestyleconsiderations after detailed discussions of the risks
of anticoagulation versus the likelihood that a second


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AVR may be necessary in the future. (Level of Evi-dence: C)

. A bioprosthesis is reasonable for AVR in patientsaged 65 years or older without risk factors for throm-boembolism. (Level of Evidence: C)

. Aortic valve re-replacement with a homograft isreasonable for patients with active prosthetic valveendocarditis. (Level of Evidence: C)

lass IIb

A bioprosthesis might be considered for AVR in awoman of childbearing age (see Sections V–E and V–F).(Level of Evidence: C)

. Mitral Valve Surgery

. Mitral Valve Repair

. Myxomatous Mitral Valve

lass I

. MV repair is recommended when anatomically pos-sible for patients with severe degenerative MR whofulfill clinical indications, and patients should bereferred to surgeons who are expert in repair. (Level ofEvidence: B)

. Patients who have undergone successful MV repairshould continue to receive antibiotics as indicated forendocarditis prophylaxis. (Level of Evidence: C)

. Patients who have undergone successful MV repairand have chronic or paroxysmal atrial fibrillationshould continue to receive long-term anticoagulationwith warfarin. (Level of Evidence: B)

. Patients who have undergone successful MV repairshould undergo 2D and Doppler echocardiographybefore discharge or at the first postoperative outpa-tient visit. (Level of Evidence: C)

. Tricuspid valve repair is beneficial for severe TR inpatients with MV disease that requires MV surgery.(Level of Evidence: B)

lass IIa

. Oral anticoagulation is reasonable for the first 3months after MV repair. (Level of Evidence: C)

. Long-term treatment with low-dose aspirin (75 to100 mg per day) is reasonable in patients who haveundergone successful MV repair and remain in sinusrhythm. (Level of Evidence: C)

. Tricuspid annuloplasty is reasonable for mild TR inpatients undergoing MV repair when there is pulmo-nary hypertension or tricuspid annular dilatation.(Level of Evidence: C)

lass IIb

In patients with MR and a history of atrial fibrilla-tion, a Maze procedure may be considered at the time
of MV repair. (Level of Evidence: B) I

yxomatous MV disease produces MR based on rupture orlongation of chordae tendineae, valve leaflet instability,nnulus dilatation, or multiple causes that result in excessive

V leaflet motion. In the majority of these conditions,xperienced surgeons can repair the MV using strategieshat involve removal of unsupported leaflet structures, trans-er of chordae (357,358), or the use of artificial chordae toupport unstable areas of the leaflet, the sliding of supportedreas of the leaflet to cover the MV orifice, and stabilizationf the size and shape of the MV annulus with an artificialing (318,319, 27,343–348). MV repair is the treatment ofhoice for degenerative valve disease, because patients ininus rhythm do not need warfarin, the thromboembolismate is low, valve efficiency and hemodynamics are good,here is little adverse effect on LV function, the risk ofndocarditis is low, and the long-term survival rate isavorable compared with MV replacement (see SectionII-F-3). Concomitant tricuspid valve repair should beerformed when there is severe TR or mild-to-moderateR and tricuspid annular dilatation (see Section III-H-2).

n patients presenting for MV repair with chronic atrialbrillation, a concomitant surgical procedure to eliminatetrial fibrillation may prevent future embolic events byestoring normal sinus rhythm (370–376). The decision toroceed with a surgical procedure to eliminate atrial fibril-

ation should be made based on the age and health of theatient, as well as the surgical expertise, because thisrocedure may add to the morbidity of the operation (seeection III-F-3-b).The likelihood of a successful MV repair is related to the

xtent of the MV dysfunction (with isolated posterior leafletysfunction being the most favorable condition); the pres-nce and extent of calcification; the amount of pliable,oncalcified valve tissue; and surgeon experience. RecurrentR after repair may occur with time, but in favorable

ituations, more than 90% of valves are still functioning wellfter 10 years (318,319).

. Rheumatic Heart Disease

lass I

Percutaneous or surgical MV commissurotomy isindicated when anatomically possible for treatment ofsevere MS, when clinically indicated. (Level of Evi-dence: C)

heumatic MR is inconsistently reparable, and the long-erm outcomes after repair are not as good as for valve repairor degenerative MV disease. Rheumatic pathology ofteneads to leaflet and chordal scarring, which restricts theeaflet motion, and leaflet scarring may be progressive afterepair. Rheumatic MS that is not associated with severehordal fusion or shortening or with calcification may bereated with either percutaneous or open mitral commissur-tomy with a high degree of long-term success. Clinicalndications for these procedures are discussed in Sections
II-D-8 and III-D-9.


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. Ischemic Mitral Valve Disease

y definition, all patients with ischemic MR have signifi-ant CAD that usually has a significant effect on long-termurvival. The pathology of ischemic MR has multipleubgroups, with the most common situation being func-ional MR, in which the valve leaflets are structurallyormal, but LV chamber enlargement and papillary muscleisplacement tether the MV via the chordal attachmentsnd prevent leaflet coaptation (379–386). When functional

R is severe, it may be corrected by placement of annnuloplasty ring that decreases the annular circumference,hortens the intertrigonal distance, reduces the septal-lateralanterior-posterior) annular diameter, and restores the ge-metry of the annulus, thereby allowing the MV leaflets tooapt (387–390,396–405). This strategy acutely decreasesr eliminates MR, but because the fundamental abnormalitys related to LV function, the late survival rate of theseatients is relatively low compared with patients with otherV pathologies, and the recurrence rate of MR is higher.

or patients with moderate functional MR, it is not yet clearhether MV repair improves outcomes.Patients with ischemic MV disease who have anatomicR based on infarction or rupture of the papillary muscles

enefit from either mitral repair or MV replacement.apillary muscle rupture often produces severe MR andemodynamic decompensation, which is an indication formergency surgery.

. Mitral Valve Endocarditis

ith increased surgical experience in mitral reparativeechniques, MV endocarditis has become more consistentlyreatable with repair (542–544). There appears to be a lowisk of recurrent infection, and in experienced hands, it isften possible to avoid the need for an MV prosthesis (seeection IV-C-1). Surgery, however, must not be delayedntil extensive valve disruption has occurred.

. Selection of Mitral Valve Prostheses (Mechanical orioprostheses)

lass I

A bioprosthesis is indicated for MV replacement in apatient who will not take warfarin, is incapable of takingwarfarin, or has a clear contraindication to warfarintherapy. (Level of Evidence: C)

lass IIa

. A mechanical prosthesis is reasonable for MV replace-ment in patients under 65 years of age with long-standing atrial fibrillation. (Level of Evidence: C)

. A bioprosthesis is reasonable for MV replacement inpatients 65 years of age or older. (Level of Evidence: C)

. A bioprosthesis is reasonable for MV replacement inpatients under 65 years of age in sinus rhythm whoelect to receive this valve for lifestyle considerations
after detailed discussions of the risks of anticoagula- v

tion versus the likelihood that a second MV replace-ment may be necessary in the future. (Level ofEvidence: C)

he selection of a valve is a multifactorial decision. TheTS National Cardiac Surgery Database (93) indicates thathe numbers of MV reparative procedures are increasingelative to MV replacement. Among patients receiving an

V replacement, more patients received mechanical valveshan bioprostheses. Medicare data indicate that the mortal-ty for isolated MV replacement in patients older than 65ears is 14.1%, which increases to 20.5% in low-volumeenters (95).When MV pathology is combined with CAD,he risks of surgery increase.

. Choice of Mitral Valve Operation

V repair should be able to be achieved by experiencedurgeons for the majority of patients with degenerative MVisease and ischemic valve disease, and patients should beeferred to surgeons expert in repair. For patients withheumatic MV disease and endocarditis, repair may be moreifficult.For patients undergoing MV replacement, preservation

f the chordal apparatus preserves LV function and en-ances postoperative survival compared with MV replace-ent, in which the apparatus is disrupted (345,353–356), as

iscussed in Section III-F-3. In the randomized trials, thereas no difference in survival rate based on valve type.owever, the failure rate of bioprostheses has been higher

n the mitral than in the aortic position (96,507–509,512–16,518,545), which adds impetus to the use of mechanicalrostheses in younger patients.The availability of surgical ablation procedures for atrial

brillation offers the possibility of converting the patient toinus rhythm and avoiding anticoagulation after MV repair oreplacement with a bioprosthesis (370–376). If patients can beaintained in sinus rhythm, the advantage of a bioprosthesis is

nhanced. For patients with a history of atrial fibrillation whore undergoing MV repair, a Maze-type procedure results ininus rhythm in 75% to 90% of cases by 6 postoperativeonths, with long-term data indicating sustained results up toyears and reduced risk of stroke (373,376).

. Tricuspid Valve Surgery

lass I

Severe TR in the setting of surgery for multivalvulardisease should be corrected. (Level of Evidence: C)

lass IIa

Tricuspid annuloplasty is reasonable for mild TR inpatients undergoing MV surgery when there is pul-monary hypertension or tricuspid annular dilatation.(Level of Evidence: C)

he most common cause of TR is dilatation of the tricuspid
alve annulus caused by pulmonary hypertension. The


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ricuspid leaflets are usually normal, and tricuspid valvennuloplasty usually corrects or improves the situation.evere TR should be treated with annuloplasty duringperations for multivalvular disease (see Section III-H-2).

hen leaflet anatomy is severely abnormal, tricuspid valveeplacement may be needed, but this situation is notommon. There are no data clearly showing the advantagef one type of tricuspid prosthesis over another.

. Valve Selection for Women of Child-Bearing Age

here is no ideal valve prosthesis for women of childbearingge who might wish to become pregnant. Bioprosthesesay be subject to premature heterograft or homograft

ailure. Because mechanical valves require anticoagulation,here is an increased risk of fetal abnormalities and mortal-ty, and there may be an increased risk of maternal compli-ations, including thromboembolism. Discussion with theatient concerning the risk of the prosthesis is important.

III. INTRAOPERATIVE ASSESSMENT

lass I

. Intraoperative TEE is recommended for valve repairsurgery. (Level of Evidence: B)

. Intraoperative TEE is recommended for valve re-placement surgery with a stentless xenograft, ho-mograft, or autograft valve. (Level of Evidence: B)

. Intraoperative TEE is recommended for valve sur-gery for infective endocarditis. (Level of Evidence: B)

lass IIa

Intraoperative TEE is reasonable for all patients under-going cardiac valve surgery. (Level of Evidence: C)

etailed and comprehensive evaluation of valve lesionsuring cardiac surgery has become possible and commonince the development of TEE. This includes confirmationf the preoperative diagnosis and associated pathology,rovision of additional detail and depth about the severitynd mechanism of valve dysfunction, detection of previouslyndiagnosed conditions, and evaluation of the surgical resultn the operating room, which makes possible the immediateorrection of detected problems. Studies have documentedhe impact of intraoperative TEE on valve surgery, withhanges in the operative plan based on TEE findingseported in 11% to 14% of cases and detection of problemsith surgical procedure and subsequent need to return to

ardiopulmonary bypass reported in 2% to 6% (546–549).ther important aspects of TEE during valve surgery

nclude assessment of ventricular function and detection ofntracardiac air and aortic dissection.

Intraoperative TEE is especially important during valveepair surgery. Examination before cardiopulmonary bypassrovides insight into the mechanism of valve dysfunctionnd therefore facilitates surgical planning. More impor-
antly, intraoperative TEE allows immediate assessment of

he repair after cardiopulmonary bypass. IntraoperativeEE during valve replacement surgery with a stentedrosthetic valve is also useful, although there will be a lowerate of problems detected after cardiopulmonary bypass.alve replacement with a stentless xenograft, homograft, or

utograft valve will have a higher likelihood of technicalroblems during surgery, and therefore, TEE is virtuallyssential in this setting because it is currently the best way tossess valve function intraoperatively.

The committee recommends that institutions performingalve surgery establish consistent and credible intraoperativechocardiography programs with knowledgeable echocar-iographers committed to and capable of providing accuratenatomic and functional information relevant to valve op-rations.

X. MANAGEMENT OF PATIENTS WITH PROSTHETICEART VALVES

he results of valve surgery with regard to survival, func-ional class, valve function, and complications are dependentn patient-related factors, cardiac function, type of surgery,ype of prosthesis, and medical comorbidities (550).

. Antithrombotic Therapy

lass I

. After AVR with bileaflet mechanical or Medtronic Hallprostheses, in patients with no risk factors,* warfarin isindicated to achieve an INR of 2.0 to 3.0. If the patienthas risk factors, warfarin is indicated to achieve an INRof 2.5 to 3.5. (Level of Evidence: B)

. After AVR with Starr-Edwards valves or mechanicaldisc valves (other than Medtronic Hall prostheses), inpatients with no risk factors,* warfarin is indicated toachieve an INR of 2.5 to 3.5. (Level of Evidence: B)

. After MV replacement with any mechanical valve,warfarin is indicated to achieve an INR of 2.5 to 3.5.(Level of Evidence: C)

. After AVR or MV replacement with a bioprosthesisand no risk factors,* aspirin is indicated at 75 to 100mg per day. (Level of Evidence: C)

. After AVR with a bioprosthesis and risk factors,*warfarin is indicated to achieve an INR of 2.0 to 3.0.(Level of Evidence: C)

. After MV replacement with a bioprosthesis and riskfactors,* warfarin is indicated to achieve an INR of2.5 to 3.5. (Level of Evidence: C)

. For those patients who are unable to take warfarinafter MV replacement or AVR, aspirin is indicated ina dose of 75 to 325 mg per day. (Level of Evidence: B)

. The addition of aspirin 75 to 100 mg once daily totherapeutic warfarin is recommended for all patients
with mechanical heart valves and those patients with


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lass IIa

. During the first 3 months after AVR with a mechan-ical prosthesis, it is reasonable to give warfarin toachieve an INR of 2.5 to 3.5. (Level of Evidence: C)

. During the first 3 months after AVR or MV replace-ment with a bioprosthesis, in patients with no riskfactors,* it is reasonable to give warfarin to achieve anINR of 2.0 to 3.0. (Level of Evidence: C)

lass IIb

In high-risk patients with prosthetic heart valves inwhom aspirin cannot be used, it may be reasonable togive clopidogrel (75 mg per day) or warfarin toachieve an INR of 3.5 to 4.5. (Level of Evidence: C)

Risk factors include atrial fibrillation, previous thromboem-olism, LV dysfunction, and hypercoagulable condition.

All patients with mechanical valves require warfarinherapy, as indicated in Table 2 (568). Aspirin is recom-ended for all patients with prosthetic heart valves: aspirin

lone in patients with bioprostheses and no risk factors, andspirin combined with warfarin in patients with mechanicaleart valves and high-risk patients with bioprostheses. Inigh-risk patients who cannot take aspirin, the addition oflopidogrel to warfarin therapy should be considered. Evenith the use of warfarin, risk of thromboembolism is 1% to% per year (99,100,102,551–553), but the risk is consid-rably higher without treatment with warfarin (554).

Almost all studies have shown that the risk of embolism isreater with a valve in the mitral position (mechanical or

Table 2. Recommendations for AntithrombotiHeart Valves

Valve TypeAspirin

(75–100 mg)

Mechanical prostheticAVR—low risk

Less than 3 months Class IGreater than 3 months Class I

AVR—high risk Class IMVR Class I

Biological prostheticAVR—low risk


AVR—high risk Class IMVR—low risk


MVR—high risk Class I

Depending on patients’ clinical status, antithrombotic therapreceiving warfarin, aspirin is recommended in virtually all sitprevious thromboembolism, and hypercoagulable condition. I2.5 and 3.5 for aortic disc valves and Starr-Edwards valves.therapy in valvular heart disease. In: Schlant R, Alexander
1998:1867–74. Reprinted with permission from the McGraw-Hill
AVR indicates aortic valve replacement; and MVR, mitral valv


iological) than with one in the aortic position (100,106,553–55). With either type of prosthesis or valve location, the riskf emboli is probably higher in the first few days and monthsfter valve insertion (556), before the valve is fully endotheli-lized (480).

. Mechanical Valves

ll patients with mechanical valves require anticoagulation.or mechanical prostheses in the aortic position, the INR witharfarin therapy should be maintained between 2.0 and 3.0 forileaflet valves and Medtronic Hall valves and between 2.5 and.5 for other disc valves and Starr-Edwards valves. For pros-heses in the mitral position, the INR should be maintainedetween 2.5 and 3.5 for all mechanical valves. There is aifference of opinion regarding the Starr-Edwards valve in theortic position, with the minority opinion recommending thatNR be maintained between 2.0 and 3.0. In patients withortic mechanical prostheses who are at higher risk of throm-oembolic complications, INR should be maintained at 2.5 to.5, and the addition of aspirin should be considered (seeelow). These include patients with atrial fibrillation, previoushromboembolism, and a hypercoagulable state. Many wouldlso include patients with severe LV dysfunction in thisigher-risk group (557).The addition of low-dose aspirin (75 to 100 mg per day)

o warfarin therapy (INR 2.0 to 3.5) not only furtherecreases the risk of thromboembolism (485,558–562) butlso decreases mortality due to other cardiovascular diseases.

slight increase in the risk of bleeding with this combina-ion should be kept in mind (558,563). The addition ofspirin (75 to 100 mg per day) to warfarin should betrongly considered unless there is a contraindication to these of aspirin. This combination is particularly appropriate

erapy in Patients With Prosthetic

arfarinR 2.0–3.0)

Warfarin(INR 2.5–3.5) No Warfarin

lass I Class IIalass I

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be individualized (see special situations in text). In patients. Risk factors: atrial fibrillation, left ventricular dysfunction,tional normalized ratio (INR) should be maintained betweenified from McAnulty JH, Rahimtoola SH. Antithromboticditors. Hurst’s The Heart. New York, NY: McGraw-Hill,

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n patients who have had an embolus while undergoingarfarin therapy, those with known vascular disease, and

hose who are known to be particularly hypercoagulable. Asn example, such combination therapy is recommended by aommittee concerning the use of antithrombotic therapy inomen during pregnancy (484). The method of anticoag-lation in pregnant patients is controversial and is discussedn Section V-F.

It is important to note that thromboembolic risk isncreased early after insertion of the prosthetic heart valve.he use of UFH early after prosthetic valve replacement,efore warfarin achieves therapeutic levels, is controversial.any centers start UFH as soon as the risk of increased

urgical bleeding is reduced (usually within 24 to 48 h), withaintenance of aPTT between 55 and 70 s. After an overlap

f UFH and warfarin for 3 to 5 days, UFH is discontinuedhen an INR of 2.0 to 3.0 is achieved. In some patients,

chievement of therapeutic INR must be delayed severalays after surgery because of mitigating complications.

. Biological Valves

ecause of an increased risk of thromboembolism duringhe first 3 months after implantation of a biological pros-hetic valve, anticoagulation with warfarin is often used,specially when the valve is in the mitral position (556),lthough most centers use only aspirin for biological valvesn the aortic position. The risk is particularly high in the firstew days after surgery, and many centers start UFH as soons the risk of increased surgical bleeding is reduced (usuallyithin 24 to 48 h), with maintenance of aPTT between 55

nd 70 s. After an overlap of UFH and warfarin for 3 to 5ays, UFH may be discontinued when an INR of 2.0 to 3.0

s achieved. After 3 months, the tissue valve can be treatedike native valve disease, and warfarin can be discontinued in

ore than two thirds of patients with biological valves102,556,564). In the remaining patients with associatedisk factors for thromboembolism, such as atrial fibrillation,revious thromboembolism, or hypercoagulable condition,

ifelong warfarin therapy is indicated to achieve an INR of.0 to 3.0. Many would also recommend continuing anti-oagulation in patients with severe LV dysfunction (ejectionraction less than 0.30) (557).

. Embolic Events During Adequate Antithromboticherapy

n the patient who has a definite embolic episode(s) whilendergoing adequate antithrombotic therapy, the dosage ofntithrombotic therapy should be increased, when clinicallyafe, as follows:

Warfarin, INR 2.0 to 3.0: warfarin dose increased toachieve INR of 2.5 to 3.5;Warfarin, INR 2.5 to 3.5: warfarin dose may need tobe increased to achieve INR of 3.5 to 4.5;Not taking aspirin: aspirin 75 to 100 mg per day
should be initiated;

Warfarin plus aspirin 75 to 100 mg per day: aspirindose may also need to be increased to 325 mg per dayif the higher dose of warfarin is not achieving thedesired clinical result;Aspirin alone: aspirin dose may need to be increasedto 325 mg per day, clopidogrel 75 mg per day added,and/or warfarin added.

. Excessive Anticoagulation

n most patients with INR above the therapeutic range,xcessive anticoagulation can be managed by withholdingarfarin and monitoring the level of anticoagulation with serial

NR determinations (480). Excessive anticoagulation (INRreater than 5) greatly increases the risk of hemorrhage.owever, rapid decreases in INR that lead to INR falling

elow the therapeutic level increase the risk of thromboembo-ism. Patients with prosthetic heart valves with an INR of 5 to0 who are not bleeding can be treated by withholdingarfarin and administering 1 to 2.5 mg of oral vitamin K1

phytonadione) (480,565). The INR should be determinedfter 24 h and subsequently as needed. Warfarin therapy isestarted and adjusted dose appropriately to ensure that theNR is in the therapeutic range. In emergency situations, these of fresh frozen plasma is preferable to high-dose vitamin1 (566), especially parenteral vitamin K1, because use of the

atter increases the risk of overcorrection to a hypercoagulabletate. Low-dose intravenous vitamin K (less than 1 mg)ppears safe in this situation (567).

. Bridging Therapy in Patients With Mechanical Valvesho Require Interruption of Warfarin Therapy for Non-

ardiac Surgery, Invasive Procedures, or Dental Care

lass I

. In patients at low risk of thrombosis, defined as thosewith a bileaflet mechanical AVR with no risk factors,*it is recommended that warfarin be stopped 48 to 72 hbefore the procedure (so the INR falls to less than1.5) and restarted within 24 h after the procedure.Heparin is usually unnecessary. (Level of Evidence: B)

. In patients at high risk of thrombosis, defined asthose with any mechanical MV replacement or amechanical AVR with any risk factor, therapeuticdoses of IV UFH should be started when the INRfalls below 2.0 (typically 48 h before surgery), stopped4 to 6 h before the procedure, restarted as early aftersurgery as bleeding stability allows, and continueduntil the INR is again therapeutic with warfarintherapy. (Level of Evidence: B)

lass IIa

It is reasonable to give fresh frozen plasma to patientswith mechanical valves who require interruption ofwarfarin therapy for emergency noncardiac surgery,
invasive procedures, or dental care. Fresh frozen


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plasma is preferable to high-dose vitamin K1. (Levelof Evidence: B)

lass IIb

In patients at high risk of thrombosis (see above),therapeutic doses of subcutaneous UFH (15 000 Uevery 12 h) or LMWH (100 U per kg every 12 h) maybe considered during the period of a subtherapeuticINR. (Level of Evidence: B)

lass III

In patients with mechanical valves who require in-terruption of warfarin therapy for noncardiac surgery,invasive procedures, or dental care, high-dose vita-min K1 should not be given routinely, because thismay create a hypercoagulable condition. (Level ofEvidence: B)

Risk factors: atrial fibrillation, previous thromboembolism,V dysfunction, hypercoagulable conditions, older generation

hrombogenic valves, mechanical tricuspid valves, or morehan 1 mechanical valve.

The risk of increased bleeding during a procedure per-ormed with a patient receiving antithrombotic therapy haso be weighed against the increased risk of a thromboem-olism caused by stopping the therapy. The risk of stoppingarfarin can be estimated and is relatively slight if the drug

s withheld for only a few days.Management of antithrombotic therapy must be individ-

alized, but some generalizations apply (568). Antithrom-otic therapy should not be stopped for procedures in whichleeding is unlikely or would be inconsequential if itccurred, for example, surgery on the skin, dental cleaning,r simple treatment for dental caries. Eye surgery, particu-arly for cataracts or glaucoma, is usually associated withery little bleeding and thus is frequently performed withoutlterations to antithrombotic treatment. When bleeding isikely or its potential consequences are severe, antithrom-otic treatment should be altered.For patients with a bileaflet mechanical aortic valve and

o risk factors, warfarin should be stopped before therocedure so that the INR is less than 1.5 (which is often 48o 72 h after warfarin is discontinued) (568,569) andestarted within 24 h after a procedure. Admission to theospital or a delay in discharge to give heparin is usuallynnecessary.Patients at high risk of thrombosis include all patients

ith mechanical mitral or tricuspid valve replacements andatients with an AVR and any risk factors. Such risk factorsnclude atrial fibrillation, previous thromboembolism, hy-ercoagulable condition, older-generation mechanicalalves, LV dysfunction (ejection fraction less than 0.30), orore than 1 mechanical valve (570–572). When UFH is

sed, it should be started when INR falls below 2.0 (i.e.,
8 h before surgery) and stopped 4 to 6 h before the

rocedure. UFH should be restarted as early after surgery asleeding stability allows, and the aPTT should be main-ained at 55 to 70 s until warfarin is therapeutic. LMWH isttractive because it is more easily used outside the hospital;owever, concerns about the use of LMWH for mechanicalalves persists, and package inserts continue to list a warningor this use of these medications (490).

High-dose vitamin K1 should not be given routinely,ecause this may create a hypercoagulable condition. Formergency situations, fresh frozen plasma is preferable toigh-dose vitamin K1 (see Section IX-A-4).

. Antithrombotic Therapy in Patients Who Need Car-iac Catheterization/Angiography

n an emergency or semiurgent situation, cardiac catheter-zation can be performed in a patient taking warfarin, butreferably, the drug should be stopped so that INR is lesshan 1.5. The drug should be restarted as soon as therocedure is completed. If a patient has more than 1 riskactor that predisposes to thromboembolism, heparinhould be started when INR falls below 2.0 and should beontinued when warfarin is restarted. After an overlap of 3o 5 days, heparin may be discontinued when the desiredNR is achieved. If the catheterization procedure is tonclude a transseptal puncture (especially in a patient whoas not had previous opening of the pericardium), patientshould be removed from all antithrombotic therapy, andNR should be less than 1.2.

. Thrombosis of Prosthetic Heart Valves

lass I

. Transthoracic and Doppler echocardiography is in-dicated in patients with suspected prosthetic valvethrombosis to assess hemodynamic severity. (Level ofEvidence: B)

. TEE and/or fluoroscopy is indicated in patients withsuspected valve thrombosis to assess valve motionand clot burden. (Level of Evidence: B)

lass IIa

. Emergency operation is reasonable for patients with athrombosed left-sided prosthetic valve and NYHAfunctional class III–IV symptoms. (Level of Evidence: C)

. Emergency operation is reasonable for patients with athrombosed left-sided prosthetic valve and a largeclot burden. (Level of Evidence: C)

. Fibrinolytic therapy is reasonable for thrombosedright-sided prosthetic heart valves with NYHA classIII–IV symptoms or a large clot burden. (Level ofEvidence C)

lass IIb

. Fibrinolytic therapy may be considered as a first-line
therapy for patients with a thrombosed left-sided


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prosthetic valve, NYHA functional class I–II symp-toms, and a small clot burden. (Level of Evidence: B)

. Fibrinolytic therapy may be considered as a first-linetherapy for patients with a thrombosed left-sidedprosthetic valve, NYHA functional class III–IVsymptoms, and a small clot burden if surgery is highrisk or not available. (Level of Evidence: B)

. Fibrinolytic therapy may be considered for patientswith an obstructed, thrombosed left-sided prostheticvalve who have NYHA functional class II–IV symp-toms and a large clot burden if emergency surgery ishigh risk or not available. (Level of Evidence: C)

. Intravenous UFH as an alternative to fibrinolytictherapy may be considered for patients with a throm-bosed valve who are in NYHA functional class I–IIand have a small clot burden. (Level of Evidence: C)

ibrinolytic therapy for a left-sided prosthetic valve ob-tructed by thrombus is associated with significant riskscerebral emboli in 12% to 15% of cases) and is oftenneffective. Fibrinolytic therapy in such patients is reservedor those in whom surgical intervention carries a high risknd those with contraindications to surgery (573–580).

In patients with a “small clot” who are in NYHAunctional class I or II, treatment with short-term intrave-ous UFH therapy or continuous infusion of fibrinolyticherapy may be considered (576–580). The size thresholdor this recommendation is difficult to define because of theack of large cohort studies and differing thresholds frommall studies (ranging from 5 to 10 mm, as determinedy TEE) below which intravenous UFH or fibrinolyticherapy is safe and effective (575,578–580). Factors thatdentify patients at risk for adverse outcomes of fibrinolyticherapy include active internal bleeding, history of hemor-hagic stroke, recent cranial trauma of neoplasm, diabeticemorrhagic retinopathy, large thrombi, mobile thrombi,ypertension (greater than 200 over 120 mm Hg), hypo-ension or shock, and NYHA functional class III–IVymptoms. If fibrinolytic therapy is successful, it should beollowed by intravenous UFH until warfarin achieves anNR of 3.0 to 4.0 for aortic prosthetic valves and 3.5 to 4.5or mitral prosthetic valves. If partially successful, fibrino-ytic therapy may be followed by a combination of subcu-aneous UFH twice daily (to achieve an aPTT of 55 to 80 s)lus warfarin (INR 2.5 to 3.5) for a 3-month period (576).Patients with small thrombi who receive intravenous

FH as first-line therapy and who do not respond success-ully may receive a trial of continuous-infusion fibrinolyticherapy. If fibrinolytic therapy is unsuccessful or there is anncreased risk associated with fibrinolytic therapy, reopera-ion should be considered. An alternative in patients whoemain hemodynamically stable is to convert intravenousFH to combined therapy with subcutaneous UFH (twiceaily to an aPTT of 55 to 80 s) and warfarin (INR 2.5 to.5) for 1 to 3 months on an outpatient basis to allow for
ndogenous fibrinolysis (576). If intravenous UFH, fibrino- e

ytic therapy, combined UFH/fibrinolytic therapy, or com-ined UFH/warfarin is successful, warfarin doses should bencreased so that INR is between 3.0 and 4.0 (approximately.5) for prosthetic aortic valves and between 3.5 and 4.5approximately 4.0) for prosthetic MVs. These patientshould also receive low-dose aspirin.

Thrombosis of mechanical tricuspid valve prostheses maye treated with fibrinolytic therapy, although experienceith this is limited (581,582).

. Follow-Up Visits

lass I

. For patients with prosthetic heart valves, a history,physical examination, and appropriate tests should beperformed at the first postoperative outpatient evalua-tion, 2 to 4 weeks after hospital discharge. This shouldinclude a transthoracic Doppler echocardiogram if abaseline echocardiogram was not obtained before hos-pital discharge. (Level of Evidence: C)

. For patients with prosthetic heart valves, routinefollow-up visits should be conducted annually, withearlier re-evaluations (with echocardiography) if there isa change in clinical status. (Level of Evidence: C)

lass IIb

Patients with bioprosthetic valves may be consideredfor annual echocardiograms after the first 5 years inthe absence of a change in clinical status. (Level ofEvidence: C)

lass III

Routine annual echocardiograms are not indicated inthe absence of a change in clinical status in patientswith mechanical heart valves or during the first 5years after valve replacement with a bioprostheticvalve. (Level of Evidence: C)

. First Outpatient Postoperative Visit

he first outpatient evaluation after valve surgery usuallyccurs 3 to 4 weeks after hospital discharge. By this time,he patient’s physical capabilities and expected improvementn functional capacity can be assessed. The workup on thisisit should include an interval or complete history andhysical examination, ECG, chest X-ray, 2D and Dopplerchocardiography, complete blood count, blood urea nitro-en/creatinine, electrolytes, lactate dehydrogenase, andNR, if indicated. Echocardiography is the most usefuloninvasive test. It provides information about prosthesistenosis/regurgitation, valve area, assessment of other valveisease(s), pulmonary hypertension, atrial size, LV and RVypertrophy, LV and RV size and function, and pericardialffusion/thickening. It is an essential component of the firstostoperative visit because it allows an assessment of the
ffects and results of surgery, as well as serving as a baseline


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or comparison should complications or deterioration occurater.

. Follow-Up Visits in Patients Without Complications

atients who have undergone valve replacement are notured but still have serious heart disease. The clinical coursef patients with prosthetic heart valves is influenced byeveral factors (550), including LV dysfunction, progressionf other valve disease, pulmonary hypertension, other car-iac diseases, complications of prosthetic heart valves, andlinical heart failure. The interval between routineollow-up visits depends on the patient’s needs.

The asymptomatic uncomplicated patient needs to beeen only at 1-year intervals, at which time a completeistory and thorough physical examination should be per-ormed. No further echocardiographic testing is requiredfter the initial postoperative evaluation in patients withechanical valves who are stable and who have no symp-

oms or clinical evidence of LV dysfunction, prosthetic valveysfunction, or dysfunction of other heart valves (1). Onceegurgitation is detected, close follow-up with 2D andoppler echocardiography every 3 to 6 months is indicated.chocardiography is indicated in any patient with a pros-

hetic heart valve whenever there is evidence of a newurmur or change in clinical status, when there are ques-

ions about prosthetic valve integrity and function, andhen there are concerns about ventricular function.

. Follow-Up Visits in Patients With Complications

lass I

Patients with LV systolic dysfunction after valvesurgery should receive standard medical therapy forsystolic heart failure. This therapy should be contin-ued even if there is improvement of LV dysfunction.(Level of Evidence: B)

V dysfunction and clinical heart failure after valve replace-ent may be the result of preoperative LV dysfunction that

ersists or improves only partially, perioperative myocardialamage, other valve disease that has progressed, complica-ions of prosthetic heart valves, and associated heart diseaseuch as CAD and systemic hypertension. Any patient withprosthetic heart valve who does not improve after surgeryr who later shows deterioration of functional capacityhould undergo appropriate testing, including 2D andoppler echocardiography and, if necessary, TEE and

ardiac catheterization with angiography to determine theause. Patients with postoperative LV systolic dysfunction,ven if asymptomatic, should receive standard medicalherapy for systolic heart failure, and this therapy should beontinued indefinitely even if there is improvement inystolic function and/or symptoms. All patients should alsoeceive primary and secondary prevention measures to re-
uce the risk of future cardiovascular events. N

. EVALUATION AND TREATMENT OF CORONARYRTERY DISEASE IN PATIENTS WITH VALVULAREART DISEASE

any patients with valvular heart disease have concomitantAD, but there are only limited data regarding the optimal

trategies for diagnosis and treatment of CAD in such patients.hus, management decisions are usually developed by blend-

ng information from the randomized studies of treatment ofAD and the smaller published series of patients undergoing

urgical treatment of valvular heart disease.

. Probability of Coronary Artery Disease in Patientsith Valvular Heart Disease

he prevalence of CAD in patients with valvular heartisease is determined by the same variables as in the generalopulation (583), and risk factors should be approachedith the prevention and risk reduction strategies that haveeen recommended for the general population (584).Ischemic symptoms in patients with valvular heart diseaseay have multiple causes, such as LV chamber enlargement,

ncreased wall stress or wall thickening with subendocardialschemia (585), and RV hypertrophy (586). Angina is thus

less specific indicator of CAD in patients with valvulareart disease than in the general population.Among patients with severe AS, angina is a common

ymptom in young patients with normal coronary arteries andongenital or rheumatic AS. On the other hand, CAD is aommon finding in older symptomatic men with AS. Inlderly patients (greater than 70 years old), angina is a strongeterminant of CAD (sensitivity 78%, specificity 82%) (587).alcification of the aortic valve is also associated with a highresence of CAD (90%) (588). In general, because angina is aoor marker of CAD in patients with AS, coronary angiogra-hy is recommended in symptomatic patients before AVR inen older than 35 years; premenopausal women older than 35

ears with coronary risk factors, as well as asymptomatic menlder than 45 years; women older than 55 years; or those withor more coronary risk factors.CAD is less prevalent in patients with AR than in those

ith AS, and the prevalence of CAD in patients with MSs lower than in patients with aortic valve disease, anbservation explained principally on the basis of differencesn age and gender. Nonetheless, because of the impact ofntreated CAD on perioperative and long-term postopera-ive survival, preoperative identification of CAD is of greatmportance in patients with AR or MS and those with AS.hus, in symptomatic patients and/or those with LVysfunction, preoperative coronary angiography is recom-ended in men aged greater than 35 years, premenopausalomen aged greater than 35 years with coronary risk

actors, and postmenopausal women.The relation between MR and CAD is unique in that CAD

s frequently the cause of this valve lesion. The management ofhese patients is discussed in Sections III-F-4 and VII-B-1-c.
either angina nor heart failure symptoms are reliable markers


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f CAD in these patients. In patients undergoing catheteriza-ion to evaluate the cause and severity of MR, CAD is presentn an average of 33% (589,590). In patients undergoingatheterization for acute ischemic syndromes, an average of0% have associated MR (591). Those with chronic CAD andR usually have lower LV ejection fractions and more

xtensive CAD than those without MR.

. Diagnosis of Coronary Artery Disease

lass I

. Coronary angiography is indicated before valve sur-gery (including infective endocarditis) or mitral bal-loon commissurotomy in patients with chest pain,other objective evidence of ischemia, decreased LVsystolic function, history of CAD, or coronary riskfactors (including age). Patients undergoing mitralballoon valvotomy need not undergo coronary an-giography solely on the basis of coronary risk factors.(Level of Evidence: C)

. Coronary angiography is indicated in patients withapparently mild to moderate valvular heart diseasebut with progressive angina (Canadian Heart Asso-ciation functional class II or greater), objective evi-dence of ischemia, decreased LV systolic function, orovert congestive heart failure. (Level of Evidence: C)

. Coronary angiography should be performed beforevalve surgery in men aged 35 years or older, premeno-pausal women aged 35 years or older who have coronaryrisk factors, and postmenopausal women. (Level ofEvidence: C)

lass IIa

Surgery without coronary angiography is reasonablefor patients having emergency valve surgery for acutevalve regurgitation, aortic root disease, or infectiveendocarditis. (Level of Evidence: C)

lass IIb

Coronary angiography may be considered for patientsundergoing catheterization to confirm the severityof valve lesions before valve surgery without pre-existing evidence of CAD, multiple coronary riskfactors, or advanced age. (Level of Evidence: C)

lass III

. Coronary angiography is not indicated in youngpatients undergoing nonemergency valve surgerywhen no further hemodynamic assessment by cathe-terization is deemed necessary and there are nocoronary risk factors, no history of CAD, and noevidence of ischemia. (Level of Evidence: C)

. Patients should not undergo coronary angiographybefore valve surgery if they are severely hemodynam-
ically unstable. (Level of Evidence: C) T

he resting ECG in patients with valvular heart diseaserequently shows ST-segment changes due to LV hypertro-hy, LV dilatation, or bundle-branch block, which reduceshe accuracy of the ECG at rest and during exercise for theiagnosis of concomitant CAD.Given the importance of determining the presence of

AD, coronary angiography remains the most appropriateethod for the definitive diagnosis of CAD. Noninvasive

maging is useful when CAD is suspected in patients withild valve stenosis or regurgitation and normal LV cavity

ize and wall thickness, but it has a limited role in patientsith severe valvular heart disease.In patients undergoing emergency valve surgery for acute

R, aortic dissection, or endocarditis with hemodynamicnstability, cardiac catheterization, aortography, and coro-ary angiography are rarely required, are associated with

ncreased risk, and might delay urgent surgery unnecessarily136,139–142). Angiography should be considered onlyhen the valve diagnosis cannot be determined by noninvasive

maging and when patients have known CAD, especially thoseith previous CABG (see Section III-B-1-b).

. Treatment of Coronary Artery Disease at the Time ofortic Valve Replacement

lass I

Patients undergoing AVR with significant stenoses(greater than or equal to 70% reduction in luminaldiameter) in major coronary arteries should be treatedwith bypass grafting. (Level of Evidence: C)

lass IIa

. In patients undergoing AVR and coronary bypassgrafting, use of the left internal thoracic artery isreasonable for bypass of stenoses of the left anteriordescending coronary artery greater than or equal to50% to 70%. (Level of Evidence: C)

. For patients undergoing AVR with moderate stenosis(50% to 70% reduction in luminal diameter), it isreasonable to perform coronary bypass grafting inmajor coronary arteries. (Level of Evidence: C)

s noted previously, more than 33% of patients with ASndergoing AVR have concomitant CAD, and more than0% of patients older than 70 years have CAD. Theddition of CABG to AVR has had little or no adverseffect on operative mortality. Moreover, combined CABGnd AVR reduces the rates of perioperative myocardialnfarction, operative mortality, and late mortality and mor-idity compared with patients with significant CAD who doot undergo revascularization at the time of AVR. It hasecome standard practice to bypass all significant coronaryrtery stenoses when possible in patients undergoing AVR.
he committee recommends this approach.


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. Aortic Valve Replacement in Patients Undergoingoronary Artery Bypass Surgery

lass I

AVR is indicated in patients undergoing CABG whohave severe AS who meet the criteria for valve replace-ment (see Section III-A-6). (Level of Evidence: C)

lass IIa

AVR is reasonable in patients undergoing CABGwho have moderate AS (mean gradient 30 to 50 mmHg or Doppler velocity 3 to 4 m per second). (Levelof Evidence: B)

lass IIb

AVR may be considered in patients undergoingCABG who have mild AS (mean gradient less than30 mm Hg or Doppler velocity less than 3 m persecond) when there is evidence, such as moderate-severe valve calcification, that progression may berapid. (Level of Evidence: C)

atients undergoing CABG who have severe AS shouldndergo AVR at the time of revascularization. Decisionaking is less clear in patients who have CAD that requiresABG when these patients have mild to moderate AS.ontroversy persists regarding the indications for “prophy-

actic” AVR at the time of CABG in such patients. Thisecision should be made only after the severity of AS isetermined by Doppler echocardiography and cardiac cath-terization.

Confirmation by cardiac catheterization is especially im-ortant in patients with reduced stroke volumes, mixedalve lesions, or intermediate mean aortic valve gradientsbetween 30 and 50 mm Hg) by Doppler echocardiography,ecause many such patients may actually have severe AS (asiscussed in Section III-A-5). The more complex andontroversial issue is the decision to replace the aortic valveor only mild AS at the time of CABG, because the degreef AS may become more severe within a few years, neces-itating a second, more difficult AVR operation in a patientith patent bypass grafts.It is difficult to predict whether a given patient with CAD

nd mild AS is likely to develop significant AS in the yearsfter CABG. As noted previously (see Section III-A-2), theatural history of mild AS is variable, with some patientsanifesting a relatively rapid progression of AS with a

ecrease in valve area of up to 0.3 cm2 per year and anncrease in pressure gradient of up to 15 to 19 mm Hg perear; however, the majority may show little or no change20,22–26,37,592–597). The average rate of reduction inalve area is on average 0.12 cm2 per year (20), but the ratef change in an individual patient is difficult to predict.Retrospective studies of patients who have come to AVR

fter previous CABG have been reported in which the mean
ime to reoperation was 5 to 8 years (598–603). The aortic

alve gradient at the primary operation was small, less than0 mm Hg, but the mean gradient increased significantly toreater than 50 mm Hg at the time of the second operation.t is important to note that these reports represent selectedatients in whom AS progressed to the point that AVR wasarranted. The number of patients in these surgical seriesho had similar gradients at the time of the primaryperation but who did not have significant progression ofS is unknown.Although definitive data are not yet available, patients

ith intermediate aortic valve gradients (30 to 50 mm Hgean gradient at catheterization or transvalvular velocity ofto 4 m per second by Doppler echocardiography) who are

ndergoing CABG may warrant AVR at the time ofevascularization (108–112), whereas patients with gradi-nts below 10 mm Hg do not need valve replacement. Theegree of mobility and calcification are also importantactors predicting more rapid progression of aortic diseasend should be taken into consideration, particularly in thoseith gradients between 10 and 25 mm Hg (29,108,112–14,604–607).

. Management of Concomitant Mitral Valve Disease andoronary Artery Disease

ost patients with both MV disease and CAD haveschemic MR, as discussed in Sections III-F-4 and VII-B--c. In patients with 1 to 2� MR, ischemic symptomssually dictate the need for revascularization. Patients withore severe ischemic MR usually have significant LV

ysfunction, and the decision to perform revascularizationnd MV repair is based on symptoms, severity of CAD, LVysfunction, and inducible myocardial ischemia.In patients with MV disease due to diseases other than

schemia, significantly obstructed coronary arteries identi-ed at preoperative cardiac catheterization are generallyevascularized at the time of MV surgery. There are no datao indicate the wisdom of this general policy, but becauseevascularization usually adds little morbidity or mortality tohe operation, the additional revascularization surgery issually recommended.

PPENDIX 1. Abbreviation List

CC � American College of CardiologyCE � angiotensin-converting enzymeHA � American Heart Association

PTT � activated partial thromboplastin timeR � aortic regurgitationS � aortic stenosisVR � aortic valve replacementABG � coronary artery bypass graft surgeryAD � coronary artery diseaseCG � electrocardiogram

NR � international normalized ratioMWH � low-molecular-weight heparinV � left ventricular

continued on next page



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PPENDIX 1. Continued

R � mitral regurgitationS � mitral stenosisV � mitral valveVP � mitral valve prolapseYHA � New York Heart AssociationV � right ventricularEE � transesophageal echocardiographyR � tricuspid regurgitationFH � unfractionated heparinD � 2-dimensional

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doi:10.1016/j.jacc.2006.05.030 2006;48;598-675 J. Am. Coll. Cardiol.

Nishimura, Richard L. Page and Barbara Riegel Jonathan L. Halperin, Loren F. Hiratzka, Sharon A. Hunt, Bruce W. Lytle, Rick

Adams, Jeffrey L. Anderson, Elliott M. Antman, David P. Faxon, Valentin Fuster,M. Shah, Jack S. Shanewise, Sidney C. Smith, Jr, Alice K. Jacobs, Cynthia D.

A. Nishimura, Patrick T. O’Gara, Robert A. O’Rourke, Catherine M. Otto, PravinDavid P. Faxon, Michael D. Freed, William H. Gaasch, Bruce Whitney Lytle, Rick

Robert O. Bonow, Blase A. Carabello, Kanu Chatterjee, Antonio C. de Leon, Jr, Society of Thoracic Surgeons

by the Society for Cardiovascular Angiography and Interventions and theCollaboration With the Society of Cardiovascular Anesthesiologists Endorsed

Developed inManagement of Patients With Valvular Heart Disease) Guidelines (Writing Committee to Revise the 1998 Guidelines for the

College of Cardiology/American Heart Association Task Force on PracticeValvular Heart Disease: Executive Summary: A Report of the American

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