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Valvular Heart Disease: Classic Teaching and Emerging Paradigms

Published:October 14, 2013DOI:https://doi.org/10.1016/j.amjmed.2013.05.022

      Abstract

      Valvular heart disease is both prevalent and increases with age. The final pathway of valvular disease is heart failure and sometimes sudden death, so clinicians must identify and treat it before these endpoints occur. Noninvasive diagnostic modalities such as echocardiography, exercise tolerance testing, and cardiac magnetic resonance provide additional quantitative, qualitative, and prognostic data. Studies have elucidated predictors of disease progression and potential medical therapies, but the niche of valvular disease has benefited relatively less from randomized controlled clinical trials than other cardiovascular disease fields. New invasive techniques like transcatheter valve replacement offer hope for high-risk operative candidates. We review classic teaching with current guidelines and emphasize recent advances in disease management.

      Keywords

      • Beyond echocardiography, cardiac magnetic resonance imaging and exercise testing may aid diagnosis in select cases.
      • Symptoms of severe disease or evidence of left ventricular dysfunction should trigger prompt referral for surgical intervention.
      • High-risk or inoperable patients may benefit from newer transcatheter therapies.
      Significant valvular heart disease affects at least 2.5% of the US population. The prevalence increases with age, such that 13% of people ≥75 years old have at least moderate aortic or mitral valve disease.
      • Nkomo V.T.
      • Gardin J.M.
      • Skelton T.N.
      • et al.
      Burden of valvular heart diseases: a population-based study.
      A thorough history and physical examination are essential but quantitatively insufficient for characterizing disease. Echocardiography should be performed as the initial evaluation for grade ≥3 systolic, any diastolic or radiating murmurs, and any murmurs associated with nonphysiologic splitting, clicks, or evidence of heart failure. Table 1 summarizes specific guidelines for follow-up of established valvular diseases.
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      Table 2 lists criteria for grading severity.
      Table 1Recommended Transthoracic Echocardiographic Follow-up
      Valve DiseaseGrade
      MildModerateSevere
      Aortic stenosis3-5 years1-2 years1 year
      Aortic regurgitation2-3 years1-2 years
      Imputed in the absence of American College of Cardiology/American Heart Association guidelines. From Bonow et al.2
      6-12 months
      Mitral regurgitationNone
      Imputed in the absence of American College of Cardiology/American Heart Association guidelines. From Bonow et al.2
      6-12 months6-12 months
      Mitral stenosis3-5 years1-2 years1 year
      Imputed in the absence of American College of Cardiology/American Heart Association guidelines. From Bonow et al.
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      Table 2American College of Cardiology/American Heart Association Recommendation Summary for Intervention in Valvular Disease
      DiseaseCriteriaSymptomsQualifiersClass
      Severe ASArea <1.0 cm2, MG >40 mm Hg, JV >4 m/sYesAll patientsI
      NoLVEF <50% or planned CABGI
      NoImpaired ETT, likely to progress, or very severe with operative mortality <1%IIb
      Severe ARRF ≥50%, RV ≥60 ml, VC >6 mm, ERO ≥0.3 cm2, JW ≥65% LVOT, 3-4+ angiographicYesAll patientsI
      NoLVEF <50%, planned CABG, or other planned valve surgeryI
      NoSevere LV dilation (EDD >75 mm or ESD >55 mm)IIa
      NoLV dilatation (EDD >70 mm or ESD >55 mm) + [progressive dilation, decrease in ETT, or abnormal hemodynamic response]IIb
      NoPlanned CABG or aortic root surgeryI
      Severe MSMG >10 mm Hg, area <1.0 cm2YesValvuloplasty versus surgery depending on valve score, NYHA symptoms, PASP, and riskI-IIb
      NoValvuloplasty if favorable and new onset AFIIb
      Moderate MSMG 5-10 mm Hg, area 1.0-1.5 cm2YesValvuloplasty versus surgery depending on valve score, NYHA symptoms, PASP, and riskI-IIb
      NoValvuloplasty if favorable and new onset AFIIb
      Severe MRRF ≥50%, RV ≥60 ml, VC ≥7 mm, >40% of LA, ERO ≥0.4 cm2, 3-4+ angiographicYesNYHA II-IV symptomsI
      YesIf repair likely, then LVEF <30% or ESD >55 mmIIa
      YesSecondary MR, LVEF<30%, and NYHA III-IV despite therapyIIb
      NoLVEF 30-60% or ESD ≥40 mmI
      No>90% chance of repair, AF, PASP >50 mm Hg (R) or 60 mm Hg (E)IIa
      Severe TRVC ≥7 mm, hepatic vein flow reversalYesPrimary TRIIa
      --Planned mitral surgeryI
      Moderate TRVC 3-7 mm--Planned mitral surgery + [PAH or annular dilatation]IIb
      Severe PRJet fills RVOT--Right ventricular dilatation or failure
      AF = atrial fibrillation; AR = aortic regurgitation; AS = aortic stenosis; CABG = coronary artery bypass graft; EDD = end diastolic diameter; ESD = end systolic diameter; ERO = effective regurgitant orifice area; ETT = exercise tolerance test; JV = jet velocity; JW = jet width; LA = left atrium; LVEF = left ventricular ejection fraction; LVOT = left ventricular outflow tract; MG = mean gradient; MR = mitral regurgitation; MS = mitral stenosis; NYHA = New York Heart Association class; PAH = pulmonary artery hypertension; PASP = pulmonary artery systolic pressure; RF = regurgitant fraction; RV = regurgitant volume; RVOT = right ventricular outflow tract; TR = tricuspid regurgitation; VC = vena contracta. Summarized from Bonow et al.
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

      Echocardiography

      Traditional transthoracic echocardiography (TTE) has good spatial and excellent temporal resolution. It remains the preferred initial test for diagnosis of suspected valvular disease. A transesophageal echocardiogram may provide better definition, especially for posterior structures like the mitral valve and for prosthetic valves, where TTE views may be limited by acoustic shadowing. Three-dimensional echocardiography is now widely available and is especially valuable for assessment of complex valvular disease, such as mitral valve prolapse, and for planning surgery.

      Cardiovascular Magnetic Resonance Imaging

      Advances in cardiovascular magnetic resonance (CMR) have made it a powerful tool for evaluating valve structure and function. CMR has excellent temporal and unparalleled spatial resolution, so it is now the gold standard for measuring cardiac volumes and function, important in regurgitant disease. Given the expertise necessary for interpreting the relatively complex images, use of CMR is currently limited primarily to tertiary-care facilities. Data for using CMR to refine prognosis of patients with valvular disease are emerging.

      Exercise Testing

      As the hemodynamic impact of valvular disease progresses, many patients gradually curtail symptom-provoking activities. Falsely assuming “asymptomatic” status in a sedentary patient is consequently a frequent cause for delay in referral for definitive therapy. Exercise testing is thus a natural modality to evaluate symptoms in sedentary patients with valvular disease and is generally both safe and prognostic. A meta-analysis of 7 trials involving patients with asymptomatic severe aortic stenosis reported no serious complications, and an abnormal response identified those at risk for sudden death.
      • Rafique A.M.
      • Biner S.
      • Ray I.
      • et al.
      Meta-analysis of prognostic value of stress testing in patients with asymptomatic severe aortic stenosis.
      In patients with mitral stenosis or regurgitation, exercise testing may reveal occult pulmonary hypertension and identify those at risk for progression to right ventricular failure.

      Surgical Valve Therapy

      Since the first mitral valve repair in 1923, surgery for valvular disease has advanced to the point where expected mortality for most elective procedures is now <5%, despite ever-increasing patient age.
      • Lee R.
      • Li S.
      • Rankin J.S.
      • et al.
      Fifteen-year outcome trends for valve surgery in North America.
      Indeed, data from the Society of Thoracic Surgery database from 1993-2007 demonstrate an unadjusted mortality for isolated aortic valve surgery of 4.4%, including procedures performed in octo- and nonagenarians. An online surgical risk calculator is available from the Society of Thoracic Surgery

      The Society of Thoracic Surgeons (STS). Online STS Risk Calculator; 2012. Available at: http://riskcalc.sts.org/. Accessed March 17, 2013.

      ; we routinely use it to include patients in assessment of their anticipated surgical risk. Many centers now perform minimally invasive valve surgery using a small thoracotomy or partial sternotomy, allowing shorter hospital stays, improved cosmesis, and better analgesia.
      • Schmitto J.D.
      • Mokashi S.A.
      • Cohn L.H.
      Minimally-invasive valve surgery.
      Table 2 lists guidelines for operative repair of specific valvular diseases. Patients over age 50 years typically undergo preoperative coronary angiography to exclude concomitant coronary artery disease.
      In cases where valve repair proves inadequate or impossible, there are a range of prosthesis choices (Figure). Mechanical valves offer longer durability than tissue prostheses but require lifelong anticoagulation with warfarin. One trial that randomized patients equivocal about valve choice to mechanical or bioprosthetic replacement found comparable long-term survival but higher risk of complications for bioprosthetic valves at 10 years.
      • Stassano P.
      • Di Tommaso L.
      • Monaco M.
      • et al.
      Aortic valve replacement: a prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 years.
      Table 3 lists factors influencing prosthesis selection. Research into new prosthetic materials has decreased mechanical valve thrombogenicity and improved tissue prosthesis longevity.
      Figure thumbnail gr1
      FigureSurgical prostheses and transcatheter devices. (A) PERIMOUNT Magna Ease bioprosthetic aortic valve, Edwards Lifesciences, Inc.; (B) On-X Standard mechanical aortic valve, Life Technologies, Inc.; (C) CoreValve transcatheter aortic valve, Medtronic, Inc.; (D) SAPIEN transcatheter aortic valve, Edwards Lifesciences, Inc.; (E) MitraClip mitral valve repair system, Abbott Vascular; (F) Melody transcatheter pulmonary valve, Medtronic, Inc. The CoreValve System is not commercially available in all countries and is an investigational device in other countries such as the US. CoreValve is a registered trademark of Medtronic CV Luxembourg S.a.r.l. All images used with permission.
      Table 3Recommendations for Prosthetic Valve Selection
      MechanicalBioprosthetic
      Age <65 years (70 if mitral position)Age ≥65 years (70 if mitral position)
      Acceptable bleeding riskHigh bleeding risk
      Existing chronic anticoagulationPatient preference

      Transcatheter Valve Therapy

      Transcatheter valve therapies have emerged primarily for use in patients who are high-risk surgical candidates due to anatomic or systemic reasons. The US Food and Drug Administration approved the first transcatheter aortic valve prosthesis in 2011, and several more are currently under investigation. Because of the complex mitral and tricuspid anatomy, comprehensive transcatheter therapies for these valves are further off, but a clip-based procedure for severe mitral regurgitation is currently undergoing late-phase clinical trials. The Figure illustrates several transcatheter devices for valvular disease.

      Aortic Valve Disease

      Aortic Stenosis

      Aortic stenosis is the most common degenerative valve lesion in North America and Europe, with severe disease affecting up to 2% of older adults. Calcific degeneration of a normal trileaflet or congenitally bicuspid aortic valve results in decreased leaflet excursion and an elevated systolic gradient between the left ventricle and aorta. Compensatory left ventricular hypertrophy leads to impaired filling, systolic dysfunction, and myocardial oxygen supply–demand mismatch. These result in the classic symptom triad of angina, syncope, and heart failure. Onset of symptoms portends a precipitous decline in prognosis, with mean survival of as little as 2 years among patients with heart failure.
      • Otto C.M.
      • Burwash I.G.
      • Legget M.E.
      • et al.
      Prospective study of asymptomatic valvular aortic stenosis.
      Sudden cardiac death is a dreaded complication of aortic stenosis, but occurs rarely in truly asymptomatic patients.
      Physical examination in aortic stenosis reveals a systolic crescendo-decrescendo murmur at the base, radiating to the neck. The intensity increases with handgrip, does not change with Valsalva, and peaks later as disease progresses. In severe disease, both murmur intensity and the aortic component of S2 may soften. Carotid pulse is slow-rising and delayed (parvus et tardus).
      TTE is the first-line modality for initial evaluation of suspected aortic stenosis. Valve area <1.0 cm2, mean gradient >40 mm Hg, and peak velocity >4 m/s characterize severe stenosis. Catheter-based evaluation of gradients is associated in a high rate of subclinical stroke so should generally be avoided.
      • Omran H.
      • Schmidt H.
      • Hackenbroch M.
      • et al.
      Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study.
      A few patients present with symptoms and signs of aortic stenosis but have low gradients on echo. Here, a dobutamine challenge with echocardiographic or invasive hemodynamic measurement can distinguish those with “pseudostenosis” (low stroke volume from heart failure with nonsevere stenosis) from those with truly severe aortic stenosis. Medical therapy for heart failure is typically appropriate for pseudostenosis, whereas surgery is needed for patients with severe aortic stenosis. For asymptomatic patients or those with vague complaints, an exercise test with careful supervision is reasonable to provoke symptoms.
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      Risk factors for aortic stenosis include age, male sex, hypertension, smoking, and dyslipidemia.
      • Stewart B.F.
      • Siscovick D.
      • Lind B.K.
      • et al.
      Clinical factors associated with calcific aortic valve disease.
      Data for specific pharmacotherapy to reduce disease progression have been inconsistent and overall discouraging. Hydroxy-methyl-glutaryl-CoA reductase inhibitors (“statins”), angiotensin-converting enzyme inhibitors, and bisphosphonates have been studied, but should not be prescribed specifically to delay aortic stenosis at this time. Antihypertensive medications are generally safe, but one must avoid hypotension in patients with severe stenosis who have limited reserve to augment their cardiac output.
      Symptom onset is the clearest trigger to perform aortic valve replacement. Guidelines recommend consideration of surgery for patients with asymptomatic, severe aortic stenosis and unexplained reduced ejection fraction, provocable symptoms, or very high peak velocity if predicted operative mortality is <1%. Careful exercise testing of selected asymptomatic patients may reveal abnormally poor performance or high-risk features
      • Lancellotti P.
      • Lebois F.
      • Simon M.
      • et al.
      Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis.
      attributable to aortic stenosis (Table 4) to trigger surgical referral. As many as 2 of every 5 eligible patients are still not referred for valve replacement despite attributable symptoms on chart review.
      • Freed B.H.
      • Sugeng L.
      • Furlong K.
      • et al.
      Reasons for nonadherence to guidelines for aortic valve replacement in patients with severe aortic stenosis and potential solutions.
      Common reasons for lack of appropriate referral include failure to recognize symptoms, advanced age, and perceived high operative risk.
      Table 4High-risk Exercise Tolerance Test Findings in Asymptomatic Severe Aortic Stenosis
      Angina or dyspnea
      Failure to augment systolic blood pressure >20 mm Hg
      ≥2 mm ST-segment depression
      Significant ventricular arrhythmia
      Mean gradient increase ≥18 mm Hg by Doppler
      Based on Lancellotti et al.
      • Lancellotti P.
      • Lebois F.
      • Simon M.
      • et al.
      Prognostic importance of quantitative exercise Doppler echocardiography in asymptomatic valvular aortic stenosis.
      Standard aortic valve replacement has generally acceptable risk in the vast majority of patients. However, patients with severe pulmonary disease, heavily calcified “porcelain” aorta, and previous mediastinal radiation or cardiac surgery often prove challenging for surgeons. Transcatheter aortic valve implantation is an emerging option for this patient population. In a randomized, prospective trial, the Placement of AoRtic TraNscathetER Valves (PARTNER) investigators demonstrated that 1-year, all-cause mortality following transcatheter implantation of the Edwards SAPIEN device (Edwards Lifesciences, Irvine, Calif) was significantly lower than with medical therapy for inoperable patients and was noninferior to surgery for high-risk patients.
      • Leon M.B.
      • Smith C.R.
      • Mack M.
      • et al.
      Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.
      • Smith C.R.
      • Leon M.B.
      • Mack M.J.
      • et al.
      Transcatheter versus surgical aortic-valve replacement in high-risk patients.
      The Medtronic CoreValve (Medtronic, Sandy Hook, Conn) also appears effective at 2 years; data from a large randomized trial in the US are expected shortly.
      • Buellesfeld L.
      • Gerckens U.
      • Schuler G.
      • et al.
      2-Year follow-up of patients undergoing transcatheter aortic valve implantation using a self-expanding valve prosthesis.
      Potential complications from transcatheter aortic valve implantation include increased risk of stroke, vascular injury, and heart block. A multidisciplinary approach to patient selection for transcatheter valve implantation is paramount and should involve the primary care physician, cardiologist, cardiac surgeon, and radiologist.

      Aortic Regurgitation

      Chronic aortic regurgitation may occur due to a primary abnormality, such as bicuspid aortic valve in younger patients or degeneration in the elderly. In addition, aortic regurgitation secondary to aortic root dilation occurs in patients with chronic hypertension, Marfan syndrome, or other abnormality of the thoracic aorta. Physical examination reveals a decrescendo, diastolic murmur at the left upper sternal border. The increased left ventricular end-diastolic volume with consequent high stroke volume manifests as wide pulse pressure. The left ventricular volume overload leads to adaptive ventricular dilation, eccentric hypertrophy, and ultimately, systolic dysfunction. Symptoms of decompensated severe aortic regurgitation include exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, supine chest discomfort, and angina. Prognosis is generally favorable while the patient is asymptomatic, but onset of symptoms or left ventricular systolic dysfunction necessitates referral for valve replacement (Table 2).
      Recent data suggest that B-type natriuretic peptide >130 pg/mL predicts progression to surgery better than echocardiographic measurements.
      • Pizarro R.
      • Bazzino O.O.
      • Oberti P.F.
      • et al.
      Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation.
      CMR accurately determines regurgitant fraction, ventricular dimensions, and aortic root diameter. In an observational study of CMR parameters in asymptomatic patients with at least moderate aortic regurgitation, regurgitant fraction >33% and regurgitant volume >42 mL had good receiver-operator characteristics and were strong predictors of subsequent indication for surgery.
      • Myerson S.G.
      • d'Arcy J.
      • Mohiaddin R.
      • et al.
      Aortic regurgitation quantification using cardiovascular magnetic resonance/clinical perspective.
      For those with regurgitation secondary to aortic root enlargement, a valve-sparing root replacement may be an attractive option, avoiding the need for anticoagulation. Medical therapy for aortic regurgitation focuses on controlling hypertension, but vasodilators have not been shown to reduce definitively either the rate of progression or the need for valve replacement.
      • Evangelista A.
      • Tornos P.
      • Sambola A.
      • et al.
      Long-term vasodilator therapy in patients with severe aortic regurgitation.
      • Scognamiglio R.
      • Rahimtoola S.H.
      • Fasoli G.
      • et al.
      Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function.

      Bicuspid Aortic Valve

      Congenital bicuspid aortic valve affects 1%-2% of the population and occurs more frequently in men. Those affected develop aortic stenosis, regurgitation, or both, and treatment is generally similar to patients with trileaflet valves. However, bicuspid aortic valve also is associated with aortic coarctation or root dilatation, so attention must be paid to aortic size and structure. Guidelines recommend annual echocardiography for aortic diameter >40 mm, and aortic root replacement at a diameter >50 mm (or >45 mm with other planned valve surgery).
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      We perform magnetic resonance imaging or computed tomography of the entire aorta upon first diagnosis of bicuspid aortic valve, which then guides subsequent follow-up. Due to increased prevalence in families, one-time echocardiographic screening for bicuspid aortic valve may be offered to first-degree relatives.

      Mitral Valve Disease

      Mitral Stenosis

      Mitral stenosis is a classic sequela of rheumatic fever but has become less prevalent in North America and Europe. Worldwide, rheumatic valve disease and mitral stenosis, in particular, still pose a significant public health challenge. Severe intracardiac calcification in the elderly or patients with renal disease can cause functional stenosis, but the barrier to left ventricular filling in these cases is primarily the mitral annulus, not immobile leaflets. Patients typically present with exercise intolerance and right heart failure due to the development of postcapillary pulmonary hypertension. Physical examination reveals an opening snap and low-pitched, diastolic rumble at the apex, best heard in left lateral decubitus position. TTE is the initial test of choice and can accurately measure the transmitral gradient and mitral valve area. Mitral valve area <1.0 cm2 constitutes severe mitral stenosis. Medical therapy aims to improve diastolic ventricular filling time with beta-blockers and reduce left atrial pressure with diuretics. Atrial fibrillation in this population is common and associated with a 15%-20% annual risk of embolic stroke, necessitating warfarin anticoagulation. Newer anticoagulants have not been tested or approved for valvular atrial fibrillation. Chronic penicillin therapy to prevent recurrent acute rheumatic fever should be considered strongly in all patients under age 40 years with evidence of rheumatic carditis.
      Patients with at least moderate mitral stenosis, New York Heart Association class II-IV symptoms, and favorable morphology should be referred for percutaneous balloon valvuloplasty, which has an excellent success rate and relatively low risk of complications in experienced hands.
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      A lower threshold is reasonable with significant pulmonary hypertension or new atrial fibrillation (Table 2). Moderate-severe mitral regurgitation or extensive leaflet calcification may mandate valve replacement.

      Mitral Regurgitation

      Primary mitral regurgitation stems from a structural abnormality of the valve, such as leaflet prolapse or endocarditis. Secondary (functional) regurgitation typically occurs from a dilated cardiomyopathy or from papillary muscle tethering after infarction. Population studies show that mild mitral regurgitation is exceedingly common and generally does not require treatment.
      • Enriquez-Sarano M.
      • Avierinos J.-F.
      • Messika-Zeitoun D.
      • et al.
      Quantitative determinants of the outcome of asymptomatic mitral regurgitation.
      With severe mitral regurgitation, however, the left ventricle responds with dilation, eccentric hypertrophy, and systolic failure. Elevated left atrial pressures lead to pulmonary hypertension. Patients develop exertional dyspnea and symptoms/signs of left ventricular failure. Physical examination reveals a pansystolic, blowing murmur at the apex that may radiate to the back or precordium with eccentric jets.
      Symptoms or evidence of left ventricular dysfunction (ejection fraction ≤60% or end-systolic diameter ≥40 mm) should prompt referral for mitral valve repair or replacement (Table 2). Valve repair generally offers lower long-term morbidity and mortality than replacement, presumably by preserving left ventricular geometry and avoiding thromboembolic risk of prostheses.
      • Mohty D.
      • Orszulak T.A.
      • Schaff H.V.
      • et al.
      Very long-term survival and durability of mitral valve repair for mitral valve prolapse.
      • Feldman T.
      • Foster E.
      • Glower D.D.
      • et al.
      Percutaneous repair or surgery for mitral regurgitation.
      Older patients with ischemic heart disease and severe secondary mitral regurgitation may do better with chord-sparing valve replacement because ongoing changes from ventricular dilation may render the primary repair inadequate.
      Controversy exists over timing of surgical referral for asymptomatic patients with severe mitral regurgitation and normal left ventricular systolic function. In one frequently cited prospective study, asymptomatic patients with severe mitral regurgitation did well with close follow-up and guideline-based surgical referral.
      • Rosenhek R.
      • Rader F.
      • Klaar U.
      • et al.
      Outcome of watchful waiting in asymptomatic severe mitral regurgitation.
      Others advocate early referral for asymptomatic patients based on quantitative markers of severe mitral regurgitation such as effective regurgitant orifice area and left atrial volume index.
      • Enriquez-Sarano M.
      • Avierinos J.-F.
      • Messika-Zeitoun D.
      • et al.
      Quantitative determinants of the outcome of asymptomatic mitral regurgitation.
      In a retrospective, propensity-matched study, early repair was associated with improved 7-year survival.
      • Kang D.H.
      • Kim J.H.
      • Rim J.H.
      • et al.
      Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation.
      Thus, for patients with high likelihood of repair and low operative risk, we favor early repair. In sedentary patients, we use exercise echocardiography to look for inducible pulmonary hypertension or onset of symptoms at a low workload. Truly asymptomatic patients should be followed closely with quantitative echocardiograms every 6-12 months to detect left ventricular dilation, systolic dysfunction, or pulmonary hypertension. CMR may detect subclinical left ventricular dysfunction in patients with severe mitral regurgitation and predict ventricular dysfunction after surgery. It should be considered in selected patients.
      • Gelfand E.
      • Haffajee J.
      • Hauser T.
      • et al.
      Predictors of preserved left ventricular systolic function after surgery for chronic organic mitral regurgitation: a prospective study.
      Transcatheter approaches to treat mitral regurgitation are under investigation. The MitraClip (Abbott Laboratories, Abbott Park, Ill), the most studied of these, is a clip that approximates opposing mitral leaflets, creating a smaller, double-orifice valve. In an initial randomized trial for patients at high risk for conventional surgery, there was significant improvement in left ventricular volume, ejection fraction, and quality of life. Nevertheless, the magnitude of improvement was inferior to surgery, and 20% of subjects still required valve surgery within 1 year.
      • Feldman T.
      • Foster E.
      • Glower D.D.
      • et al.
      Percutaneous repair or surgery for mitral regurgitation.
      There is little evidence for effective medical therapy in chronic severe mitral regurgitation. Small trials of vasodilators failed to demonstrate consistently improvement in hemodynamics or need for surgery. Standard pharmacotherapy for concomitant heart failure is appropriate, but surgery remains the cornerstone of treatment. Cardiac resynchronization may benefit eligible patients with functional mitral regurgitation.
      • van Bommel R.J.
      • Marsan N.A.
      • Delgado V.
      • et al.
      Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk.

      Mitral Valve Prolapse

      Mitral valve prolapse affects up to 3% of the population.
      • Freed L.A.
      • Levy D.
      • Levine R.A.
      • et al.
      Prevalence and clinical outcome of mitral-valve prolapse.
      Physical examination classically reveals a mid-systolic click that varies with ventricular loading. Palpitations, atypical chest pain, and orthostasis probably occur more frequently in mitral valve prolapse,
      • Hayek E.
      • Gring C.N.
      • Griffin B.P.
      Mitral valve prolapse.
      but most patients have no more than mild mitral regurgitation and may be reassured that their condition is not life threatening. Those with moderate/severe mitral regurgitation or systolic left ventricular dysfunction constitute a higher-risk cohort and should be referred to a cardiologist.
      • Avierinos J.-F.
      • Gersh B.J.
      • Melton L.J.
      • et al.
      Natural history of asymptomatic mitral valve prolapse in the community.
      Management for concomitant mitral regurgitation is as discussed above.

      Right-sided Valve Disease

      Pulmonic Stenosis

      Pulmonic stenosis is typically congenital. Severe obstruction leads to right ventricular failure, producing exertional dyspnea, syncope, and angina. Examination shows a systolic crescendo–decrescendo murmur, widely split S2, and soft P2. TTE is diagnostic. Guidelines recommend percutaneous valvuloplasty for severe disease (symptomatic with peak gradient >30 mm Hg or asymptomatic with peak gradient >40).
      • Bonow R.O.
      • Carabello B.A.
      • Chatterjee K.
      • et al.
      2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the Americal College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

      Pulmonic Regurgitation

      Mild pulmonic regurgitation is physiologic and requires no further evaluation. Severe pulmonic regurgitation most frequently occurs from pulmonary artery dilation in pulmonary hypertension or prior congenital heart surgery. It may lead to right ventricular dilation and failure. For patients with a dysfunctional right ventricular outflow tract conduit, transcatheter pulmonary valve replacement with the Melody valve may improve hemodynamics.
      • McElhinney D.B.
      • Hellenbrand W.E.
      • Zahn E.M.
      • et al.
      Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US Melody valve trial.

      Tricuspid Stenosis

      Tricuspid stenosis predominantly occurs with rheumatic multivalvular disease or carcinoid syndrome. Treatment involves balloon valvotomy or open commissurotomy, but bioprosthetic replacement may be necessary for concomitant regurgitation. Mechanical valves in the tricuspid position are highly prone to thrombosis and should be avoided.

      Tricuspid Regurgitation

      Most severe tricuspid regurgitation is secondary to right ventricular/annular dilation. Pacemaker and defibrillator lead-related tricuspid regurgitation has been described and may become more prevalent with expanding indications for such devices.
      • Lin G.
      • Nishimura R.A.
      • Connolly H.M.
      • et al.
      Severe symptomatic tricuspid valve regurgitation sue to permanent pacemaker or implantable cardioverter-defibrillator leads.
      Symptoms include fatigue, bloating, and peripheral edema. Physical examination may reveal a holosystolic blowing murmur at the left lower sternal border, as well as hepatomegaly, ascites, and elevated jugular venous pressure. Longstanding severe tricuspid regurgitation may cause congestive hepatopathy and cardiac cirrhosis. Diuretics and sodium restriction alleviate congestion, but surgical annuloplasty is sometimes recommended either primarily or at the time of otherwise-scheduled mitral valve surgery to prevent progressive tricuspid regurgitation.
      • Dreyfus G.D.
      • Corbi P.J.
      • Chan K.M.J.
      • Bahrami T.
      Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair?.

      Conclusions

      An increased prevalence of valvular heart disease has been accompanied by proliferation of the modalities used to diagnose and treat valvular heart disease. Nevertheless, a carefully performed history and physical examination remain the most prudent initial method of evaluating suspected disease. TTE is the principal imaging modality. The future challenge for both primary care physicians and cardiologists is to appropriately select patients who will benefit from additional diagnostic and therapeutic technologies. Volumetric echocardiography, CT/MRI imaging, transcatheter interventions, and safer valve surgery are likely to be part of this process. The frequent “gray zone” of time to intervene surgically likely will shrink, and long-term outcomes will improve. In the meantime, ongoing emphasis on good history-taking and physical examination skills for trainees and organization of more randomized clinical trials for valvular heart disease should be encouraged.

      Acknowledgements

      The authors thank Dr Warren J. Manning for his valuable suggestions on the manuscript.

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