1. 1
    Current Diagnosis

    • The diagnosis of severe aortic valve stenosis is based on an integration of clinical symptoms and hemodynamic echocardiographic criteria.

    • Classic symptoms of severe aortic stenosis include fatigue, dyspnea on exertion, angina, near syncope or syncope, and congestive heart failure.

    • Chronic mitral regurgitation tends to be a slowly progressive disease and symptoms may not be apparent.

    • Cardiac imaging, especially echocardiography, is crucial to the management of patients with valvular heart disease.

    •   Diagnostic echocardiographic findings of severe aortic stenosis are peak aortic valve velocity of greater than or equal to 4 m/sec, transaortic mean gradient of greater than or equal to 40 mm Hg, and aortic valve area less than or equal to 1 cm2 or aortic valve area index of less than or equal to 0.6 cm2/m2.

    •   Echocardiography should be performed to determine the etiology of and characterize the severity of mitral regurgitation.

    •   Left ventricular size and function should be assessed in patients with mitral regurgitation.

  2. 2
    Current Therapy

    • Medical therapy has not been shown to change hemodynamic progression or clinical outcomes in patients with aortic stenosis.

    • Reevaluation for early symptoms and transthoracic echocardiography should be performed every 6 to 12 months in asymptomatic patients with severe aortic stenosis and normal left ventricular systolic function.

    • Transcatheter aortic valve replacement is currently approved in patients with severe symptomatic aortic stenosis with intermediate to high surgical risk and patients who have a prohibitive surgical risk. It is currently utilized in clinical trials in low-surgical-risk candidates.

    •   The etiology of mitral regurgitation dictates its treatment.

    •   Degenerative (primary) mitral regurgitation typically requires surgical repair or replacement.

    •   The management of functional (secondary) mitral regurgitation requires treatment of the underlying cardiomyopathy.

    • The decision-making process in the management of patients with severe aortic stenosis or severe mitral regurgitation is best achieved by a heart valve team and should include a systematic risk assessment of the patient’s comorbidities and estimation of the 30- day cardiac surgical mortality using the Society of Thoracic Surgeons’ Predicted Risk of Mortality (STS-PROM) score.

  3. 3
    Aortic Stenosis

    Aortic stenosis (AS) is the most common form of adult valvular heart disease, becoming more prevalent in the aging population. It is estimated that more than 4% of the U.S. population over age 75 have AS. Aortic valve stenosis is the most common cause of left ventricular outflow tract obstruction, while less common causes of obstruction may also occur above (supravalvular) or below (subvalvular) the level of the aortic valve and will not be discussed in this chapter.

  4. 4

    There are three main causes of valvular AS: congenital in origin (which is usually a bicuspid aortic valve), rheumatic valve disease, and degenerative calcification of a normal aortic valve. Congenitally affected aortic valves may be unicuspid or bicuspid and may become stenotic during childhood. In the majority of cases, a congenital bicuspid valve will develop significant calcific stenosis later in life, usually presenting after the fifth decade.

    Rheumatic AS is an important cause of aortic valve disease worldwide; however, with the decline of rheumatic fever in developed countries, it is now a rare cause of AS in the United States. Rheumatic valve disease is characterized by commissural fusion, fibrosis, and calcification. Rheumatic AS is also commonly associated with rheumatic involvement of the mitral valve.

    Degenerative or calcific AS is now the most common cause of AS in adults in North America. It has been associated with the same risk factors as vascular atherosclerosis including age, smoking, hypertension, diabetes, and hyperlipidemia. Histopathologic data suggest that calcific aortic valve disease is a chronic inflammatory process with lipid deposition and active leaflet calcification leading to restriction of the cusps.

  5. 5

    In adults with AS, the gradual obstruction of the left ventricular (LV) outflow produces a systolic pressure gradient between the left ventricle and aorta. The average time interval of disease progression from nonobstructive valve thickening (aortic sclerosis) to severe AS is 8 years. However, only 16% of individuals with aortic sclerosis will develop any grade of valve obstruction. The average rate of hemodynamic progression once moderate AS is present is an increase in aortic jet velocity of 0.3 m/s per year and mean pressure gradient of 7 mm Hg per year with a decrease in aortic valve area of 0.1 cm2/year. Left ventricular response to chronic pressure overload ultimately leads to concentric wall hypertrophy. This compensatory mechanism helps maintain normal LV contractile function to counteract the gradual increase in afterload at the expense of decreased LV compliance and delayed relaxation resulting in diastolic dysfunction.

  6. 6
    Clinical Presentation

    The cardinal symptoms of severe AS are angina, syncope, and congestive heart failure. Because symptoms in severe AS may not occur until late in the disease process, usually in the sixth to ninth decades of life, clinicians should obtain a careful history of symptoms during the patient’s initial assessment. Particular attention must be directed at early symptoms of fatigue or decreased exercise tolerance as elderly patients may minimize and attribute these symptoms to aging.

    Dyspnea on exertion occurs once the pulmonary capillary pressure increases as a result of excessive elevation in LV end-diastolic pressure in a poorly compliant ventricle. Symptoms of angina pectoris in severe AS may occur in a similar manner as in coronary artery disease, with symptoms precipitated by exertion and relieved by rest even in the absence of obstructive epicardial coronary artery disease.

    Syncope may result from the inability of the heart to increase cardiac output from the stenotic valve in the setting of transient vasodilatation during physical activity, resulting in decreased cerebral perfusion.

    Other causes of syncope may also be attributable to arrhythmias, either advanced forms of atrioventricular blocks from calcification impinging on the conduction system or tachyarrhythmias causing a sudden decline in cardiac output such as in atrial fibrillation.

  7. 7
    Diagnosis and Management

    Diagnosis of AS is usually suspected after a systolic ejection murmur is heard during cardiac auscultation. The classic physical findings in patients with severe AS are a loud, late-peaking systolic murmur at the base of the heart radiating to the carotid arteries with a delayed and diminished carotid upstroke (pulsus parvus et tardus). The latter physical finding may be masked in elderly patients with stiff, inelastic arterial walls. Distinctively, a normally split second heart sound is the only reliable physical finding to help exclude the diagnosis of severe AS.

    A transthoracic echocardiogram (TTE) is recommended as the initial diagnostic test in the evaluation of patients with aortic valve stenosis to determine hemodynamic severity, left ventricular size and function, and prognosis and to evaluate timing of valve intervention.

    Echocardiographic valve hemodynamics define the severity of AS (Table 1). Severe AS is characterized by a peak aortic valve velocity of 4 m/s or higher, transaortic mean gradient of 40 mm Hg or higher, and aortic valve area of less than or equal to 1 cm2  or aortic valve area index of less than or equal to 0.6 cm2/m2. In patients with abnormal left ventricular function and low- gradient severe AS, a dobutamine stress echocardiogram is used to differentiate between true severe AS and pseudo-severe AS.

    Table 1

    Echocardiographic Stages of Aortic Valve Stenosis and Frequency of Echocardiograms in Asymptomatic Patients with Aortic Stenosis and Normal LVEF

    Abbreviations: LVEF = left ventricular ejection fraction; TTE = transthoracic   echocardiogram.

    Patients with asymptomatic AS require frequent monitoring owing to the progressive nature of the disease. The frequency of echocardiograms in asymptomatic patients with AS and normal left ventricular systolic function should be performed every 6 to 12 months for reevaluation in severe AS, every 1 to 2 years for moderate AS, and every 3 to 5 years for mild AS (see Table 1). In seemingly asymptomatic patients with severe AS, exercise testing is safe and helpful to expose symptoms, arrhythmias, or abnormal blood pressure response. Exercise testing should not be performed in symptomatic patients.

  8. 8

    Indication for intervention in patients with severe AS is dependent on the presence or absence of symptoms, the severity of AS, and left ventricular function. Routine aortic valve replacement in asymptomatic AS is currently not recommended. Importantly, event- free survival at 2 years in asymptomatic patients with severe AS (jet velocity > 4.0 m/s) is 30% to 50%, and as low as 21% in those with very severe AS (jet velocity > 5.0 m/s). Therefore, close clinical follow-up to evaluate for early-onset AS symptoms and education regarding the disease course should be performed routinely.

    Medical therapy has not been shown to change hemodynamic progression or clinical outcomes in patients with AS. Clinical data have failed to support the use of statins specifically for the prevention of progression of AS. However, all patients with concomitant coronary artery disease or hypercholesterolemia should be treated per established guidelines. Likewise, concurrent hypertension in patients with severe AS is common and should receive appropriate treatment per standard guidelines starting at a low dose and slowly titrating upward with frequent blood pressure monitoring. Although indicated in the treatment of acute heart failure, diuretics should be used with caution to avoid volume depletion, which may result in marked reduction in cardiac output.

  9. 9
    Surgical Treatment

    Transcatheter aortic valve replacement (TAVR) has expanded rapidly as an alternative to surgical aortic valve replacement (SAVR) since its approval in 2011, with more than 50,000 patients treated in the United States alone. It is currently approved for use in patients with severe symptomatic AS with intermediate to high surgical risk and patients who have a prohibitive surgical risk. It is currently utilized in clinical trials in low-surgical-risk candidates and will likely be commercially available in the future for this indication.

    Recommendations and timing of intervention for aortic valve stenosis by either SAVR or TAVR are summarized in Table 2. Once the patient with AS is considered to meet an indication for aortic valve replacement, an important component when choosing between SAVR and TAVR is the underlying risk assessment for SAVR. In the United States, the Society of Thoracic Surgeons’ Predicted Risk of Mortality (STS-PROM) risk score calculator is the initial step in predicting 30- day mortality for SAVR, with three categories: low risk defined as less than 4%, intermediate risk defined as 4% to 8%, and high risk defined as greater than 8% STS mortality risk. This risk calculator, however, does not include certain comorbid conditions that would also increase the surgical mortality risk such as frailty, porcelain aorta, liver cirrhosis, severe pulmonary hypertension, chest wall abnormalities, and hostile mediastinum. Hence the risk assessment is a combination of the STS-PROM score, frailty, disability, and major cardiovascular and noncardiovascular comorbidities.

    Table 2

    ACC/AHA Recommendations for Timing of Intervention in Patients with Aortic Stenosis

    Modified from Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57–185.

    Abbreviations: ACC/AHA = American College of Cardiology/American Heart Association; AS = aortic stenosis; AVR = aortic valve replacement by either surgical or transcatheter approach; BP = blood pressure; COR = class of recommendation; LVEF = left ventricular ejection fraction.

    The final treatment decision should be individualized with a risk- benefit assessment by a multidisciplinary heart valve team (including structural interventional cardiologists, imaging specialists, cardiovascular surgeons, and nursing professionals). The heart valve team assesses potential procedural outcomes based on the patient’s individual procedural risk, comorbidities, goals, expectations, life expectancy, and potential quality-of-life improvement with SAVR or TAVR. The importance of a collaborative and multidisciplinary heart team approach to the evaluation and management of patients with complex AS has been endorsed by professional guidelines to maximize appropriate outcomes.

    Once the patient is considered to be a suitable candidate for TAVR, the evaluation of all patients undergoing the procedure should include (1) right and left heart catheterization to assess hemodynamic pressures and presence for coronary disease and (2) computed tomography of the chest, abdomen, and pelvis to determine preferred vascular access or contraindications to it and aortic annulus dimension for prosthesis sizing (Figure 1).

    FIGURE 1    Multidetector computed tomography measurements of  the aortic valve complex and peripheral vascular assessment. (A) Aortic annulus perimeter, area, and diameter measurement. (B) The maximum sinus of Valsalva diameters. (C) Height of the left coronary artery from the annular base. (D) Reconstructed view of the ileofemoral anatomy. (E) Left subclavian view with measurement obtained (left of image).

    There are currently two available TAVR valve types approved by the United States Food and Drug Administration (FDA): the balloon- expandable Edwards Sapien 3 (Edwards Lifesciences) and self- expandable Evolut R (Medtronic) systems. The choice of valve mostly depends on anatomic reasons and operator preference and experience. In general, self-expanding prostheses are preferred over balloon expandable in patients with a dense left ventricular outflow tract and annular calcifications owing to the risk of annular rupture.

    Conversely, a balloon-expandable valve is the only option available for the transapical approach, when vascular access is contraindicated owing to severe peripheral artery disease. Although there is no evidence comparing long-term clinical outcomes between balloon- and self-expandable valve technologies, both valves have shown similar mortality and stroke rates.

    A series of major procedural cardiovascular complications have been described after TAVR, including paravalvular aortic regurgitation, ischemic strokes, conduction disturbances, cardiac perforation, coronary occlusion, and vascular access complications. With the advancement of valve technology and increase in operator experience, the frequency of procedural complications has reduced since the arrival of TAVR procedures. Preprocedure planning by an expert heart valve team is essential to recognize and prevent expected complications during and after transcatheter valve implantation.

    Currently the optimal antithrombotic regimen following TAVR is daily clopidogrel (Plavix)1 75 mg and aspirin1 75 to 100 mg for 3 to 6 months followed by daily aspirin alone for life. If there is an indication for chronic anticoagulation, it should follow current guidelines’ recommendations for each individual condition (e.g., atrial fibrillation, deep venous thrombosis). The safety of antiplatelet therapy use in conjunction with oral anticoagulation should be individualized based on the patient’s bleeding risk.


  10. 10
    Mitral Regurgitation

    Mitral regurgitation (MR) is a common valvular disease, and pathology in any of the structures of the mitral valve apparatus may lead to dysfunction of the valve. The base of the leaflets of the mitral valve are attached to the annulus, and the leaflets themselves are attached to the papillary muscles of the left ventricle by the chordae tendineae. The mitral valve is an integral part of both the left atrium and left ventricle, and disorders of these structures affect mitral valve function; likewise, disorders of the mitral valve lead to abnormalities of the left atrium and left ventricle.


    Mitral regurgitation can be divided into degenerative (primary) MR and functional (secondary) MR (Figure 2). Degenerative MR refers to pathology of the mitral valve leaflets and chordae tendineae that results in valve dysfunction. The most common etiology is mitral valve prolapse, where the underlying pathology is myxomatous mitral valve degeneration that results in redundant leaflets, causing prolapse of the leaflets. A myxomatous mitral valve is also prone to rupture of the chordae tendineae, leading to a flail leaflet or segment of a leaflet. Other common etiologies of MR include rheumatic heart disease and endocarditis. Mitral annular calcification may cause mild to moderate MR, but severe regurgitation is uncommon.

    FIGURE 2    (A) Transthoracic echocardiogram of a patient with  a dilated cardiomyopathy with annular dilatation resulting in incomplete coaptation of the mitral valve leaflets and severe functional (secondary) mitral regurgitation. The regurgitant jet is central. (B) Transesophageal echocardiogram reveals a markedly myxomatous mitral valve with a large flail segment of the posterior leaflet resulting in severe degenerative (primary) mitral regurgitation. This jet is extremely eccentric. Abbreviations: LA = left atrium; LV = left  ventricle; MV = mitral valve.

    In contrast, in functional MR, the mitral valve itself has a relatively normal structure. Instead, the pathology is an abnormality of the left ventricle. This most commonly occurs after myocardial infarction, with focal wall motion abnormalities and displacement of the papillary muscle causing tethering of the chordae and leaflets, along with dilatation of the mitral valve annulus, resulting in incomplete coaptation of the mitral valve leaflets during systole. Functional MR may also occur in a dilated cardiomyopathy.

    Clinical Manifestations

    The clinical presentation of MR is extremely variable and depends largely on the severity of the regurgitation and its acuity. Mitral regurgitation tends to be asymptomatic when mild to moderate, but severe MR frequently results in symptoms. Acute MR occurring from papillary muscle rupture complicating an acute myocardial infarction leads to rapid hemodynamic collapse and carries a high risk of mortality. These patients experience pulmonary edema due to the acute volume overload of the left ventricle and left atrium. In contrast, chronic severe MR may have a relatively indolent course, with some patients reporting few symptoms. While chronic MR typically manifests as congestive heart failure, with exertional dyspnea, orthopnea, and lower extremity edema as the hallmark symptoms, owing to the insidious nature of the disease, patients may not always recognize their symptoms. A detailed history with a specific focus on symptoms of congestive heart failure in addition to fatigue and effort intolerance must be elicited. Atrial fibrillation is a common complication of MR and is associated with worse outcomes.


    Physical examination classically may reveal a soft S1 and a holosystolic murmur at the apex that radiates to the left sternal border or to the axilla. However, the intensity of the murmur does not correlate to the severity of disease, nor does the absence of a murmur reliably rule out severe MR. Physical examination is important to assess the patient’s volume status, with pulmonary rales and lower extremity edema suggesting congestive heart failure, and an irregularly irregular rhythm indicative of atrial fibrillation.

    Cardiac imaging, in particular echocardiography, is crucial in the evaluation of suspected MR. Transthoracic echocardiography can reveal abnormalities of the mitral valve and provide important information on left ventricular size and function and estimation of pulmonary arterial pressure. Given the orientation of the mitral valve and the limits of transthoracic echocardiography, the severity of MR can be grossly underestimated, particularly if the regurgitant jet is eccentric. Transesophageal echocardiography, especially with the availability of three-dimensional imaging, provides higher-quality images of the mitral valve and allows more precise evaluation of the severity and etiology of MR, and has become the gold-standard test in the evaluation of patients with clinically significant MR. Echocardiography with color Doppler can be used to provide a visual estimate of the severity of regurgitation. The presence of reversal of flow into the pulmonary veins during systole suggests severe regurgitation. Quantitative analysis can also be performed to determine the volume of regurgitation and the orifice of the regurgitant jet. There is currently no single echocardiographic parameter to define severe MR, but integration of multiple qualitative and quantitative measurements is recommended. Accurate assessment of left ventricular dimensions and function is important in patients with chronic severe MR. Methods of determining the left ventricular ejection fraction include visual estimation and volumetric analysis. Owing to the volume of blood exiting the left ventricle through both the mitral and aortic valves during systole, the ejection fraction will be increased. In the presence of severe MR, a normal left ventricular ejection fraction approaches 70%, and left ventricular dysfunction is deemed anything less than 60%. Even what would otherwise be considered a mildly reduced ejection fraction may indicate significant myocardial dysfunction in the presence of MR. Left atrial enlargement as a rule is found in chronic severe MR, and its absence should lead to reconsideration of the diagnosis. Exercise echocardiography can play an important role in patients with MR, especially in those with severe MR who report few symptoms, as it is an objective means to assess functional capacity and can also be used to assess changes in pulmonary pressures with exercise. In patients who have mild MR at rest but severe exertional symptoms, exercise echocardiography can identify ischemic MR with concomitant regional wall motion abnormalities.

    Cardiac catheterization is performed in many patients with suspected severe MR. Right heart catheterization with measurement of right atrial, right ventricular, pulmonary arterial, and pulmonary capillary wedge pressures and cardiac outputs can help determine volume status and assess for pulmonary hypertension. Attention should be paid to the pulmonary capillary wedge waveform, with large “v” waves, corresponding to ventricular systole, suggestive of severe MR. Left heart catheterization with selective coronary angiography is recommended to identify concomitant obstructive coronary artery disease. Left ventriculography using contrast is commonly performed, and the presence of contrast in the left atrium suggests MR. However, the clinical utility of left ventriculography is limited with the ready availability of echocardiography. The visual estimation of MR by contrast ventriculography is subjective, and the etiology of valve pathology is unable to be defined precisely.

    Furthermore, in a patient with congestive heart failure, the contrast load may result in acute decompensation.

    Magnetic resonance imaging (MRI) is not currently a routinely used test in the evaluation of severe MR but may provide more reproducible quantification of the regurgitant volume and fraction and more accurate measurements of left ventricular size and function. Given the importance of defining the severity of the MR and abnormalities of left ventricular function in the management of MR, MRI may eventually have a central role in the evaluation of patients and is strongly recommended when echocardiographic data is not satisfactory.

    Management and Treatment

    The etiology of MR dictates its treatment (Table 3). Degenerative (primary) MR is a mechanical problem of the valve or its apparatus and requires a mechanical solution such as a surgical or percutaneous repair or replacement. Functional (secondary) MR is a problem of the left ventricle and treatment of the underlying ventricular pathology is indicated, and the role of mitral valve intervention is less clear.

    Table 3

    Paradigm for Management of Mitral Regurgitation Based on Etiology and Surgical Risk

    Degenerative  (Primary)                           Functional (Secondary)
    Low surgical risk Surgical repair or replacement CHF therapy

    Surgery in selected patients

    High surgical risk Percutaneous repair in selected patients CHF therapy

    Abbreviation: CHF = congestive heart  failure.

    In patients with acute severe MR, the role of medical therapy is to stabilize the patient until surgery. Afterload reduction is the initial treatment strategy, which allows for greater flow through the aortic valve, thereby increasing cardiac output while diminishing the MR. Afterload reduction may be accomplished with intravenous vasodilators such as sodium nitroprusside (Nitropress)1 or with an intraaortic balloon pump if the clinical situation requires. The role of medical therapy for chronic severe degenerative MR is less clear, especially in asymptomatic patients with normal left ventricular function. Symptomatic patients with a reduced ejection fraction (< 60%) may be treated with heart failure therapy such as angiotensin- converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta-adrenergic blockers, or aldosterone antagonists, in addition to loop diuretics for symptomatic relief while awaiting surgery. Ultimately most patients with severe degenerative MR will be referred to surgery (Table 4), and valve repair is preferable to replacement provided the anatomy is amenable to repair. If valve replacement is necessary, options include mechanical and bioprosthetic valves. Mechanical valves provide superior hemodynamic results and durability but are prone to thrombus formation and therefore require lifelong anticoagulation with warfarin (Coumadin). If after consultation with a cardiac surgeon the patient is deemed a prohibitive risk for surgery, percutaneous mitral valve repair with the MitraClip device (Abbott) is a reasonable alternative.

    This procedure is performed under general anesthesia with fluoroscopic and transesophageal echocardiographic guidance, and from the femoral vein via transseptal access, a clip is delivered to the regurgitant orifice of the mitral valve, grasping the anterior and posterior leaflets, thereby improving leaflet coaptation.

    Table 4

    Indications for Intervention in Severe Degenerative (Primary) Mitral Regurgitation


    Recommended if LVEF > 30% May be considered if LVEF ≤ 30%

    TMVR may be considered if severely symptomatic with reasonable life expectancy but prohibitive surgical risk Asymptomatic

    Recommended if LV dysfunction (LVEF 30%–60% or LVESD < 40 mm)

    Reasonable if preserved LV function (LVEF > 60% and LVESD > 40 mm) if > 95% chance of successful repair with

    < 1% mortality risk

    Reasonable if preserved LV function with new-onset atrial fibrillation or PASP > 50 mm Hg if high likelihood of successful repair

    Abbreviations: LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic dimension; PASP = pulmonary arterial systolic pressure; TMVR = transcatheter mitral valve repair.

    For patients with functional MR, the target for treatment is the left ventricle. Medical therapy for the underlying cardiomyopathy is recommended, with administration of ACE inhibitors or ARBs, aldosterone antagonists, and beta-blockers. If indicated, these patients may require cardiac resynchronization therapy. With medical and device therapy, left ventricular remodeling and function may improve, with reduction in the degree of MR. If severe MR persists despite maximally tolerated medical therapy, there may be a role for surgical valve repair or replacement. In patients with ischemic cardiomyopathy secondary to obstructive coronary artery disease with severe functional MR, surgical revascularization and concomitant mitral valve repair is frequently performed if the surgical risk is not prohibitive.

    Mitral regurgitation can progress over time, as the volume overload can lead to left ventricular dilatation and worsening mitral leaflet coaptation. As the disease process may be slow and without sudden worsening of symptoms, patients will require close follow-up. Mild MR can be followed by serial transthoracic echocardiography every 3 to 5 years, and moderate MR every 1 to 2 years. In patients with asymptomatic severe MR who do not undergo surgery, transthoracic echocardiography should be performed at least annually, with special attention to left ventricular dimensions and function.

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    Nkomo V.T., Gardin J.M., Skelton T.N., et al. Burden of valvular heart diseases: A population- based study. Lancet.


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    Freeman R.V., Otto C.M. Spectrum of calcific aortic valve disease: Pathogenesis, disease progression, and treatment strategies. Circulation. 2005;111:3316–3326.

    Cosmi J.E., Kort S., Tunick P.A., et al. The risk of the development of aortic stenosis in patients with “benign” aortic valve thickening. Arch Intern Med. 2002;162:2345–2347.

    Dal-Bianco J.P., Khandheira B.K., Mookadam F., et al.

    Management of asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2008;52:1279–1292.

    Nishimura R.A., Otto C.M., Bonow R.O., et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:e57–e185.

    Zilberszac R., Gabriel H., Schemper M., et al. Asymptomatic severe aortic stenosis in the elderly. J Am Coll Cardiol Img. 2017;10:43–50.

    Otto C.M., Kumbhani D.J., Alexander K.P., et al. 2017 ACC Expert Consensus Decision Pathway for Transcatheter Aortic Valve Replacement in the Management of Adults with Aortic Stenosis. J Am Coll of Cardiol. 2017;69(10):1313–1346. doi:10.1016/j.jacc.2016.12.006.

    Feldman T., Foster E., Glower D.D., et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011;364:1395– 1406.

    Wu A.H., Aaronson K.D., Bolling S.F., et al. Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol. 2005;45:381–387.

    Ling L.H., Enriquez-Sarano M., Seward J.B., et al. Early surgery in patients with mitral regurgitation due to flail leaflets: A long-term outcome study. Circulation. 1997;96:1819–1825.

    1  Not FDA approved for this  indication.

    1  Not FDA approved for this  indication.

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