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(See also Overview of Cardiac Valvular Disorders.)
Aortic stenosis (AS) is narrowing of the aortic valve, obstructing blood flow from the left ventricle to the ascending aorta during systole. Causes include a congenital bicuspid valve, idiopathic degenerative sclerosis with calcification, and rheumatic fever. Untreated AS progresses to become symptomatic with one or more of the classic triad of syncope, angina, and exertional dyspnea; heart failure and arrhythmias may develop. A crescendo-decrescendo ejection murmur is characteristic. Diagnosis is by physical examination and echocardiography. Asymptomatic AS in adults usually requires no treatment. Once symptoms develop, surgical or percutaneous valve replacement is required. For severe or symptomatic AS in children, balloon valvotomy is effective.
In elderly patients, the most common precursor to aortic stenosis is
Aortic sclerosis is a degenerative aortic valve disease with thickening of aortic valve structures by fibrosis and calcification initially without causing significant obstruction. Over years, aortic sclerosis progresses to stenosis in as many as 15% of patients. Aortic sclerosis resembles atherosclerosis, with deposition of lipoproteins and inflammation and calcification of the valves; risk factors are similar. Patients with psoriasis are at increased risk for atherosclerosis, and more recently psoriasis has been tied to an increased risk of aortic stenosis.
In patients < 70 yr, the most common cause of aortic stenosis is
Congenital aortic stenosis occurs in 3 to 5/1000 live births and affects more males; it is associated with coarctation and progressive dilatation of the ascending aorta, causing dissection.
In developing countries, the most common cause of aortic stenosis in all age groups is
Supravalvular AS caused by a discrete congenital membrane or hypoplastic constriction just above the sinuses of Valsalva is uncommon. A sporadic form of supravalvular AS is associated with a characteristic facial appearance (high and broad forehead, hypertelorism, strabismus, upturned nose, long philtrum, wide mouth, dental abnormalities, puffy cheeks, micrognathia, low-set ears). When associated with idiopathic hypercalcemia of infancy, this form is known as Williams syndrome.
Subvalvular AS caused by a congenital membrane or fibrous ring just beneath the aortic valve is uncommon.
The increased pressure load imposed by aortic stenosis results in compensatory hypertrophy of the left ventricle (LV) without cavity enlargement (concentric hypertrophy). With time, the ventricle can no longer compensate, causing secondary LV cavity enlargement, reduced ejection fraction (EF), decreased cardiac output, and a misleadingly low gradient across the aortic valve (low-gradient severe AS). Patients with other disorders that also cause LV enlargement and reduced EF (eg, myocardial infarction, intrinsic cardiomyopathy) may generate insufficient flow to fully open a sclerotic valve and have an apparently small valve area even when their AS is not particularly severe (pseudosevere AS). Pseudosevere AS must be differentiated from low-gradient severe AS because only patients with low-gradient severe AS benefit from valve replacement.
Elevated shear stress across the stenosed aortic valve degrades von Willebrand factor multimers. The resulting coagulopathy may cause GI bleeding in patients with angiodysplasia (Heyde syndrome).
Congenital AS is usually asymptomatic until age 10 or 20 yr, when symptoms develop insidiously. In all forms, progressive untreated aortic stenosis ultimately results in exertional syncope, angina, and dyspnea (SAD triad). Other symptoms and signs may include those of heart failure and arrhythmias, including ventricular fibrillation leading to sudden death.
Exertional syncope occurs because cardiac output cannot increase enough to meet the demands of physical activity. Nonexertional syncope may result from altered baroreceptor responses or ventricular tachycardia. Exertional angina pectoris affects about two thirds of patients; about half have significant coronary artery atherosclerosis, and half have normal coronary arteries but have ischemia induced by LV hypertrophy and altered coronary flow dynamics.
There are no visible signs of aortic stenosis. Palpable signs include carotid and peripheral pulses that are reduced in amplitude and slow rising (pulsus parvus, mollus et tardus) and an apical impulse that is sustained (thrusts with the 1st heart sound [S1] and relaxes with the 2nd heart sound [S2]) because of left ventricular hypertrophy. The LV impulse may become displaced when systolic dysfunction develops. A palpable 4th heart sound (S4), felt best at the apex, and a systolic thrill, corresponding with the murmur of AS and felt best at the left upper sternal border, are occasionally present in severe cases. Systolic BP may be high even when AS is severe but ultimately falls when the LV fails.
On auscultation, S1 is normal and S2 is single because aortic valve closing is delayed and merges with the pulmonic (P2) component of S2. The aortic component may also be soft. Paradoxical splitting of S2 may be heard. A normally split S2 is the only physical finding that reliably excludes severe AS. An S4 may be audible. An ejection click may also be audible early after S1 in patients with congenital bicuspid AS when valve leaflets are stiff but not completely immobile. The click does not change with dynamic maneuvers.
The hallmark finding is a crescendo-decrescendo ejection murmur, heard best with the diaphragm of the stethoscope at the right and left upper sternal border when a patient who is sitting upright leans forward. The murmur typically radiates to the right clavicle and both carotid arteries (left often louder than right) and has a harsh or grating quality. But in elderly patients, vibration of the unfused cusps of calcified aortic valve leaflets may transmit a louder, more high-pitched, “cooing” or musical sound to the cardiac apex, with softening or absence of the murmur parasternally (Gallavardin phenomenon), thereby mimicking mitral regurgitation. The murmur is soft when stenosis is less severe, grows louder as stenosis progresses, and becomes longer and peaks in volume later in systole (ie, crescendo phase becomes longer and decrescendo phase becomes shorter) as stenosis becomes more severe. As LV contractility decreases in critical AS, the murmur becomes softer and shorter. The intensity of the murmur may therefore be misleading in these circumstances.
The murmur of AS typically increases with maneuvers that increase LV volume and contractility (eg, leg-raising, squatting, Valsalva release, after a ventricular premature beat) and decreases with maneuvers that decrease LV volume (Valsalva maneuver) or increase afterload (isometric handgrip). These dynamic maneuvers have the opposite effect on the murmur of hypertrophic cardiomyopathy, which can otherwise resemble that of AS. The murmur of mitral regurgitation due to prolapse of the posterior leaflet may also mimic AS.
Diagnosis or aortic stenosis is suspected clinically and confirmed by echocardiography. Two-dimensional transthoracic echocardiography is used to identify a stenotic aortic valve and possible causes, to quantify LV hypertrophy and degree of systolic dysfunction, and to detect coexisting valvular heart disorders (aortic regurgitation, mitral valve disorders) and complications (eg, endocarditis). Doppler echocardiography is used to quantify degree of stenosis by measuring jet velocity, transvalvular systolic pressure gradient, and aortic valve area
Severity of aortic stenosis is characterized echocardiographically as
Clinical judgment is used to resolve any discordance among these parameters (eg, moderate valve area but severe mean gradient). When LV function is normal, the valve area is the least accurate.
The gradient may be overestimated when aortic regurgitation is present. The gradient may under-represent severity when the stroke volume is low, eg, in patients with LV systolic dysfunction (low-gradient AS with reduced EF) or a small, hypertrophied LV (low-gradient AS with normal EF). Sometimes LV systolic dysfunction results in low ventricular pressure that is inadequate to open nonstenotic valve leaflets, causing echocardiographic appearance of low valve area in the absence of stenosis (pseudostenosis).
Prior to intervention, cardiac catheterization is necessary to determine whether coronary artery disease (CAD) is the cause of angina and, occasionally, to resolve inconsistency between clinical and echocardiographic findings.
An ECG and chest x-ray are obtained. ECG typically shows changes of LV hypertrophy with or without an ischemic ST- and T-wave pattern. Chest x-ray findings may include calcification of the aortic cusps (seen on the lateral projection or on fluoroscopy) and evidence of HF. Heart size may be normal or only mildly enlarged.
In asymptomatic patients with severe aortic stenosis, closely supervised exercise ECG testing is recommended in an attempt to elicit symptoms of angina, dyspnea, or hypotension—any of these symptoms, when due to the AS, is an indication for intervention. Failure to normally increase BP and development of ST segment depression are less predictive of adverse prognosis. Exercise testing is contraindicated in symptomatic patients. When there is LV dysfunction and the aortic valve gradient is low but the valve area is small, then low-dose dobutamine stress echocardiography distinguishes low-gradient AS from pseudostenosis.
Aortic stenosis progresses faster as severity increases, but the wide variability in progression rates requires regular surveillance, particularly in sedentary elderly patients. In such patients, flow may become significantly compromised without triggering symptoms.
Asymptomatic patients with severe AS and normal systolic function should be reevaluated every 6 mo because 3 to 6% will develop symptoms or LVEF impairment every year. The risk of surgery outweighs the survival benefit in asymptomatic patients, but with the onset of symptoms the mean survival plummets to 2 to 3 yr, and prompt valve replacement is indicated to relieve symptoms and improve survival. Risk of surgery increases for patients who require simultaneous coronary artery bypass graft (CABG) and for those with depressed systolic LV function.
In patients with severe AS, about 50% of deaths occur suddenly, and these patients should be advised to limit physical exertion.
Nothing has yet been proved to slow the progression of AS. In randomized trials, statin therapy has been ineffective.
Drugs that can cause hypotension (eg, nitrates) should be used cautiously, although nitroprusside has been used as a temporizing measure to reduce afterload in patients with decompensated heart failure in the hours before valve replacement. Patients who develop heart failure but are too high risk for valve intervention benefit from cautious treatment with digoxin, diuretics, and ACE inhibitors.
The benefits of intervention do not outweigh the risks until patients develop symptoms and/or meet certain echocardiographic criteria. Thus, patients should have periodic clinical evaluations, including echocardiography and sometimes exercise testing, to determine the optimal time for valve replacement. Valve replacement is recommended for
Symptomatic patients (including those with symptoms or reduced effort tolerance on exercise testing) with
Asymptomatic patients with any one of the following:
Balloon valvotomy is used primarily in children and very young adults with congenital AS. In older patients who are not candidates for surgery, balloon valvuloplasty may be used as a bridge to valve replacement but it has a high complication rate and provides only temporary relief.
Surgical aortic valve replacement is the best choice for most patients but transcatheter (percutaneous) valve replacement (TAVR) may be chosen instead when surgical risk is high (as long as coexisting conditions do not preclude benefit from relieving the AS). TAVR affords better survival and quality of life than medical therapy and is safer than surgery in many high-risk patients ( 1, 2). Surgery usually involves replacement with a mechanical or bioprosthetic valve, but in younger patients, the patient’s own pulmonic valve can be used, and a bioprosthesis is then used to replace the pulmonic valve (Ross procedure). Preoperative evaluation for CAD is indicated so that CABG and valve replacement, if indicated, can be done during the same procedure. An aortic bioprosthetic valve does not require anticoagulation beyond the immediate postoperative period but a mechanical valve requires lifetime anticoagulation using warfarin. Newer novel oral anticoagulants (NOAC) are ineffective and should not be used.
1. Kapadia SR, Leon MB, Makkar RR, et al . Five-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 385:2485–2491, 2015.
2. Mack MJ, Leon MB, Smith CR, et al . Five-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 385:2477–2484, 2015.
The most common cause of AS in patients < 70 yr is bicuspid aortic valve; aortic sclerosis is the most common precursor in the elderly.
Untreated AS ultimately results in exertional syncope, angina, and dyspnea; sudden death may occur.
Typical heart sounds are a crescendo-decrescendo ejection murmur that increases with maneuvers that increase LV volume and contractility (eg, leg-raising, squatting, Valsalva release) and decreases with maneuvers that decrease LV volume (Valsalva maneuver) or increase afterload (isometric handgrip).
Nitrates may cause dangerous hypotension and should be used with caution for angina in patients with AS.
Replacement is indicated once symptoms begin or LV dysfunction occurs.
Surgical valve replacement is the best option for most patients, but transcatheter replacement is now available for patients at high surgical risk.
Drug NameSelect Trade
dobutamineNo US brand name
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