J Am Coll Cardiol 1998;32:1486

Cause: AS: Congenital—unicuspid (severe stenosis in infancy), bicuspid (AS in adulthood; AI if infectious endocarditis develops), or tricuspid with commissural fusion; rheumatic; degenerative

AI: Rheumatic fever; infectious endocarditis; diseases of aortic root; VSD; RA; SLE; ankylosing spondylitis; Takayusu’s disease; Whipple’s disease; Crohn’s disease

Epidem: Rheumatic fever and rheumatic AS are decreasing in frequency in the industrialized countries. Degenerative disease remains the most common and most frequent cause of aortic valve replacement (AVR).

Bicuspid valves occur in 1-2% of the population and are associated with dilation of the ascending aorta (Circ 2002; 106:900).

At surgery, 54% of adults with isolated AS are found to have a congenitally malformed valve (Circ 2005;111:920).

In AS, the annual reduction in the aortic valve area is greater in those with milder degrees of stenosis and is accelerated in presence of smoking, hypercholesterolemia, and elevated serum creatinine and Ca⁺⁺ levels (Circ 2000;101:2497).

Pathophys: AS: Gradual progression with development of progressive concentric LVH; sarcomeres replicate in parallel and wall
thickness/cavity radius ratio increases; critical obstruction develops at valve area/index of 0.8/0.5 cm² and transvalvular gradient ≥ 50 mm Hg; CO is then normal at rest but falls with exercise

AI: Volume overload; sarcomeres elongate and replicate in series; chambers dilate but wall thickness/cavity radius ratio remains unchanged; in chronic AI, increased preload produces hemodynamic compensation (Frank Starling law), and EF and CO remain normal until late in disease; with acute AI (endocarditis, trauma, aortic dissection), CHF develops rapidly

In ankylosing spondylitis, development of AI is unrelated to other clinical features and can resolve or progress over time (J Am Coll Cardiol 1998;32:1397).

Sx: AS: Angina (2/3 ofpts with critical AS; half of these also have significant CAD) (Am Hrt J 1980;100:441); syncope; dyspnea; orthopnea/PND; decreased exercise capacity

AI: Exertional dyspnea; orthopnea/PND; palpitations; syncope is rare

Si: AS: Pulsus parvus et tardus; prominent jugular venous A wave; sustained PMI; decreased A2 (in acquired AS); S4; late-peaking harsh systolic murmur at upper-right sternal border and apex that may radiate to carotids—more severe stenosis produces a longer murmur, but murmur may diminish with LV failure; murmur increases with squatting or with administration of amyl nitrite; murmur decreases with standing, moderate exercise, Valsalva maneuver (during strain); murmur is louder after extrasystole and varies in Afib; AI murmur may also be present

AI: Collapsing (water hammer, Corrigan’s) pulse; capillary pulsations in lips or fingertips (Quincke’s sign); booming femoral pulses (pistol-shot sounds, Traube’s sign); widened pulse pressure; PMI laterally displaced or diffuse; systolic thrill; decreased A₂; S₃ gallop; blowing diastolic murmur at left sternal border, 3rd-4th intercostal space; short mid-systolic mumur at base; diastolic
rumble at apex (Austin Flint murmur); AI murmur increases when pt is sitting forward or squatting; murmur decreases with administration of amyl nitrite or Valsalva maneuver (strain)

Crs: AS: Myocardial ischemia can occur without CAD in severe AS; it is due to inadequate LVH with high systolic and diastolic wall stresses and reduced coronary flow reserve (Circ 1997;95:892). Overall survival with medical rx after dx is 40-65% at 5 yr and 20% at 10 yr (Am J Cardiol 1975;35:221). Asymptomaticpts do well (J Am Coll Cardiol 1990;15:1012; Cardiol Rev 1993;1:344), but the average time to death is 2 yr from onset of CHF, 3 yr from onset of syncope, and 5 yr from onset of angina (Circ 1968;37 suppl V:61; Brit Hrt J 1973;35:41). Statin rx appears to slow the progression of AS; its mechanism of action may not be related to cholesterol lowering (Circ 2004;110:1291).

AI: Asymptomaticpts with nl LV systolic function have mortality < 0.2%/yr, but oncepts develop LV dysfunction, 25%/yr develop sx. The mortality rate of symptomaticpts > 10%/yr. Predictors of survival include age, functional class, comorbid conditions, Afib, and LV end-systolic diameter. EF is an independent predictor of overall survival. Surgery for class II sx reduces cardiac mortality rates (J Am Coll Cardiol 1997;30:746; Circ 1999;99:1851).

Fen-phen: Initial reports indicated that 8% ofpts who have taken fenfluramine and phentermine (fen-phen) had moderate or severe AI. The prevalence of valvular regurgitation was 1-2 orders of magnitude lower in a study based on clinical records, and the incidence of clinically overt valvular disease after < 3 mon was < 1 case/1000 pt-yr after 4-yr follow-up (Nejm 1998;339:765). In 1163pts who had taken fen-phen, mild or greater AI was present in 8.8% of treatedpts and 3.6% of controls and moderate or greater MR in 2.6% of treatedpts and 1.5% of controls, suggesting that the predominant abnormality is mild AI not accompanied by significant cardiovascular sx (Circ 2000;
101:2071). Spontaneous improvement in AI has been documented in follow-up echocardiograms (Mayo Clin Proc 1999; 74:1191; Circ 1999;100:2161).

Cmplc: Infectious endocarditis; embolic events and angiodysplasia with gi bleeding in calcific AS. Acquired type 2A von Willebrand’s disease is common inpts with severe AS (Nejm 2003;349:343).

Lab: EKG: LAE; LVH may develop; EKG recommended q 2 yr in adolescents/young adults with AS; q 1 yr if Doppler peak velocity > 3 m/sec because the correlation between EKG findings and severity of AS is better in congenital than acquired AS

Echocardiogram: AS: In allpts for initial evaluation to assess LVH, LV systolic function, severity of AS, valve morphology, presence and severity of other valvular disease; q 2 yr in adolescents/young adults with AS; q 1 yr if Doppler peak velocity > 3 m/sec; Doppler velocity > 4 m/sec indicates > 95% likelihood that AS is severe and pt will require AVR

If pt has vague sx, Doppler echocardiogram; if peak velocity > 3m/sec, exercise test (see below)

If pt is asymptomatic, repeat test annually, advise re sx for Doppler velocity < 3 m/sec, q 6 mon if velocity 3-4 m/sec (pt is unlikely to be asymptomatic if Doppler velocity > 4 m/sec) (Circ 1997;95:2241)

AI: In allpts, to confirm presence and severity of acute AI or chronic AI, assess etiology of regurgitation, valve morphology and aortic root size and morphology, LVH, LV systolic function; if EF abnormal or LV end-diastolic dimension 60-70 mm or endsystolic dimension > 55 mm, pt requires AVR; if LV end-diastolic dimension > 75 mm or end-systolic dimension 45-50 mm, echo q 3 mon if unstable; all others: echo q 12 mon

Fen-phen: Pts should be examined clinically; echocardiography forpts who have a heart murmur or evidence of valvular disease or who received drugs for > 3 mon

Stress test: AS: Contraindicated inpts with severe AS; forpts with vague sx and Doppler echocardiogram peak velocity 3-4 m/sec, consider AVR if pt develops sx, VT, or hypotension during/after exercise test; otherwise follow medically

AI: Assess functional capacity and symptomatic responses, especially in athletes andpts with possible LV dysfunction;pts with normal EF and LV end-diastolic dimension 70-75 mm or end-systolic dimension 50-55 mm on echo will need AVR if sx or EF falls during exercise (measured by echocardiogram or radionuclide imaging)

Consider stress test for adolescents/young adults with AS if Doppler velocity > 3 m/sec and pt plans athletic participation or if clinical findings and echo-Doppler are disparate

See also the recommendations for follow-up in Section 8.4 on prosthetic heart valves.

X-ray: CXR: Cardiomegaly in AI; absence of calcium (fluoroscopy) in adults rules out severe AS

Radionuclide ventriculogram: For assessment of LV volume and function inpts with suboptimal echocardiograms or in asymptomaticpts with echocardiogram evidence of significant/progressive LV dysfunction but discordant clinical picture

Cardiac catheterization: In AS if other findings indicate severe disease requiring AVR, if noninvasive tests are inconclusive or the clinical picture and test results are inconsistent, or if angiography is required to assess possible concomitant CAD

Up to 22% ofpts who undergo retrograde catheterizaton of the aortic valve have MRI evidence of acute cerebral embolic events, though only 3% have clinically apparent neurological deficits (Lancet 2003;361:1241).

In AI forpts at risk for CAD or if noninvasive tests are inconclusive or discordant with clinical findings regarding the severity of AI, degree of LV dysfunction, or need for surgery (J Am Coll Cardiol 1998;32:1486)

Rx: AS: Symptomaticpts (CHF, syncope, chest pain): valve area < 0.8 cm² requires aortic valve replacement; area 0.8-1 cm² is “gray area”; if area > 1 cm², seek other causes of sx. Pts with moderate or severe AS who are scheduled for CABG or surgery of aorta of other valves also should have AVR; see also the recommendations under stress testing. In asymptomaticpts with AS, surgery may be delayed until sx develop; however,pts with moderate or severe valvular calcification and a rapid increase in aortic-jet velocity are candidates for early valve replacement (Nejm 2000;343:611).

Pts with AS and LV dysfunction (EF < 35%): Operative mortality is 9%. Approximately 58% are alive at 7 yr. Of those surviving, 80% had symptomatic improvement and 76% had improved EF (Circ 1997;95:2395). Thesepts should be considered for AVR independent of their sx.

Balloon valvotomy is reserved for thosepts with severe AS requiring urgent noncardiac surgery or for thosepts who are too sick or unstable to undergo AVR immediately but who are likely to be candidates for AVR in future, and for adolescents/young adults with normal CO and catheterization peak gradient > 60 mm Hg or peak gradient ≥ 50 mm Hg and who are symptomatic (angina, syncope, DOE), have new-onset EKG changes (ST depression, T-wave inversions at rest or during exercise), or want to play competitive sports or become pregnant.

It appears to be relatively safe to delay surgery until sx develop in asymptomaticpts with AS, but the presence of moderate or severe valvular calcification plus a rapid increase in aortic-jet velocity identifiespts with a very poor prognosis who should be considered for early valve replacement independent of their sx (Nejm 2000;343:611).

Inpts with severe AS and decompensated CHF, iv nitroprusside may improve LV function acutely; it is safe if the pt is not in cardiogenic shock (Nejm 2003;348:1756).

AI: Fen-phen: Pts should receive endocarditis prophylaxis if they have a heart murmur, “silent” moderate or severe AI on Doppler echocardiography, or mild AI associated and structural valvular lesions (Nejm 1998;339:ed).

Vasodilator rx: Forpts with AI and CHF prior to surgery; forpts with severe AI who are symptomatic and/or have LV dysfunction and for whom surgery is not an option; forpts with persistent LV dysfunction after AVR (ACEIs); for asymptomaticpts with severe AI and LV dilatation with normal LV systolic function or who have any degree of AI and HT

AVR: In chronic severe AI, forpts with functional class III or IV sx and preserved LV systolic function; usually forpts with class II sx and preserved LV systolic function and definitely if progressive LV dilatation is present; forpts with declining EF, decreasing exercise capacity, or angina; forpts with only LV dysfunction, especially those receiving nifedipine (J Am Coll Cardiol 2005;45:1025); forpts undergoing CABG, aortic or other valve surgery; and for asymptomaticpts with LV end-diastolic dimension > 75 mm or end-systolic dimension > 55 mm, orpts whose EF falls during exercise (Circ 2003;108:2432). Operative mortality is 2-8% and depends on sx and EF (Nejm 2004;351:1539). Pts with severe AS but low transvalvular gradient due to poor LV function may have their survival rate improved by AVR (J Am Coll Cardiol 2002;40:410).

In adolescents/young adults, AVR is definitely recommended for symptomaticpts or in asymptomaticpts with LV with EF < 0.50 on serial studies 1-3 mon apart or with progressive LV enlargement. The presence of moderate AS or the appearance of ST depressions or T-wave inversions on EKG may also be indications for AVR.

Pts with severe AI due to disease of the aortic root may require surgical repair/graft of aorta (J Cardiovasc Surg 1994;9 suppl:182).

Percutaneous aortic valvuloplasty does not change the natural course of AI and is not recommended (Circ 2004;109:1572).

See also the recommendations for antithrombotic rx in Section 8.4 on prosthetic heart valves.

J Am Coll Cardiol 1998;32:1486; Ann IM 1989;111:305

Cause: MS: Rheumatic fever (Lutembacher syndrome: MS with ASD); congenital very uncommon, seen in infancy

MR: Rheumatic fever, infectious endocarditis, mitral valve prolapse, calcification of mitral annulus, collagen vascular disease (SLE, scleroderma), Marfan syndrome, Ehlers-Danlos syndrome, amyloidosis, sarcoidosis, LA myxoma, trauma, ischemia, congenital abnormalities

Mitral prolapse: Most frequently occurs as a primary condition; also seen in collagen-vascular disease, Marfan syndrome, von Willebrand’s disease, myotonic dystrophy

Epidem: Rheumatic: 2/3 ofpts are women; 25% ofpts with rheumatic fever develop pure MS; another 40% have MS and MR (Eur Hrt J 1991;12 suppl B:77)

In a community-based sample, the prevalence of mitral valve prolapse (MVP) was 2.4% (incidence was previously reported as 3-5%) (Nejm 1999;341:1). Women with this condition outnumber men 2:1.

Pathophys: MS: Normal mitral orifice is 5-6 cm²; orifice is reduced in MS due to fusion of commissures and thickening of cusps and/or chordae. A gradient develops when valve area is reduced to 2 cm². LA pressure ≥ 25 mm Hg when valves ≤ 1 cm² (critical MS).

MR: Disorders of mitral leaflets, chordae, or papillary muscles produce a leak. Impedance to LV emptying in systole is reduced and EF remains normal or increased until LV pump failure develops.

Mitral prolapse: Myxomatous proliferation of mitral leaflets and chordae cause billowing of mitral leaflets.

Sx: Exertional dyspnea; orthopnea; palpitations. Sx are usually less in chronic MR than in MS but are acute and severe in acute MR. 15% ofpts with MS have angina-like chest pain (Prog Cardiovasc Dis 1973;15:491).

The frequencies of chest pain and dyspnea are similar among subjects with and without prolapse (Nejm 1999;341:1).

Si: MS: Prominent jugular A wave; RV heave (if RV enlarged); increased S₁ and P₂; opening snap; diastolic rumble at apex; longer murmur = more severe MS

MR: S₁ normal or decreased; S₂ widely split; P₂ increased in pulmonary HT; S₃ gallop; late/holosystolic murmur radiating to axilla that varies little with cycle length or inspiration