Aortic Stenosis

Introduction
Background


Aortic stenosis is a narrowing or obstruction of the aortic valve. With the aging of the United States population, diseases in the elderly are a major interest among health care professionals. Valvular aortic stenosis (AS) is no exception; senile degenerative aortic stenosis is now the leading indication for aortic valve replacement (AVR). The favorable long-term outcome following aortic valve surgery and the relatively low operative risk emphasize the importance of an accurate and timely diagnosis.


Stenotic aortic valve (macroscopic appearance).

Pathophysiology

The pathophysiologic mechanisms responsible for symptoms (ie, angina, syncope, congestive heart failure) in patients with aortic stenosis include an increase in left ventricular (LV) afterload, progressive LV hypertrophy, and a decrease in systemic and coronary flow as consequences of valve obstruction.

In adults with aortic stenosis, LV outflow obstruction increases gradually over a long period of time, during which time the patient is asymptomatic. This progressive outflow obstruction results in increased LV mass by parallel replication of sarcomeres producing concentric hypertrophy, which is a compensatory mechanism to normalize LV wall stress. Inadequate development of hypertrophy, depression of myocardial contractility, or a combination of these factors may lead to impairment of LV performance (so-called afterload mismatch) and congestive heart failure (CHF) symptoms. Indeed, wall thickness appears to be a critical determinant of ventricular performance in patients with aortic stenosis. If afterload mismatch occurs, the LV ejection fraction, cardiac output, stroke volume, and transvalvular pressure gradient decline.

In most patients with aortic stenosis, LV systolic function is preserved and cardiac output is maintained for many years despite an elevated LV systolic pressure. Despite the fact that cardiac output at rest is normal, it often fails to increase appropriately during exercise, which may result in exercise-induced syncope or near syncope.

In the patient with aortic stenosis, diastolic dysfunction may occur as a consequence of impaired LV relaxation and/or decreased LV compliance, as a result of increased afterload, LV hypertrophy, or myocardial ischemia. LV hypertrophy often regresses following relief of valvular obstruction. However, in some individuals, extensive myocardial fibrosis develops, which may not disappear despite regression of hypertrophy.

In patients with severe aortic stenosis, atrial contraction plays a particularly important role in diastolic filling of the LV. Thus, development of atrial fibrillation in aortic stenosis is often catastrophic to the maintenance of normal forward stroke volume.

Increased LV mass, increased LV systolic pressure, and prolongation of the systolic ejection phase all elevate the myocardial oxygen requirement, especially in the subendocardial region. Coronary blood flow at rest is increased but normal when corrected for LV mass; however, coronary flow reserve is often reduced. Myocardial perfusion is also compromised by the relative decline in myocardial capillary density and by a reduced diastolic transmyocardial (coronary) perfusion gradient due to elevated LV diastolic pressure. Therefore, the subendocardium is susceptible to underperfusion, which results in myocardial ischemia.

Frequency
United States

Aortic sclerosis (considered a precursor of calcific degenerative aortic stenosis) increases in incidence with age and is present in 29% of individuals older than 65 years and in 37% of individuals older than 75 years. In elderly persons, the prevalence of aortic stenosis is between 2% and 9%.
Mortality/Morbidity

Patients with severe aortic stenosis may be asymptomatic for many years despite the presence of severe LV outflow tract obstruction. Such patients have a survival similar to those without aortic stenosis. With the appearance of symptoms, however, their survival is reduced; onset of angina is associated with an average survival of 5 years, syncope with an average survival of 2-3 years, and congestive heart failure with an average survival of 1.5-2 years.

Among symptomatic patients with medically treated moderate-to-severe aortic stenosis, mortality rates from the onset of symptoms are approximately 25% at 1 year and 50% at 2 years. More than 50% of deaths are sudden.
Asymptomatic patients, even with critical aortic stenosis, have an excellent prognosis regarding survival, with an expected death rate of less than 1% per year; only 4% of sudden cardiac deaths in severe aortic stenosis occur in asymptomatic patients.
Although the obstruction tends to progress more rapidly in patients with degenerative calcific aortic valve disease than in those with congenital or rheumatic disease, predicting the rate of progression in individual patients is not possible. Therefore, careful clinical follow-up is mandatory in all patients with moderate-to-severe aortic stenosis. Catheterization and echocardiographic studies suggest that, on average, the valve area declines 0.1-0.3 cm2 per year; the systolic pressure gradient across the valve can increase by as much as 10-15 mm Hg per year. A more rapid rate of progression is observed in elderly patients with coronary artery disease (CAD) and chronic renal insufficiency.

Race

No racial predilection is associated with congenital or acquired aortic stenosis.
Age

Severe aortic stenosis is rare in infancy, occurring in 0.33% of live births and is due to a unicuspid or bicuspid valve. Most patients with a congenitally bicuspid aortic valve who develop symptoms do not do so until middle age or later. Patients with rheumatic aortic stenosis typically present with symptoms after the sixth decade of life, and those with senile degenerative aortic stenosis may not manifest symptoms until their mid 70s to early 80s.
Clinical
History

In aortic stenosis, a long latent period exists during which time the LV outflow obstruction and the pressure load on the myocardium gradually increase while patients remain asymptomatic.

The classic symptom triad of aortic stenosis includes angina pectoris, syncope, and heart failure, which most commonly manifest after the sixth decade of life.
Some patients remain asymptomatic, but others develop exertional chest pain, effort dizziness or lightheadedness, easy fatigueability, and progressive inability to exercise.
Exertional dyspnea is the most common initial complaint, even with normal LV systolic function, and it often relates to abnormal LV diastolic function.
Angina pectoris occurs in approximately two thirds of patients with critical aortic stenosis, of which 50% have significant coronary artery disease. Because angina commonly is precipitated by exertion and relieved by rest, it simulates symptoms of coronary artery disease. Angina results from a concomitant increased oxygen requirement by the hypertrophic myocardium and diminished oxygen delivery secondary to diminished coronary flow reserve, decreased diastolic perfusion pressure and relative subendocardial myocardial ischemia. Of course, angina also can result from coexistent coronary artery disease.
The cause of syncope is multifactorial. It often occurs upon exertion when systemic vasodilatation causes the arterial systolic blood pressure to decline in the presence of a fixed forward stroke volume. It also may be caused by atrial or ventricular tachyarrhythmias.
Syncope at rest may be due to transient ventricular tachycardia, atrial fibrillation, or atrioventricular block, with the latter due to extension of the calcification of the valve into the conduction system. Another cause of syncope is abnormal vasodepressor reflexes caused by increased LV intracavitary pressure (vasodepressor syncope).
Congestive heart failure symptoms (ie, paroxysmal nocturnal dyspnea, orthopnea, dyspnea on exertion, and shortness of breath) may be due to systolic dysfunction from afterload mismatch, ischemia, or a separate cardiomyopathic process. Alternatively, diastolic dysfunction from LV hypertrophy or ischemia may also result in congestive heart failure symptoms.
In patients in whom the aortic valve obstruction remains unrelieved, the onset of symptoms predicts a poor outcome with medical therapy; the approximate time interval from the onset of symptoms to death is 2 years for congestive heart failure, 3 years for syncope, and 5 years for angina.
Gastrointestinal bleeding due to angiodysplasia or other vascular malformations is present at a higher than expected frequency in patients with calcific aortic stenosis; it usually resolves following aortic valve surgery.
The risk of infective endocarditis is higher in younger patients with mild valvular deformity than in older patients with degenerated calcified aortic valves, but it can occur in either. It can occur at any age with hospital-acquired Staphylococcus aureus bacteremia, which frequently results in aortic valve replacement.
Calcific aortic stenosis rarely may cause emboli of calcium to various organs, including the heart, kidney, and brain.
Sudden cardiac death is rare and usually occurs in symptomatic patients.

Physical

In severe aortic stenosis, the carotid arterial pulse is typically diminished and rises slowly (pulsus parvus et tardus); however, in elderly individuals with rigid carotid vessels, this may not be present. A lag time may be present between the apical impulse and the carotid impulse. Systolic hypertension can coexist with aortic stenosis, but a systolic blood pressure higher than 200 mm Hg is rare in patients with critical aortic stenosis.
Pulsus alternans can occur with the onset of LV dysfunction. The jugular venous pulse may show prominent a waves reflecting reduced RV compliance consequent to hypertrophy of the interventricular septum.
At the apex, a precordial a wave often is visible and palpable. A hyperdynamic LV is unusual and suggests concomitant aortic regurgitation or mitral regurgitation. A systolic "thrill" may be present at the second right intercostal space or at the suprasternal notch. The thrill is best felt while the patient is leaning forward. On occasion, it can be transmitted to the carotids.
S1 is usually normal or soft.
The aortic component of the second heart sound, A2, is usually diminished or absent because the aortic valve is calcified and immobile and/or aortic ejection is prolonged and it is obscured by the prolonged systolic ejection murmur. The presence of a normal or A2 speaks against the presence of severe aortic stenosis. Paradoxical splitting of the S2 also occurs because of late closure of A2. P2 may also be accentuated when LV failure leads to secondary pulmonary hypertension.
The presence of an ejection sound (eg, ejection click) is dependent on the mobility of the valve cusps and disappears when they become immobile and severely calcified. Thus, an ejection click is common in children and young adults with congenital aortic stenosis but rare in elderly individuals with acquired calcific aortic stenosis. This sound occurs approximately 40-60 milliseconds after the onset of S1 and is frequently heard best along the mid to lower left sternal border; it is often well transmitted to the apex and may be confused with a split S1.
A prominent S4 is usually present due to forceful atrial contraction into a hypertrophied left ventricle. The presence of an S4 in a young patient with aortic stenosis indicates significant aortic stenosis, but with aortic stenosis in an elderly person, this is not necessarily true.
The classic crescendo-decrescendo systolic murmur of aortic stenosis is best heard at the second intercostal space in the right upper sternal border; it is harsh at the base and radiates to one or both carotid arteries. However, it may be more prominent at the apex in elderly persons with calcific aortic stenosis due to radiation of the high-frequency components of the murmur to the apex (Gallavardin phenomenon) leading to its misinterpretation as a murmur of mitral regurgitation. Accentuation of the aortic stenosis murmur following a long R-R interval (as in atrial fibrillation or following a premature beat) distinguishes it from the mitral regurgitation murmur, which usually does not change.
The intensity of the systolic murmur does not correspond to the severity of aortic stenosis, rather, the timing of the peak and the length or duration of the murmur corresponds to the severity of aortic stenosis. The more severe the stenosis, the longer the duration of the murmur and the more likely it peaks at mid-to-late systole.
The murmur of valvular aortic stenosis is augmented upon squatting or following a premature beat; the murmur intensity is reduced during Valsalva strain, which is contrary to what occurs with hypertrophic obstructive cardiomyopathy where a Valsalva maneuver increases the intensity of the murmur.
When the left ventricle fails and cardiac output falls, the aortic stenosis murmur becomes softer and may be barely audible. Atrial fibrillation with short R-R intervals can also decrease the murmur intensity or make it appear absent.
Rarely, RV failure with systemic venous congestion, hepatomegaly, and edema precede LV failure. This is probably due to the bulging of the interventricular septum into the right ventricle, with impedance in filling, elevated jugular venous pressure, and a prominent a wave (Bernheim effect).

Causes

Most cases of aortic stenosis are due to the obstruction at the valvular level. Common causes are summarized in Table 1. Valvular aortic stenosis can be either congenital or acquired.
Congenital valvular aortic stenosis
Congenitally unicuspid, bicuspid, tricuspid, or even quadricuspid valves may be the cause of aortic stenosis. In neonates and infants younger than 1 year, a unicuspid valve can produce severe obstruction and is the most common anomaly in infants with fatal valvular aortic stenosis.
In patients younger than 15 years, unicuspid valves are most frequent in cases of symptomatic aortic stenosis.
In adults, congenital aortic stenosis is usually due to a bicuspid valve. It does not cause significant narrowing of the aortic orifice during childhood. The altered architecture of the bicuspid aortic valve induces turbulent flow with continuous trauma to the leaflets, ultimately resulting in fibrosis, increased rigidity and calcification of the leaflets, and narrowing of the aortic orifice in adulthood.
Congenitally malformed tricuspid aortic valves with unequally sized cusps and commissural fusion can also cause turbulent flow leading to fibrosis and, ultimately, to calcification and stenosis. Clinical manifestations of congenital aortic stenosis in adults usually occur after the fourth decade of life.
Acquired valvular aortic stenosis
The main causes of acquired aortic stenosis include rheumatic heart disease and senile degenerative calcification.
In rheumatic aortic stenosis, the underlying process includes progressive fibrosis of the valve leaflets with varying degrees of commissural fusion, often with retraction of the leaflet edges and, in certain cases, calcification. As a consequence, the rheumatic valve often is regurgitant and stenotic. Coexistent mitral valve disease is common.
Degenerative (senile) calcific aortic stenosis involves progressive calcification of the leaflet bodies resulting in limitation of the normal cusp opening during systole. This represents a consequence of long-standing hemodynamic stress on the valve and is currently the most frequent cause of aortic stenosis requiring aortic valve replacement. It usually occurs in individuals older than 75 years. Cellular aging and degeneration have been implicated. Diabetes mellitus and hypercholesterolemia are risk factors for the development of this lesion. The calcification may also involve the mitral annulus or extend into the conduction system, resulting in atrioventricular or intraventricular conduction defects.
The available data suggest that the development and progression of calcific aortic stenosis are due to an active disease process at the cellular and molecular level that shows many similarities with atherosclerosis, ranging from endothelial dysfunction to, ultimately, calcification.
Calcific aortic valve disease is associated with older age, male sex, serum LDL and Lp(a) levels, systemic arterial hypertension, diabetes mellitus, and smoking.
Other infrequent causes of aortic stenosis include obstructive vegetations, homozygous type II hypercholesterolemia, Paget disease, Fabry disease, ochronosis, and irradiation.
Table 1. Common Reasons of Aortic Stenosis Requiring Surgery


Open table in new windowAge <70 years (n=324)
Bicuspid AV (50%)
Postinflammatory (25%)
Degenerative (18%)
Unicommissural (3%)
Hypoplastic (2%)
Indeterminate (2%)

Age >70 years (n=322)
Degenerative (48%)
Bicuspid (27%)
Postinflammatory (23%)
Hypoplastic (2%)

http://emedicine.medscape.com/article/150638-overview