INTRODUCTION	Section 2 of 11
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Background: With the increase in age of the United States population, disease processes in elderly individuals have become a major point of interest among health care professionals. Valvular aortic stenosis (AS) is no exception to this trend because senile degenerative AS currently is the leading indication for aortic valve replacement (AVR). Obviously, accurate diagnosis and efficient treatment of this clinical entity are becoming increasingly more important. Two-dimensional (2D) and Doppler echocardiographic methods have become invaluable tools for estimating the degree of stenosis and hence, for assisting in management guidance in most patients. Magnetic resonance imaging (MRI) has also proven useful in evaluating aortic valve stenosis, but its accessibility and practicality has limited its use. The favorable long-term outcome following aortic valve (AV) surgery and the relatively low operative risk emphasize the importance of an accurate and timely diagnosis.

Pathophysiology: The pathophysiologic mechanisms that are operative in patients with AS include an increase in afterload, progressive hypertrophy of the left ventricle, and a decrease in systemic and coronary flow as consequences of valve obstruction.

In infants and children with congenital AS, the increase in obstruction occurs gradually because the valve orifice shows little change as the child grows. Similarly, left ventricular (LV) obstruction usually develops and increases gradually over a long period of time in adults. The progressive LV outflow obstruction results in increased LV mass by parallel replication of sarcomeres producing concentric hypertrophy at the expense of cavity size. This increase in wall thickness is a compensatory mechanism to normalize LV wall stress. Indeed, wall thickness appears to be a critical determinant of ventricular performance in patients with AS; an inverse relationship exists between LV wall stress and ejection fraction (EF). Inadequate development of hypertrophy, depression of myocardial contractility, or a combination of these factors usually leads to impairment of ventricular performance.

LV systolic function usually is well preserved, and cardiac output (CO) is maintained for many years despite a large pressure gradient across the AV without a reduction in resting CO, LV dilatation, or development of symptoms. Although an elevated left ventricular end-diastolic pressure (LVEDP) may be an indicator of impending LV failure, it often reflects diminished compliance of a hypertrophic LV wall.

In patients with severe AS, the left atrial (LA) pressure waveform usually demonstrates a large a wave because of a combination of vigorous contraction of a hypertrophic left atrium and reduced LV compliance. Atrial contraction plays a particularly important role in mitral valve conductance and filling of the left ventricle in AS. It raises LVEDP while preventing a concomitant elevation of mean LA pressure. This prevents pulmonary venous and capillary pressures from rising to levels that would normally produce pulmonary congestion, while at the same time elevating LVEDP sufficiently to ensure effective LV contraction. Therefore, development of atrial fibrillation in AS is often catastrophic to the maintenance of normal forward stroke volume.

Although the CO at rest is normal in most patients with severe AS, it often fails to rise significantly during exercise. Late in the course of the disease, the CO, stroke volume, and the left ventricle and aorta pressure gradient all decline, whereas the mean left atrium, pulmonary capillary wedge, pulmonary artery, right ventricle systolic and diastolic, and right atrial (RA) pressures rise, often sequentially. AS intensifies the severity of existing mitral regurgitation (MR) by increasing the ventricular pressure gradient responsible for driving blood from the left ventricle to the left atrium.

Additionally, functional MR as a consequence of LV dilatation in late stages of AS may superimpose the hemodynamic changes associated with this lesion on those produced by AS. Consequent to secondary pulmonary hypertension, bulging of the hypertrophied interventricular septum into the right ventricular (RV) cavity, or both, the RA a wave becomes prominent. LVEDV usually remains normal or low until quite late in the course; however, LV mass increases in response to LV chronic pressure overload, resulting in an elevated LV mass-to-volume ratio.

Another consequence to the pathophysiologic response to AS, LV diastolic function, commonly is abnormal, resulting in elevated LV filling pressures, which is reflected onto the pulmonary circulation. Diastolic dysfunction occurs as a consequence of both impaired LV relaxation and decreased LV compliance that is caused by increased afterload, a thick noncompliant LV, and relative myocardial ischemia. Chamber stiffness can revert toward normal as LV hypertrophy regresses following relief of valvular obstruction, and in some patients, muscle stiffness also may revert to normal. Extensive myocardial fibrosis develops with long-standing hypertrophy, which may not disappear despite regression of hypertrophy.

Coronary blood flow at rest is increased in absolute terms but is normal when corrected for LV mass. However, myocardial blood flow reserve often is reduced. 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. Myocardial perfusion also is compromised by the relative decline in myocardial capillary density and by a reduced diastolic transmyocardial (coronary) perfusion gradient due to elevated LVEDP. Therefore, the subendocardium is susceptible to low nutrient flow, and this underperfusion results in myocardial ischemia.

Frequency:

• In the US: Aortic sclerosis (considered a precursor of calcific degenerative AS) increases 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 AS is between 2% and 9%.

• Asymptomatic patients, even with critical AS, 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 AS occur in asymptomatic patients.

• Although the obstruction tends to progress more rapidly in patients with degenerative calcific AV 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 AS. Catheterization and echocardiographic studies suggest that the valve area may decline 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 higher 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 AS.

	CLINICAL	Section 3 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

History: In AS of adults, a long latent period exists during which the LV outflow obstruction and the pressure load on the myocardium gradually increase while patients remain asymptomatic.

• The classic symptom triad of AS includes angina pectoris, syncope, and heart failure, which most commonly manifest after the sixth decade of life.

• In patients in whom the AV obstruction remains unrelieved, the onset of these symptoms predicts a poor outcome. The approximate time interval from the onset of symptoms to death is 2 years for heart failure, 3 years for syncope, and 5 years for angina.

• Exertional dyspnea is the most common initial complaint, even with normal LV systolic function, and it relates to abnormal LV diastolic function.

• Angina pectoris occurs in approximately two thirds of patients with critical AS, of which 50% have significant CAD. Because angina commonly is precipitated by exertion and relieved by rest, it often simulates symptoms of CAD. Angina results from a concomitant increased oxygen requirement by the hypertrophic myocardium and diminished oxygen delivery secondary to the excessive compression of coronary vessels and relative subendocardial myocardial ischemia. Of course, angina also can result from coexistent CAD.

• The cause of syncope is multifactorial. It often occurs upon exertion when the arterial systolic blood pressure drops because of systemic vasodilatation in the presence of a fixed forward stroke volume. Exertional hypotension also may manifest as blackout spells, lightheadedness, or dizziness upon effort. It also may be caused by atrial or ventricular tachyarrhythmias, commonly with premonitory symptoms.

• Syncope at rest may be due to transient ventricular tachycardia from which the patient recovers spontaneously. Episodes of atrial fibrillation with precipitous decline in CO or transient AV block due to extension of the calcification of the valve into the conduction system also can be culprits. Another cause of syncope is abnormal vasodepressor reflexes caused by increased LV intracavitary pressure (vasodepressor syncope), which is probably a common mechanism in patients with severe AS.

• Paroxysmal nocturnal dyspnea, orthopnea, and pulmonary edema usually are late-occurring symptoms of heart failure.

• Gastrointestinal bleeding, idiopathic or due to small bowel angiodysplasia or other vascular malformations, is present at a higher than expected frequency in patients with calcific AS; it usually resolves following AV surgery.

• Risk of infective endocarditis is higher in younger patients with mild valvular deformity than in older patients with degenerated calcified AVs, but it can occur in both. It can occur frequently at any age with hospital-acquired Staphylococcus aureus bacteremia, which frequently results in aortic valve replacement.

• Calcific AS may cause emboli of calcium in various organs, including the heart, kidney, and brain.

• Because resting CO usually is well maintained for many years in patients with severe AS, marked fatigability, debilitation, peripheral cyanosis, and other manifestations of a low CO usually are not prominent until quite late in the natural history of the disease.

• Atrial fibrillation, pulmonary hypertension, and systemic venous hypertension in patients with isolated AS are preterminal findings.

• Sudden cardiac death is rare and usually occurs in symptomatic patients.

Physical: In severe AS, the carotid arterial pulse is small and rises slowly (pulsus parvus et tardus); however, in elderly individuals, it may not be present despite severe stenosis because of a more rigid aorta. A lag time may be present between the apical impulse and the carotid impulse. Systolic hypertension can coexist with AS, but a systolic blood pressure higher than 200 mm Hg is rare in patients with critical AS. In advanced-stage AS, both systolic blood pressure and pulse pressure are decreased.

• 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. The v wave also may become prominent as pulmonary hypertension leads to RV failure and tricuspid regurgitation.

• At the apex, a precordial a wave often is visible and palpable. A hyperdynamic LV is unusual and suggests concomitant aortic regurgitation (AR) or MR. A systolic "thrill" may be present at the second right intercostal space or at the suprasternal notch and usually indicates a mean AV gradient higher than 50 mm Hg. The thrill is best felt while the patient is leaning forward. On occasion, it can be transmitted to the carotids.

• Rarely, RV failure with systemic venous congestion, hepatomegaly, and edema precede LV failure. This probably is 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).

• S₁ usually is normal or soft. The aortic component of the second heart sound, A₂, usually is diminished or absent because the AV is calcified and immobile and/or aortic ejection is prolonged or buried in the prolonged systolic ejection murmur. Paradoxical splitting of the S₂ also occurs because of late closure of A₂; its absence usually excludes severe AS. P₂ also may be accentuated when LV failure leads to secondary pulmonary hypertension.

• The presence of an ejection sound is dependent on the mobility of the valve cusps and disappears when they become immobile and severely calcified. Thus, it is common in children and young adults with congenital AS but rare in elderly individuals with acquired calcific AS with rigid valves. This sound occurs approximately 40-60 milliseconds after the onset of S₁ and frequently is heard best with the diaphragm of the stethoscope along the mid-lower left sternal border; it often is well transmitted to the apex and may be confused with a split S₁. In contrast to a pulmonic ejection sound, the aortic ejection sound usually does not vary with respiration.

• A prominent S₄ usually is present due to forceful atrial contraction and presystolic partial closure of the mitral leaflets. Presence of an S₄ in a young patient with AS indicates significant AS, but with AS in an elderly person, this is not necessarily true.

• The classic crescendo-decrescendo systolic murmur of AS is best heard at the second intercostal space in the right upper sternal border; it is harsh and rasping at the base and radiates to both carotid arteries. However, it may be more prominent at the apex in elderly persons with calcific AS due to radiation of the high-frequency components of the murmur to the apex (Gallavardin phenomenon) leading to its misinterpretation as a murmur of MR. Accentuation of the AS murmur following a long R-R interval (as in atrial fibrillation or following a premature beat) distinguishes it from the MR murmur, which usually does not change. Nevertheless, coexistent MR can be present, due to progressive LV dilatation, CAD, or mitral annular calcification. A high-pitched decrescendo diastolic murmur secondary to aortic regurgitation is common in many patients with dominant AS.

• The intensity of the systolic murmur does not correspond to the severity of AS, rather, the timing of the peak and the length or duration of the murmur corresponds to the severity of AS. 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 AS is augmented by the inhalation of amyl nitrite upon squatting or in a postpremature beat; the murmur intensity is reduced during Valsalva strain, which usually increases in hypertrophic obstructive cardiomyopathy.