eMedicine Specialties > Cardiology > Valvular Heart Disease

Aortic Stenosis

Author: James V Talano, MD, MBA, MM, FACC, FAHA, Director of Cardiovascular Medicine, SWICFT Institute
Coauthor(s): Bekir Hasan Melek, MD, Assistant Professor of Clinical Medicine, Department of Medicine, Section of Cardiology, Tulane University School of Medicine
Contributor Information and Disclosures

Updated: Jun 28, 2007

Introduction

Background

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 AS is now the leading indication for aortic valve replacement (AVR). 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 responsible for symptoms 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 changes little as the child grows. Similarly, in adults with AS, left ventricular (LV) obstruction usually develops and increases gradually over a long period of time. 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 (so-called afterload mismatch).

LV systolic function is usually well preserved, and cardiac output (CO) is maintained for many years despite a large pressure gradient across the AV. During this time, the patient does not experience a reduction in resting CO, LV dilatation, or development of symptoms. Although the CO at rest is normal in most patients with severe AS, it often fails to rise significantly during exercise. If afterload mismatch occurs, the CO, stroke volume, and the left ventricle and aorta pressure gradient all decline.

Another consequence to the pathophysiologic response to AS, LV diastolic function, is commonly 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.

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.

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.

Coronary blood flow at rest is increased in absolute terms but is normal when corrected for LV mass. However, myocardial blood flow reserve is often 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 is also 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

United States

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%.

Mortality/Morbidity

The natural history of AS is well known. Patients with severe AS may be asymptomatic for many years despite the presence of severe left ventricular outflow tract (LVOT) obstruction. The peak AV systolic pressure gradient can exceed 150 mm Hg, and peak LV pressure can reach 300 mm Hg with normal end-diastolic volume (EDV) and end-systolic volume (ESV). In one series, 40% of patients with severe AS treated medically survived 5 years, whereas the 10-year survival rate was 20%. In another series of patients with significant AS treated medically, the 5-year survival rate was 64%. With the appearance of symptoms, a rapidly progressive downhill course is observed. Onset of angina is associated with an average survival of 5 years, the onset of syncope is associated with an average survival of 2-3 years, whereas the onset of congestive heart failure (CHF) is associated with an average survival of 1.5-2 years.

• Among symptomatic patients with moderate-to-severe AS treated medically, mortality rates from the onset of symptoms were approximately 25% at 1 year and 50% at 2 years. More than 50% of deaths were sudden. Death in general, including sudden death, occurs primarily in symptomatic patients.
• 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.

Age

See Causes.

Clinical

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 is usually well maintained for many years in patients with severe AS, marked fatigability, debilitation, peripheral hypoperfusion, and other manifestations of a low CO are usually 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, this may not be present despite severe stenosis because of more rigid aorta and carotid vessels. 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.
• 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 is usually normal or soft. The aortic component of the second heart sound, A₂, is usually diminished or absent because the AV is calcified and immobile and/or aortic ejection is prolonged or buried in the prolonged systolic ejection murmur. The presence of a normal or A ₂ speaks against the presence of severe AS. 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, 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 is frequently heard best with the diaphragm of the stethoscope along the mid-lower left sternal border; it is often 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 is usually present due to forceful atrial contraction into a hypertrophied left ventricle. The 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 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 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 AS murmur becomes softer and may be barely perceptible. Atrial fibrillation with short R-R intervals can also decrease the murmur intensity or make it appear absent. In an elderly person with symptoms of CHF and a soft systolic ejection murmur, noninvasive evaluation for AS is needed because occult AS may be a cause of intractable heart failure. Embolization from a calcified or infected AV that results in unilateral vision loss, focal neurologic signs, and myocardial infarction can be the first signs of AV pathology.
  

Causes

Most cases of AS are due to the obstruction at the valvular level. Common causes are summarized in Table 1. Valvular AS can be either congenital or acquired.

• Congenital valvular aortic stenosis
  • Congenitally unicuspid, bicuspid, tricuspid, or even quadricuspid valves may be the cause of AS. In neonates and infants younger than 1 year, a unicuspid valve can produce severe obstruction and is the most common anomaly in patients with fatal valvular AS.
  • In general, unicuspid valves are most frequent in cases of symptomatic AS in patients younger than 15 years. In adults, congenital AS is usually due to a bicuspid valve but usually does not cause significant narrowing of the aortic orifice during childhood because most of the bicuspid valves are not stenotic at birth. Their altered architecture 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.
  • These anatomical/pathological changes are similar to those observed in senile degenerative calcific stenosis of a tricuspid AV, except that in congenital bicuspid valve, these changes occur several decades earlier. Congenitally malformed tricuspid AVs with unequally sized cusps and some commissural fusion can also cause turbulent flow leading to fibrosis and, ultimately, to calcification and stenosis. Clinical manifestations of congenital AS in adults usually occur after the fourth decade of life.
• Acquired valvular aortic stenosis
  • The main causes of acquired AS include rheumatic heart disease and senile degenerative calcification.
  • In rheumatic AS, 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. This form of AS is uncommon in the United States.
  • Degenerative (senile) calcific AS 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 AS requiring AV surgery. 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 pathophysiologic changes are preceded by structural changes in the valvular apparatus. Recent histopathologic studies have provided important insight into the pathogenesis of calcific AS. The available data suggest that the development and progression of calcific AS 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.
    • These similarities between calcific AV disease and atherosclerosis at tissue level imply that they may share similar association with clinical risk factors. Indeed, the Cardiovascular Health Study has suggested that calcific AV disease is associated with older age, male sex, serum LDL and Lp(a) levels, systemic arterial hypertension, diabetes mellitus, and smoking.
    • The early lesion in the pathogenesis of degenerative calcific AV disease is focal endothelial thickening on the aortic side of the cusps that is initiated by endothelial disruption due to increased mechanical stress and decreased shear stress. These lesions consist of intracellular and extracellular lipids (mainly LDL and Lp[a] with evidence of lipoprotein oxidation), inflammatory cells (mainly macrophages with some foam cells and few T lymphocytes), extracellular matrix, and microscopic calcification associated with active production of osteopontin protein by a subset of macrophages. The upregulated matrix metalloproteinase expression induces remodeling of the extracellular matrix via cytokine stimulation. Phenotypically altered fibroblasts and HLA-DR also accumulate in the abnormal region of the AV.
    • Another important finding is the presence of angiotensin-converting enzyme and angiotensin II, which suggests a potential role of the renin-angiotensin system in the lesion pathogenesis. After initial inflammatory changes, calcification predominates later in the process. The extension of the lesion into adjacent fibrosa of the cusps leads to disruption of the normal collagen fiber architecture that provides tensile strength to valve leaflets, resulting in dysfunction.
  • Coexistent coronary artery calcification is also common and has been found to be correlated with aortic-valve calcium based on electron beam computed tomography (EBCT) findings, also called Ultrafast CT. Calcific AS is also observed in end-stage renal disease. Rheumatoid involvement of the valve (ie, systemic lupus erythematosus, rheumatoid arthritis) can result in nodular thickening of the valve cusps and involvement of the proximal part of the aorta but is a rare cause of AS.
• Other infrequent causes of AS include obstructive vegetations, homozygous type II hypercholesteroemia, Paget disease, Fabry disease, ochronosis, and irradiation.
• The likely cause of AS depends on the age of the patient at presentation. In patients who develop symptoms in their teens and early twenties, the cause usually is a congenitally unicuspid or fused bicuspid AV. If symptoms arise between the fifth and seventh decade, the culprit is either a calcified bicuspid AV or it is degenerative in nature. Nowadays, the most common presentation is an elderly patient with senile degenerative AV with calcific deposits at the base of the cusps in the absence of commissural fusion. Table 1. Common Reasons of Aortic Stenosis Requiring Surgery
  

  Open table in new window

  [ CLOSE WINDOW ]

  Table

  Age <70 years (n=324)	Age >70 years (n=322)
  Bicuspid AV (50%) Postinflammatory (25%) Degenerative (18%) Unicommissural (3%) Hypoplastic (2%) Indeterminate (2%)	Degenerative (48%) Bicuspid (27%) Postinflammatory (23%) Hypoplastic (2%)

  Age <70 years (n=324)	Age >70 years (n=322)
  Bicuspid AV (50%) Postinflammatory (25%) Degenerative (18%) Unicommissural (3%) Hypoplastic (2%) Indeterminate (2%)	Degenerative (48%) Bicuspid (27%) Postinflammatory (23%) Hypoplastic (2%)

• Search for CME/CE on This Topic »

• Aortic Stenosis, Supravalvar (Pediatrics: Cardiac Disease and Critical Care Medicine)
• Aortic Stenosis, Subaortic (Pediatrics: Cardiac Disease and Critical Care Medicine)
• Aortic Stenosis (Emergency Medicine)
• Aortic Stenosis (Radiology)

• Circulatory Problems Center
• Angina Pectoris Causes
• Angina Pectoris Symptoms
• Angina Pectoris Treatment
• Angina Pectoris Overview

• First Hint of a Benefit for Statins in Rheumatic Valve Disease
• Exercise Training Boosts Benefits of Cardiac Resynchronization Therapy
• UK Guidelines Address Care of Fertile Women With Familial Hypercholesterolemia

• Simvastatin and Ezetimibe in Aortic Stenosis (SEAS)
• Does Lowering Cholesterol Have an Impact on the Progression of Aortic Stenosis?
• Statins for Aortic Stenosis?