Aortic stenosis overview


 * Mohammed A. Sbeih, M.D. [mailto:msbeih@perfuse.org]; Assistant Editor-In-Chief: Kristin Feeney, B.S. [mailto:kfeeney@perfuse.org]

Overview
The aortic valve assures that blood moves forward the from the left ventricle into the aorta and that it does not leak backward during diastole. When functioning appropriately, the aortic valve does not impede the flow of blood between the left ventricle and the aorta and it does not leak. Under some circumstances, the aortic valve becomes narrower than normal, impeding the flow of blood. This is known as aortic valve stenosis, or aortic stenosis, often abbreviated as AS.

Classification
Aortic stenosis can be classified broadly in two main categories: acquired and congenital. Further classification can be applied based on the origin of the stenosis such as acquired rheumatic, congenital bicuspid, congenital subaortic, congenital subvalvular, and congenital supravalvular aortic stenosis.

Pathophysiology
The impedance to antegrade blood flow as a result of aortic stenosis results in chronic pressure overload of the left ventricle. The most common complication of aortic stenosis is left ventricular hypertrophy. The obstruction of flow in aortic stenosis can obviously occur at the level of the aortic valve itself, but can also occur at the subvalvular (below the aortic valve) or supravalvular (above the aortic valve) level as well.

Left Ventricular Hypertrophy
Long-standing aortic stenosis exposes the left ventricle to prolonged pressure overload which leads to concentric hypertrophy. The left ventricular wall increases in thickness (i.e. concentric hypertrophy occurs) as a result of the parallel replication of the sarcomeres.

Diastolic Dysfunction
During the initial period of concentric hypertrophy, the left ventricle is not dilated and there is preservation of left ventricular systolic function. Diastolic function, however, may be reduced due to a reduction in diastolic compliance.

This diastolic dysfunction may in turn lead to a rise in pulmonary capillary wedge pressure and dyspnea. Cardiac output may also be reduced as a result of diastolic dysfunction and impaired filling of the left ventricle. Early in the course of aortic stenosis, there may be a failure to augment cardiac output during exercise resulting in dyspnea on exertion.

Systolic Dysfunction
Later in the course of aortic stenosis, left ventricular dysfunction may develop due to a variety of pathophysiology processes. Systolic dysfunction is associated with a poor prognosis, and often does not partially or fully reverse following operative repair.

Excess Hypertrophy Causes Systolic Dysfunction
Although, this massive concentric hypertrophy characterized by a reduced diastolic radius-to-wall thickness ratio has shown to initially counter balance the increased systolic left ventricular pressure, if this process continues, an inverse relationship has been observed such that ejection fraction eventually goes down as left ventricular mass increases beyond a certain point. .

Myocardial Ischemia
The hypertrophied left ventricle and the prolonged ejection time (the time for the heart to eject blood) results in increased myocardial oxygen requirements. The elevated diastolic filling pressure also reduces the gradient between the aorta and the right atrium ("the height of the waterfall") that drives coronary blood flow. There may be a relative reduction in the density of the capillary network. The hypertrophied ventricle may also compress the capillaries. All of the above lead to a reduction in coronary blood flow even in the absence of obstructive epicardial stenoses. This may lead to subendocardial ischemia during stress or exercise. .

Myocardial Fibrosis
Myocardial scarring or fibrosis may develop with prolonged aortic stenosis, perhaps due to chronic subendocardial ischemia or increased wall stress.

Dyssynchronous Contraction
Another factor that may contribute to reduced left ventricular systolic function is dyssynchronous contraction subsequent to regional wall motion abnormalities, fibrosis or ischemia.

Atrial Fibrillation
The stiff, non-compliant left ventricle can become increasingly dependent upon the left atrium for filling. The development of atrial fibrillation and the loss of atrial contractility can result in reduced left ventricular filling and reduced cardiac output.

Epidemiology and Demographics
Aortic stenosis primarily affects older adults and the majority of cases are due to calcific degeneration. Aortic stenosis tends to affect approximately 2% of patients over the age of 65, 3% the age of 75, and 4% over the age 85.

Risk Factors
The most common risk factor for the subsequent development of aortic stenosis arises is a congenital bicuspid aortic valve. Rheumatic fever is a risk factor for the subsequent development of aortic stenosis (rheumatic heart disease). Risk factors that may speed up the progression of degenerative calcific aortic stenosis include:
 * Hypertension
 * Diabetes mellitus
 * Hyperlipoproteinemia
 * Uremia
 * Smoking

Causes
Aortic stenosis can be categorized under two methods of causation: acquired and congenital.

Valvular Aortic Stenosis:
====Acquired ====
 * Calcific degeneration
 * Rheumatic fever
 * Infective endocarditis
 * Systemic lupus erythromatosis
 * Fabry's disease
 * Aortic sclerosis

====Congenital ====
 * Bicuspid aortic valve
 * Hypoplastic annulus
 * Three cuspid valve with commissural fusion

Subvalvular Aortic Stenosis:

 * Membranous diaphragm
 * Hypertrophic cardiomyopathy

Supravalvular Aortic Stenosis:

 * Hypoplasia of aorta
 * Hourglass constriction of aorta
 * Fibromembranous aortic lesion

A complete list of causes in alphabetic order includes the following:
 * Age-induced calcification of normal tricuspid aortic valve with degenerative 'wear and tear'.
 * Congenital bicuspid aortic valve
 * Endocarditis
 * Fabry disease
 * Homozygous type II hypercholesterolemia
 * Ochronosis
 * Paget disease
 * Prosthetic aortic valve
 * Radiation treatment to the chest
 * Rheumatic fever (slowly progressive stenosis)
 * Subvalvular aortic stenosis
 * Supravalvular aortic stenosis
 * Williams syndrome, autosomal dominant trait is associated with supravalvular aortic stenosis

Differential Diagnosis
Aortic stenosis must be differentiated from other cardiac or pulmonary causes of dyspnea, weakness, and dizziness. Furthermore, if there is left ventricular outflow tract obstruction, it is critical to identify if the obstruction is subvalvular, valvular or supravalvular or due to Hypertrophic Cardiomyopathy (HOCM).

Degenerative Calcific Aortic Stenosis
Aortic stenosis due to degeneration of a calcified aortic valve has a prolonged latent period during which time symptoms may be minimal or even lacking. This form of aortic stenosis presents later in life, usually after the age of 75. The average rate of progression in valvular aortic stenosis, once moderate stenosis is present and symptomatic, is a decrease in valve area of 0.1 cm2 per year. Also on average, there is an increase in the jet velocity of 0.3 m / second per year and an increase in the mean pressure gradient of 7 mm Hg per year. There is tremendous individual variability in the rate of progression of aortic stenosis. Risk factors for atherosclerosis, such as age, smoking, hypertension, obesity and diabetes, lipid abnormalities, chronic renal failure and dialysis, and atherosclerotic disease itself, such as concomitant coronary artery disease are associated with more rapid rates of aortic stenosis progression.

Aortic Stenosis Due to Rheumatic Heart Disease
These patients generally become symptomatic after the sixth decade.

Bicuspid Aortic Valve Disease
Bicuspid aortic valve stenosis presents one to two decades earlier. The rate of progression of degenerative aortic stenosis can be faster than in those with congenital or rheumatic disease. Bicuspid aortic valve, during childhood functions without any significant pressure gradient. However, the thickening and calcification of the valves may be detectable pathologically and on echocardiography by second decade. This progresses to aortic stenosis requiring operative correction in approximately 75% of cases.

Bicuspid aortic stenosis progressively leads to heart failure, arrythmias, angina and other symptoms which generally manifests between 40 to 60 years of age which is relatively younger to manifestation of aortic stenosis otherwise. However, children who develop early pathologic changes in bicuspid aortic valve are more likely to develop aortic insufficiency than stenosis.

Aortic Sclerosis
Aortic sclerosis (defined as aortic valve thickening without obstruction to ventricular outflow) may progress to narrowing of the aortic valve or aortic stenosis. If the pulse pressure or upstroke of the pulse diminishes in the patient with aortic sclerosis, this can be a sign of progression to aortic stenosis.

Degenerative Calcific Aortic Stenosis
If left untreated, aortic stenosis may lead to complications such as angina, syncope, or heart failure. A complete list of complications of aortic stenosis includes the following:


 * Angina
 * Arrhythmias
 * Atrial fibrillation
 * Bleeding. Impaired platelet function and coagulation abnormalities as decreased levels of Von Willebrand factor can be seen in most patients with severe AS. This resolves after valve replacement procedure. 20% of patients have clinical bleeding, most often epistaxis or ecchymoses Aortic stenosis may result in a form of von Willebrand disease due to an increased turbulence around the stenosed aortic valve WHICH subsequently triggers a break down of coagulation factor VIII-associated antigen, (also called von Willebrand factor) and results in a variant of von Willebrand disease.
 * Congestive heart failure, particularly left-sided heart failure or systolic dysfunction
 * Endocarditis
 * Fainting or syncope. Since the stenosed aortic valve may limit the heart's output, people with aortic stenosis are at risk of syncope and dangerously low blood pressure should they use any of a number of common medications. Ironically, these same medicines are used to treat a variety of cardiovascular diseases, many of which may co-exist with aortic stenosis. Examples include nitroglycerin, nitrates, ACE inhibitors, terazosin (Hytrin), and hydralazine. Note that all of these substances lead to peripheral vasodilation. Normally, however, in the absence of aortic stenosis, the heart is able to increase its output and thereby offset the effect of the dilated blood vessels. In some cases of aortic stenosis, however, due to the obstruction of blood flow out of the heart caused by the stenosed aortic valve, cardiac output cannot be increased. Low blood pressure or syncope may ensue.
 * Left ventricular hypertrophy
 * Myocardial infarction

Bicuspid Aortic Valve Disease
Bicuspid aortic valve disease is associated with the following complications:
 * Aortic stenosis in the majority (75%) of patients.
 * Aortic insufficiency
 * Endocarditis
 * Aortic aneurysm
 * Aortic dissection
 * Sudden death can occur in children during and immediately after exertion especially among those with pressure gradient > 50 mmHg across the aortic valve.

Asymptomatic Patients
The prognosis of patients with aortic stenosis who do not have symptoms is quite good. The annual mortality rate is < 1% per year in asymptomatic patients. Only 4% of sudden cardiac deaths that occur in patients with aortic stenosis occur in those patients who are asymptomatic.

Symptomatic Patients
Medical treatment of newly diagnosed moderate to severe symptomatic aortic stenosis is associated with a 25% mortality at one year, and a 50% mortality at two years. Half the deaths are due to sudden cardiac death.

Left untreated, the average survival is 5 years after the onset of angina, 3 years after the onset of syncope, and 1 year after the onset of congestive heart failure.

History and Symptoms
The main symptoms of aortic stenosis include angina, syncope and congestive heart failure. Left untreated, the average survival is 5 years after the onset of angina, 3 years after the onset of syncope, and 1 year after the onset of congestive heart failure. Other symptoms include dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea.

Physical Examination
Aortic stenosis is most often diagnosed when it is asymptomatic and can sometimes be detected during routine examination of the heart and circulatory system. The major signs include pulsus parvus et tardus (a slow-rising, small volume carotid pulse), a lag time between apical and carotid impulses, and a distinct systolic ejection murmur.

Electrocardiogram
The electrocardiogram in the patient with moderate to severe aortic stenosis may reveal left ventricular hypertrophy and heart block.

Chest X-ray
Chest x ray may be used as a diagnostic tool in the evaluation of aortic stenosis. Findings associated with aortic stenosis include left ventricular hypertrophy and calcification of the aortic valve.

MRI
Magnetic resonance imaging is rarely used in the diagnosis of aortic stenosis, except in rare cases where the echocardiographic findings are inconclusive. There is a signal void where the high velocity jet exits the aortic valve.

CT
Computed tomography can be helpful as a diagnostic tool in conditions where the echocardiographic findings are inconclusive.

Echocardiography
Echocardiography is the best non-invasive test to evaluate the aortic valve anatomy and function. Echocardiography can be used to estimate the gradient across the aortic valve using the modified Bernoulli equation (gradient = 4 X velocity2). The flow must be constant, so as the velocity increases, the valve area decreases proportionally. Echocardiography can also be used to assess the severity of left ventricular hypertrophy.

Cardiac Catheterization
Left and right heart catheterization as well as angiography may be useful in the assessment of the patient prior to aortic valve replacement surgery.

Aortic Valve Area
The aortic valve area is the size of the orifice for blood to flow from the left ventricle to the aorta. The aortic valve area is reduced in aortic stenosis, and the aortic valve area is the metric that is used to gauge the need for aortic valve replacement surgery. The pressure gradient across a narrowed aortic valve cannot be used to gauge the need for valve replacement as the gradient may be low in patients with impaired left ventricular function.

Aortic Valve Area Calculation
Aortic valve area calculation is an indirect method of determining the area of the aortic valve. The calculated aortic valve orifice area is currently one of the measures for evaluating the severity of aortic stenosis. A valve area of less than 0.8 cm² is considered to be severe aortic stenosis.

There are many ways to calculate the valve area of aortic stenosis. The most commonly used methods involve measurements taken during echocardiography. For interpretation of these values, the area is generally divided by the body surface area, to arrive at the patient's optimal aortic valve orifice area.

Treatment
Once a patient becomes symptomatic with aortic stenosis, aortic valve replacement should be performed. Medical therapy reduces symptoms but does not prolong life. If a patient has extensive co-morbidities, transcatheter aortic valve implantation can be considered. Aortic valvuloplasty can be considered in those patients who are too sick for surgery or transcatheter aortic valve implantation.


 * Aortic stenosis surgery via aortic valve replacement
 * Transcatheter aortic valve implantation
 * Percutaneous aortic balloon valvotomy (PABV) or aortic valvuloplasty

Medical Therapy
While medical therapy may improve the symptoms of patients with aortic stenosis, medical therapy does not prolong life expectancy. Aortic valve replacement remains the definitive treatment of symptomatic aortic stenosis and it improves both the symptoms and life expectancy of patients with aortic stenosis. When pharmacological therapies are used, extreme caution must be exercised in the administration of vasodilators as excess vasodilation may lead to hypotension, a reduction in perfusion pressure to the heart, a further decline in cardiac output and further hypotension. This downward spiral can be fatal and must be avoided at all costs.

Percutaneous Aortic Balloon Valvotomy (PABV) or Aortic Valvuloplasty
Although surgical aortic valve replacement is the mainstay of treatment of aortic stenosis as it improves both symptoms and life expectancy, some patients may not be surgical candidates due to comorbidities, and minimally invasive treatment such as percutaneous aortic balloon valvotomy (PABV) maybe an alternative to surgery as a palliative strategy. PABV is a procedure in which 1 or more balloons are placed across a stenotic valve and inflated to decrease the severity of aortic stenosis. This is to be distinguished from transcatheter aortic valve implantation (TAVI) which is a different method that involves replacement of the valve percutaneously.

Transcatheter aortic valve implantation
Untill recently, aortic valve replacement (AVR) was the only effective treatment for severe symptomatic aortic stenosis. However, over the past decade percutaneous treatment of aortic valve disease with implantation of a stent-based valve prosthesis has been introduced as a new treatment in patients considered inoperable because of severe co-morbidities. In Transcatheter Aortic Valve Implantation (TAVI) also known as Percutaneous Aortic Valve Replacement (PAVR), a synthetic valve is advanced to the heart through a small hole made in groin. This procedure is similar in its mechanism to the insertion of a stent, or performing balloon angioplasty albeit with much larger equipment. Traditional aortic valve replacement is an invasive surgical procedure, with considerable mortality and morbidity, especially in more fragile patients. In the newly developed TAVI procedure, the dysfunctional aortic valve is replaced percutaneously, which obviates the need for open heart surgery.

Surgery
Aortic stenosis requires aortic valve replacement once the patient becomes symptomatic.

Prevention
Aortic stenosis associated with rheumatic heart disease can be minimized with antibiotic therapy in patients with documented streptococcal pharyngitis (strep throat). Bicuspid aortic valve disease is a congenital variant and cannot be prevented. Calcific degeneration of the valve can potentially be minimized by rosouvistatin and other measures targeting atherosclerosis prevention.

Precautions and Prophylaxis
People with aortic stenosis of any etiology are at risk for the development of infection of their stenosed valve, i.e. infective endocarditis and antibiotic prophylaxis should be considered. Patients with severe aortic stenosis should avoid strenuous exercise and any exercise that greatly increases afterload such as weight lifting.