Albany Medical Review

Topic Review - Aortic Stenosis

Aortic stenosis (AS) leads to destruction of the normal aortic valve which results in obstruction of left ventricular outflow. The normal aortic valve is tricuspid and consists of: the posterior or non-coronary cusp, the right cusp which gives rise to the right coronary artery orifice, and the left cusp which gives rise to the left main coronary artery orifice. Although AS is most commonly an acquired condition, congenital manifestations also exist. Acquired causes include age-related degenerative calcific disease, rheumatic heart disease, end-stage renal disease, and Paget's disease. Congenital presentations include unicuspid, bicuspid, abnormal tricuspid, and even quadricuspid valves. Congenital hyperlipoproteinemia represents both an acquired and congenital etiology of aortic stenosis.

CLASSIFICATION

A bicuspid aortic valve is the most common congenital valvular disorder seen, with an inheritance pattern of autosomal dominance with incomplete penetration.¹ Bicuspid valves induce turbulent flow, which over time causes the valve leaflets to fibrose and calcify, thereby resulting in a narrowed valve orifice during systole. Among bicuspid valves, the most common anatomic form involves a posterior cusp and a makeshift anterior cusp composed of a combination of the right and left cusps. Unicuspid valves are most common in infancy and typically cause severe obstruction to left ventricular outflow. This variant is commonly fatal, and death usually occurs before the first year of life. It is an exceedingly rare cause of AS and is almost never seen in adult medicine. Abnormal tricuspid aortic valves may also lead to stenosis if the valve cusps are unequally sized. These patients are usually asymptomatic unless the stenosis is severe. Quadricuspid valves have been noted, and are the most uncommon type of the congenital aortic valve disorders. This condition is often diagnosed as a secondary finding on echocardiograms as these patients are mostly asymptomatic.

The most common cause of acquired AS is age-related degenerative calcification or "senile stenosis". Age-related disease induces calcification of the valve edges, which creates stiffening of the cusps and impaired opening of the valve during systole. Gradual, progressive changes to the valvular cusps over time lead to frank bone formation within the valve edges, which causes cusp immobilization and a reduced orifice. This condition is present in roughly 2% of Americans over 65 years of age. The risk factors include elevated LDL, diabetes, hypertension, and tobacco use. It also carries with it an increased risk of cardiovascular death and myocardial infarction.² In this type of AS, concurrent aortic regurgitation is very uncommon. Thus, age-related degenerative calcific disease usually induces only systolic and not diastolic flow disturbances at the aortic valve. Age-related degenerative calcific stenosis is also the most common reason for aortic valve replacement (AVR).¹

Another common cause of AS is rheumatic valve disease which induces fusion of the valve commissures, narrowing the aortic valve orifice during systole. Rheumatic disease is becoming an increasingly less common cause of AS, due to the wide use of antibiotics. This form of AS is often accompanied by aortic regurgitation and mitral valve disease.³ Rheumatic disease may affect any of the four cardiac valves, but pulmonic involvement is uncommon.

Aortic stenosis differs greatly from the more common aortic sclerosis. Whereas stenosis is present in about 2% of Americans over the age of 65 years, sclerosis is about 15 times as prevalent in patients over the age of 65 years.⁴ By definition, sclerosis involves focal areas of increased echogenicity and leaflet thickening without restriction to blood flow and an associated peak velocity of less than 2.0 meters/second.

PATHOGENESIS

The pathophysiology involved in the obstruction to left ventricular outflow develops over many years.¹ The left ventricle hypertrophy (LVH) that develops is an adaptive mechanism to compensate for outflow obstruction and thus allows for maintenance of the cardiac output (CO). Ventricular hypertrophy causes decreased left ventricular compliance, elevated end diastolic pressures and eventually diastolic dysfunction as the disease process progresses. It should also be noted that atrial contraction becomes very important to patients with AS. The atrial contraction allows for elevated left ventricular end diastolic pressures without significantly elevated left atrial pressures and thus avoids pulmonary congestion. If these patients develop atrial fibrillation, the atrial contraction is lost and rapid deterioration with acute pulmonary edema may ensue.¹

The basic tenet of aortic stenosis is that patients with AS live with a fixed CO secondary to the limited valvular orifice. Thus, when they exert themselves, they are unable to increase their CO to compensate and they develop symptoms of dyspnea, angina, fatigue, and/or lightheadedness with exertion. They may also develop ischemia, even in the absence of coronary artery disease.¹ The oxygen demand for the hypertrophied left ventricle requires increased coronary flow in order to maintain adequate resting perfusion. As a consequence of left ventricular hypertrophy, systolic time increases which causes a shorter diastolic time. At a fixed heart rate, this shorter diastole leads to less coronary flow. These factors eventually lead toischemia, and this gradual ischemia in turn leads to left ventricular failure. Compensatory tachycardia worsens ischemia, as it further decreases diastolic filling time.

CLINICAL PRESENTATION

Although at the time of initial symptoms the aortic valve area is typically 0.6 cm², the disease is progressive and the valve area decreases by about 0.12 cm² per year. The pressure gradient across the valve has also been shown to rise by about 7 mm Hg per year. The progression seems to be more prominent and aggressive in the degenerative calcific type versus the rheumatic variant.⁴ In asymptomatic patients the overall prognosis is good, but this is dependent on the peak jet velocity: the higher the peak velocity, the sooner symptoms will develop (Figure 1)

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The three cardinal clinical manifestations of AS include angina, syncope, and exertional dyspnea. These symptoms usually arise between the ages of 40 and 50 for congenital or rheumatic AS and between the ages of 60 and 70 for the degenerative type.¹ The angina, as described above, is secondary to increased oxygen demand, and resultant ischemia despite normal coronaries. Syncope results from decreased cerebral perfusion, atrial fibrillation, or less commonly, extension of calcification to the cardiovascular conducting system. Exertional dyspnea is usually a late finding, but if present, indicates the presence of pulmonary congestion. Mitral valve disease should also be investigated in patients with exertional dyspnea.

In asymptomatic patients with AS, regardless of the underlying cause, the risk of sudden death is low, at less than 0.5% per year.⁴ However once symptoms arise, the prognosis is poor without valve replacement. The average survival without valve replacement, after initial presentation, depends on which of the three cardinal symptoms is the initial presenting symptom. For angina, the average survival is five years, for syncope it is three years, and for left ventricular failure it is two years.¹ Thus once patients become symptomatic, surgery must be considered promptly (Figure 2).

Examination of these patients will typically reveal the well-known systolic murmur of AS. This murmur is harsh in nature and heard best over the right upper sternal border with bilateral radiation to the carotid arteries. The murmur intensity can be increased with squatting, which increases stroke volume. The typical murmur of aortic sclerosis is more musical than that of AS, and is typically heard throughout the precordium. Other findings that indicate a more severe stenosis include a late-peaking of the murmur with a longer duration, a masked second heart sound, and the presence of a fourth heart sound. The second heart sound may be inaudible due to the severity of limited valve motion or it may be masked by the lateness of the murmur. The fourth heart sound indicates vigorous atrial contraction against the non-compliant hypertrophied left ventricle. Occasionally, the second heart sound may even be paradoxically split.¹ This may occur due to the prolongation of systole and hence, later closure of the aortic valve in relation to the pulmonic valve.

Another characteristic physical exam finding of AS is pulsus parvus et tardus or a weak and late carotid upstroke. There may also be a lower pulse pressure and systolic blood pressure but these findings are very non-specific. A left-sided pressure tracing, if available, may show large, left-sided a-waves secondary to decreased left ventricular compliance from the LVH. Large right-sided a-waves may be seen with examination of the jugular venous system which may indicate the presence of pulmonary hypertension or interventricular septal hypertrophy, both leading to decreased right ventricular compliance.⁵

INVESTIGATIVE STUDIES

The electrocardiogram may show evidence of left ventricular hypertrophy or strain. In rare cases, there may even be various forms of atrioventricular block secondary to extension of calcifications to the conducting system.⁶ Another non-specific EKG finding may include evidence of left atrial enlargement. A plain chest radiograph is not very sensitive or specific. There may be evidence of calcific deposits in the area of the aortic valve but the presence of this finding does not indicate aortic stenosis as it could be sclerosis without stenosis. However, the absence of any calcific deposits on an adequate radiograph essentially rules out severe, age-related degenerative calcific AS.¹

The diagnosis of aortic stenosis is made by echocardiogram. Current guidelines indicate that any systolic murmur grade three or higher, any late systolic murmur, any holosystolic murmur or any murmur that radiates to the neck be evaluated with an echocardiogram.⁴ The severity of the stenosis can be estimated closely with a good echocardiogram in conjunction with the modified Bernoulli equation. This equation allows the calculation of the pressure gradient across any restrictive barrier and may be applied to calculate the pressure gradient across the aortic valve, between the left ventricle and the ascending aorta. The modified Bernoulli equation states that:

Peak Gradient = ΔP = P₁ - P₂ = 4 * velocity²

Echocardiography and Doppler techniques allow the calculation of the velocity across the stenosis in question.

An estimation of the aortic valve area (AVA) can be made in the cardiac catheterization lab using Gorlin's equation:

AVA = CO / 44.3 * SEP * HR *SqRt (Mean Gradient)

Where:CO = Cardiac Output; SEP = Systolic Ejection Period (seconds / beat); HR = Heart Rate

These values of gradient, valve area, jet velocity (which can be estimated with Doppler on echocardiogram) and valve area index (valve area adjusted for body surface area) can be used to evaluate the severity of aortic stenosis (Figure 3).

The valve gradient value can be misleading in some patients who have low CO and can be clarified by a dobutamine stress test. Dobutamine should increase the stroke volume and in patients with severe aortic stenosis whose valve area is essentially fixed, dobutamine should increase the gradient across the valve. Conversely, patients with mild, moderate or no aortic stenosis will have an increase in the valve area after dobutamine has been given and therefore the valve gradient should have little or no change.⁴

TREATMENT

The treatment of aortic stenosis predominantly involves surgery over conservative management, regardless of severity, in patients with symptomatic aortic stenosis who can tolerate valve replacement. Patients who are asymptomatic should undergo routine follow-up transthoracic echocardiograms every six months to five years, depending on severity. All patients documented to have aortic stenosis should receive endocarditis prophylaxis.^1,2

Patients with severe aortic stenosis should avoid vigorous activity as they have a fixed CO and are unable to increase it in order to compensate for the increased demands of activity. In patients thought to be asymptomatic with deconditioning, very careful stress testing may be performed to differentiate this deconditioning from possible early symptoms of AS (hypotension during the stress testing). In patients who are symptomatic, stress testing should be avoided.⁴ Symptomatic AS derives little benefit from medical management and valve replacement should be considered early.^1,2

1) Any patient with aortic stenosis who is symptomatic

2) Patients with moderate or severe aortic stenosis undergoing CABG or other valve surgery

3) Patients with asymptomatic, but critical aortic stenosis

4) Patients with asymptomatic severe aortic stenosis with left ventricular dysfunction (not secondary to coronary disease) or high likelihood of rapid progression or an abnormal response to stress testing

Risk factors for a poor surgical outcome include high NYHA Class, left ventricular dysfunction, associated coronary artery disease, age of 70 years or more, or pre-operative ventricular arrhythmias. The overall 10-year survival rates for AVR is about 85%.¹ The peri-operative risk for a patient over age 65 undergoing AVR alone is about 9% compared to less than 1% for patients under 70 years of age. However, it should be noted that age alone is not a contraindication to surgery.

Aortic stenosis affects a significant number of Americans each year, and successful management depends on a good physical exam, clear history of the symptoms, accurate diagnosis, and prompt initiation of surgical intervention in those patients who develop symptoms, regardless of the severity of stenosis.

REFERENCES

1. Zipes, Libby, Bonow & Braunwald. Braunwald’s Heart Disease: A Textbook Of Cardiovascular Medicine – 7th Edition. Elsevier Saunders. Philadelphia, PA. 2005
2. Otto, Lind, Kitzman et al.  Association of Aortic Valve Sclerosis With Cardiovascular Mortality and Morbidity in the Elderly. New England Journal of Medicine, 341 (3): 142-147. 1999.
3. Carabello. Aortic Stenosis. New England Journal of Medicine, 346 (9): 667-676. 2002.
4. Bonow et al.: ACC/AHA 2006 Guidelines For The Management of Patients With Valvular Heart Disease: A Report of The American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease). Journal of the American College of Cardiology, 48(3): 598-675. 2006.
5. Guyton & Hall. Textbook Of Medical Physiology - 10th Edition. Saunders. Philadelphia, PA. 0032000.
6. Surawicz & Knilans. Chou’s Electrocardiography in Clinical Practice: Adult and Pediatric – 5th Edition. Saunders. Philadelphia, PA. 2001.

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