Aortic Stenosis

Etiology
Aortic stenosis (AS) is often caused by agerelated degenerative calcifi c changes of
thevalve, formerly termed senile AS. CalcifiC changes that progress to AS may also develop in
patients with congenitally deformed aortic valves (about 1% to 2% of the population is born with
an abnormal bicuspid aortic valve). Most patients who present with AS after the age of 65 have
the age-related form, whereas younger patients usually have calcifi cation of a congenitally
bicuspid valve. AS may also result from chronic rheumatic valve disease, although the prevalence
of this condition
has decreased dramatically in recent decades in the United States. Approximately 95% of
patients who are found to have rheumatic AS have coexisting rheumatic involvement of the
mitral valve.

Pathology
The pathologic appearance in AS is dependent on its etiology. In age-related degenerative
AS, the classic teaching is that the cumulative wear and tear of valve motion over many years
leads to endothelial and fi brous damage,
causing calcifi cation of an otherwise normal trileafl et valve. However, there is also evolving
evidence of a common etiology with atherosclerotic vascular disease. Studies have shown that,
as in atherosclerosis, the valve tissue of
patients with this form of AS display cellular proliferation, infl ammation, lipid accumulation, and
increased margination of macrophages and T lymphocytes.

In the case of a congenitally deformed valve, years of turbulent fl ow across the valve
disrupt the endothelium and collagen matrix of the leafl ets, resulting in gradual calcium
deposition. In rheumatic AS, endocardial infl
ammation leads to organization and fi brosis of the valve, and ultimately fusion of the
commissures and the formation of calcifi ed masses within the aortic cusps.

Pathophysiology
In AS, blood fl ow across the aortic valve is impeded during systole (Fig. 8.8). When the
valve orifi ce area is reduced by more than 50% of its normal size, signifi cant elevation of left
ventricular pressure is necessary to drive
blood into the aorta (Fig. 8.9).
 Since AS develops over a chronic course, the LV is able to compensate initially by
undergoing concentric hypertrophy in response to the high systolic pressure it must generate.
Such hypertrophy serves an important role in
reducing ventricular wall stress (remember from Chapter 6 that wall stress _ (P _ r) _ 2h, in which
h represents wall thickness); however, it also reduces the compliance of the ventricle. The
resulting elevation of diastolic LV pressure also causes the LA to hypertrophy in order to fi ll the
stiff LV. Whereas left atrial contraction contributes only a small portion of the left ventricular
stroke volume in normal individuals, it may provide more than 25% of the stroke volume to the
stiffened LV in AS patients. Thus, left atrial hypertrophy is beneficial, and the loss of effective
atrial contraction
(e.g., development of atrial fi brillation) can cause marked clinical deterioration.

Three major manifestations occur in patients with advanced AS: (1) angina, (2)
exertionalsyncope, and (3) congestive heart failure, all of which can be explained on the basis of
the underlying pathophysiology. Each manifestation,
in order, heralds an increasingly ominous prognosis (Table 8.2).

AS may result in angina because it creates a substantial imbalance between myocardial

oxygen supply and demand. Myocardial oxygen demand is increased in two ways. First, the
muscle mass of the hypertrophied LV is
increased, requiring greater-than-normal perfusion. Second, wall stress is increased because of
the elevated systolic ventricular pressure. In addition, AS reduces myocardial oxygen supply
because the elevated left ventricular diastolic
pressure reduces the coronary perfusion pressure gradient between the aorta and the
myocardium.

AS may cause syncope during exertion. Although left ventricular hypertrophy allows the
chamber to generate a high pressure and maintain a normal cardiac output at rest, the ventricle
cannot signifi cantly increase its cardiac output during exercise because of the fi xed stenotic
aortic orifi ce. In addition, exercise leads to vasodilatation of the peripheral
muscle beds. Thus, the combination of peripheral vasodilatation and the inability to augment
cardiac output contributes to decreased cerebral perfusion pressure and, potentially, loss of
consciousness on exertion

Finally, AS can result in symptoms of heart failure. Early in the course of AS, an
abnormally increased left atrial pressure occurs primarily at the end of diastole, when the LA
contracts into the thickened noncompliant LV. As a result, the mean left atrial pressure and the
pulmonary venous pressure are not greatly affected early in the disease. However, with
progression of the stenosis, the LV may develop contractile dysfunction because of the
insurmountably high
afterload, leading to increased left ventricular diastolic volume and pressure. The accompanying
marked elevation of LA and pulmonary venous pressures incites pulmonary alveolar congestion
and the symptoms of heart failure.
 The normal aortic valve cross-sectional area is 3 to 4 cm2. When the valve area is reduced
to less than 2 cm2, a pressure gradient between the LV and aorta fi rst appears (mild AS).
Moderate AS is characterized by a valve area of 1.0 to 1.5 cm2. When the aortic valve area is
reduced to less than 1.0 cm2, severe valve obstruction is said to be present.

Clinical Manifestations and Evaluation

Presentation
Angina, syncope, and congestive heart failure may appear after many asymptomatic
years of slowly progressive valve stenosis. Once these symptoms develop, they confer a signifi
cantly decreased survival if surgical correction of AS
is not undertaken (see Table 8.2).

Examination
Physical examination often permits accurate detection and estimation of the severity of
AS. The key features of advanced AS include (1) a coarse late-peaking systolic ejection murmur
and (2) a weakened (parvus) and delayed
(t ardus) upstroke of the carotid artery pulsations owing to the obstructed LV outfl ow. Other
common fi ndings on cardiac examination include The presence of an S4 (because of atrial
contraction into the stiff LV) and reduced intensity, or complete absence, of the aortic
component of the second heart sound (see Fig. 8.9).

On the electrocardiogram, left ventricular hypertrophy is common in advanced AS, but

echocardiography is a more sensitive technique to assess LV wall thickness. The transvalvular
pressure gradient and aortic valve area can be
calculated by Doppler echocardiography (see Chapter 3). Cardiac catheterization is sometimes
used to confi rm the severity of AS and to defi ne the coronary anatomy, because concurrent
coronary artery bypass surgery is often necessary at the time of aortic valve replacement in
patients with coexisting coronary disease.

Natural History and Treatment

The natural history of severe, symptomatic, uncorrected AS is very poor. Data from the
Mayo Clinic indicate that the 1-year survival rate is 57% for patients with advanced disease.
Effective treatment requires replacement of the valve.
Aortic valve replacement (AVR) is indicated when patients with severe AS develop symptoms, or
when there is evidence of progressive LV dysfunction in the absence of symptoms. The left
ventricular ejection fraction almost always increases after valve replacement, even in patients
with impaired preoperative left ventricular function. The effect of AVR on the natural history of AS
is dramatic, as the 10-year survival rate rises to approximately 60%.

Unlike its successful role in mitral stenosis, percutaneous valvuloplasty has been
disappointing in the treatment of AS in adults. Although balloon dilatation of the aortic valve orifi
ce can fracture calcifi ed commissures leading to some immediate relief of outfl ow obstruction,
up to 50% of patients develop restenosis within 6 months. Valvuloplasty is
occasionally a suitable option for patients who are poor surgical candidates or as a temporizing
measure in patients too ill to proceed directly to valve replacement. Valvuloplasty is also
sometimes effective in young patients
with congenitally bicuspid valves.

Mild, asymptomatic AS has a slow rate of progression such that over a 20-year period,
only 20% of patients will progress to severe or symptomatic disease. Appropriate therapy for
asymptomatic AS includes caution in the use of medications that could result in hypotension in
this condition (e.g., vasodilators, diuretics, nitroglycerin). There is no current effective therapy for
slowing the actual progression of aortic stenosis. Given the similar risk factors that lead to both
atherosclerosis and calcific aortic stenosis, ongoing research trials are testing whether statin
therapy administered to
patients with mild AS might retard worsening over time.