CLINICIAN UPDATE
Evaluation and Management of Patients With Aortic Stenosis
Blase A. Carabello, MD
C
ase presentation: A 66-year-old man is referred to a
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cardiologist for the evaluation of a heart murmur. The
patient claims to be entirely asymptomatic, although
his wife notes that he has decreased his physical activity over
the past two years because he is getting old. At physical
examination, his blood pressure was 120/70 mm Hg; pulse,
80 bpm; respiration, 13 breaths per minute; and temperature,
99.0F. Cardiovascular examination revealed normal central
venous pressure. His carotid upstrokes were reduced in
volume and delayed in upstroke. Cardiac examination re-
vealed a forceful sustained apical impulse in its normal
position. There was a 3/6 late-peaking systolic ejection
murmur heard at the right upper sternal border radiating to the
neck. The rest of the physical examination was unremarkable.
Echo-Doppler evaluation revealed an ejection fraction of
0.60, a left ventricular free wall thickness of 1.3 cm, and a
peak transaortic flow velocity of 4.5 m/s. How should this
patient be managed? Should he undergo aortic valve replace-
ment now? Should he undergo longitudinal follow-up to
monitor progression of his aortic stenosis?
Over the past 40 years, diagnostic techniques, substitute
cardiac valves, and valve implantation surgery have undergone
continued improvement, reducing the risk of the valve replace-
ment and enhancing its benefits. Thus, the risk-benefit analysis
of valve surgery has tilted in favor of increasingly early inter-
vention for valve disease. The following is a summary incorpo-
rating this concept into the current strategy for managing patients
with aortic stenosis such as the one described above.
Patients With Severe Symptomatic
Aortic Stenosis
The patient with severe aortic stenosis who presents with
symptoms represents the most straightforward management
From the Department of Medicine, Baylor College of Medicine, and
the Houston Veterans Affairs Medical Center, Houston, Tex.
Correspondence to Blase A. Carabello, MD, 2002 Holcombe Blvd (111
MCL), Houston, TX 77030. BlaseAnthony.Carabello@med.va.gov
(Circulation. 2002;105:1746-1750.)
2002 American Heart Association, Inc.
Circulation is available at http://www.Circulationaha.org
DOI: 10.1161/01.CIR.0000015343.76143.13
1746
strategy for the disease. Survival is nearly normal until the
classic symptoms of angina, syncope, or dyspnea develop.1
However, only 50% of patients who present with angina
survive 5 years, whereas 50% survival is 3 years for patients
who present with syncope and 2 years for patients who
present with dyspnea or other manifestation of congestive
heart failure. In all, 75% of symptomatic patients with severe
aortic stenosis succumb unless the aortic valve is replaced.
On average, symptoms develop once the aortic valve area has
become 1.0 cm2, although there is extraordinary case-to-
case variation in valve area at the time symptoms first
develop.2 Thus, some patients may become symptomatic at
valve areas 1.0 cm2, and other patients do not develop
symptoms until the aortic valve orifice area is 0.5 cm2.
Once surgery has been performed, age-corrected survival is
nearly normal after surgery.3 Thus, the large contrast between
a 75%, 3-year mortality for symptomatic patients who do not
undergo surgery versus a nearly normal postoperative sur-
vival rate makes the decision to perform aortic valve replace-
ment in symptomatic patients with severe aortic stenosis an
obvious choice in the absence of surgical contraindications.
Asymptomatic Patients With Severe
Aortic Stenosis
The asymptomatic patient with aortic stenosis has an excel-
lent prognosis despite severe left ventricular outflow obstruc-
tion. Nonetheless, the outcome for such patients is not
perfect, and there is a small risk of sudden death or of rapid
advancement from the asymptomatic phase to symptoms to
sudden death.1,4 6 Several studies have attempted to ascertain
the risk of sudden death in the population of asymptomatic
patients with severe aortic stenosis. Table 12,4 10 tabulates
many of these studies and demonstrates that the overall risk
of sudden death in this group of patients is 2%.
One strategy advocated to circumvent this risk is to operate
on all patients with severe aortic stenosis. Unfortunately,
there are several difficulties with this approach. First, it is not
clear what constitutes severe aortic stenosis. Whereas some
authorities have used a valve area of 1.0 cm2, others have
used a value of 0.75 cm2. The Figure shows the extreme
 Carabello Management of Patients With Aortic Stenosis 1747

TABLE 1. Studies of the Natural History of Asymptomatic Patients With Aortic Stenosis
Number Mean Sudden Death
of Follow-Up, Severity of Aortic Without Symptoms,
Study Patients years Stenosis No. of Patients Comments
Chizner et al, 1980 7 8 5.7 AVA 1.1 cm 2
0 Retrospective study
Turina et al, 19878 17 2.0 AVA 0.9 cm2 0 Retrospective study
Horstkotte and Loogen, 19889 35 years AVA0.40.8 cm2 3 Retrospective study
Kelly et al, 1988 5 51 1.5 PV3.55.8 m/s 0 Prospective study
Pellikka et al, 19904 113 1.7 PV 4.0 m/s 0 Prospective study
Faggiano et al, 199210 37 2.0 AVA0.850.15 cm2 0 Prospective study
Otto et al, 19972 114 2.5 PV3.60.6 m/s 0 Prospective study
Pellikka, 20016 610 5.1 PV4.0 12 Prospective study
Total 985 4.0 15 Average risk of sudden
death0.4%/y
AVA indicates aortic valve area; PV, peak instantaneous velocity.

heterogeneity of valve areas at which patients become symp- of patients to the operative risk, plus the risk of living with a
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tomatic (and therefore, more liable to sudden death). Thus, in
my view, it is impossible to define a single critical valve area.
Even if a critical valve area could be defined, to use it, valve
area would have to be calculated accurately. It should be
noted that although one formula for calculating valve area
was validated for the mitral valve, it has never been well
validated for the aortic valve.11 Indeed, the discharge coeffi-
cients for the Gorlin formula for the aortic valve were never
developed, which raises issues concerning accuracy. Further-
more, valve area calculated either by the Gorlin or continuity
equation is flow dependent and thus dependent on the
patients cardiac output at the time the valve area is being
calculated.1214 Therefore, although aortic valve area is and
will continue to be an important indicator of stenosis severity,
this parameter does not stand alone and must be integrated
into the patients whole presentation, which includes physical
examination and invasive and noninvasive hemodynamic
data.
A second problem with surgery for all patients with severe
disease is that in adult acquired aortic stenosis, valve repair is
virtually impossible; thus aortic valve replacement is almost
inevitable. Even if replacement is performed using a pulmo-
nary autograft, a substitute valve must be placed in the
pulmonary position. Therefore, the strategy of operating on
all asymptomatic patients with aortic stenosis exposes 100%
Valve area for patients who developed symptoms and required
an aortic valve replacement (AVR) (left) is compared with valve
area of asymptomatic patients (right). The average final valve
area before surgery was 0.9332 cm2. Reproduced with per-
mission from Otto et al.2
prosthetic valve, in order to benefit the 2% who are at risk of
sudden death. The risk of living with a prosthesis, tabulated
from several studies, is at least 1% per year.1516
A more practical approach is to identify that group of
asymptomatic patients at highest risk for sudden death and to
consider aortic valve replacement in them. Otto and col-
leagues2 demonstrated that transaortic flow velocity, a guide
to aortic stenosis severity, was a useful predictor of the
eventual development of symptoms. When the initial flow
velocity was 3 m/s, the risk of developing symptoms
requiring an aortic valve replacement was 15% in the next
5 years. However, when initial flow velocity exceeded 4 m/s,
there was 70% chance that an aortic valve replacement would
be required in the next 2 years. Thus, transaortic flow velocity
helped to define a high-risk group of patients.
A second strategy used to screen for high-risk patients is
exercise testing. Although exercising symptomatic patients
with aortic stenosis has increased risk and should be avoided,
exercise testing in patients with asymptomatic aortic stenosis
seems to be safe and is a logical extension of the patients
natural activities. That is, if patients are asymptomatic, they
are going to exercise anyway, and it seems wise to have at
least one such episode observed by a physician. In the study
by Otto et al,2 each patient underwent exercise testing every
6 months, and there were no cardiac deaths in asymptomatic
patients. When coupled with a report from Das et al,17 who
found that 40% of patients claiming to be asymptomatic
developed symptoms for the first time during exercise, it
seems that exercise testing may help to further define a
high-risk group. Clearly, if patients develop symptoms on the
treadmill, they then should be labeled symptomatic and
undergo aortic valve replacement. This strategy should ex-
tend to patients with unexpectedly low exercise tolerance. In
addition, it is probable, but unproved, that the development of
hypotension or ventricular arrhythmias during the study
should also be an indication for aortic valve replacement.
However, it is unclear what impact ST-segment depression, a
manifestation of left ventricular hypertrophy from any cause,
should have for such patients.
 1748 Circulation April 16, 2002
TABLE 2. Hemodynamic Manipulation of Aortic Stenosis Patients With Low
Gradient and Low Output
True Aortic Stenosis
Rest Dobutamine
CO, L/min 3.0 5.0
LVP, mm Hg 130/20 160/20
AoP, mm Hg 90/60 100/60
G, mm Hg 25 50
AVA, cm2 0.6 cm2 0.7
AoP indicates aortic pressure; AVA, aortic valve area; CO, cardiac output; G, mean gradient; and
LVP, left ventricular pressure.
Patients With Severely Reduced Ejection
Fraction and Aortic Stenosis
At the opposite end of the spectrum from the asymptomatic
patient is that patient with advanced heart failure and de-
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pressed ejection fraction. Depressed ejection fraction in aortic
stenosis has two basic causes: afterload mismatch and con-
tractile dysfunction.18 Huber and colleagues19 have demon-
strated that afterload mismatch is at least partially responsible
for left ventricular dysfunction in approximately three quar-
ters of the patients who have it. The greater the role of
afterload mismatch for reduced ejection fraction, the better
the response to surgery. In other words, if excessive afterload
has primarily caused a reduction in ejection fraction, then
relief of the valve obstruction will cause a sudden fall in
afterload with a substantial rise in ejection fraction. Although
wall stress is usually used as a measure of afterload, its
calculation is tedious and not often applied clinically. How-
ever, mean transvalvular gradient forms a reasonable surro-
gate for afterload mismatch. The higher the gradient, the
greater the afterload and usually the better the response to
surgery.18
Most problematic in the group of aortic stenosis patients
with heart failure and reduced ejection fraction are those with
low transvalvular gradient and low ejection fraction. In
general, reports of outcome for these patients have demon-
strated a poor prognosis after surgery.18,20 22 In this group,
irreversible left ventricular dysfunction rather than afterload
mismatch is the primary cause for reduced ejection perfor-
mance and poor outcome. A study by Connolly and col-
leagues21 demonstrated a 21% operative mortality for this
group, with only 50% surviving for 4 years. Despite such
poor results, some patients do improve with aortic vale
replacement. At issue is the need for the clinician to decide
preoperatively which patients with low gradient, low ejection
fraction, and low output might benefit from an aortic valve
replacement versus those patients who will not. Currently, the
mainstay in making this distinction is to identify patients who
have truly severe aortic stenosis versus those patients who
have a small calculated valve area without true aortic steno-
sis, a condition that I refer to as aortic pseudostenosis. In the
first situation, severe valve disease has led to severe left
ventricular dysfunction, and therefore, correction of the valve
disease (which was the primary defect) might lead to im-
provement in left ventricular function and in outcome. In the
second condition (aortic pseudostenosis), a left ventricle
Aortic Pseudostenosis
Nitroprusside Rest Dobutamine Nitroprusside
3.2 3.0 5.0 4.5
120/10 130/20 140/20 120/10
80/50 90/60 100/70 90/60
30 25 30 25
0.6 0.6 cm2 0.9 0.9
weakened from another process, such as coronary disease or
idiopathic cardiomyopathy, is unable to open a mildly but not
severely stenotic aortic valve. In both conditions, the calcu-
lated valve area may lie in the range considered to indicate
severe aortic stenosis, but only in the first condition is there
truly severe valve disease. The current standard for divorcing
these two conditions is to increase cardiac output either by
using positive inotropic agents such as dobutamine or to
reduce total peripheral resistance with a vasodilator.12,13
These two interventions can lead to the same conclusion
through somewhat different mechanisms. As shown in Table
2, when cardiac output is increased through the use of
dobutamine in a patient with a severely stenotic valve, output
and gradient increase in tandem, and calculated valve area
increases only slightly. On the other hand, in aortic pseudo-
stenosis, when output increases substantially, gradient in-
creases only slightly or not at all, leading to a large increase
(0.3 cm2) in calculated valve area.
If a vasodilator is used, the same changes occur in
calculated valve area through somewhat different mecha-
nisms. In principle, if the most severe resistance to outflow is
the stenotic aortic valve itself, then a decrease in total
peripheral resistance does not permit an increase in cardiac
output; thus, a vasodilator causes downstream pressure to fall
and gradient to increase, demonstrating that the aortic steno-
sis is severe. On the other hand, if valve resistance is small
and it is total peripheral resistance that is the resistance most
limiting to flow, then decreasing total peripheral resistance
permits increased forward output, reducing the gradient in
some cases and producing a dramatic rise in calculated valve
area.
Although the need to separate true aortic stenosis from
aortic pseudostenosis is now generally accepted, it is not clear
what the result would be if surgery were performed on only
those patients in whom pharmacological manipulation had
been used preoperatively to divorce the two groups. It is
likely that the prognosis would not be as good as that for
patients with aortic stenosis with preserved left ventricular
function, but it probably would be better than the prognosis
for a mixed group of patients with true and pseudoaortic
stenosis undergoing aortic valve replacement.
Pathophysiology of the Valve Lesion and
Its Management
In developed countries, rheumatic fever has become a rare
cause of aortic stenosis. Instead, calcific disease most often
 Carabello
affects patients born with a bicuspid valve, a condition that
affects 1% to 2% of the population and predominates in men.
When stenosis develops on a bicuspid valve, it usually occurs
relatively early in life (ie, in the fifth and sixth decades).
When aortic stenosis develops in a previously normal tricus-
pid valve, it typically develops later in life (ie, in the sixth,
seventh and eight decades). Until recently, the process of
developing aortic stenosis was considered degenerative, in
some way reflecting the concept of wear and tear on the
aortic valve. In the past decade, the concept of degenerative
disease has given way to that of an active inflammatory
process related in some ways to coronary artery disease.
Supporting this concept are the following data: (1) The early
lesion of aortic stenosis resembles that of the initial plaque of
coronary disease.23 (2) Studies have demonstrated that some
risk factors for coronary disease, such as elevated serum
cholesterol, are also related to the development of aortic
stenosis.24 (3) There is a close correlation between calcifica-
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tion found in the coronary arteries, which is indicative of the
development of coronary disease, to the amount of the
calcification found in the aortic valve.25 Most intriguing is
evidence that HMG CoA reductase inhibitors (statins) retard
the progression of both coronary disease and of aortic
stenosis.26 In some studies, this retardation is related to a fall
in cholesterol, but in others, retardation has occurred without
a consistent relationship to cholesterol, suggesting that statin
agents may have effects other than simple cholesterol lower-
ing to account for their effects on the aortic valve. Although
aortic valve replacement and its timing have been the major
foci of the therapy of aortic stenosis, it is possible that in the
future, aggressive therapy with statins and other agents might
block or slow the progression of the valve lesion, forestalling
or even preventing the need for aortic valve replacement.
Disease in Elderly Patients
Aortic stenosis occurs as a process of aging, and therefore,
severe symptomatic disease often occurs in elderly patients.
Although advanced age has been a risk factor for operative
mortality in patients with aortic stenosis, these data must be
interpreted with caution because increasing age is a risk
factor for death in everyone. In other words, the life expect-
ancy of an 80-year-old patient is 6 years, whether or not the
patient has aortic stenosis. Several studies examining out-
come in very elderly patients with aortic stenosis have been
performed. Lindblom et al3 found that age-corrected survi-
vorship for patients over the age of 65 was not different from
that of a normal population. In general, most studies come to
the same conclusion: that there is almost no age limit for
aortic valve surgery in patients with aortic stenosis in the
absence of comorbid conditions.27 However, once coronary
disease, other valvular heart disease, neurological deficits,
and renal failure are added to the clinical setting, outcome
worsens, and these factors must be taken into consideration
when deciding whether to correct aortic stenosis in elderly
patients.
Summary
In patients with aortic stenosis who develop the classic
symptoms of angina, syncope, or dyspnea, prompt aortic
Management of Patients With Aortic Stenosis 1749
valve surgery should be performed to prevent sudden death.
In view of the known risk of sudden death in this group, delay
for even a month or two is likely to incur some mortality.
Thus, I believe aortic valve replacement should be performed
within 30 days after symptoms develop.
Asymptomatic patients with severe aortic stenosis can be
managed medically, but such management has taken on a
more active investigative strategy. In my view, all such
patients should undergo exercise testing if they can exercise.
If unexpectedly poor exercise tolerance is demonstrated or if
there is exercise-induced hypotension or ventricular arrhyth-
mia, aortic valve replacement seems wise, although benefit in
this group is not absolutely proven.
In the case of patients with poor left ventricular function
because of excess afterload (high gradient), aortic valve
replacement leads to improved ejection performance and a
good outcome. In the group of patients with low gradient and
low ejection fraction, the distinction should be made preop-
eratively between true and pseudoaortic stenosis. In patients
with true aortic stenosis who respond to dobutamine, aortic
valve replacement should be offered with the advice that
postoperative prognosis is likely to be reduced.
Finally, the possibility of retarding the progression of
aortic stenosis or even preventing severe obstruction with
statin drugs and other agents is a new and exciting prospect
for the management of this disease.
With regard to the patient presented above, I would
recommend a physician-performed exercise study. If, during
exercise, there was earlier-than-predicted fatigue or dyspnea
or if ventricular tachycardia or hypotension was induced, I
would refer the patient for aortic valve replacement.
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KEY WORDS: valves heart diseases stenosis aorta
 Evaluation and Management of Patients With Aortic Stenosis
Blase A. Carabello

Circulation. 2002;105:1746-1750
doi: 10.1161/01.CIR.0000015343.76143.13
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