Should early elective surgery be performed in patients with severe but asymptomatic aortic stenosis?
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ABSTRACT: Degenerative aortic stenosis (AS) has become the most common valvular heart disease and the definitive treatment of symptomatic, severe AS is surgical valve replacement. In the absence of symptoms, the presence of left ventricular (LV) systolic dysfunction is pivotal in making treatment decisions for patients with AS. However, the LV ejection fraction is not a sensitive marker of global LV systolic function in the presence of LV hypertrophy, implying that asymptomatic patients with AS can have myocardial dysfunction with preserved LV ejection fraction. Abnormal myocardial mechanics might explain the pathophysiological processes underlying chronic pressure overload in AS. In this article, we review how new echocardiographic deformation parameters--such as myocardial strain, strain rate, and twist measurements--offer the potential for clinicians to monitor the course of LV dysfunction in patients with AS. Quantifying disturbances in LV function might provide insight into the timing of aortic valve replacement and into the improvement of LV systolic and diastolic properties through regression of LV hypertrophy and fibrosis after valve implantation.Nature Reviews Cardiology 06/2011; 8(9):494-501. · 10.40 Impact Factor
- 10/2011; , ISBN: 978-953-307-660-7
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ABSTRACT: Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of valvular degeneration with clear functional link between shifted cell-cycle control, calcification and tissue remodelling of aortic valves. Bioactivity of implanted bioprosthesis is assumed to result in its dysfunction. Age, gender (females), smoking, Diabetes mellitus, and high cholesterol level dramatically shorten the re-operation time. Therefore, predictive and preventive measures would be highly beneficial, in particular for young female diabetes-predisposed patients. Molecular signature of valvular degeneration is reviewed here with emphases on clinical meaning, risk-assessment, predictive diagnosis, individualised treatments.EPMA Journal, The 03/2011; 2(1):91-105.
European Heart Journal (2002) 23, 1417–1421
doi:10.1053/euhj.2002.3163, available online at http://www.idealibrary.com on
Should early elective surgery be performed in patients
with severe but asymptomatic aortic stenosis?
It has been well known for many years that sympto-
matic patients with severe aortic stenosis have a very
poor outcome. Average survival after the onset of
symptoms has been reported to be less than 2 to
3 years[1–10]. In this situation, valve replacement not
only results in dramatic symptomatic improvement
but also in good long-term survival[2,11–16]. This holds
true even for patients with already reduced left ven-
tricular function, as long as functional impairment is
caused by aortic stenosis[12,16]. There is general agree-
ment that, in the absence of serious co-morbidity,
surgery must be strongly recommended for patients
with severe aortic stenosis who develop symptoms
of congestive heart failure, exertional angina and
dizziness or syncope during exercise.
In contrast, the management of asymptomatic
patients with severe aortic stenosis remains a matter
of controversy. Many cardiologists are reluctant to
send asymptomatic patients for surgerywhile
others are concerned about following these patients
Because of the widespread use of Doppler echo-
cardiography and because aortic valve replacement is
offered regardless of age, cardiologists are increas-
ingly faced with the difficult decision of whether to
operate on these patients or not.
Arguments in favour of early elective
Risk of sudden cardiac death
When following asymptomatic patients with aortic
stenosis conservatively, sudden death is probably
the major concern. Prospective data in this respect
are still limited. In three studies where significant
numbers of patients with non-severe stenosis were
included, no sudden death was reported: Otto et al.
followed 123 patients with an average peak velocity
of 3·6?0·6 m . s?1for 30 months. The two other
series with 51and 37 patientshad follow-up
periods of 1·5 and 2·0 years, respectively. Only two
studies reported the outcome of larger cohorts of
patients with exclusively severe stenosis as defined
by a peak aortic jet velocity ?4·0 m . s?1. Pellikka
et al.observed two sudden deaths among 113
patients during a mean follow-up of 20 months. Both
patients, however, had developed symptoms at least
3 months before death. Rosenhek et al.reported
one sudden death that was not preceded by any
symptoms among 104 patients followed for 27
months on average. Thus, sudden death may indeed
occur even in the absence of preceding symptoms in
patients with aortic stenosis, but this appears to be a
very uncommon event, with a rate of probably less
than 1% per year during the asymptomatic phase of
the disease. Finally, it has to be considered, that
sudden death has even been reported after successful
valve replacement and that therefore this risk cannot
be entirely eliminated by surgical treatment[23,24].
Risk of death between onset of symptoms
and surgical treatment
The fact that patients do not always promptly report
their symptoms while at high risk of abrupt deterio-
ration and sudden death is an important concern. For
example, Pelikka and co-workerslost two patients
from sudden death who were retrospectively found
to have developed symptoms over recent months.
Despite proper education, not all patients will
seek immediate medical help with the first onset of
In addition, it has to be considered that, at least in
some countries, patients may wait several months for
surgery. In a Scandinavian study, for example, seven
of 99 patients with severe aortic stenosis who were
Revision submitted 31 December 2001 and accepted 2 January
Correspondence: Helmut Baumgartner, MD, Department of
Cardiology, Vienna General Hospital, University of Vienna,
Wa ¨hringer Gu ¨rtel 18–20, A–1090 Wien, Austria.
? 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
scheduled for surgery died during an average waiting
period of 6 months.
Risk of developing irreversible myocardial
In contrast to valvular regurgitation, patients with
asymptomatic severe aortic stenosis who have already
developed impaired systolic left ventricular function
are extremely uncommon. There is speculation that
myocardial fibrosis and severe left ventricular hyper-
trophy, that may not be reversible after delayed
surgery, could preclude an optimal postoperative
outcome. However, there are, so far, no data to
support this hypothesis. Considering the excellent
outcome after valve replacement in isolated aortic
stenosis with normal systolic left ventricular function,
it is unlikely that the risk of developing irreversible
myocardial damage will play a major role.
Rapid development of symptoms
Some studies reported a very poor outcome with up
to 80% of the patients requiring valve replacement
within 2 years. Such observations have also raised
the question as to whether it is worthwhile delaying
surgery in patients who are still asymptomatic. How-
ever, other investigators have reported better out-
come, and individual outcome varies widely. For
example, survival free of death or valve replacement
indicated by the development of symptoms was
56?5% at 2 years in the series reported by Rosenhek
et al.. These discrepant results may be explained by
the fact that in some studies patients underwent
surgery without having developed symptoms while
these interventions were, nevertheless, counted as
events. Thus, the event-free survival reported in the
literature has to be viewed with caution.
Increased operative risk in severely
Patients with severe symptoms have been found to
have a significantly higher operative mortality than
those with no or only mild symptoms. According to
the STS U.S. cardiac surgery database 1997, patients
in NYHA classes I or II had an operative mortality of
less than 2% compared with 3·7% and 7·0% for
patients in NYHA class III and IV, respectively. In
addition, urgent or emergency valve replacement car-
ries a significantly higher risk than elective surgery.
Arguments against early elective
decreased in recent decades it must be considered to
be in the range of at least 2 to 3%[11,26]. Operative
mortality may be as high as 10% in the elderlyand
even markedly higher in the presence of co-
morbidities such as coronary artery disease. In an
asymptomatic patient this risk has to be outweighed
by a proven benefit.
Prosthetic valve related long-term morbidity
After valve replacement with a mechanical or bio-
prosthetic valve, valve related complications such
as thromboembolism, bleeding, endocarditis, valve
thrombosis, paravalvular regurgitation and valve fail-
ure occur at the rate of at least 2 to 3% per year.
Death directly related to the prosthesis has been
reported at a rate of up to 1% per year.
Individual variation of outcome
The individual course of the disease is highly variable
and some patients have been followed for many years
without developing symptoms. As valve replacement
does not represent a cure in this disease, a general
recommendation of early surgery cannot, therefore,
Thus, the decision over valve replacement in
asymptomatic patients remains difficult. Waiting too
long may put the patient at an increased risk of
sudden death and higher operative mortality whereas
operating on a patient too early puts him at an
anticipated operative risk and risk of prosthetic-valve
related complications. Thus, predictors of outcome
that help us to identify high-risk patients who are
likely to benefit from early elective surgery are
Predictors of outcome in
asymptomatic, severe aortic stenosis
Clinical predictors of outcome
Several clinical variables have been evaluated with
respect to their value as predictors of outcome. How-
ever, age, gender, hypertension, hypercholesterolae-
mia, diabetes mellitus, left ventricular hypertrophy,
ventricular ectopic activity, coronary artery disease,
1418 Clinical Perspective
Eur Heart J, Vol. 23, issue 18, September 2002
cigarette smoking, use of digoxin, use of a diuretic
drug, and the cause of aortic stenosis were found not
to be independent predictors and may not be helpful
in selecting asymptomatic patients for surgery[19,21,22].
Echocardiographic predictors of outcome
Among the echocardiographic parameters, peak
aortic jet velocity and ejection fractionas well as
the rate of haemodynamic progression
identified as independent predictors of outcome.
However, these findings were obtained retrospectively
and did not allow any specific recommendations on
how to prospectively select high-risk patients who
may benefit from early elective surgery.Quantification
of aortic stenosis and the definition of haemodynami-
cally severe stenosis may be problematic. Although
there is no general agreement, a cut-off value of
4 m . s?1for the peak aortic jet velocity (correspond-
ing to a peak gradient of 64 mmHg) and/or an aortic
valve area of less than 1·0 cm2has been used in recent
studies to define severe aortic stenosis[19,21,22]. For
individual decision making, however, body size and
weight should be considered when using such cut-off
In a more recent study, aortic valve calcification
turned out to be a powerful independent predictor of
outcome. Event-free survival at 4 years was 75?9%
in patients with no or only mild calcification vs
20?5% in those with moderately or severely calcified
valves. The worse outcome of patients with more
severe calcification appeared to be paralleled by more
rapid haemodynamic progression. However, even in
the presence of calcification the rate of haemo-
dynamic progression varies widely[29,30]. In fact,
haemodynamic progression, as determined by serial
echocardiographic examination, appears to yield
important prognostic information in addition to the
degree of calcification. The combination of a calcified
valve witha rapidincrease
?0·3 m . s?1from one visit to the next within 1 year
has been shown to identify a high risk group
of patients. Approximately 80% of them required
surgery or died within 2 years.
Although Otto et al.reported in their group of
asymptomatic patients with aortic stenosis, that those
with an end point had a smaller exercise increase in
valve area, blood pressure and cardiac output, none
of these variables were independent predictors of
outcome by multivariate analysis. Amato et al.
recently suggested that exercise testing may provide
helpful information in the selection of high risk
patients, but more data are needed for final conclu-
sions. Nevertheless, exercise testing has been shown
to be helpful for the evaluation of reportedly asymp-
tomatic patients. Das et al.recently reported that
36% of 58 consecutive patients with aortic stenosis,
who had denied symptoms, experienced significant
symptoms during exercise testing. In addition, despite
the lack of solid evidence, most physicians believe
that an abnormal haemodynamic response to exercise
(e.g. hypotension) in a patient with severe aortic
stenosis is a sufficient reason to consider surgery. It
has to be emphasized that exercise testing is only
appropriate in asymptomatic patients and should
definitely not be performed in symptomatic patients.
When properly performed, exercise testing in asymp-
tomatic patients with severe aortic stenosis has been
shown to be safe.
Current practice guidelines for the
management of asymptomatic patients
with severe aortic stenosis and clinical
impact of recently identified predictors
Based on the data showing that it is relatively safe to
delay surgery until symptoms develop, current AHA/
ACC practice guidelines definitely recommend aortic
valve replacement only in symptomatic patients with
severe aortic stenosis and in those asymptomatic
patients who undergo cardiac surgery for any other
reason such as coronary artery bypass surgery, sur-
gery of the aorta or other heart valves (Class I).
Although controversial, weight of evidence/opinion
is considered in favour of surgery (class IIa) in
asymptomatic patients with severe aortic stenosis
who present with impaired systolic left ventricular
function and in patients with an abnormal response
to exercise (e.g. hypotension).
Ventricular tachycardia, marked or excessive left
ventricular hypertrophy (15 mm) and a valve area
<0·6 cm2are less well established as indications for
surgery and are thus considered class IIb indications.
Taking into account more recent findings, we
would suggest expanding the recommendations for
asymptomatic severe aortic stenosis by using echocar-
diography for risk stratification in the following
Patients with no or only mild calcification of their
stenotic aortic valve represent a group with a low
likelihood of developing symptoms and requiring
surgery in the near future. They may remain asymp-
tomatic for many years. Annual follow-up visits and
the advice to promptly report the development of any
Clinical Perspective 1419
Eur Heart J, Vol. 23, issue 18, September 2002
exertional chest pain, dyspnea or lightheadedness at
exercise appears to be appropriate for these patients.
Patients with moderately or severely calcified
valves represent a group with significantly worse
outcome. Rapid progression must be expected and a
closer follow-up is required.
Patients with moderately or severely calcified
valves in whom serial echocardiographic testing
reveals rapid progression with a steep increase in jet
velocity (?0·3 m . s?1. year?1) identifies a high risk
patient group. As patients do not always promptly
report the development of symptoms and since there
is risk of death on the waiting list for surgery, and
patients, it may be worthwhile considering elective
valve replacement instead of waiting for symptoms in
this high risk group.
Considerations in specific patient subgroups
There is general agreement, that patients with severe
asymptomatic aortic stenosis who undergo other
cardiac surgery, such as coronary artery bypass graft-
ing, surgery of other valves or the aorta should have
aortic valve replacement at the same time.
stenosis undergoing non-cardiac surgery the risks of
the procedures have to be carefully weighed.
Finally, in young patients who plan to become
pregnant, aortic valvuloplasty must be strongly
In addition to these considerations, it has to be
emphasized that the decision of performing valve
replacement must be individualized, taking into ac-
count the patients risk profile and willingness to
Currently available data suggest that careful weighing
of risk and benefit does not justify the general recom-
mendation of early elective surgery in asymptomatic
patients with severe aortic stenosis. Echocardio-
graphic assessment of the extent of valve calcification
and of haemodynamic progression appears to be
helpful for risk stratification. Future studies must
focus on the identification of additional predictors of
outcome to expand our knowledge on how to
optimally select patients at risk who may benefit from
early elective surgery.
R. ROSENHEK, G. MAURER,
Department of Cardiology, Vienna General Hospital,
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