From the Cardiology Division, San Francisco General Hospital, San
Francisco, Calif.
Correspondence to Melvin D. Cheitlin, MD, Emeritus Professor of Medicine, Cardiology Division, Room 5G1, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110.
The decision to
recommend operative intervention to the patient with valve disease is
the most difficult when the valve disease is severe chronic aortic
regurgitation and the patient is
asymptomatic or minimally symptomatic. Because
aortic valve replacement is almost always necessary and because the
biological and mechanical valves still have problems resulting in
significant mortality and morbidity, the decision to recommend surgery
in an asymptomatic patient must wait until there are
indications that changes are occurring that will predict an increased
risk of death or congestive heart failure even after valve
replacement.
The goals of operative intervention in valve disease are to (1)
decrease or diminish symptomatology and thus to improve the quality of
life for the patient; (2) prevent "catastrophes" or problems that
are irreversible, such as myocardial infarction, left
ventricular (LV) fibrosis, decreasing myocardial
contractility, thromboemboli, and sudden death; and (3)
prolong life. There is little doubt that the first goal is achievable,
that of decreasing symptomatology. Every study reported of aortic valve
replacement succeeds in that goal. If the patient survives, the chances
of improvement in symptoms and functional classification are
excellent.
Success of the third goal, that of prolonging life, is difficult to
prove. The problem is that the mortality rate in patients with aortic
regurgitation, especially those who are
asymptomatic or only mildly symptomatic, is
very low, and it would take large numbers of patients followed for a
long period of time to randomize for study. This is not likely to be
done. To randomize patients who are symptomatic would be
unethical because surgery would improve the quality of life, even if it
did not prolong survival.
Consequently, the most difficult task for the cardiologist who is
following an asymptomatic or minimally
symptomatic patient with moderate to severe aortic
regurgitation is to choose which parameters
to watch that will predict a less-than-optimal result if the patient is
operated on. The time to replace the valve is, therefore, just before
that happens. In this issue of Circulation, Borer and
colleagues1 offer evidence that they have found
"just the right moment" to recommend surgery in the
asymptomatic or minimally symptomatic patient
with chronic severe aortic regurgitation and normal LV
performance.
There have been many attempts to define the preoperative clinical or
hemodynamic parameters that would be
predictive of cardiac death, poor left ventricular
function, or congestive heart failure—that is, predictive of
less-than-optimal results after valve replacement. Ideally, we would
like to look at the state of myocardial contractility.
Conventional wisdom says that once contractility has
decreased, it will remain impaired even after valve replacement, and
many patients will continue to progress to early congestive heart
failure and premature cardiac death in the years after valve
replacement. As physicians, we can follow LV performance but
have difficulty finding a way of detecting a decrease in myocardial
contractility as distinct from changes in LV preload
and afterload. Most valuable was the work of Suga and
Sagawa2 in 1974 in which they described the
end-systolic pressure-volume relationship as being independent
of preload and afterload. With decreasing myocardial
contractility, the slope of this relationship decreases
and moves to the right. In practical terms, this rightward shift and
change in slope of the end-systolic pressure-volume
relationship are detected by following the LV systolic and
end-diastolic volumes. An increasing end-systolic
and end- diastolic LV volume and decreasing ejection
fraction indicate a probable decrease in myocardial
contractility.
In patients with aortic regurgitation, this principle
has been applied in a number of studies, most notably a study by Henry
and colleagues3 4 in 1980, in which LV
end-systolic diameter by M-mode
echocardiography of >55 mm and fractional
shortening of <25% predicted operative mortality and postoperative
late mortality and congestive heart failure. This report stimulated
other studies that threw doubt on the findings, notably a study by
Daniel and colleagues,5 in which the same M-mode
end-systolic diameter or percent fractional shortening was not
predictive of late mortality. The reason for this discrepancy is
possibly explained by the fact that many of the patients of Henry and
colleagues at the National Institutes of Health were seen early in the
era of aortic valve replacement, when myocardial preservation during
surgery was poor. It is not surprising that the larger the heart before
surgery, the more likely is intraoperative myocardial damage and late
postoperative mortality, and the chance of developing congestive heart
failure.
Subsequently, other studies considered symptoms and other measures of
LV performance, mainly resting LV ejection fraction (LVEF) and
exercise capacity, and all showed varying success in predicting
postoperative improvement in ventricular
performance and even survival. Combinations of several of these
factors made prediction of survival even better. For instance, in the
study of Greves and colleagues,6 patients
operated on for aortic insufficiency had a low 5-year cardiac mortality
if resting LVEF was >50% regardless of the degree of symptomatology.
Even patients with LVEF of <50% did well if they were relatively
asymptomatic. Only those with New York Heart Association
(NYHA) functional class III and IV symptoms and a decreased LVEF had a
significantly poorer 5-year survival. Bonow and
colleagues7 showed in symptomatic
patients with severe aortic regurgitation that those
who had good exercise capacity on the treadmill had no operative
mortality and 100% survival at 3 years and had a greater return toward
normal of the LV performance than did those with poor exercise
capacity.
Gaasch and colleagues8 used an index of
preoperative resting peak LV wall stress ([LV systolic
pressurexLV end-diastolic radius]/LV wall thickness)
combined with LV end-systolic dimension to predict late
postoperative survival. Carabello and colleagues9
looked at afterload-corrected end-systolic volume index
(end-systolic stress/end-systolic volume index) before
surgery and showed that a high ratio predicted a significantly poor
postoperative outcome, high mortality, and persistent symptoms.
However, they had only nine patients with aortic
regurgitation.
In this issue of Circulation, Borer and
colleagues1 made an important contribution to the
evidence that stress-normalized LV performance is an important
predictor of the development of symptomatology, LV dysfunction, and
even sudden death in asymptomatic or mildly
symptomatic patients with aortic
regurgitation. It is remarkable, indeed, that in this
era in which the rush to publication is so frantic, Borer and
colleagues at New York Hospital-Cornell Medical Center have persisted
in performing a prospective study over a period of 15 years. Starting
in 1979, they systematically collected clinical information on patients
with asymptomatic or mildly symptomatic aortic
regurgitation. It was a complicated study requiring
rest and exercise radionuclide angiograms and a resting echocardiogram
and then follow-up yearly to document the development of cardiac end
points: symptoms justifying valve replacement, cardiac death, or the
development of resting LV dysfunction as defined by an LVEF below their
laboratory's normal limits.
They had a total of 104 patients: 83 asymptomatic patients
and 21 with "early NYHA II." Patients without valve replacement
were followed for a mean of 7.3 years (range, 1 to 15 years). There
were 39 patients who developed a cardiac end point: 4 died suddenly, 22
developed symptoms leading to surgery, and 13 developed subnormal LV
performance with or without symptoms. The annual rate of
progression was 6.2%, which is similar to the rate of progression to
aortic valve replacement in other studies by Bonow et al
(5%)10 and Siemienczuk et al
(4%).11
Univariate analysis of potential LV function or
volume predictors of adverse outcomes showed the only variables
significantly predicting all cardiac end points were
The authors are to be congratulated for such a difficult study, which
took a very long time to accumulate the sufficient number of cardiac
end points to develop the statistical power to identify clinical and
ventricular performance variables that were
independent predictors of these cardiac end points.
There are several problems, however, that must be considered in
interpreting the results of the study and the recommendations for use
of this complicated, load-adjusted performance variable for
following patients.
Even with such a long-term prospective study, the number of end points
was small. The most frequent end point was the development of symptoms
that the patient's physician believed sufficient to justify valve
replacement. There were too few hard end points (sudden death in 4
patients and decreased LV function in 13 patients) to justify
multivariate analysis. Symptoms, as such, are a
soft end point in that they are subjective. Patients have a remarkable
ability to rationalize what they feel, overlook the importance of the
sensation, and therefore fail to inform the physician about the
symptom. This is especially true if a patient recognizes that the
consequence of reporting the feeling is an operation. It is also
questionable whether any test is needed to predict the development of
symptoms that the patient will report to the physician. It is
interesting that in those who initially were "mildly
symptomatic" or had "early" NYHA II symptoms, merely
the presence of the symptoms by multivariate
analysis was an independent predictor of cardiac endpoints.
This is not surprising because a principle end point was the
development of symptoms of late NYHA II or greater.
For the hard end points of cardiac death and the development of
decreased LV function, the univariate analysis
showed that the
Furthermore, the mass of the LV was assumed to be unchanged from rest
to exercise. However, the blood in capillaries and arterioles
constitute a major component of wall mass, and this may change with
exercise in a patient with aortic regurgitation.
Finally, peak indirectly measured arterial systolic
pressure was used as near-equivalent to end-systolic pressure.
Although this is reasonable in normal individuals, in the patient with
severe chronic aortic regurgitation, the
peak-systolic pressure and the end-systolic pressure
are markedly different.
Prediction of risk of cardiac end points was made on the basis of
studies done on entrance of the patient into the study. The end point
in most cases occurred months or years later. The significant finding
of this study is that when first studied, if the
There are several reasons why a study done at one point in time might
not predict future problems. The most common identified etiology for
aortic regurgitation seen in this study was
non–Marfan's idiopathic aortic root dilatation, which was present
in 26 patients, and infective endocarditis, which was present in 10
patients. Progressive aortic regurgitation, as a result
of aortic root dilatation, fibrosis, or tearing of the valve, cannot be
predicted by any clinical or LV performance variable done
at the time the patient is first seen. Some valves develop progressive
calcification, as occurred in three of the patients in this study,
which increases LV afterload, and again is not predicted by the initial
evaluation. Finally, the indication for surgery may not be symptoms or
LV dysfunction but instead the presence of progressive
aneurysmal dilatation of the root of the aorta.
The most important problem with this load-adjusted index of LV
performance (
This study supports the practice of following the
asymptomatic patient with chronic aortic
regurgitation by evaluating the LV systolic
performance. Common clinical practice is to repeat
echocardiograms periodically in asymptomatic patients with
moderate-to-severe chronic aortic regurgitation to
detect a decrease in LVEF and an increase in end-systolic
volume and, if confirmed by a second study repeated shortly thereafter,
to recommend surgery. There are numerous studies, albeit without as
long a follow-up period as the present study, that support this
approach for predicting good postoperative survival without heart
failure. It is not clear whether this approach is inferior
to the more complicated study proposed by Borer and
colleagues.1
Finally, we should remember that there is no proof when such an
abnormal stress LV performance is found that
prophylactic valve replacement is beneficial in preventing
a less-than-optimal post–valve replacement result. In dealing with a
patient with valve disease, no matter how severe, it is always easier
to recommend surgery to the symptomatic patient who
recognizes that the risks taken are balanced by the benefits of symptom
relief. Remember, it is never possible to make a really
asymptomatic patient feel better through surgery. To advise
surgery in an asymptomatic patient, there must be
unequivocal evidence that the future benefits make the present real
risks of surgery worthwhile.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
References
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Circulation. 1998;97:525–534.
2.
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© 1998 American Heart Association, Inc.
Editorial
Finding `Just the Right Moment' for Operative Intervention in the Asymptomatic Patient With Moderate to Severe Aortic Regurgitation
Key Words: Editorials • regurgitation • valves • follow-up studies
LVEF,
rest-to-exercise alone, and LVEF rest-to-exercise normalized for
end-systolic stress (ESS), rest-to-exercise. Significant
associations were present between at least one, but not all, end
points for other predictors by analysis constructing a
multivariate Cox proportional hazards model. The only
independent objective predictor of risk of end points was
LVEF/ESS. However, the much simpler LVEF alone was almost as
efficient in predicting the risk of developing operable symptoms and LV
dysfunction with or without symptoms. LVEF rest-to-exercise was as good as the more
complicated LVEF rest-to-exercise/ESS rest-to-exercise. The
complicated variable of LVEF/ESS required a rest and exercise
radionuclide angiogram and a resting echocardiogram. The formulae used
to derive LVESS were from M-mode measurements and required a
complicated set of assumptions to calculate ESS with exercise. Using
M-mode echocariography, there were no measurements of LV length.
Whether in these patients with moderate to severe aortic
regurgitation there is a change in sphericity of the LV
with exercise is unknown. In a study by Tischler and
colleagues,12 it was found that in patients with
diseases other than aortic regurgitation causing LV
dysfunction, with exercise there is a change in shape of the LV, with
the sphericity increasing. This strongly correlated with the patient's
ability to exercise, whereas the conventional descriptors of LV
function, such as LVED volume, LVES volume, and LVEF, were poor
predictors of exercise capacity. Whether the patients with moderate to
severe aortic regurgitation in this study changed the
sphericity of the LV with exercise is unknown because the length of the
LV was not measured. LVEF/ESS is
abnormal, even with normal resting LVEF and no symptoms, the patient
who is likely to have future problems is already identified. LVEF rest-to-exercise/ESS rest-to-exercise)
is that it is too impractical to be clinically useful. The unadjusted
LVEF rest-to-exercise, which was recognized by Greenberg and
colleagues13 as an indicator of probable increase
in LV end-systolic wall stress and decreased
ventricular reserve, is, however, useful and had almost the
same power to predict the development of symptoms and/or decrease in LV
function justifying surgery. Finally, we are not certain of what the
prophylactic use of afterload-reduction drugs will do to
the predictive value of any of these indices. To the authors' credit,
most of these problems are recognized in the report.
This article has been cited by other articles:
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  P. Tornos, A. Sambola, G. Permanyer-Miralda, A. Evangelista, Z. Gomez, and J. Soler-Soler Long-Term Outcome of Surgically Treated Aortic Regurgitation: Influence of Guideline Adherence Toward Early Surgery J. Am. Coll. Cardiol., March 7, 2006; 47(5): 1012 - 1017. [Abstract] [Full Text] [PDF]
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