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Balloon Valvuloplasty in Adult Aortic Stenosis:
Determinants of Clinical Outcome
Warren Sherman, M D ; R o n n i e H e r s h m a n , M D ; Charles L a z z a m , M D ;
M a r c C o h e n , M D ; J o h n A m b r o s e , M D ; and R i c h a r d Gorlin, M D
Study Objective: To determine the clinical variables affecting outcome after balloon aortic valvuloplasty.
Design: Longitudinal follow-up of consecutive case series.
Patients: Consecutive sample of 36 patients with severe
calcific aortic stenosis, and without active infection or left
ventricular mural thrombus.
Interventions: Percutaneous transluminal dilatation of the
aortic valve until the peak gradient was reduced by 50% or a
maximal balloon size was used. Hemodynamic measurements taken before and after dilatation.
Measurements and Main Results: Thirty-three patients
had a successful dilatation. Eighty-nine percent (95% confidence interval [ C I ] , 74% to 97%) improved symptomatically at 2 weeks, but by 26 weeks only 56% (CI, 35% to
76%) remained improved (P = 0.0078). Mortality rates
were high at 8 ( 9 % ) and 26 (28%) weeks. Predictors of
adverse events included left ventricular ejection fraction
(P = 0.04, r = 0.46), pulmonary artery systolic pressure
(P = 0.048, r = 0.65), pulmonary vascular resistance
(P = 0.008, r = 0.69), and right ventricular end-diastolic
pressure (P = 0.009, r = 0.43) at 8 weeks and all these factors except left ventricular ejection fraction at 26 weeks.
These clinical outcomes were unrelated to other cardiac or
pulmonary diseases.
Conclusions: Symptomatic improvement is only temporary in many patients undergoing balloon aortic valvuloplasty, and the mortality rate in the mid-term follow-up period is high. Valve surgery remains the treatment of choice
for aortic stenosis in the adult.
Annals of Internal Medicine.
From Mount Sinai Hospital, New York, New York. For
current author addresses, see end of text.
treatment of patients with symptomatic aortic
stenosis is based o n the k n o w l e d g e o f the natural history of the disease and o n the success achievable by surgical correction o f the diseased valve. In all but the
very high-risk patient, surgery is r e c o m m e n d e d . H o w ever, several c h a n g e s have occurred over the last 10
years to alter both the spectrum and treatment o f this
W h e n survival curves for patients with severe aortic
stenosis were first described ( 1 ) , rheumatic heart disease w a s m u c h m o r e prevalent than it is today. Currently, the c o m m o n e s t cause o f aortic stenosis is the
degeneration of a bicuspid valve or of a previously
normal, trileaflet valve, as s o m e t i m e s occurs in the elderly patient. Patients are therefore presenting w i t h
aortic stenosis at an older age, causing the prognosis to
be influenced by a m o r e c o m p l e x set of underlying
medical illnesses. In addition, before 1985, the only
available n o n m e d i c a l treatment for severe aortic stenosis w a s valve surgery (replacement or d e b r i d e m e n t ) .
T h e results are generally g o o d for all age groups under
75 years ( 2 ) . In 1985 balloon dilatation of the aortic
valve b e c a m e available t o patients w i t h severe aortic
stenosis ( 3 , 4 ) . Little has been published thus far regarding the course of s u c h patients after discharge. W e
describe the clinical follow-up o f our first 36 patients
undergoing balloon aortic valvuloplasty w i t h special
emphasis o n defining predictors of clinical success.
In October 1986 a protocol for the dilatation of aortic valves
was approved by the Mount Sinai Hospital Institutional Review Board. Patients were considered to be candidates for
the procedure if the following factors existed: severe aortic
stenosis as documented by both echocardiography and cardiac catheterization (mean transaortic gradients 40 mm
Hg or calculated valve area [5] less than 1.0 cm 2, or both)
grade 3 or 4 symptoms according to the New York Heart
Association ( N Y H A ) Functional Classification system ( 6 ) ,
and a high surgical risk as assessed by both cardiologist and
cardiovascular surgeon. The latter category was defined as
including patients having one or more of the following conditions: severe left ventricular dysfunction (ejection fraction
< 0.30), debilitating diseases that would significantly increase operative morbidity, age greater than 80 years, and
multivalvular disease that would require a prolonged surgical procedure for correction. Patients with diseases associated with limited life expectancies or who had strong desires to
avoid a more corrective surgical procedure were also eligible
to participate in the study.
The assessment of left heart valvular regurgitation was
based on echocardiographic (with Doppler) studies or angiographic criteria, or both. Contraindications to participation
in this study included the presence of left ventricular mural
thrombus, current or recent endocarditis, and active infec-
©1989 American College of Physicians
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Table 1. Hemodynamic
before and after Balloon Aortic
Total Number
of Measurements
Pressure, mm Hg
Pulmonary artery systolic
Pulmonary artery wedge
Left ventricular end diastolic pressure
Aortic systolic
Mean gradient
Cardiac output, L/min
Valve area, cm2
Hemodynamic Measurements*
15 ± 7
15 ± 7
137 ± 2 5
23 ± 14
3.9 ± 1.3
0.9 ± 0.3
P Value
* Mean ± standard deviation.
tion. Patients eligible for the study signed informed consent
to have the procedure.
Cardiac Catheterization and Balloon Dilatation
After being premedicated with a benzodiazepine and 325 mg
of aspirin, patients had routine right and left heart catheterization by either the transfemoral or transbrachial approach;
this procedure included coronary angiography (34 patients), aortography (35 patients), and left ventriculography
(23 patients). Heparin, 5000 units, was given intra-arterially
to all patients before dilatation; it was not reversed after the
procedure. Thirty-two patients had a percutaneous approach; in order to facilitate passage of balloon catheters,
however, the remaining 4 patients (who had severe peripheral vascular disease) had direct surgical exposure of the femoral artery. The standard left ventricular catheter was
exchanged for a balloon dilating catheter (Mansfield Company, Mansfield, Massachusetts). The initial balloon size
was chosen according to echocardiographic and angiographic aortic anulus dimensions. Balloons smaller than the anulus diameter were chosen when extensive calcification of the
aortic valve was seen during angiography. Larger or several
balloons were used when initial dilatations were felt to be
inadequate (that is, when the gradient reduction was less
than 5 0 % ) . All but 1 patient had single-balloon dilatation
(maximal size = 23 m m diameter). The two-balloon technique was necessary in a patient with severe peripheral vascular disease in whom a single large balloon could not be
passed transfemorally. After the procedure, the catheter was
removed and each patient was monitored for 1 or more days
in the coronary care unit. Hemodynamic data (pressure and
cardiac output by either thermodilution or oxygen consumption methods) were recorded before and after balloon dilatation. Medical therapy after the procedure included aspirin,
75 mg orally per day, and other cardiac medicines deemed
necessary by the attending physician.
Adverse events occurring during hospitalization and after
discharge were defined as death (all causes), myocardial infarction (defined as chest pain with an elevation of serum
creatine kinase of twice the upper normal level), progression
or the recurrence of symptoms, aortic valve replacement,
and stroke.
Statistical Analysis
Continuous variables were expressed as means ( + standard
deviations) and were compared by paired Mests. Ninety-five
percent confidence intervals ( C I ) were applied where appropriate. Follow-up data were compared by paired £-tests.
Mortality rates (number of deaths/number of patients) at 8,
26, and 52 weeks were calculated using only those patients
who had had balloon dilatation at least 8, 26, and 52 weeks,
respectively, before data analysis. Clinical and hemodynamic
variables were analysed by multiple regression techniques to
define predictors of subsequent events at 8 weeks (for all
patients) and at 26 weeks (for 25 patients). In this model
the variables tested were age, gender, predilatation ejection
fraction, existence of moderate or severe mitral valve disease, presence of coronary artery disease, cross-sectional balloon dilation area, and hemodynamic variables. The latter
category included predilatation and postdilatation pressures
(pulmonary artery, pulmonary artery wedge, left ventricular, and aortic), pulmonary vascular resistance valve gradients, and cardiac outputs. Among the variables examined,
pulmonary artery pressures, pulmonary vascular resistance,
and right ventricular end-diastolic pressure were highly correlated. Additional regressions were carried out with a reduced number of variables in order to minimize the dependence among the independent variables. The M c N e m a r test
for matched pairs (7) was applied (with CIs) to the proportions of patients symptomatically improved at 2 and 26
weeks. Data were dichotomized by the presence or absence
of an adverse event. Unpaired t-tests and chi-square analyses
(with Fisher exact test) were then used where applicable.
T h i r t y - s i x p a t i e n t s (fifteen m e n a n d t w e n t y - o n e w o m en) entered this study. T h e m e a n age was 77. T h e
p r e s e n t i n g s y m p t o m w a s d y s p n e a in 34 p a t i e n t s a n d
e x e r t i o n a l a n g i n a in 2 p a t i e n t s . C o r o n a r y a r t e r y d i s ease w a s p r e s e n t in 19 of 34, m i t r a l r e g u r g i t a t i o n in 16
of 34, ( m o d e r a t e t o severe in 9 ) , m i t r a l s t e n o s i s in 2 of
36, m i l d a o r t i c insufficiency in 2 0 of 36, a n d c a r d i o m y o p a t h y ( s e c o n d a r y t o a d r i a m i c i n toxicity in 1 p a t i e n t a n d i d i o p a t h i c in 1 p a t i e n t ) in 2 of 36 p a t i e n t s .
O n e p a t i e n t h a d h a d a o r t i c valve d e b r i d e m e n t for sev e r e a o r t i c s t e n o s i s 5 y e a r s before p a r t i c i p a t i n g in t h i s
s t u d y . T h e m e a n ejection fraction (for 2 3 p a t i e n t s )
w a s 0.45 ± 0.19.
Before d i l a t a t i o n t h e a o r t i c valve m e a n g r a d i e n t w a s
4 8 + 1 8 m m H g ; c a r d i a c o u t p u t , 3.8 ± 1.3 L / m i n ;
a n d c a l c u l a t e d valve a r e a , 0.5 + 0.2 c m 2 for t h e e n t i r e
g r o u p . T h e r e w e r e m i l d e l e v a t i o n s of p u l m o n a r y a r t e r y systolic ( 4 3 + 19 m m H g ) , a n d p u l m o n a r y a r tery wedge (16 + 8 m m H g ) pressures, and m a r k e d
e l e v a t i o n of t h e left v e n t r i c u l a r e n d d i a s t o l i c p r e s s u r e
( 2 0 + 8 m m H g ) in t h e 36 p a t i e n t s ( T a b l e 1 ) .
A n adequate balloon position could not be obtained
in 1 p a t i e n t . I n 2 o t h e r p a t i e n t s p o s t d i l a t a t i o n h e m o d y n a m i c d a t a w e r e n o t a v a i l a b l e b e c a u s e of t e c h n i c a l
r e a s o n s for o n e p a t i e n t a n d p r o c e d u r e - r e l a t e d d e a t h in
a n o t h e r . I n t h e r e m a i n i n g 33 p a t i e n t s t h e a o r t i c m e a n
g r a d i e n t w a s r e d u c e d t o 2 3 m m H g , a d e c r e a s e of 2 4 . 4
15 March 1989 • Annals of Internal Medicine • Volume 110 • Number 6
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mm Hg (CI, 20.1 to 28.7; P < 0.001). In 30 patients,
the aortic valve area changed from 0.5 to 0.9 cm 2 , an
increase of 0.33 cm 2 (CI, 0.25 to 0.41; P < 0.001). In
3 patients the postdilatation valve area could not be
calculated because gradient was not measurable. The
left ventricular end diastolic pressure decreased significantly to 15 ± 7 mm Hg (P = 0.004) after balloon
dilatation. The mean paired difference for left ventricular end diastolic pressure was 4.5 m m Hg (CI, 1.4 to
7.6). The cardiac output, pulmonary artery wedge
pressure, and pulmonary artery systolic pressure did
not change significantly after dilatation.
There were two ( 6 % , CI, 0.7 to 19) acute major
complications in this series of patients. One 89-yearold patient died from refractory hypotension and
severe left ventricular dysfunction immediately after
balloon dilatation. Another patient developed a nonQ-wave myocardial infarction (creatine kinase peak of
3.67 /xkat/L). There were no acute strokes. In the 32
patients who had the percutaneous procedure, 2 required surgical repair of the femoral arterial puncture
site (1 because of persistent bleeding and 1 because of
an arterial thrombosis). Two patients, one with previous aortic valve debridement, developed severe aortic
insufficiency after balloon dilatation. All other patients
had either no change or a mild increase in the degree
of aortic insufficiency.
The mean length of hospitalization after balloon
aortic valvuloplasty was 8.3 + 7 days (Figure 1).
The mean follow-up period was 7 + 4 months. During the first two weeks after the procedure, 32 of 36
( 8 9 % , CI, 74 to 97) patients improved one to three
N Y H A functional classes. In 3 patients (2 with severe
aortic insufficiency and 1 with an inadequate balloon
dilatation), symptoms did not improve. At 8 weeks, 2
of the 3 patients who had not improved, died; 25 of the
32 patients maintained the same level of improvement;
and 5 patients reverted by one or more N Y H A function classes to a level similar to that existing before the
valvuloplasty was done. In the remaining 2 patients a
function limiting stroke (1 patient) and progression of
symptoms to a degree not as severe as before the procedure occurred between 2 and 8 weeks after balloon
dilatation. Between 8 and 26 weeks there were 8 new
adverse events (5 deaths, 2 patients with aortic valve
replacement, and 1 patient who again had N Y H A
class 4 symptoms).
Of the 25 patients followed for 26 weeks (Figure 1),
improvement in symptoms was sustained in 14 ( 5 6 % ,
CI, 35 to 76). In the remaining 11 patients, 3 were
unimproved initially at 2 weeks and 8 experienced a
deterioration of symptoms between 2 and 26 weeks.
The worsening of symptoms seen between 2 and 26
weeks in 3 2 % (CI, 10 to 54) of patients was significant (P = 0.0078 by McNemar test). Five patients
underwent further mechanical procedures for residual
aortic valve disease: 4 required aortic valve replacement at 2, 2.5, 4, and 8 months, and 1 patient had a
repeat aortic valvuloplasty 1 month after the original
There was one in-hospital death in this series and
ten patients died following discharge. Seven of the ten
Figure 1. Clinical follow-up after balloon aortic valvuloplasty in 36
patients. BAV = balloon aortic valvuloplasty; N Y H A = New York
Heart Association; AVR = aortic valve replacement.
deaths resulted from recurrent or refractory congestive heart failure, or both, 6 occurring more than 8
weeks after dilatation. One such patient died after a
repeat balloon aortic valvuloplasty at another institution and another died from postoperative (aortic valve
replacement) septic shock. Two patients died of presumably noncardiac causes, one from pneumonia and
another after a noncardiac surgical procedure, both
more than 8 weeks after their respective dilatations.
Mortality rates at 8, 26, and 52 weeks were 9 % , 2 8 % ,
and 5 5 % , respectively.
The increment (absolute or fractional) in valve area
did not correlate with any of the following predilatation variables: gender, age, pulmonary artery or left
ventricular pressure, valve gradient, cardiac output,
valve area, or balloon size. The absolute valve area
following dilatation correlated only with predilatation
area. We analyzed the ability of predilatation variables
to predict clinical success. Several multiple regression
analyses using varying subsets of the variables listed in
the methods section were done. No variables other
than pulmonary artery systolic pressure, pulmonary
vascular resistance, right ventricular end-diastolic
pressure, and left ventricular ejection fraction were
found to have statistically significant effects. Because
pulmonary artery systolic pressure, pulmonary vascular resistance, and right ventricular end-diastolic pres-
15 M a r c h 1989 • Annals of Internal Medicine
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• Volume 110 • N u m b e r 6
(P = 0.006, r = 0.60) but not with that at 26 weeks.
As with predilatation variables, this correlation applied to the occurrence of all adverse events, not only
those that could clearly be ascribed to cardiac causes.
No other postdilatation variable had predictive capability.
Figure 2 shows the distribution of pulmonary artery
systolic pressures according to clinical outcome at 26
weeks; significant differences occur in pulmonary artery systolic pressures, whether measured before or after dilatation, when patients are grouped according to
the occurrence of adverse clinical events. Of the 9 patients with postdilatation pulmonary artery pressures
equal to or greater than 50 m m Hg, 7 encountered at
least one adverse event by 26 weeks. Of the 16 patients
with pulmonary artery pressures of less than 50 mm
Hg, 4 had at least one adverse event at 26 weeks
(P = 0.017 by Fisher exact test). Using a similar
analysis of predilatation pulmonary artery systolic
pressures, a comparable but insignificant trend was observed.
Figure 2. Pulmonary artery systolic pressures before (top) and after
(bottom) balloon aortic valvuloplasty in patients without (closed circles) and with (open circles) untoward events at 26 weeks. Solid lines
indicate mean values and dashed lines indicate standard deviations.
sure correlate strongly clinically, each was used in separate multiple regression analyses. Pulmonary artery
systolic pressure correlated well with adverse events at
8 (P = 0.048, r = 0.65) and at 26 (P = 0.004,
r = 0.57) weeks. Similar findings were seen for pulmonary vascular resistance and right ventricular enddiastolic pressure at 8 weeks (P = 0.008, r = 0.69,
and P = 0.009, r = 0.43, respectively), as well as at
26 weeks (P = 0.0006, r = 0.79, and P = 0.0008,
r = 0.62, respectively). Clinical outcome was also
correlated with ejection fraction, but only with events
at 8 weeks (P = 0.04, r = 0.46). N o other predilatation clinical, hemodynamic, or angiographic variable
predicted an improvement in symptoms or the development of an adverse event.
The correlation between clinical success and postdilatation variables was comparable. Here, pulmonary
artery systolic pressure showed a good correlation
with clinical events at 8 weeks (P = 0.007, r — 0.65)
and 26 (P = 0.014, r = 0.60). Pulmonary vascular
resistance was well correlated with 8-week outcome
15 March 1989 • Annals of Internal Medicine
Patients with severe aortic stenosis have an extremely
poor prognosis when the obstructive lesion is not corrected. In one series (1) such patients experienced a
5 0 % mortality rate in the first 5 years after the onset
of congestive heart failure. An even worse prognosis
awaits the elderly patient with more severe symptoms,
where survival at 1, 2, and 3 years of 5 7 % , 3 7 % , and
2 5 % , respectively, has been reported ( 8 ) . Because operative mortality for aortic valve surgery increases significantly in patients over 75 years, an alternative to
surgery has long been needed.
The advent of balloon aortic valvuloplasty in 1985
was followed by a fairly broad application of the technique to patients with severe aortic stenosis of all ages.
Our study, like others before it, shows the efficacy of
the procedure in relieving symptoms and in improving
functional capacity in a group of largely elderly patients. The degree of improvement afforded to most of
our patients was considerable; indeed, an immediate
good effect was described by some patients within
minutes or hours of the procedure. However, this clinical effect did not persist in all patients. At 8 weeks
after dilatation, 6 9 % of patients demonstrated an improvement of one to three N Y H A functional classes.
When followed for 26 weeks, 5 6 % of patients remained at the same level without the need for further
interventions and without the occurrence of other adverse events. The 8- and 26-week survival rates were
9 2 % and 7 2 % , respectively. Therefore, progression of
symptoms is common and mortality rates are high in
this population of patients. Caution must be exercised
in recommending this procedure as standard therapy,
even in elderly persons.
The ability to predict clinical outcome in patients
following balloon aortic valvuloplasty has been described (9, 10). In these reports, left ventricular ejection fraction before dilatation and aortic valve area
• Volume 110 • Number 6
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after dilatation were correlated with clinical success,
defined as 3 or more months of symptomatic improvement. From our data, the predilatation variables capable of predicting clinical outcome included left ventricular ejection fraction, pulmonary artery systolic
pressure, pulmonary vascular resistance, and right
ventricular end-diastolic pressure. Pulmonary artery
pressure, measured after dilatation, was equally good
as a predictor of subsequent adverse events. Low left
ventricular ejection fraction and high right heart pressures both predicted a poor clinical outcome. Left ventricular ejection fraction was more predictive of a poor
outcome early (8 weeks) than late (26 weeks) during
follow-up. The reasons for this finding are unclear.
Right heart pressures, on the other hand, predicted
both early and late events. Over 7 5 % of patients with
pulmonary artery systolic pressure over 50 m m Hg
had at least one adverse clinical event by 26 weeks.
These findings were independent of other causes of
pulmonary hypertension (for example, mitral valve
disease) and raise the important question of the effect
of right ventricular dysfunction on prognosis in patients with aortic stenosis.
One possible determinant of clinical success is the
anatomic lesion itself, that is, bicuspid compared with
degenerative or rheumatic tricuspid aortic valve disease. Such a determination could not be made from
available echocardiographic and angiographic studies
in most of our patients. Because too few patients had
rheumatic disease we could not detect any significant
difference in their response to balloon dilatation. In
addition, to the extent that it reflects the incidence of
bicuspid disease (generally present in younger patients), age was not a significant predictor of clinical
The mechanisms underlying clinical failure after
balloon aortic valvuloplasty have not been fully elucidated. Residual aortic valve disease or restenosis, or
both quite likely play major roles in such situations,
and repeated evaluations of the valve after dilatation
will help to clarify this issue. Whether right ventricular function assumes an independent prognostic role in
aortic stenosis as it does in other valvular diseases and
as our data suggest, must be critically evaluated.
Again, repeated evaluations of ventricular function after valvuloplasty, as we continue to do, will also shed
light on this issue.
Balloon dilatation of the aortic valve provides a very
safe and effective means of treating patients with severe aortic stenosis. Unfortunately, the benefit is short
lived in many patients. Pulmonary artery systolic pressure, pulmonary vascular resistance, right ventricular
end-diastolic pressure, and left ventricular ejection
fraction are useful as predictors of clinical success; in
our patients absolute or fractional increase in valve
area was not a good predictor. Patients with a pulmonary artery systolic pressure of 50 mm Hg or greater
may be better served by a more aggressive surgical
form of treatment. We currently recommend valve
surgery to all but very high risk patients. Balloon aortic valvuloplasty remains a very good, although only
palliative, treatment when no other medical alternatives exist.
The authors thank Valentin Fuster, M D and Paul
Meier, PhD for their critical reviews of this paper.
Requests for Reprints: Warren Sherman, MD, Division of Cardiology,
Mount Sinai Hospital, One Gustave Levy Place, New York, NY 10029.
Current Author Addresses: Drs. Sherman, Hershman, Cohen, Ambrose,
and Gorlin: Division of Cardiology, Mount Sinai Hospital, One Gustave
Place, New York, NY 10029.
Dr. Lazzam: Toronto General Hospital, Eaton Building, 200 Elizabeth
Street, Toronto, Ontario, Canada M5G ZC4.
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