ORIGINAL ARTICLES
Observations on the Optimum Time for Operative
Intervention for Aortic Regurgitation
I.
Evaluation of the Results of Aortic Valve Replacement
in Symptomatic Patients
WALTER L. HENRY, M.D., ROBERT 0. BONOW, M.D., JEFFREY S. BORER, M.D.,
JAMES H. WARE, PH.D., KENNETH M. KENT, M.D., PH.D., DAVID R. REDWOOD, M.D.,
CHARLES L. MCINTOSH, M.D., ANDREW G. MORROW, M.D., AND STEPHEN E. EPSTEIN, M.D.
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
SUMMARY Fifty consecutive patients undergoing aortic valve replacement for isolated aortic regurgitation
studied prospectively by echocardiography, electrocardiography and cardiac catheterization. Good
quality echocardiograms were obtained in 49 of the 50 patients. Left ventricular (LV) dilatation was present in
all 49 patients. LV systolic function, as assessed by echocardiographic percent fractional shortening, was normal in many patients but was moderately to severely reduced (< 25%) in 14 patients (29%). Echocardiographic studies 6 months postoperatively revealed significant reductions in LV end-diastolic dimension (73.8
mm vs 58.7 mm; p < 0.01), and serial echocardiographic studies early and late after operation revealed that
the decrease in LV size had occurred by the time of the early study (8-22 days postoperatively), with little additional change thereafter. Operative deaths occurred in three of the 49 patients (6%). Eight of the 49 patients
(16%) died of congestive heart failure (CHF) after hospital discharge at times ranging from 5-43 months after
operation. Preoperative echocardiographic measurements of the LV end-systolic dimension and percent fractional shortening were strongly associated (p < 0.01) with these late CHF deaths. Preoperative LV endsystolic dimension > 55 mm and fractional shortening < 25% identified the high-risk group: nine of 13
patients (69%) in this group died either at operation or subsequently from CHF. In contrast, of 32 patients with
LV end-systolic dimension < 55 mm, only one died at operation and one died late from CHF. Thus, the population at high risk of late death from CHF was identified before operation by echocardiography.
were
MOST PATIENTS who undergo aortic valve
replacement for aortic regurgitation survive operation
and have sustained relief of symptoms for many years.
Others survive operation but later develop progressive symptoms of congestive heart failure and die
several months to years after valve replacement. It is
usually assumed that irreversible left ventricular dysfunction occurred before operation in these patients
and produced symptoms of congestive heart failure
after operation.'-"
In this paper, we describe the results of a prospective study of patients undergoing aortic valve replacement for isolated aortic regurgitation. The study had
three goals: 1) to define the echocardiographic and
hemodynamic characteristics of symptomatic patients
who require operation because of severe aortic
regurgitation; 2) to determine the changes that occur
in these echocardiographic and hemodynamic
measurements after successful aortic valve replacement; and 3) to identify variables measured before
operation that were associated with a high risk of dying at operation or developing symptoms of congestive
heart failure and dying after operation. If factors
highly associated with mortality could be identified, it
might be possible to predict the result of operation in
individual patients more reliably and, more important, to determine the optimum timing of operative intervention.
Methods
Patients
The patient population consisted of all patients with
long-standing aortic regurgitation who had aortic
valve replacement between January 1972 and June
1977. Patients were included in the study population if
they had aortic regurgitation visualized by cineangiography after injection of dye into the aortic root that
was severe enough to produce opacification of the left
ventricle that failed to clear during the subsequent cardiac cycle. Patients were excluded if the gradient
across the aortic valve exceeded 20 mm Hg, if
dysfunction of other heart valves was severe enough to
require valve replacement, if aortic root disease existed requiring aortic root reconstruction at the time
of valve replacement, or if valvular surgery had been
performed previously. All patients had severe dyspnea
on exertion, overt congestive heart failure (orthopnea,
paroxysmal nocturnal dyspnea, pulmonary edema),
From the Cardiology and Surgery Branches, NHLBI, NIH,
Bethesda, Maryland.
Address for correspondence: Walter L. Henry, M.D., University
of California at Irvine Medical Center, Cardiology Division, 101
City Drive South, Building 53, Orange, California 92668.
Received September 21, 1978; revision accepted November 15,
1979.
Circulation 61, No. 3, 1980.
471
472
CIRCULATION
VOL 61, No 3, MARCH 1980
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angina pectoris or syncope. The presence of coronary
artery disease or left ventricular dysfunction was not
used to exclude patients from study.
Forty-nine of the 50 patients who met the selection
criteria had good-quality preoperative echocardiograms and were accepted into the study. There were 40
men and nine women, ages 19-68 years (mean 46
years). Forty-one patients had either 2320 series (30
patients) or 2400 series (11 patients) Starr-Edward
prosthetic valves, two had Bj'ork-Shiley valves and six
had porcine heterograft valves placed at operation.
Coronary artery perfusion was used during cardiopulmonary bypass in 31 patients, coronary perfusion
plus topical iced saline was used in nine patients, and
topical iced saline alone was used in six patients.
Three patients had neither coronary artery perfusion
nor topical iced saline.
Ten of the 49 patients (20%) had coexistent coronary artery disease. Four of these 10 patients (40%)
had saphenous vein bypass grafts placed at the time of
aortic valve replacement. Figure 1 is a flow chart of
the results and follow-up of all patients in the study.
The patient who was excluded from the study because
of poor-quality echocardiographic records both before
and after operation is still alive.
Patient Studies
History, physical examination, 12-lead ECG,
echocardiogram, and left- and right-heart cardiac
catheterization were obtained before and 6 months
(range 5-11 months) after operation. In the
preoperative studies, left-heart catheterization was
performed retrogradely from the aorta. Six-month
postoperative studies were performed using either the
transseptal or percutaneous ventricular puncture technique. Cardiac output was obtained using the indocyanine green dye technique. Digitalis and diuretics
were discontinued for at least 3 days before cardiac
catheterization.
Left ventricular contrast cineangiography was
attempted in most patients before operation, but images satisfactory for volume analysis were available in
only 23 patients. In many patients, premature ventricular depolarizations, inadequate dye concentration, hemodynamic instability or technical factors
prevented the angiographic data from being useful.
Preoperative ventriculograms were available in only
three patients who either died at operation or during
follow-up. Because of the small number of patients,
the ventriculographic data could not be evaluated for
their association with mortality.
Coronary artery anatomy was assessed in 47 of 49
patients by preoperative coronary cineangiography
(36 patients), 6-month postoperative coronary cineangiography (eight patients) or autopsy examination
(three patients).
Twelve-lead ECGs were obtained in every patient
before operation and at 6-month postoperative study
in all patients who returned for follow-up evaluation.
Romhilt-Estes scores were computed, as previously
described,5 for all patients, including the three patients
with complete left bundle branch block.
v
30 Patients with Postop Echos
Still Alive (Avg Follow-up 42 Mos)
32 Patients Still
Alive
(Avg Follow-Up
44 Mos)
FIGURE 1. Flow diagram of the follow-up experience for
the 49 patients with satisfactory echocardiograms who had
aortic valve replacement (A VR) for isolated aortic
regurgitation. CHF = congestive heart failure; Ao V = aortic valve; MI = myocardial infarction; cabg = coronary
artery bypass graft.
Echocardiograms were performed in all 49 patients
before operation, and 6 months after operation in 39
patients. Echocardiographic studies were performed
in 26 patients 8-22 days (mean 11 days) after operation ("early" postoperative studies). In 16 patients,
studies were performed "late" (21-63 months, mean
34 months) after operation. It is not clear whether any
important selection factors determined what patients
had early or late postoperative echocardiographic
studies. However, comparison of the preoperative
echocardiographic data from these patients with the
preoperative data from the rest of the patient population failed to reveal any significant differences (p >
0.05).
Echocardiograms were obtained using either an
Ekoline 20A or a Hoffrel 201 ultrasound transceiver
interfaced to a Honeywell 1856 strip-chart recorder. A
1.25-cm diameter, 2.25-MHz unfocused ultrasound
transducer was used; a switched-gain circuit was used
to simplify measurement of left ventricular posterior
VALVE REPLACEMENT IN AR/Henry et al.
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free wall thickness.`3 Echocardiographic measurements included heart rate, left ventricular transverse
dimensions at end-diastole and end-systole, and ventricular septal and left ventricular free wall thicknesses.'4, 15 These measurements were made using the
T-scan technique,'6' 17 with the ultrasound beam passing through the left ventricle just caudal to the tips of
the mitral leaflets. From these primary measurements, percent fractional shortening of the left ventricle was calculated as the ratio of the difference
between the left ventricular diastolic and systolic
dimensions to the left ventricular diastolic dimension.'8 Left ventricular ejection fraction and mass were
estimated using the cubed assumption.12' 19 Aortic root
and left atrial dimensions were measured in all
patients before operation,14 but not after operation,
because the presence of the prosthetic valve made it
difficult to identify the posterior wall of the aorta. In
two patients, the aortic root dimension slightly above
the aortic leaflets was significantly greater than that at
the level of the aortic valve. In these two patients, the
larger measurement was used.
Mortality Analysis
The association between the several patient
variables and overall mortality was tested by Cox's
method of life-table analysis.20 The total survival experience of the 49 patients was studied using the
preoperative findings as the independent variable and
death from any cause as the end point. The survival
experience beginning 30 days after operation was also
analyzed using preoperative measurements, with
death related to congestive heart failure as the end
point. Death was assumed to be related to congestive
heart failure if patients died after experiencing
postoperative symptoms of severe dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, or
pulmonary edema. The mortality experience of the
patients who survived operation and returned for
repeat study 6 months after operation was also
analyzed separately using measurements from the 6month follow-up study as independent variables and
subsequent death from congestive heart failure as the
end point.
Results
Patient Follow-up
Three in-hospital deaths occurred among the 49
patients (fig. 1); none of the three patients who died at
operation had coronary artery disease. Forty-six
patients survived operation and were discharged from
the hospital. Eight patients with symptoms of congestive heart failure died 5-42 months after operation;
two of these patients died before the 6-month postoperative study. The mean age of the eight patients
who died late of congestive heart failure was 47.6
years (range 28-64 years), which did not differ from
the mean age (47.2 years) of the other 41 patients.
These eight patients could not be distinguished from
the other patients based on sex, duration of symptoms,
preoperative digitalis therapy, type of prosthetic valve
473
or type of myocardial preservation. Only one of the
eight patients (13%) who died late due to congestive
heart failure had coronary artery disease.
Three patients without symptoms of congestive
heart failure died 23, 42 and 46 months after operation. Two of these three deaths were related to complications of coronary artery disease (see below). The
third patient, who did not have coronary artery disease, died while swimming; we do not know whether
this represented sudden cardiac death or drowning. If
all the patients with follow-up information of any kind
are included, 32 are alive, with a mean follow-up of 44
months. Thirty patients with postoperative echocardiograms are still alive, with a mean follow-up of 42
months. The overall mortality was 14 of 49 patients
(29%). Operative mortality was three of 49 patients
(6%). Late mortality due to any cardiac cause
(including the death while swimming) was 1 1 of 46
patients (24%), giving an average annual late mortality of 7% per year.
Of the 10 patients with coronary artery disease, six
did not have saphenous vein bypass grafts at valve
replacement. Three of these six patients subsequently
had acute myocardial infarctions (one of the three
died), and one patient developed severe angina several
months after valve replacement. This patient died during a coronary artery bypass operation performed at
another institution. No coronary-related events have
occurred in the four patients who had saphenous vein
grafts placed at valve replacement. Only two of the 10
patients with coronary artery disease had fractional
shortening less than 25% preoperatively, and one of
these patients was the only patient of the 10 that
developed congestive heart failure and died during
long-term follow-up after operation.
Preoperative Evaluation
The preoperative echocardiographic measurements
obtained in the 49 patients with satisfactory echocardiograms are shown in figures 2 and 3. Figure 2 gives
direct echocardiographic measurements and the
calculated left ventricular fractional shortening. The
data in figure 3 are expressed as a percentage of the
expected value corrected for age and body surface
area obtained using regression equations derived from
a large series of younger'4 and older'5 normal subjects.
Left ventricular fractional shortening is independent
of body surface area;14 the normal range for our
laboratory is given in figure 2. The internal dimensions
of the left ventricle at end-diastole and at end-systole
were increased in nearly every patient, often
markedly. The thicknesses of the left ventricular free
wall and the ventricular septum were increased in 38
of 49 patients (78%). The ratio of ventricular septal
thickness divided by left ventricular free wall
thickness'7 ranged from 0.77-1.19 (mean ± SEM 0.96
+ 0.01). Estimated left ventricular mass was increased
above the normal range in every patient. Fractional
shortening of the left ventricle was below the normal
range in 28 of 49 patients (57%); in 14 of 49 patients
(29%), fractional shortening was less than 25%. The
results were similar when estimated ejection fraction
CIRCULATION
474
AORTIC REGURGITATION
(preop)
45
90 -
0 8H
O
r
-
70
-
0so
-
VOL 61, No
3, MARCH
1980
Operative Deaths or Perioperative Myocardial Damage
Three patients died of low cardiac output early after
operation. Six other patients who survived operation
40
and were discharged from the hospital had evidence of
u, .
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HJlr.
operative myocardial damage. Three had postoperative ECGs indicating a new transmural myocardial in70
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2
involving regions other than the apical vent site at
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cineangiography 6 months postoperatively. Only one
2
50
of these nine
hadhadcoronary
artery disease.
five patients
of the nine
a left ventricular ende:
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dimension at preoperative echocardiographic
Z 4 EL |I | a L. systolic
study that was greater than 55 mm and a fractional
shortening that was less than 25%.
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LVD
LVD
(DIA) (SYS)
Ao
LA
'*
iq
<i
Septum LV PW
<
30
yF
;
p <0.01
Fractional
AORTIC REGURGITATION
(preop)
Shortening
FIGURE 2. Preoperative echocardiographic measurements. The mean value is indicated by the open symbol with
the horizontal line at the extreme right of each column. Left
ventricular fractional shortening in percent is shown on the
right; the stippled area represents the normal range.
L VD(DIA) = left ventricular dimension at end-diastole;
L VD(SYS) = left ventricular dimension at end-systole; Ao
= aortic root dimension; LA = left atrial dimension; L VPW
left ventricular posterior wall.
LVD
(DIA)
LVD
(SYS)
LV
PW
275
450
.
400
250
=
3.
z
cc
a
Six-month Postoperative Evaluation
Forty-one of the 49 patients underwent hemodynamic evaluation 6 months after operation. Postoperative pressure gradient measurements across the
prosthetic aortic valve were less than 30 mm Hg in all
~~~*
but five patients. One of the five patients had a gradient of 60 mm Hg and a perivalvular leak. This patient
1
*
W
X 350 _
*
,
W
J
W
225
z Z
was used. The aortic root and left atrial dimensions
were both significantly increased (p < 0.01).
LV Mass
LA
Ao
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.
150
200
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1 °..00 _ . _. . _. ._. . . . . .
is alive and well after a second aortic valve replacement. The other four patients, all with prosthetic valve
100..-..
gradients of 35-45 mm Hg, are alive and well. __.Postoperative valve areas were not computed because
-- _~
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of the small mean valvular gradient (14 mm Hg). The
hemodynamic data before and after operation, as wellp<01<.1pO01p.1pOOl<01
as Romhilt-Estes scores, are summarized in table 1.
5
Thirty-nine patients had both preoperative and 6FIGURE 3. Preoperative echocardiographic measurements
month postoperative echocardiographic studies (table
in the 49 patients expressed as a percentage of the expected
1 and fig. 4). The mean left ventricular dimensions at
value (expected value computed from the patient's age and
end-diastole decreased significantly (p < 0.01) after
body surface area using previously derived regression
operation. Mean ventricular septal and left ventricular
equations).14' 15 The 95% confidence limit for normal data is
posterior wall thicknesses, however, were unchanged
indicated by the stippled area. The p value indicates whether
(p > 0.05). Because of the marked decrease in the
the mean value is significantly dif3ferent from normal. See
mean internal dimension of the left ventricle, the mean
legend to figure 2 for symbols and abbreviations. The mean
estimated left ventricular mass decreased markedly
value is indicated by the open symbol with the horizontal
after operation (p < 0.01).
line at the extreme left of each column.
VALVE REPLACEMENT IN AR/Henry et al.
475
TABLE 1. Mean Values and Standard Deviations in Patients with Both Pre- and Postoperative Measurements
6-month
Variable
Preop value
postop value
p
LV dimension (diastole) (mm)
73.8 - 8.0
58.7 = 11.0
< 0.01
13.5 - 1.9
13.7 - 1.8
Septal thickness (mm)
NS
LV free wall thickness (mm)
14.1
1.9
13.9 - 1.8
NS
LV fractional shortening (%)
27.6 7.4
27.1 - 9.6
NS
LV ejection fraction (%)
12.2
60.9
59.2
16.8
NS
Estimated LV mass (g)
684
176
477 - 180
< 0.01
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Heart rate (beats/min)
Romhilt-Estes score
80.9
6.2
14.6
2.3
76.9 - 18.8
5.1 - 2.4
< 0.01
LV systolic pressure (mm Hg)
LV end-diastolic pressure (mm Hg)
Aortic systolic pressure (mm Hg)
Aortic diastolic pressure (mm Hg)
Cardiac output (1/min)
Cardiac index (1/min/m2)
Aortic valve peak gradient (mm Hg)
Pulmonary systolic pressure (mm Hg)
Pulmonary diastolic pressure (mm Hg)
Pulmonary wedge pressure (mm Hg)
Abbreviation: LV = left ventricular.
147
23.7
150
52
4.6
2.6
2.2
38.5
17.8
17.6
29
10.6
31
8.7
0.87
0.52
4.6
17.8
8.9
8.7
154
13.4
141
76
5.65
3.09
13.5
29.0
12.8
< 0.01
< 0.01
< 0.01
< 0.01
< 0.01
< 0.01
< 0.01
< 0.01
tion or had evidence of operative damage. In contrast,
operative death or damage occurred in four of 36
patients (1 1 %) who had either a left ventricular endsystolic dimension less than or equal to 55 mm or a
fractional shortening equal to or greater than 25%.
This difference is statistically significant (p < 0.05) by
Fisher's exact test.2'
30
5.8
29
12
1.35
0.78
16.6
8.5
4.5
NS
AORTIC REGURGITATION
LVD (DIA)
LV Mass
1278
LV PW
90
1000 H
80
900 H
Serial Echocardiographic Evaluation
Twenty-six patients had both preoperative and early
postoperative echocardiograms. Three of these 26
patients had evidence of intraoperative myocardial
damage by ECG changes (one patient) or new ventricular dyskinesia on contrast cineangiography (two
patients). Two other patients who were studied early
postoperatively died before discharge from the
hospital after operation. These five patients had a
decrease in the left ventricular end-diastolic dimension
at the early postoperative study of only 6 mm or less.
All of the remaining 21 patients had at least an 1 1-mm
decrease in the end-diastolic dimension at the early
postoperative study. The preoperative and early postoperative paired echocardiographic data for these 21
patients are summarized in table 2. Paired measurements obtained at study early and 6 months
postoperatively in 20 patients are also summarized in
table 2.
Left ventricular diastolic dimensions had decreased
significantly at the early postoperative study and did
not change further between the early study and the 6month postoperative study. Heart rate was increased
at the early postoperative study, but decreased to the
preoperative values between the early and 6-month
NS
cn
1060
800 H
70
cn
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cc
z
Z 50
cc
700
z
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600
z
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z
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0
Z 40
2W 400
pc
> 30
300 _
20
200 _
in1
lu
~~2
-100
p < 0.01
N.S.
Preop 6 Mos
Postop
Preop 6 Mos
Postop
p < 0.01
Preop 6 Mos
Postop
FIGURE 4. Plot of echocardiographic left ventricular enddiastolic dimension (L VD/DIAJ), posterior free wall
(L VPW) and left ventricular mass (L V mass) obtained in 39
patients before and 6 months after operation. See legend to
figure 2 for abbreviations and symbols.
476
VOL 61, No 3, MARCH 1980
CIRCULATION
TABLE 2. Serial Changes in Echocardiographic Variables (Paired Data)
6-month
Early
postop
Early
postop
(n = 20)
(n = 21)
p
postop
Variable
Preop
LV dimension
(diastole)
60.7 - 10.9
76.4 - 8.1
57.0 - 10.4 < 0.01 60.4 - 9.5
(mm)
LV wall
thickness
14.3
1.9
13.2 4.6
12.4 - 5.1
NS
14.2 2.0
(mm)
< 0.01 483
522 - 203
224
LV mass (g)
724 180
413 - 226
Heart rate
(beats/min) 78.9 + 13.6 88.6 -= 18.1 < 0.01 93.0 -4 19.3 79.3 - 20.8
p
6-month
postop
NS
60.2
NS
NS
13.6
485
<
0.01 77.5a
-
-
Late postop
(n = 16)
p
11.1
NS
1.1
136
NS
NS
18.6
NS
9.2
59.4
1.3
138
13.4
462
25.3
69.5
-
-
-
*Two patients who died in the perioperative period and three patients with evidence of operative myocardial damage (see
text) are not included. These five patients had changes in LV diastolic dimension ranging from a 3-mm increase to a 6-mm decrease early postoperatively.
Abbreviations: LV = left ventricular; postop = postoperative; preop = preoperative.
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postoperative studies. Left ventricular wall thickness
had not changed at either study. Most patients
developed flat or paradoxical septal motion after
operation; therefore, left ventricular systolic dimension and fractional shortening data are not included in
table 2.
Sixteen patients had both 6-month and late
postoperative echocardiograms. Little change appeared in any of the echocardiographic parameters
between the 6-month study and the late postoperative
study (table 2), except for one patient whose left ventricular diastolic dimension increased from 70 mm to
84 mm between 6 months and 33 months. This patient
died from congestive heart failure 37 months after
operation.
Mortality Experience
The results of the mortality analysis for the
preoperative measurements are shown in table 3. The
Cox method used in the mortality analysis was
developed for regression analysis of survival data
when subjects have follow-up experience of variable
length. This method is a more powerful and appropriate technique for identifying risk variables than
a simple comparison of mean values for those who
died and those who survived. Therefore, although
mean and standard deviation values are shown in table
3, the p value indicates the predictive strength of each
measurement by the Cox method.
Several preoperative echocardiographic measurements, including left ventricular end-systolic dimension, fractional shortening and ejection fraction, as
well as heart rate, were associated with overall mortality (p < 0.05). Percent shortening of the left ventricle, left ventricular ejection fraction and left ventricular dimension at end-systole were all strongly
associated (p < 0.01) with late deaths due to congestive heart failure. When the 10 patients with coronary artery disease are excluded, these echocardiographic measurements were still strongly
associated (p < 0.01) with late deaths from congestive
heart failure. Left ventricular dimension at end-
diastole was also associated with late deaths from congestive heart failure (p < 0.05).
Preoperative left ventricular fractional shortening
less than 25% was found in 14 of the 49 patients (29%).
Nine of the 14 (64%) either died at operation (two
patients) or developed symptoms of congestive heart
failure and died during long-term follow-up after
operation (seven patients) (fig. 5). In contrast, of 35
patients with a preoperative fractional shortening of at
least 25%, one (3%) died at operation and another
(3%) developed symptoms of congestive heart failure
and died during long-term follow-up. The mean age of
the patients with fractional shortening less than 25%
(49.5 years) was slightly greater than the mean age of
the patients with fractional shortening greater than
25% (45.5 years), but the difference was not
statistically significant (p = 0.34).
Similar findings were noted for the left ventricular
dimension at end-systole (fig. 6). Nine of seventeen
patients (53%) with a preoperative end-systolic dimension greater than 55 mm either died at operation (two
patients) or developed symptoms of congestive heart
failure and died after operation (seven patients). This
contrasts with one operative death (3%) and one late
death due to congestive heart failure (3%) in the 32
patients whose dimension was 55 mm or less.
The fractional shortening data and the follow-up experience for the 17 patients who had a preoperative
end-systolic dimension greater than 55 mm are summarized in figure 7 and table 4. All 17 patients had a
subnormal fractional shortening (i.e., < 29%). Four of
the 17 patients (24%) had a preoperative left ventricular fractional shortening of at least 25%. Eleven
of the 13 patients (85%) with a preoperative endsystolic dimension greater than 55 millimeters and a
preoperative fractional shortening less than 25% are
either dead (nine patients) or, if still alive, have
reduced left ventricular systolic function and symptoms of congestive heart failure postoperatively (two
patients).
A left ventricular ejection fraction (by echocardiography using the cubed assumption"2) less than 58%
also identified patients with a high risk of developing
VALVE REPLACEMENT IN AR/Henry et al.
477
diastolic dimension was a stronger predictor of subsequent late death from congestive heart failure than
the preoperative value. Death from congestive heart
failure occurred in five of seven patients with
postoperative diastolic dimensions of 70 mm or
greater. Moreover, as was the case preoperatively, late
deaths due to congestive heart failure were also
strongly associated (p < 0.001) at 6-month
postoperative study with left ventricular fractional
shortening and left ventricular dimension at endsystole (table 3), despite the questionable validity of
congestive heart failure and dying. Also, pulmonary
artery wedge pressure was associated with late deaths
related to congestive heart failure, but with a lower
correlation (table 3).
The results of the analysis for the measurements obtained during study 6 months after operation are also
shown in table 3. Late deaths due to congestive heart
failure were strongly associated (p < 0.001) with
postoperative left ventricular end-diastolic dimension.
Pre- and postoperative left ventricular diastolic
dimensions are shown in figure 8. Postoperative
TABLE 3. Relation of Preoperative and Postoperative Data to Overall and Late Congestive Heart Failure Mortality
6-month postoperative data
Preoperative data
Late CHF
Late CHF
deaths
All deaths
Alive
deaths
Alive
(n = 35)
(n = 14)
(n = 8)
(n = 6)
(n = 30)
Variable
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Echo
LV dimension (diastole)
(mm)
LV dimension (systole)
(mm)
LV fractional shortening
73
7
-
51 8
29=- 8
(%)
64 - 10
LV ejection fraction (%)
14 - 2
LV wall thickness (mm)
655- 162
LV mass (g)
Aortic root dimension (mm) 37 - 5
Left atrial dimension (mm) 45 - 4
ECG
Romhilt-Estes score
Heart rate (beats/min)
(mm Hg)
Aortic pressure (diastole)
(mm Hg)
PA wedge pressure (mm Hg)
PA pressure (systole)
(mm Hg)
PA pressure (diastole)
(mm Hg)
Cardiac index (1/min/m2)
Other
Coronary artery disease
(percent of patients)
Age (years)
Values
are
mean
-
80 =7*
59 -13*
66-1 Ot
(40 =1=9)
22:91
18
44
13
(29
(64
51
16t
-
-
7t
-
13t
56
76
-
10t
(67
-
12)$
8
-
-
7)
12)
(12
(31
2
157
14
709
Abbreviations: LV
11)t
-
4
723- 175
47 - 6
47 - 5
7.0 - 2.6
90 - 20t
6.6 - 2.9
83 - 20
143 =1=34
146
-
30
134
-
18
-
10
13
-
5
16=- 9
11
9*
75
-
18
71== 8
-
3.9
6
2
14
446
-
4.5
74
2.1
15
t
-
154 -27
22
-
11
26
-
10
30
53
17
-
9
8
52
-
10
53
-
21 ==8
24
-
16
40
-
14
42
-
16
29 -8
8
0.5
19
-
7
22
-
6
13
2.6
-
2.7
-
40
16
2.6
-
21%
20%
45
-13
0.6
49
-
15
0.4
3.2
-
-
6.3
99
46
14
-
26t
30
12
9
19
3
0.8
2.8
-
131=- 1St
2.4 =1
13
0.3t
19%
13%
13%
47
137t
=
3
35
42
-
14
SD.
Postoperative left ventricular systolic dimension, fractional shortening and ejection fraction
theses because most patients developed abnormal septal motion after operation.
Statistical significance determined by the Cox method of life-table analysis 20:
*p < 0.05;
tp < 0.01;
tP < 0.001.
5)t
-
14- 2
636 - 238
35- 3
5.4
80
Hemodynamics
LV pressure (systole)
(mm Hg)
LV pressure (end-diastole)
75- 10
left ventricular; CHF
=
congestive heart failure; PA
=
are in
pulmonary artery.
paren-
478
these latter measurements as a precise index of left
ventricular contractile function bcause of the
postoperative development of abnormal septal motion
in the majority of the patients. Other variables
45
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30
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I
(J)
z
U)
0
cr.
..
..
(D
z
z
W
.........bPeqb
-.
associated with late deaths from congestive heart
failure were estimated left ventricular mass, left ventricular systolic pressure, cardiac index and heart rate.
Discussion
The results of this prospective study show that the
most striking abnormality in patients with longstanding aortic regurgitation was left ventricular
dilatation, manifested by increases in both the enddiastolic and end-systolic dimensions of the left ventricle. Left ventricular fractional shortening was normal
in many patients, but occasionally was reduced
markedly. These findings are consistent with previous
angiographic3 10, 22-26 and echocardiographic27-3'
studies. The aorta and left atrium also were dilated.
After replacement of the aortic valve, the internal
dimensions of the left ventricle decreased in nearly
every patient.25' 27, 291, 31 In contrast, left ventricular
-
co0000
25
80
20
E
E
z
70h
0
0
0
0
0
151-
0
0
-j
0
8
0
W
0
601-
n
z
z
50
U)
z
CD
0
W
10o
LL
Ccc
0
r-
00
0
:D
00
VOL 61, No 3, MARCH 1980
CIRCULATION
5
5-
40
0
..............
er
30
.............
LATE
DEATHS DEATHS DEATHS
CABG, MIQ (CHF)
LATE
OP
L
sudden
z
H
W
LL
1
a
ALIVE
I
j
LW
11
20
_J
0-
FIGURE 5. Preoperative left ventricular fractional shortening. The 35 patients who are known to be alive (32 patients)
or lost to follow-up (three patients) are shown in the far left
column (open symbols). The three patients who died at
operation (OP) are shown in the left-middle column, the
eight who died late of congestive heart failure (CHF) are
shown in the far right column, and the three whose late
deaths are unrelated to CHF are shown in the right-middle
column (filled symbols). The patients with coronary artery
disease are identified by a diagonal line, including the patient
who died during a subsequent coronary bypass operation
(CA BG) and the patient who died of an acute myocardial infarction (MI). The normal range is shown by the stippled
legend to figure Sfor a description of the four patient groups
area.
and abbreviations.
0~
ALIVE
LATE
LATE
OP
DEATHS DEATHS DEATHS
CABG, M1 (CHF)
L sudden]
FIGURE 6. Preoperative left ventricular end-systolic
dimension is shown for the same 49 patients in figure 5. See
VALVE REPLACEMENT IN
PREOP
AR/IHenry et al.
6 MOS POSTOP
479
FOLLOW UP
8/17 (47%)
STILL ALIVE
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
9/17 (53%)
DEAD
FIGURE 7. Diagram of the follow-up experience in 17 patients with a preoperative left ventricular endsystolic dimension (L VDS) > 55 mm. % FS = left ventricular fractional shortening; CHF = congestive
heart failure.
wall thickness did not change appreciably after operation. Estimated left ventricular mass decreased in
nearly every patient as a result of the decrease in left
ventricular internal dimension, but rarely returned to
normal. Serial evaluation of the left ventricle after
operation revealed that most of the changes in the left
ventricular internal dimensions occurred early after
operation. In fact, when the left ventricular enddiastolic dimension failed to decrease significantly
(i.e., 1 1 mm or more) by the time of early study (8-22
days) after operation, patients either died in the
perioperative period or had evidence of myocardial
damage by electrocardiography or contrast angi-
ography.
Echocardiographic evaluation of the size and function of the left ventricle is potentially problematic.
One problem involves inferring overall size and function of the left ventricle from measurements made at
its base. Five patients in the present series had an area
of ventricular dyskinesia noted on cineangiograms
before operation. However, both echocardiographic
and angiographic assessments indicated good left ventricular function in these five patients. A few patients
developed new ventricular dyskinesia after operation,
but, most patients had symmetrical ventricular contraction both before and after operation (except for a
small region of akinesia postoperatively at the site of
the apical vent).
Another problem is that the markedly dilated ventricle is more spherical than normal,23 and measurements of ventricular size at the tip of the mitral leaflets
therefore yield different values than measurements obtained below the tips. In the present study, assessment
of the size and function of the left ventricle was standardized by making measurements when the ultrasound beam was passing through the left ventricle
below the tips of the mitral leaflets. Also, the T-scan
technique'7 was used in order to identify the maximum
left ventricular end-diastolic dimension. By using the
largest measurement, variations in heart size due to
respiration were minimized.32
Estimation of left ventricular mass from measurements at the base of the heart also contains many
sources of error. The changes in mass reported in this
study, however, are similar to those reported by Kennedy et al.25 and Pantely et al.26 using angiographic
methods.
Nonetheless, preoperative echocardiographic
evaluation of symptomatic patients with aortic
regurgitation identifies factors strongly associated
with death after aortic valve replacement. For example, echocardiographic assessment of left ventricular
fractional shortening and end-systolic dimension identifies patients at high risk of developing congestive
heart failure and dying after operation despite
successful valve replacement. The high-risk group is
identified by preoperative values of left ventricular
fractional shortening less than 25% and left ventricular end-systolic dimension greater than 55 mm
(figs. 9 and 10). Nine of 13 patients (69%) who fell into
this group preoperatively either died at operation or
late postoperatively of congestive heart failure. These
associations support previous suggestions that late
deaths due to congestive heart failure after successful
operation in symptomatic patients with aortic
regurgitation result from left ventricular systolic
480
CI RCULATION
VOL 61, No 3, MARCH 1980
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
TABLE 4. Seventeen Patients with Preoperative Left Ventricutar Systolic Dimension > 55 mm
Preoperative data
LVD
LVD
Age
(D)
(S)
FS
LVEDP
Valve
Pt
(years)
Sex
CAD
(mm)
(mm)
(mm Hg)
size and type
(%)
0
m
1
36
90
26
80
11
12A, 2320 SE
m
28
0
2
85
75
12
33
12, 2320 SE
0
84
3
72
M
14
29
33
12, 2320 SE
M
4
94
34
0
70
26
23
11, 2320 SE
0
83
69
5
M
50
17
28
25 mm, BSh
m
6
64
0
85
67
21
40
9, 2400 SE
7
51
M
79
65
+
40
18
25 mm, porciine
F
56
0
72
64
8
26
23 mm, porcine
11
62
9
0
76
M
64
16
18
10, 2400 SE
46
0
10
88
63
28
M
20
27 mm, porcine
F
11
29
0
60
25
80
18
1OA, 2320 SE
61
0
75
12
59
21
M
20
10, 2320 SE
m
0
60
71
13
17
59
35
10, 2320 SE
14
26
0
M
59
26
80
40
10, 2400 SE
0
M
43
75
59
21
15
26
10, 2400 SE
16
56
74
56
M
24
+
45
10, 2400 SE
m
0
56
69
17
65
19
36
IIA, 2320 SE
*Myocardial damage at operation (see text).
Abbreviations: IS = iced saline; CP = coronary perfusion; SE Starr-Edward prosthesis; BSh = Bjork-Shiley prosthesis;
LVD = left ventricular dimension at end-diastole (D) and end-systole (S); FS = fractional shortening; CAD - coronary artery
disease; CHF = congestive heart failure; LVEDP = left ventricular end-diastolic pressure; + - present; 0 = absent.
dysfunction that had developed before operation
because of the long-standing and severe left ventricular volume overload. Preoperative diastolic
dimension of the left ventricle is also associated with
late death from congestive heart failure, but it is not as
sensitive a predictor as measurements of left ventricular systolic size and function.
The end-systolic dimension and the degree of
systolic shortening of the left ventricle were both good
measurements for predicting late deaths due to congestive heart failure. These measurements were closely
associated (fig. 9) and both reflect the systolic function
of the left ventricle. The left ventricular end-systolic
dimension alone is a less powerful preoperative predictor than it is when combined with fractional
shortening (53% of congestive failure deaths when
end-systolic dimension exceeded 55 mm vs 69% when
end-systolic dimension exceeded 55 mm and fractional
shortening was less than 25%).
All patients operated upon in this series had either
severe dyspnea on exertion, angina, syncope or
evidence of overt left ventricular failure (orthopnea,
paroxysmal nocturnal dyspnea or one or more
episodes of pulmonary edema). Hence, while we have
shown that several echocardiographically derived indices are predictive of late death due to congestive
heart failure in patients with moderate-to-severe
symptoms, different results might be found in patients
with echocardiographic evidence of severe left ventricular dysfunction who were operated upon with no
symptoms or with mild symptoms. Because the
patients in this series had long-standing aortic
regurgitation, our results are not applicable to the
patient with acute aortic regurgitation.
As there were only three operative deaths, a
statistical analysis of operative mortality was not performed. However, two of the three patients who died
at operation had a left ventricular fractional shortening less than 25% and a left ventricular dimension at
end-systole greater than 55 mm. Moreover, it appears
that the large and poorly functioning left ventricle
may be more susceptible to operative damage.
Preoperative left ventricular fractional shortening was
less than 25% and end-systolic dimension was greater
than 55 mm in five of the nine patients with operative
damage, as evidenced by electrocardiographic
evidence of myocardial infarction, new postoperative
wall motion abnormalities or low output deaths. Only
one of these nine patients had coronary artery disease.
Echocardiographic assessment of global left ventricular systolic function after operation is subject to
additional sources of potential error because of the
development of abnormal septal motion.27 It is clear,
however, that the diastolic size of the left ventricle at
6-month postoperative study was even more strongly
associated with late congestive heart failure deaths
than was the preoperative value (fig. 8). Thus, severe
ventricular dilatation that persisted after technically
successful valve replacement identified patients at high
risk of late death from congestive heart failure.
Moreover, despite the questionable relationship
between postoperative left ventricular fractional
shortening and actual left ventricular systolic function
(because of abnormal septal motion), the post-
VALVE REPLACEMENT IN AR/Henry et al.
481
TABLE 4. (Continued)
Myocardial
preservation
IS/CP
IS/CP
CP
IS/CP
CP
IS/CP
CP
CP
IS/CP
CP
CP
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
IS
CP
CP
CP
IS/CP
CP
LVD
(D)
(mm)
81
90
70
71
50
6-month postoperative data
Aortic
gradient
LV
FS
(mm Hg)
damage*
(%)
10
10
0
49
LVD
(S)
(mm)
73
83
61
54
32
33
56
54
80
36
36
72
36
33
10
0
10
20
65
54
62
74
57
43
49
64
12
20
21
27
0
10
0
8
13
28
37
33
14
operative left ventricular fractional shortening and
end-systolic dimension were also valuable in identifying patients at high risk of late death from congestive heart failure. Hemodynamic data indicated that
the left ventricular systolic pressure and the cardiac
index were significantly reduced at the 6-month
postoperative study in patients who died late after
operation of congestive heart failure. Thus, at the 6month postoperative study, patients whose subsequent deaths were related to congestive heart failure
had large, poorly contracting left ventricles that
appeared to have an impaired ability to generate
pressure and stroke volume.
The presence or absence of coronary artery disease
was not significantly associated with mortality,
perhaps in part because only 10 patients had coexistent coronary artery disease. Of these 10, four had
saphenous vein bypass grafts. Thus, the number of
patients who had valve replacement and unoperated
coronary artery disease is too small to draw meaningful conclusions.
In summary, the results of this study show that
echocardiography provides preoperative data that can
be used to predict the likelihood of a good or poor
FIGURE 8. Left ventricular end-diastolic dimension in the
39 patients with echocardiographic nseasurements before
and 6 months after operation. Large open circles with
horizontal bars indicate mean values. See legend tofigure 5
for a description of the three patient groups. Two patients
died from congestive heart failure (CHF) before
postoperative study. Their preoperative data are shown
(open circles in far right column) but not included in the
mean. MI = myocardial infarction; CABG = coronary
artery bypass graft.
7
12
5
0
25
-
0
0
0
0
0
0
0
0
0
0
+
0
0
+
+
0
LVEDP
(mm Hg)
10
30
8
8
10
28
4
22
23
12
9
9
10
Follow-up
Died (CHF) 42 mo
Died (CHF) 10 mo
Died (CHF) 37 mo
Alive 27 mo
Alive 20 mo
Died (CHF) 5 mo
Alive 22 mo
Died (CHF) 5 mo
Died (operative)
Alive 20 mo
Alive 29 mo
Died (CHF) 18 mo
Died (operative)
Alive 67 mo
Alive 26 mo
Died (CHF) 34 mo
Alive 72 mo
EFFECT OF OPERATION ON LEFT VENTRICULAR
DIMENSION AT END-DIASTOLE
90
80
- 70
z
0
.XL
D 60
z
0
uzC4O
w 5C
r
S
40
Uc
> ,
J
20
10
0
PREOP POSTOP PREOP POSTOP PREOP POSTOP
LATE DEATHS LATE DEATHS
ALIVE
CABG, MI,]
L sudden J
[CHFI
CIRCULATION
482
VOL 61, No 3, MARCH 1980
AORTIC REGURGITATION
r
60
Late non CHF j2
*'
Late CHF
*
OP Death
Still Alive0
z
LL
I.)
ui
50 -
Normal Range
z
(D
z
e
40
High Risk
I
30
e-
20
e-
r
z
0
0.
0
, ........
LL-
-1
0~
. .
-----
..
...
--
c 'd
CLU 10 H
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
1..
20
.-
:
::0--- ...........:
-:-: :::.. : ::---y
- --
60
70
50
30
40
PREOP LV DIMENSION (SYSTOLE) IN MILLIMETERS
result after operation in symptomatic patients with
aortic regurgitation; the systolic size and function of
the heart appear to be the most powerful predictors.
Specifically, when the left ventricular percent fracAORTIC REGURGITATION
100
'
()
z
LVD (SYS) <55mm
(excluding CAD deaths)
80
LVD (SYS)<55mr
>
(all deaths)
zn
ALL PATIENTS
(all deaths)
n
z
60
--
----
..
FIGURE 9. Plot of preoperative left ventricular (LV) fractional shortening (vertical
axis) vs preoperative L V end-systolic
dimension (horizontal axis). The elliptically
shaped stippled area indicates the 95% confidence region for normal subjects computed
from our older normal data.t.5 The high-risk
area, also stippled, is the region in which the
left ventricular end-systolic dimension is
> 55 mm and the fractional shortening is
< 25%. Operative (OP) deaths, late deaths
from congestive heart failure (CHF) and
late deaths not related to congestive heart
failure (non-CHF) are indicated.
---
80
tional shortening is less than 25%, and the internal
dimension of the left ventricle at end-systole is greater
than 55 mm, the chances of suffering perioperative
myocardial damage appear to be increased, and the
risk of developing congestive heart failure and dying
several months to years after operation is high. As a
result of this study and follow-up data obtained in initially asymptomatic patients with aortic regurgitation
(and reported in a separate manuscript33), we have
changed our approach to the patient with aortic
regurgitation and now recommend operation not only
to symptomatic patients, but also to asymptomatic
patients whom we believe are at high risk because of
severe left ventricular systolic dysfunction.33
C:
LL
0
Acknowledgment
40
z
cc
1LI
20
1
2
3
4
5
TIME FOLLOWING OPERATION IN YEARS
FIGURE 10. Plot of the percentage of patients surviving
after operation (vertical axis) vs time after operation
(horizontal axis) for the 49 patients in the present study.
Survival curves calculated using the method of Kaplan and
MeierP4 are shown for patients with left ventricular endsystolic dimension (LVD[SYSJ) 55 mm and those with
L VD(SYS) < 55 mm. These two curves were different from
each other at a statistical significance of p = 0.006. Two
patients died late from complications of coronary artery disease (CAD) and both had end-systolic dimensions < 55 mm.
A third survival curve is shown with these deaths excluded.
This survival curve is different from the survival curve of
55 mm at a p
patients with an end-systolic dimension
value of 0.0009. Vertical bars indicate the SEE for the curves.
The survival curve for the entire patient group is shown by
the dashed line.
The authors acknowledge the excellent technical assistance of
Cora Burn, Estelle Cohen and Joyce McKay, who performed the
echocardiographic studies. The dedication of Erica Britain in
assisting with the statistical analysis of the data has been invaluable
to the completion of the study. The authors also greatly appreciate
the assistance of Exa Murray, who typed the manuscript. Also, the
authors acknowledge the important contributions of several
previous members of the staff of the National Heart, Lung, and
Blood Institute, including Drs. Chester E. Clark, David M. Conkle,
D. Luke Glancy, Leonard B. Grauer, Samuel B. Itscoitz, Lawrence
L. Michaelis, and Richard Shephard.
References
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performance following correction of free aortic regurgitation.
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2. Goldschlager N, Pfeifer J, Cohn K, Popper R, Seizer A: The
natural history of aortic regurgitation: a clinical and
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3. Cohn PF, Gorlin R, Cohn LH, Collins JJ Jr: Left ventricular
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1974
4. Isom OW, Dembrow JM, Glassman E, Pasternack BS, Sackler
JP, Spencer FC: Factors influencing long-term survival after
VALVE REPLACEMENT IN AR/Henry et al.
5.
6.
7.
8.
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Selzer A: Cardiac valve replacement: an unanswered question.
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Henry WL, Ware J, Gardin JM, Hepner S, McKay J, Weiner
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Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy (ASH): echocardiographic identification of the
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483
19. Troy BL, Pombo J, Rackley CE: Measurement of left ventricular wall thickness and mass by echocardiography. Circulation 45: 602, 1972
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New York, Hafner Publishing Co, 1961
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26. Pantely G, Morton M, Rahimtoola SH: Effects of successful
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W L Henry, R O Bonow, J S Borer, J H Ware, K M Kent, D R Redwood, C L McIntosh, A G
Morrow and S E Epstein
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Circulation. 1980;61:471-483
doi: 10.1161/01.CIR.61.3.471
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