Download Prognosis of Patients with Acute Pulmonary After Acute

Prognosis of Patients with Acute Pulmonary
Edema and Normal Ejection Fraction
After Acute Myocardial Infarction
MARY ANN WARNOWICZ, D.O., HOWARD PARKER, M.D.,
AND
MELVIN D. CHEITLIN, M.D.
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SUMMARY To assess the prognostic importance of resting left ventricular function in survivors of acute
myocardial infarction with pulmonary edema, we retrospectively identified 39 consecutive patients who
presented with acute pulmonary edema and myocardial infarction. Sixteen patients had radionuclide
ejection fractions 10 2 days postinfarction of > 0.45 (group A, mean 0.55 0.06), and 23 patients had
ejection fractions S 0.45 (group B, 0.32 + 0.06). There were no significant differences between the two
groups for age or sex, but group A patients had a significantly greater incidence of first myocardial
infarction predominantly inferior in location. The calculated stroke work index during the acute event was
significantly greater in group A than in group B (33.4 + 2.4 vs 23.4 + 2.0) (p < 0.05). During a follow-up of
9 3 months, mortality was not significantly different between the two groups: Four (25%) died in group A
and seven (30%) died in group B. In addition, eight patients (50%) in group A were hospitalized for
recurrent angina, new myocardial infarction or recurrent pulmonary edema, compared with 11 (48%) in
group B (NS). Three deaths in group A were preceded by infarction of the anterior wall of the left ventricle,
confirmed at autopsy, and two nonfatal infarctions were anterior by electrocardiography. Four patients in
group A had coronary arteriography performed during the follow-up period because of unstable angina,
and all had significant (Dr 70% stenosis) three-vessel disease and two had left main coronary artery disease.
Therefore, the predischarge ejection fraction did not predict prognosis for this group of patients.
Patients with acute pulmonary edema in the course of myocardial infarction form a high-risk group
despite good resting left ventricular function at discharge. They have a significant incidence of recurrent
myocardial infarction and death and, because they have good residual left ventricular function, are
excellent candidates for surgical intervention.
816
infarction generally predicts a good prognosis,' 1 we
postulated that patients with pulmonary edema whose
predischarge ejection fraction was within normal limits or only mildly depressed should have a good
prognosis.
Accordingly, we retrospectively evaluated the clinical course and determined the morbidity and mortality
of 39 consecutive patients with acute myocardial infarction and pulmonary edema who survived for at
least 8 days in the hospital and underwent radionuclide
angiocardiography.
THE EARLY and late prognoses for acute myocardial
infarction are adversely affected by the occurrence of
left ventricular failure. 1-3 The manifestation of acute
pulmonary edema is particularly lethal.' 4, 10 Presumably, pulmonary edema reflects the severity and extent
of acute and chronic abnormalities in left ventricular
contraction. Thus, pulmonary edema is more common
in patients with a history of infarction and in patients
with large initial infarctions, which are usually anterior
wall infarctions. It is not surprising that in a study by
Schelbert et al.,14 measuring radionuclide ejection
fractions after myocardial infarction, patients with pulmonary edema had severely depressed ejection fractions and no patient had a normal ejection fraction (>
0.52).
Since January 1980, we have routinely obtained a
predischarge radionuclide angiocardiogram for all survivors of acute myocardial infarction. It became apparent that certain patients who had manifested pulmonary edema had an unexpectedly normal or only mildly
depressed ejection fraction at the time of discharge.
This was distinctly in contrast to other reports.14' 11
Possible explanations were either that acute transient
abnormalities had occurred in left ventricular function
or that acute preload or afterload burdens had existed
early after the infarction. Because a good left ventricular ejection fraction at discharge after a myocardial
Methods
Patients
Between January 1980 and March 1981, 39 survivors of acute myocardial infarction had overt pulmonary edema (Killip class IHI)'7 during the early postin-
farction period and had predischarge ejection fractions
determined by radionuclide angiocardiography. They
were 45-83 years old (mean 64.9 years). Twenty-eight
patients (72%) were men. The ejection fractions were
determined 10 ± 2 days after infarction.
Acute myocardial infarction was diagnosed when at
least two of the following were present: a history of
typical prolonged chest pain, evolution of electrocardiographic changes of acute transmural infarction or
ST-T changes and characteristic serial elevations of
serum enzymes (creatine kinase and MB fraction or
lactic dehydrogenase isoenzymes).
Equilibrium-gated radionuclide angiocardiography
was performed after injection of 24 mCi of 99mTc
tagged to human serum albumin. Technetium albumin
was the sole agent used for the equilibrium radionuclide angiocardiogram in the course of this study. La-
From the Medical Service, San Francisco General Hospital Medical
Center, and the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California.
Address for correspondence: Mary Ann Warnowicz, D. 0., 5G 1 Cardiology, San Francisco General Hospital, San Francisco.
Received April 9, 1982; revision accepted July 29, 1982.
Circulation 67, No. 2, 1983.
330
PROGNOSIS AFTER AMI/Warnowicz et al.
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beling of red blood cells in vivo has now largely replaced this technique. Despite somewhat greater liver
and spleen activity, the usual background levels subtracted in our laboratory are not significantly greater
than those for in vivo labeled red blood cells. Although
measurement of the distribution of technetium indicates a highly variable proportion in hydrolized form,
the ratio of free to bound is more constant and, in most
batches, averaged 0.05 (range 0.003-0.20). Correlation with contrast angiography in our laboratory has
been performed with -the human serum albumin technique and the results of the latter are consistently higher, but the correlation coefficient is good (0.82). Images were obtained in multiple projections, including
at least the 450 left anterior oblique, anterior and 300
right anterior oblique, using a General Electric portable scintillation camera with a "MED III" computer.
After equilibration of the radionuclide in the blood
pool, 14 frames of 128 X 128 matrix image data,
gated by the R wave of the ECG, were acquired from
the first three-fourths of the cardiac cycle, acquiring
200,000 counts/frame, which required 5-7 minutes
per projection.
Left ventricular ejection fraction was measured with
the Muge program, which uses a semiautomatic edgefinding algorithm to place a region of interest on the
borders of the left ventricle in each of the 14 frames of
the left anterior oblique projection. The program also
places a background region of interest over the nearby
left lung, subtracts background from each frame and
uses the curve of corrected count rate over the left
ventricle to compute global left ventricular ejection
fraction. Operator intervention was rarely necessary
except, at times, in the case of a very large ventricle.
Inter- and intraoperator tests of reproducibility of the
ejection fraction by this method in our laboratory has
been excellent. The method is essentially that of Maddahi et al.'8
The clinical records were reviewed for site of infarction, history of myocardial infarction and hemodynamic measurements performed at the time of the acute
infarction. The presence or absence of a regurgitant
murmur was noted. Patients who had clinically significant mitral or aortic regurgitation were not included in
the study.
Twenty-four of the 39 patients had hemodynamic
measurements made within 12 hours of admission.
Pulmonary arterial wedge pressure was measured
through a flow-directed, balloon-tipped catheter19 and
cardiac output by thermodilution.20
The patients were divided into two groups, based on
ejection fraction. Group A patients had an ejection
fraction > 0.45, and group B patients an ejection fraction 0.45. During the late follow-up period (mean 9
months, range 1-15 months), a new event was defined
as death, reinfarction, recurrent angina (New York
Heart Association functional class III or IV) or hospital
admission for recurrent acute pulmonary edema.
Late follow-up data were obtained from clinic and
hospital records in 36 of 39 patients; three patients
were followed by telephone interview only. All pa,
331
tients in groups A and B were managed medically, and
cardiac catheterization or coronary arteriography was
not performed unless unstable angina developed during follow-up.
Statistical analysis was performed using the t test for
unpaired data or the chi-square method. The Z test was
used for differences in proportions. Survival was analyzed by life-table method.2' Results are expressed as
mean ± SD.
Results
Ejection Fractions
In the 39 patients, the ejection fraction obtained 10
± 2 days after infarction averaged 0.41 ± 0.13 (fig.
1). Sixteen patients had ejection fractions > 0.45 and
constitute group A (mean ejection fraction 0.55 ±
0.06). Twenty-three patients had ejection fractions S
0.45 and constitute group B (mean ejection fraction
0.32 ± 0.06). Eleven patients in group A had normal
ejection fractions (> 0.52).
Clinical and Hemodynamic Findings (table 1)
Age or sex ratios did not differ significantly between
groups A and B. Three patients in group A and six in
group B had nonholosystolic murmurs at the' apex. No
patient was considered to have clinically significant
mitral regurgitation. The two groups did not differ
significantly with respect to a history of hypertension.
However, there were significant differences between
the two groups with respect to the site of myocardial
infarction and history of myocardial infarction. Group
.7 r
0*
.6 V
z
0
0
0*
A
0,
0@0
.5
-
1-
U
0O0
@0
z .41
0
0
00
*0 0 0
00 0
0 0 00
S
-
U
LUJ
1-J
.3 F
0*
.2 1
GROUP (®)
0.55 + .06 S.D.
GROUP ®
0.32 ±.06 S.D.
FIGURE 1. Ejection fractions of both groups. LV = left
ventricular.
332
CIRCULATION
TABLE 1. ClinicalandHemodynamicCharacteristicsofPatients
with Myocardial Infarction and Acute Pulmonary Edema
Significance
of
Group A
Group B
Variable
(EF > 0.45) (EF S 0.45) difference
n
n = 16
23
Clinical
NS
62.8±9.4 66.4±10.6
Age (years)
11:5
17:6
Sex (male:female)
NS
Location of
infarction
0
Anterior
8
1
2
Anteroseptal
0.005
11
2
Inferior
4
11
Subendocardial
History of
3 (19%)
19 (83%) p < 0.005
infarction
n - 15
n = 9
Hemodynamic
(obtained 6 ± 1.4
hours after
admission)
Mean pulmonary
capillary wedge
NS
pressure (mm Hg) 16.8 ±2.0 17.4 ± 2.2
Mean arterial
96± 10
NS
pressure (mm Hg) 104± 12
Stroke work index
33.4± 2.4 23.4 ± 2.0 p < 0.005
(g-mIm2)
Abbreviation: EF = ejection fraction.
p
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B had a significantly greater incidence of anterior and
subendocardial infarctions, whereas group A predominantly had inferior infarctions. Group B also had a
significantly higher percentage of previous myocardial
infarctions compared with group A. Hemodynamic
measurements were obtained in nine of 16 patients in
group A and 15 of 23 patients in group B. Acute
pulmonary capillary wedge pressure and mean arterial
pressures recorded on admission did not differ significantly. However, the calculated stroke work index was
significantly greater in group A than in group B.
Drug therapy in both groups was initiated with digitalis, diuretics or antihypertensive agents alone or in
combination. Two patients in group A and three patients in group B required early support of blood pressure with pressor agents. Initial hemodynamic values
tended to improve in both groups after therapy but
were not uniformly recorded. In general, patients in
group A responded rapidly to therapy; 20 patients in
group B were taking digitalis at the time of discharge,
whereas only three in group A were receiving digitalis
therapy.
TABLE 2. New Events in Follow-up Period
Group A
(n = 16)
Events
(%)
Death
4 (25)
New myocardial infarction
5 (31)
Recurrent angina
8 (50)
Recurrent pulmonary edema
6 (38)
During a follow-up of 9 ± 3 months, occurrence of
new myocardial events did not differ significantly between the groups (table 2), and survival probability
was similar for the two groups (fig. 2).
Group A
Four patients in group A died. In three, death was
Group B
= 23)
(%)
7 (30)
6 (26)
4 (17)
10 (43)
(n
preceded by clinically documented anterior myocardial infarctions. Autopsies confirmed the recent infarctions. One death was an out-of-hospital sudden death.
Five patients had new myocardial infarctions, and in
three the infarctions preceded death. Recurrent angina
was the most frequent reason for hospitalization (50%)
and preceded infarction and death in two patients. Four
patients had cardiac catheterization and coronary arteriography in the follow-up period because of severe
recurrent angina. All had significant (Da 70% stenosis)
three-vessel disease and two also had left main coronary artery disease. One patient was considered not to
be a candidate for coronary bypass surgery because of
diffuse distal vessel disease and one patient refused
surgery; two others eventually had surgery. One of the
patients who had surgery had persistent angina in the
postoperative period after development of a new anterior myocardial infarction, and died.
Group B
Within 9 ± 3 months after the index episode, 78%
of the patients in group B with poor ejection fractions
had had a new event, including seven deaths (30%).
All deaths were attributed to cardiovascular disease;
two were sudden. In two cases, a documented new
myocardial infarction had occurred before death.
Of nonfatal events, recurrent pulmonary edema was
the most frequent, with 43% of the group requiring
another hospitalization. New myocardial infarctions
occurred in four (17%), two of which preceded death.
Cumulative Proportion Surviving
1.00
1
.-.-1---A
* -6
.7501
z
a~~~~~~
_~~~~~
-_ An
Ci)
z
0
0
0
a-
Late Follow-up (table 2)
VOL 67, No 2, FEBRUARY 1983
.5001
.250 _
(16,23) (15,21)
0
(4, 7J
(7,12)
11,16)
1l
l
2
4
8
6
MONTHS
10
12
14
FIGURE 2. Life-table survivorship. Numbers in parenthesis
represent the number ofpatients in group A andB, respectively.
333
PROGNOSIS AFTER AMI/Warnowicz et al.
Angina pectoris alone as a reason for readmission to
the hospital was least common (17%). Five patients
underwent catheterization in the follow-up period because of severe recurrent angina or left ventricular
failure and two eventually had surgery.
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Discussion
The patients in group A were remarkable in that they
had unexpectedly normal or only mildly depressed
,ejection fractions (0.55 ± 0.06). This was in contrast
to the study by Schelbert et al.,14 which showed that
patients who had manifested overt pulmonary edema
in the course of acute myocardial infarction had ejection fractions that were severely depressed (0.33 +
0.07). In their study, however, the ejection fractions
were measured less than 5 days after infarction, compared with more than 10 days in our study. Also,
Schelbert et al. showed serial improvement in ejection
fractions for 27 patients (54%) during the early postinfarction period. Therefore, the higher mean ejection
fraction in our group could reflect the serial improvement described by Schelbert et al., although their data
did not reveal whether the subgroup of patients with
overt pulmonary edema had a rate of improvement
similar to that of the whole group.
A significant number of survivors of acute myocardial infarction with pulmonary edema have good residual left ventricular function. Those who have good
residual function (group A) are more likely to have had
their first myocardial infarction, predominantly inferior in location.
Our patients could have had severe transient left
ventricular dysfunction earlier in the clinical course of
infarction, as suggested by the serial studies of Schelbert et al.14 The patients in our group were not studied
serially, but serial radionuclide ejection fractions were
performed in two similar patients with acute inferior
myocardial infarction and pulmonary edema. These
two patients showed marked improvement between the
acute measurement of left ventricular ejection fraction
(0.32 and 0.38 12 hours after admission) and the late
value (0.52 and 0.54 10 days after admission).
The possibility that acute mitral insufficiency could
account entirely for this disparity in acute clinical presentation and the predischarge ejection fraction is unlikely. The incidence of regurgitation murmurs was no
greater in group B than in group A, and no patient with
clinically significant regurgitation was included. Another explanation for transient myocardial dysfunction
might be acute impedance or afterload burden, either
because of increased sympathetic tone or acute hypertension. Acute afterload burdens are possible because
group A had a greater mean blood pressure, but individual variation was great. In addition, group B had a
significantly lower stroke work index that probably
indicated more depressed left ventricular function.
The late prognosis after acute myocardial infarction
for any individual patient is influenced by many clinical and laboratory features. However, the left ventricular ejection fraction is a powerful predictor of shortand long-term survival.8' 14, 16 Nelson et al.8 found that
ejection fraction was a more discriminant prognosticator than the severity of angiocardiographic coronary
disease or the clinical functional class. Schulze et al.22
found that survivors of acute myocardial infarction
with a predischarge radionuclide ejection fraction >
0.40 had an overall good prognosis. The history of first
myocardial infarction, inferior location and good residual left ventricular function in group A patients
should therefore characterize a low-risk subgroup of
survivors of acute myocardial infarction, even if they
have a history of pulmonary edema. However, our
follow-up of patients showed that morbidity and mortality were similarly high for those with normal and
low ejection fractions. More recently, some investigators have shown that the resting left ventricular ejection fraction alone does not completely predict outcome. Corbett et al.23 used exercise radionuclide
angiograms to reflect permanently damaged myocardium as well as "myocardium at risk" during exercise.
The exercise measurements proved to be better prognostic indicators. In addition, Silverman et al.24 studied 42 patients within 15 hours of myocardial infarction with thallium-201 scintigraphy and found that this
early measurement of the perfusion defect was a significant prognostic indicator. This early study was
considered to reflect the permanently injured myocardium as well as that "at risk. " In our study, the pulmonary edema may also be reflecting "myocardium at
risk." Three of the patients in group A who died had
ischemia and eventual infarction of the anterior wall of
the left ventricle; two nonfatal infarctions were also
anterior. In no case was arrhythmia a primary cause of
death. Thus, one explanation for the pulmonary edema
occurring with the original inferior infarction is that
ischemia of the anterior wall with consequent poor
function had also occurred but resolved.
These data suggest that patients with myocardial
infarction and pulmonary edema form a high-risk
group despite good resting left ventricular function.
They have severe coronary artery disease and in a
medically treated group have a significant incidence of
recurrent transmural myocardial infarction and death.
The identification of this high-risk subgroup of medically managed patients with good residual left ventricular function is particularly important because they are
excellent candidates for surgical intervention.25
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Prognosis of patients with acute pulmonary edema and normal ejection fraction after
acute myocardial infarction.
M A Warnowicz, H Parker and M D Cheitlin
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Circulation. 1983;67:330-334
doi: 10.1161/01.CIR.67.2.330
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