Download Value of left ventricular ejection fraction during exercise in

1002
J AM COLL CARDIOL
1983;1(4).1002-10
Value of Left Ventricular Ejection Fraction During Exercise in
Predicting the Extent of Coronary Artery Disease
NICHOLAS L. DePACE, MD, ABDULMASSIH S. ISKANDRIAN, MD, FACC,
A-HAMID HAKKI, MD, FACC, SALLY A. KANE, RN, BERNARD L. SEGAL, MD, FACC
Philadelphia, Pennsylvania
To determine the relation between left ventricular performance during exercise and the extent of coronary
artery disease, the results of exercise radionuclide ,:entriculography were analyzed in 65 patients who also
underwent cardiac catheterization. A scoring system was
used to quantitate the extent of coronary artery disease.
This system takes into account the number and site of
stenoses of the major coronary vesselsand their secondary branches. The conventional method of interpreting
the coronary angiograms indicated that 26 patients had
significant coronary artery disease (defined as 70% or
more narrowing of luminal diameter) of one vessel, 21
had multivessel disease and 18 had no significant coronary artery disease.
Although the exercise left ventricular ejection fraction was significantly higher in patients with no coronary
artery disease than in patients with one or multivessel
disease (probability [p] < 0.001), there was considerable
overlap among the three groups. With the scoring system, a good correlation was found between the coronary
Coronary arteriography for detecting coronary artery narrowing is useful in defining regions of potential ischemia.
Because anatomic information may not provide an accurate
physiologic assessment of the functional importance of coronary stenosis, regional and global left ventricular function
during stress has emerged as a complementary aspect to
arteriography (I). Radionuclide angiography permits noninvasive evaluation of left ventricular function at rest and
during exercise, and detection of functional abnormalities
in patients with coronary artery disease (2-5). The magnitude of exercise-induced left ventricular dysfunction has
From the Likoff Cardiovascular Institute of Hahnemann University and
Hospital, Philadelphia, Pennsylvania. Manscript received August 17, 1982;
revised manuscript received November 16, 1982, accepted November 19,
1982.
Address for reprints: Abdulmassih S. Iskandrian, MD, Likoff Cardiovascular Institute, Hahnemann University and Hospital, 230 North Broad
Street, Philadelphia, Pennsylvania 19102.
© 1983 by the Arnencan College of Cardiology
artery disease score and the exercise left ventricular ejection fraction (r = - 0.70; p < 0.001). If the exercise
heart rate was 130 beats/min or greater or the age of
the patient was 50 years or less, an even better correlation was found (r = - 0.73 and r = - 0.82, respectively). The exerciseejection fraction (but not the change
in ejection fraction, end-diastolic volume and end-systolic volume from rest to exercise) correlated with the
extent of coronary artery disease.
The exercise ejection fraction is the most important
exercise variable that correlates with the extent of coronary artery disease when the latter is assessed quantitatively by a scoring system rather than the conventional
method of reporting coronary angiograms. Younger age
and greater exercise heart rate strengthened the correlation. The change in ejection fraction from rest to exercise is useful in the diagnosis of coronary artery disease, but it was the absolute level of exercise ejection
fraction that predicted the extent of disease.
been correlated with the anatomic extent of disease; patients
having multivessel disease show more deterioration in left
ventricular function during exercise than do patients with
one vessel disease (6).
Considerable individual variation is observed among patients grouped according to the number of stenosed vessels.
Recently, it has been shown that proximal stenotic lesions
in the left anterior descending artery resulted in more pronounced abnormality of left ventricular function during exercise than similar lesions located more distally (7). This
has also been shown with proximal and distal lesions of the
right coronary artery affecting right ventricular function during exercise (8). Individual variation in ventricular performance during exercise may result not only from differences
in location of stenosis but also from variations in collateral
vessels, severity of stenosis, cardiac medications, age, sex,
level of exercise, associated cardiomyopathic and valvular
processes, conditioning and other factors (9). This has been
supported by the individual hemodynamic changes during
0735-1097/83/0401002-9$03.00
J AM COLL CARDIOL
1983;1(4):1002- 10
EXERCISE LEFT VENTRICULAR EJECTION FRACTION
exercise observed in patient groups with a similar anatomic
extent of disease (5) .
In this study , we evaluated left ventricular function at
rest and during exercise, and determined the extent of coronary artery disease by using an angiographically computed
scoring system. We undertook the study to determine which
exercise variables correlate best with the extent of angiographic coronary disease.
Methods
Study patients. Between January 1980 and January 1982, approximately 800 patients underwent exercise testing, of these, 106
consecutive patients had radionuclide angiographic rest and exercise tests within 2 months of cardiac catheterization. Forty-one
of these patients were excluded from this analysis because of
previous cardiac surgery or concomitant valvular or congenital
heart disease or primary cardiomyopathy. The remaining 65 patients formed the study group. Fifty-five patients were studied
before and 10 patients after cardiac catheterization. It is not clear
whether the results of the exercise studies were used in the decisionmaking for subsequent catheterization. Forty-eight patients (73%)
had volumetric determinations in addition to left ventricular ejection fraction at rest and during exercise. There were 59 men and
6 women between 28 and 78 (mean 60.4) years of age.
Coronary arteriography. Left heart catheterization was performed by standard techniques. The coronary arteriograms were
reviewed and interpreted by two experienced cardiologists. The
three major coronary arteries were visualized in multiple projections, and were scored to determine the extent of disease by means
of a modified scoring system (10). Each coronary artery was studied in three segments: proximal, middle and distal; the left main
artery was analyzed separately. The degree of narrowing was scored numerically from I to 5: 1, 25% diameter narrowing; 2, 25
to 49% narrowing; 3, 50 to 74% narrowing; 4,75 to 99% narrowing
and 5, total occlusion. This score was then multiplied by a factor
that takes into consideration the location of disease, that is, 6, left
main; 3, proximal disease; 2, middle and I. distal disease. If a
major diagonal or marginal branch was involved proximally. this
factor was considered to be I and multiplied by the degree of
narrowing. The total score could thus range from 0 (no coronary
disease) to a maximal score of 45 (complete occlusion of all three
vessels). Using the conventional method of reporting coronary
arteriograms. at least 70% luminal diameter narrowing of a coronary vessel was used to diagnose significant coronary artery disease.
Radionuclide angiographic test. We performed radionuclide
angiography with the patient in the upright position at rest and
during exercise, using a variable-load bicycle ergometer (Quinton
Instruments)and acomputerized multicrystalgammacamera (BairdAtomic System-77) equipped with a I inch (2.54 cm) parallel-hole
collimator positioned anterior to the precordium . A 20 gauge polyethylene catheter was inserted into a basilic vein. The radionuclide
angiogram was obtained after administration of 15 millicuries (mCi)
of technetium-99m pertechnetate dissolved in a volume of less
than I cc. Precordial counts were recorded at 50 ms frame intervals
for the rest studies and 25 ms frame intervals for the exercise
studies during the initial pass of the radionuclide through the central
1003
circulation. Exercise was begun at a work load of 200 kpm/min
and increased by 100 kpm/min increments every 1-112 minutes.
The electrocardiogram was continuously monitored and blood
pressure was recorded at 2 minute intervals during exercise and
the recovery period.
Two electrocardiographic leads (eMs and aVFj were monitored constantly (11) . The end points of exercise are defined as
follows: severe angina pectoris. 2 mm or more ST segment depression with or without angina pectoris, excessive fatigue, leg weakness, shortness of breath, hypotension, dizziness and frequent premature ventricular complexes. At the onset of any of these end
points, a second bolus of 15 mCi of technetium-99m pertechnetate
was given and exercise was continued for the 30 seconds required
for data acquisition.
The radionuclide angiograms were analyzed with computer
software incorporated into a multicrystal gamma camera. Left
ventricular ejection fraction , end-diastolic volume and end-systolic
volume were measured according to the method previously described by this and other laboratories (\ 2-17). Validation data for
measuring ejection fraction and volumes have been previously
described by this laboratory (\ 3). A normal response to exercise
in our laboratory is defined as a 5% or greater increase in ejection
fraction.
Regional wall motion was assessed using static images and a
cinematic display of the entire representative cycle. Grading of
three wall segments in the anterior view (anterior. apical, inferior)
was as follows: 4, normal; 3, mild hypokinesia; 2, moderate hypokinesia; I. severe hypokinesia and 0, akinesia or dyskinesia.
Statistical analysis. Differences in clinical characteristics for
the group studied were compared by chi-square analysis or Student' s t test. Individual changes in hemodynamic measurements
from rest to exercise were compared by the paired t test. Standard
regression analysis was used when appropriate. A probability (p)
value of less than 5% was considered significant. Results are expressed as mean values ± standard deviation (SD) when appropriate.
Results
Coronary angiographic and clinical findings. Of the
65 patients who underwent exercise rad ionuclide angiography , 11 ( 17%) had comp letely normal coronary arteries
(coronary artery disease score of 0) and 7 ( I 1%) had coro nary stenos is that did not exceed 70 % of the diameter of a
major coro nary artery (co ronary artery score of 10.5 ± 7 .0 ,
range 1 to 22). Th e co ronary artery score for these 18 patients wa s 4 .2 ± 7.4. The remaining 47 patients had severe
coronary artery disease ( ~ 70% diameter narrowing of at
least one major coronary vessel) . There were 26 patients
(40%) with one ves sel disease (coronary artery disease score
14. 8 ± 3 .90, range 9 to 22) and 2 1 p atients (32%) with
multivessel disea se (coronary artery score 30.4 ± 8 .1, ran ge
18 to 45) . Four of the 2 1 patients with multivessel di sease
had left main coronary artery disease. Eight ( 17%) of the
47 patients (26 with one vessel disease + 2 1 with multivessel disease ) had a documented hi story of myocardial
infarction . The coronary arte ry score for the 65 patients was
16.9 ± 12.2 (range to 45) .
°
1004
J AM
cou, CARDIOl
DePACE ET Al
1983;1(4); 1002-10
Thirty-four patients were in functional class I, 22 in class
II and 9 in class III according to the New York Heart Association classification. Electrocardiographic evidence of
previous transmural infarction (abnormal Q waves) was
present in seven patients. Twenty-eight patients were on
maintenance doses of propranolol at the time of the study.
Rest left ventricular function. The heart rate at rest
was 68 ± 12 beats/min (range 45 to 97). The blood pressure
at rest was 124 ± 19 mm Hg (range 90 to 170). Left
ventricular ejection fraction at rest was 51 ± 12% (range
18 to 73). Neither heart rate nor blood pressure at rest
showed a significant correlation with ejection fraction at
rest. The correlation between rest ejection fraction and coronary artery score was weak (r = -0.35, p < 0.01) (Fig.
1). The end-diastolic volume at rest ranged from 109 to 332
ml, and the end-systolic volume at rest ranged from 37 to
273 ml. The rest ejection fraction, end-diastolic volume and
end-systolic volume for the three subgroups of patients are
shown in Table 1.
Exercise Left Ventricular Function
Of the 65 patients who underwent exercise radionuclide
angiography, exercise was terminated in 27 (42%) because
of a positive exercise electrocardiogram, in 5 (7.5%) because of attainment of at least 85% of predicted maximal
heart rate without chest pain or electrocardiographic changes,
Figure 1. Correlation between rest left ventricular ejection fraction and
coronary artery disease (CAD) score. No propranolol = patients not on
propranolol therapy; propranolol = patients on propranolol therapy.
85
.-
-
n:65
r= -.39
y 57.9 - O.39x
p<O.01
o no propranolol
=
• propranolol
"if.
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CAD Score
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Table 1. Rest and Exercise Left Ventricular Function
In
the
Three Subgroups
No CADt
(n = 18)
CAD score
4.2 ± 7.4
Rest LYEF (%)
56 ± 7
Ex LYEF (%)
66 ± 10
Rest EDY* (ml) 160 ± 26
Ex EDY* (mil 163 ± 19
Rest ESY* (mil 69 ± 16
Ex ESY* (mil
61 ± 15
IYD
(n = 26)
14.8
52
52
156
206
76
113
±
±
±
±
±
±
±
3.9
II
9
56
50
41
77
MYD
(n = 2 I)
30.4
46
42
212
230
118
155
±
±
±
±
±
±
±
8.1
15
II
53
49
68
72
Total
(n = 65)
16.7
51
52
169
201
89
100
±
±
±
±
±
±
±
12.3
13
14
57
50
51
53
'Volumes available for 47 of 65 patients. tNormal coronary artenes or coronary
stenosis not exceeding 70% of the diameter of a major coronary artery.
CAD = coronary artery disease; EDV = end-diastohc volume; ESV = endsystohc volume; Ex = exercise; LVEF = left ventricular ejection fraction: MVD
= multivessel disease, n = number, IVD = one vessel disease
in 28 (43%) because of fatigue, and in 5 (7.5%) because
of chest pain without electrocardiographic changes.
Ejection fraction. Correlation with exercise duration. The duration of exercise was 7.4 ± 3.1 minutes (range
2 to 14.5) for the entire group of patients. There was poor
correlation between rest left ventricular ejection fraction and
exercise duration (r = 0.22, P = not significant [NS]). The
exercise ejection fraction showed a weak correlation with
exercise duration (r = 0.41, P < 0.001). A weak inverse
correlation was also observed between the coronary artery
score and exercise duration (r = -0.37, P < 0.01). There
was no correlation between the change in ejection fraction
(the change in left ventricular ejection fraction from rest to
exercise) and exercise duration. Because the work load was
increased every 1-112 minutes, the peak work load attained
was proportional to the duration of exercise.
The heart rate for the 65 patients at peak exercise was
123 ± 22 beats/min (range 74 to 180). The blood pressure
was 165 ± 31 mm Hg (range 90 to 260), and blood pressureheart rate product was 21 ± 7 x 103 (range 7.5 to 33.8).
Twenty-eight patients (42%) achieved an exercise heart rate
of 130 beats/min or greater.
Correlation with coronary angiographic findings. The
left ventricular ejection fraction at peak exercise ranged from
18 to 86%. There was a weak correlation between the change
in ejection fraction and the ejection fraction at rest (r =
-0.34, P < 0.01) and during exercise (r = 0.46, P <
0.001). The ejection fraction for patients with no coronary
disease increased from 56 ± 7% at rest to 66 ± 10% with
exercise (p < 0.001) for patients with single vessel disease
it was 52 ± 11% at rest and 52 ± 9% with exercise (p =
NS), and for patients with multivessel disease it decreased
from 46 ± 15% at rest to 42 ± 11% during exercise (p =
NS) (Fig. 2, Table I). The exercise ejection fraction was
higher in patients with no coronary disease than in patients
with one vessel disease or multivessel disease (p < 0.00l)
(Fig. 3). An abnormal ejection fraction response to exercise
« 5% increase) was present in 17 (65%) of the 26 patients
J AM COLLCARDIOL
EXERCISE LEFf VENTRICULAR EJECTION FRACTION
1983;1(4):1002-10
with one vessel disease and in 16 (76%) of the 21 patients
with multivessel disease (p == NS).
Five of the 18 patients with normal arteries or mild coronary artery disease had an increase in left ventricular ejection
fraction of less than 5% with exercise. In a separate group
of 20 subjects with low probability of coronary disease who
did not undergo cardiac catheterization, all 20 had a normal
rest ejection fraction (64 ± 7%) and 17 (85%) of the 20
subjects had a 5% or greater increase in ejection fraction
during exercise. The remaining three subjects who failed to
have an increase of 5% or greater in ejection fraction during
exercise had a hyperkinetic left ventricle at rest with a rest
ejection fraction of 70% or greater. The exercise ejection
fraction for the 20 subjects (75 ± 4%) was significantly
higher than the rest ejection fraction (p < 0.001).
Correlation with probability of coronary heart disease. On the basis of clinical evaluation and rest electrocardiograms, the probability of coronary heart disease was
considered high in 32 of the 47 patients with angiographically documented coronary artery disease and was considered intermediate in the remaining 15 patients. An abnormal
rest ejection fraction or abnormal ejection fraction response
to exercise, or both, was present in 30 patients (94%) with
high probability and in 11 patients (73%) with intermediate
probability of coronary artery disease. All 18 patients with
normal coronary angiograms or insignificant coronary artery
disease were thought to have a low probability of coronary
disease, but 5 (28%) of the 18 patients had an abnormal
ejection fraction at rest or abnormal response to exercise.
The rest ejection fraction was normal (2 50%) in 25 of the
47 patients with coronary artery disease; of these patients,
19 had abnormal ejection fraction response to exercise (11
with one vessel and 8 with multivessel disease). The remaining six patients (five with one vessel and one with
multivessel disease) had a normal response to exercise. The
ejection fraction at rest was depressed « 50%) in 22 of the
47 patients with coronary artery disease; of these, 14 had
abnormal response to exercise (6 with one vessel and 8 with
multivessel disease) and 8 had a normal response (4 with
one vessel and 4 with multivessel disease).
Exercise-induced regional wall motion abnormality or an
increase of less than 5% in left ventricular ejection fraction
during exercise was seen in 20 patients (77%) with one
vessel disease, although 20 patients (95%) with multivessel
disease had abnormal rest ejection fraction, abnormal ejection fraction response to exercise, abnormal wall motion at
rest or during exercise or a combination of these findings.
Correlation with coronary artery disease score. The
change in ejection fraction showed a weak correlation with
coronary artery disease score (r > - 0.42, P < 0.001) (Fig.
4). When only the 28 patients with an exercise heart rate
of 130 beats/min or greater were considered, the correlation
was improved (r := -0.59, p < 0.001).
The exercise left ventricular ejection fraction showed a
strong correlation with coronary artery disease score in the
65 patients (r := -0.70; p < 0.001) (Fig. 5A). The correlation was good even in patients on propranolol therapy
(r > - 0.66; P < 0.001). Of the 28 patients with a normal
exercise ejection fraction (2: 55%), only 1 had a coronary
artery disease score of more than 24 points. If exercise
Figure 2, Left ventricular ejection fraction at rest and during exercise in
patients with no coronary artery disease (CAD), patients with one vessel
disease (lVD) and patients with multivessel disease (MVD).
i
C
0
75
.
70
65
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60
0
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Gl
55
.
50
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40
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Gl
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IVO
(n:26)
P:NS
MVO
(n:21)
P:NS
80
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III
LL
NoCAO
(n:18)
p<O.OO1
90
85
45
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35
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20
15
01"
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1
<->
30
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Rest
I
Exercise
I
Rest
1005
I
Exercise
~
I
Rest
~
I
I
Exercise
J AM COLL CARDIOL
1006
DePACE ET Al
1983;1(4)'1002-10
disease was distal in all vessels (36 ± 7% versus 48 ±
11%, p < 0.02).
0
Ventricular volume changes. The end-diastolic volume
ifor
all patients in this study increased with exercise from
0
c: 80
0
174 ± 49 ml at rest to 200 ± 50 ml during exercise (p <
(J
~
0.001). In patients with no coronary disease, end-diastolic
«I
~
70
volume increased from 160 ± 26 ml at rest to 163 ± 19
u,
•
0
0
c:
0
0
ml during exercise (p < 0.05). In patients with single vessel
~0
0
disease,
the end-diastolic volume increased from 156 ± 56
60
(J
Q)
0
8
ml at rest to 206 ± 50 ml during exercise (p < 0.01); in
W
oe
patients with multivessel disease, the volume increased from
•.0
212 ± 53 ml at rest to 230 ± 50 ml during exercise (0.10
.! 50
~
•
i
(J
> p > 0.05) .
't:
O.
An increase in end-systolic volume during exercise was
0
c: 40
Q)
seen in 18 (86%) of 21 patients with one vessel disease and
>
•
in 12 (86%) of 14 patients with multi vessel disease. Three
:::Q) 30
8
patients
with one vessel disease and two patients with mul0
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•
tivessel disease who had a normal ejection fraction response
Q)
0
II)
n:65
to exercise had an increase in end-systolic volume during
(J
• :propranolol
20
o
:no
propranolol
exercise.
However, minimal increase in end-systolic volume
Q)
)(
during
exercise
was also seen in four subjects with no sigW
O~
nificant coronary artery disease. There was no correlation
NoCAO
IVO
MVO
between change in end-diastolic volume (change from rest
Figure 3. Exercise left ventricular ejecnon fraction in patients with no to exercise) and coronary artery disease score (r = 0.005;
coronary artery disease, patients with one vessel disease and patients with
p = NS).
multivessel disease, Mean ± standard deviation for the three groups are
The end-systolic volume for all patients in the study inshown, Abbreviations as in Figure 2.
creased from 87 ± 50 ml at rest to 100 ± 51 ml during
exercise (p < 0.001). There was no correlation between the
ejection fraction was less than 40%, 11 (92%) of 12 patients
were found to have extensive coronary artery disease. Of
the 28 patients with exercise heart rate of 130 beats/min or
greater, a slightly better correlation was found between exercise ejection fraction and coronary artery disease score (r
Figure 4. Correlation between changes in left ventncular ejection fracnon
(DEF) from rest to exercise and coronary artery disease (CAD) score.
= - 0.73; P < 0.00 I). The correlation was also strong if
the exercise duration was longer than 8 minutes (n = 24,
35
r = -0.78, P < 0.001). In patients under the age of 60
n:65
30
years, the correlation between coronary score and exercise
r= -.42
p<O.OO1
25
ejection fraction was slightly better (n = 45, r = -0.74,
P < 0.001) (Fig. 5B). Patients younger than 50 years of
20
•
• •
age showed even better correlation between exercise left
15 •
ventricular ejection fraction and coronary artery disease score
•
10
•
(n = 27, r = -0.82, P < 0.001) (Fig. 5C).
• • •• I••
•
Proximal versus distal coronary stenosis. In patients with
5
•
•
LL.
• •••
W
••
one vessel disease, the coronary stenosis was proximal in
•
0
<]
••
•
20 patients and distal in 6 patients. In patients with proximal
•
••
-5
stenosis, the ejection fraction was 53 ± 13% at rest and
•
•
·10
51 ± 9% during exercise. In patients with distal stenosis,
• • •
•
the ejection fraction was 51 ± 6% at rest and 57 ± 7%
-15
• ••
•
• ••
during exercise. The change in ejection fraction from rest
•
-20
to exercise was significantly different in the two groups of
-.-
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.
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patients (- 2 ± 10% versus 6 ± 4%, p < 0.05). Similarly,
the exercise ejection fraction was significantly lower in the
12 patients with multivessel disease in whom the disease
was proximal in all vessels than in 5 patients in whom the
•t
-25
0"•
0
•
· ..
i
I
5
15
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25
35
45
CAD Score
J AM tOLL CARDIOL
1983;1(4): 1002-10
EXERCISE LEFT VENTRICULAR EJECTION FRACTION
-i
e
85
85
(A)
75
n:65
y 65.8 + O.77x
r -0.70
p<0.OO1
=
=
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ono propranolol
• propranolol
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CAD Score
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CAD Score
85
0
(C)
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r = -0.82
p<0.OO1
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Figure 5. Correlation between exercise left ventricular ejection fraction and coronary
artery disease (CAD) score.
years of age; and C, results
A, results
In
in 65 patients; B, results in patients under 60
patients under 50 years of age.
...
•
•
.!
:;,
e
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0
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ono prbpranelol
• propranolol
65
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~
CD
)(
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15
0<
5
i
i
15
25
35
45
CAD Score
change in end-systolic volume with exercise and coronary
artery disease score (r = 0.24, P = NS).
Positive versusinconclusive electrocardiographic stress
tests. Twenty-seven patients had a positive electrocardiographic stress test and 33 had an inconclusive test (because
of submaximal heart rate). The remaining five patients had
a normal exercise electrocardiographic test. There were no
significant differences between the two groups in regard to
rest ejection fraction, exercise ejection fraction and coronary
artery disease score (Table 2). However, the group with a
positive stress test had a blood pressure-heart rate product
at peak exercise of 22.8 ±5.i x 103 versus 17.9 ± 5.8
1008
J AM COLL CARDIOL
DePACE ET AL
1983;1(4): 1002-10
103 for the group with an inconclusive test (p < 0.01)
and a change in ejection fraction from rest to exercise of
-4 ± 12% versus 5 ± 8%, respectively (p < 0.001) .
X
Discussion
The results of our study are consistent with the hypothesis
that it is not the magnitude of change in global left ventricular function during exercise but the absolute level of
global function at exercise that correlates best with the extent
of coronary artery disease. The exercise left ventricular ejection fraction represents a combination of the muscle mass
in jeopardy during ischemia along with the degree of fibrosis . The former is affected by many factors such as age,
exercise heart rate, medications, exercise duration and extent of coronary disease.
Variations in individual hemodynamic change during exercise have been observed in patients grouped by similar
anatomic extent of disease, thus confirming this heterogeneous response (6). However, previous reports on exerci se
radionuclide angiography have dealt with a conventional
method of analysis of presence and extent of coronary artery
disea se (no coronary disease or single, double and triple
vessel disease) (18). Significant disease has been variably
defined as stenosis greater than 50 or 70% of the luminal
diameter of the vessel. Although convenient, this evaluation
of coronary disease is simpli stic because it does not take
into account the location and degree of stenosis and the
number of stenoses.
Ejection fraction and coronary artery disease
score. The coronary artery disease scoring system employed in our present study is not ideal. However, it determine s the extent of disease much more closely than the
conventional method because it provides a better estimate
of the extent of myocardium at jeopardy during exercise.
As seen in Table 1 and Figure 3, the mean values for exercise
Table 2. Comparison Between Patients With Positive and
Those With Inconclusive Exercise Electrocardiograms
Positive Ex ECG
(n = 27)
Propranolol
Rest EF (%)
Ex EF (%)
CAD score
6 EF
BP x HR
13 (48 %)
53
49
19.0
-4
22.8 ±
± II
± II
± 10.3
± 12
5.1 x 103
Inconclusive Ex ECG
(n =' 33)
p Value
15 (44%)
50 ± 14
55 ± 14
16.1 ± 13.9
+5 ± 8
17.9 ± 5.8 x 103
NS
NS
NS
NS
< 0.001
< 0.01
Th e results represent the number of patien ts and percent In each group or mean
standard devia tion . Five patient s achieved at least 85% of the maximal predicted
heart rate and had normal exercise electrocardiograms . The se patients were exclud ed
from the above analysis .
BP x HR = blood pressure x heart rate (rnrn Hg x beats/min). CAD =
coronary artery disease; ECG = electr ocardiogram; D EF = change In ejection
fraction from rest to exercise. EF = ejection fraction; Ex = exercise. n = number.
NS = not significant.
1:
ejection fraction were significa ntly higher amon g patients
with no significant coronary disease than among patients
with single or multive ssel disease; the overlap , howe ver ,
was considerable . For example, the exercise ejection fraction in patients with no significant disea se ranged from 53
to 86%. On the other hand . the coronary artery disea se
scores in these patient s varied from a to 18 point s. One
patient with single vessel left anterior descending disease
had a coronary artery disease score of 9. This patient had
a normal exerci se ejection fraction of 58%; in another patient
with proximal left anterior descend ing disease and a coronary artery disease score of 21 , the exercise ejection fraction
was 27%. Likewise, patients with multivessel disease showed
a wide scatter of exercise ejection fractions and coronary
artery disease scores. We found that if the exercise left
ventricular ejection fraction was 55% or greater, most (27
of 28 patients, or 96%) patients will have a low coronary
artery disease score « 24) . Likewi se , if the exercise ejection fraction is less than 40 %, more than 90% of patients
will have extensive coronary artery disea se shown at
catheterization.
Effect of age. Age has been shown to affect the exercise
but not the rest ejection fraction in patients without coronary
artery disease (9). However, there is no reason to doubt the
exerci se response in patients with coronary artery disease
is also affected by age. In the present study , the correlation
between extent of disease and exerci se ejection fraction was
greater in the younger patient s, with the best correlation
seen in patients under 50 year s of age .
Effect of propranolol. The effect of propranolol on exercise left ventricular ejection fraction in patients with COfOnary artery disease shows individual variation (19). Battler
et al. (20) showed an improvement in exercise ejection
fraction with propranolol admini stration. Rainwater et al.
(21) reached similar conclusions in patients with coronary
artery disease without prior infarcti on . We found that in our
patients, the extent of coronary disease correlated well with
exercise ejection fraction whether or not the patients were
on propranolol therapy . These differences are not difficult
to reconcile becau se of the individual differences mentioned
earlier; thus. even in patient s on propranolol therapy, we
found an excellent correlation between exercise ejection
fraction and extent of angiographic coronary artery disea se.
Effect of exercise heart rate and blood pressure. We
also found that the exerci se left ventricular ejection fraction
correlated better with coronary arter y disease score if an
exercise heart rate of 130 beats/min or greater was obtained.
The correlation was not improved if heart rate and blood
pressure product was used. Both heart rate and blood pressure have been shown to be good predictors of myocardial
oxygen demand during exercise in normotensive patients
with ischemic heart disease (22). However, it seems that
the exercise heart rate alone may be used to assess adequate
myocardial stress.
J AM COLLCARDIOL
1983;1(4).1002-10
EXERCISE LEFf VENTRICULAR EJECTION FRACTION
Correlation with extent of coronary artery disease.
Despite the different levels of exercise end points as usually
encountered in practice, we found the exercise ejection fraction to be the best exercise variable to correlate with extent
of coronary artery disease. Although there has been a tendency to rely on the change in ejection fraction from rest
to exercise (change in left ventricular ejection fraction) as
a predictor of coronary artery disease, we found a weak
correlation between this variable and extent of coronary
disease. Also because the changes in left ventricular volumes and absolute exercise volumes showed considerable
overlap in relation to the number of diseased vessels and
extent of coronary disease, they were not useful in predicting
the extent of coronary disease. Patients with a positive stress
electrocardiogram did not differ in extent of coronary disease, rest or exercise ejection fraction from patients with an
inconclusive exercise electrocardiogram (Table 2), but the
change in ejection fraction differed in the two groups. This
fact could be due to the higher exercise blood pressure and
heart rate achieved in the patients with a positive stress test.
Correlation with exercise electrocardiogram. Exercise electrocardiographic results have been used as indicators of presence and severity of coronary disease. Specifically, ischemic changes appearing in the first 3 minutes of
exercise and persisting for 8 minutes or longer in the recovery period have been correlated with extensive coronary
disease (23). The exercise electrocardiographic results have
also been useful prognosticators, thus, a higher incidence
of ischemic events has been found in patients with early
onset of ischemia (24). However, the diagnostic usefulness
of exercise electrocardiography is limited (25). We found
a weak correlation between exercise duration, extent of
coronary artery disease and exercise ejection fraction.
Clinical implications. The changes in ejection fraction
from rest to exercise and exercise-induced wall motion abnormalities are useful in the detection of coronary heart
disease. The exercise ejection fraction is strongly correlated
with the extent of coronary artery disease as determined by
a scoring system. The younger the patient and the higher
the exercise heart rate, the better the correlation. Precatheterization testing showing a normal exercise ejection fraction may reduce the number of catheterizations performed
in patients with minimal or no symptoms in the search for
extensive operable coronary disease. Further study is necessary to evaluate the prognostic value of the exercise ejection fraction in patients with coronary artery disease who
are being treated medically.
1009
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