Download Response of Right Ventricular Ejection Fraction to Upright Bicycle

Response of Right Ventricular Ejection Fraction to
Upright Bicycle Exercise in Coronary Artery Disease
HARVEY J. BERGER, M.D., DAVID E. JOHNSTONE, M.D., JAY M. SANDS, M.D.,
ALEXANDER GOTTSCHALK, M.D., AND BARRY L. ZARET, M.D.
With the technical assistance of Linda Pytlik, R. T.
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SUMMARY The right ventricular (RV) response to exercise was assessed in 32 patients with angiographically documented coronary artery disease and in 14 normal controls without cardiopulmonary disease.
The relationships between exercise RV reserve, exercise left ventricular (LV) reserve, and the presence of
proximal right coronary stenosis were also evaluated. RV and LV ejection fractions were determined using
first-pass radionuclide angiocardiograms. The normal response to exercise was at least a 5% absolute increase
in RV and LV ejection fractions. In the group with coronary artery disease, RV ejection fraction either
decreased or remained the same with exercise (abnormal exercise RV reserve) in 19 of 32 patients. LV exercise reserve was abnormal in 26 of 32 patients. All 19 patients with abnormal exercise RV reserve had abnormal exercise LV reserve, and all six patients with normal LV reserve had normal RV reserve. There was a
significant linear relationship between the direction and magnitude of change from rest to exercise of LV ejection fraction and RV ejection fraction (r = 0.77). In contrast, the RV response to exercise was not primarily
dependent upon the presence or absence of proximal right coronary stenosis. These data suggest that abnormal
exercise RV reserve occurs frequently in coronary artery disease and that the concomitant LV response to exercise appears to be its major determinant.
IN ASYMPTOMATIC coronary artery disease,
right ventricular (RV) performance usually is normal
in the resting state. Abnormal RV function in patients
with acute myocardial infarction occurs almost exclusively when the infarction involves the inferior wall,
where the ischemic process probably extends beyond
the borders of the left ventricle to the adjacent right
ventricle.'`6 RV infarction in the absence of LV infarction occurs rarely' and is usually associated with complete occlusion of the right coronary artery.7
While previous radionuclide studies have evaluated
LV performance during exercise in patients with coronary artery disease,8'" little is known about concomitant RV responses to either exercise or transient
myocardial ischemia. We studied RV performance
during exercise in patients with coronary artery disease and in normal subjects using first-pass
radionuclide angiocardiography, a technique well
suited for assessing RV and LV ejection fractions during stress,12 and evaluated the relationships between
exercise RV reserve, exercise LV reserve, and the
presence of right coronary artery stenosis.
Methods
Patient Population
Thirty-two patients with angiographically documented coronary artery disease and 14 normal
controls were studied. Of the 14 control subjects, eight
were normal volunteers without clinical or electrocardiographic evidence of cardiopulmonary disease. The
remaining six controls were patients who underwent
diagnostic cardiac catheterization for evaluation of
chest pain and whose hemodynamic and angiographic
studies were normal. Of the 32 patients with coronary
artery disease, 26 were male and six female; their
mean age was 52 years (range 33-66 years).
Within 2 months of their exercise radionuclide
study, all patients with coronary artery disease underwent selective coronary angiography in multiple
views. Patients were clinically stable, without any
symptomatic changes between the two studies. Two
experienced observers without knowledge of the
radionuclide data reviewed the coronary angiograms,
and a consensus was used in data analysis. Coronary
artery disease was defined angiographically by the
presence of at least 50% decrease in luminal diameter
in one or more of the coronary arteries. The severity
of coronary artery stenosis was judged on the basis of
the view that showed the maximal decrease in luminal
diameter. Stenoses of the right coronary artery were
defined as either proximal (involving the major blood
supply to the right ventricle) or distal (primarily involving the blood supply to the inferior wall of the left
ventricle and not primarily the right ventricle).
Stenoses of major marginal branches of the proximal
right coronary artery that also supplied the right ventricle were classified as proximal lesions of the right
coronary artery. Stenoses were considered distal
From the Cardiology Section, Department of Internal Medicine,
and the Nuclear Medicine Section, Department of Diagnostic
Radiology, Yale University School of Medicine, New Haven,
Connecticut, and the Department of Medicine, New Britain
General Hospital, New Britain, Connecticut.
Supported in part by grant ROI HL-21690-02 from the NHLBI,
Bethesda, Maryland.
Presented in part at the 51st Scientific Sessions of the American
Heart Association, Dallas, Texas, November 1978.
Address for correspondence: Harvey J. Berger, M.D., Cardiology
Section, 87 LMP, Yale University School of Medicine, 333 Cedar
Street. New Haven, Connecticut 065 10.
Received January 10, 1979; revision accepted May 15, 1979.
Circulation 60, No. 6, 1979.
1292
1293
EXERCISE RV FUNCTION IN CAD/Berger et al.
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lesions when they occurred past the origin of the last
major RV marginal branch. Fourteen patients had
single-vessel disease (four proximal right coronary
artery, two distal right coronary artery, five left
anterior descending and three left circumflex); twelve
had double-vessel disease (five with proximal right
coronary stenosis); and six had triple-vessel disease
(all with proximal right coronary stenosis). Thus, 15
patients had proximal right coronary artery stenosis.
Seven patients had a documented transmural
myocardial infarction at least 6 months before the exercise radionuclide study. Based upon standard electrocardiographic criteria,'3 infarction was inferior in
four patients and anterior in three (including one each
with proximal right coronary artery disease). No
patient had significant valvular heart disease or unstable angina or was receiving propranolol or digitalis
at the time of study. No patient had clinical or
radiographic evidence of pulmonary disease.
Pulmonary function tests were obtained routinely in
23 of 32 patients and were normal in each case.
Informed consent was obtained from all participants in the study.
Exercise Protocol
First-pass radionuclide angiocardiograms were obtained with a computerized, multicrystal scintillation
camera (Cordis-Baird System-77, Bedford, Massachusetts) first at rest and again during peak exercise.8
Before the actual study, patients were familiarized
with the imaging laboratory and the exercise protocol.
Heart rate, sphygmomanometric blood pressure and
ECGs (including three orthogonal leads and a bipolar
CC5 lead) were obtained at rest before exercise and at
1-2-minute intervals during and after exercise.
Upright exercise was performed on a variable-load
bicycle ergometer (Tunturi Co., Amerac Corporation,
Bellevue, Washington) according to a previously
described protocol.8 Briefly, patients pedaled at a constant speed, beginning at a load of 300 kilopondmeters (kpm)/min. Every 3 minutes, the load was
increased by 150 kpm/min. Maximal exercise was
continued until the development of either symptomlimiting fatigue or at least 0.1 mV (1 mm) horizontal
or downsloping ST-segment depression at least 0.08
second in duration. Exercise was not terminated
because of chest pain alone, leg discomfort or achievement of predicted heart rate.
Radionuclide Technique
An 18-gauge, 11/2-inch polyethylene catheter was
placed in a right antecubital vein for radionuclide injection. All studies were performed with the patient in
the anterior position with the camera's detector
rotated from the conventional horizontal orientation
so that it was directly in front of the chest. For the
resting study, the patient sat on the bicycle with his or
her feet on the pedals in a position identical to that
used during the subsequent exercise study. The exercise radionuclide angiocardiogram was performed
either on the same day as the rest study or on the
following day, as previously described.8 High-specificactivity technetium-99m pertechnetate or technetium99m sulfur colloid (10-15 mCi) was used. The exercise
radionuclide angiocardiogram was obtained at the
peak exercise load. As the radionuclide injection was
made, patients were instructed to stop pedaling
abruptly. Radionuclide data were recorded as the
bolus traversed the central circulation without artifacts from vigorous exercise. At exercise heart rates,
the RV and LV phases of the first-pass study were
both completed in less than 10 seconds. In no case did
heart rate drop by more than 5 beats/min during the
brief period of data acquisition.
Radionuclide Data Processing
RV and LV ejection fractions were determined
from first-pass quantitative radionuclide angiocardiograms using standardized techniques previously
reported by this laboratory.'2 14-i6 Ejection fractions
were calculated from end-diastolic and end-systolic
counts using background-corrected regional radionuclide time-activity curves emanating from the individual cardiac chambers. The same techniques for
background correction were used for both rest and exercise studies. These approaches were initially
validated in patients studied at rest, and errors might
be introduced when these same techniques are applied
to patients during exercise. Nevertheless, this approach already has been applied to the study of LV
function during exercise and has yielded consistent
and reliable results.8 These measurements of ventricular function can be obtained with minimal interand intraobserver variabilities and are reproducible in
sequential studies.',2 14-16
Statistical Methods
Data are expressed as the mean ± SEM. Comparisons of radionuclide data at rest and during exercise were made using the paired t test. Analysis
between groups was made using the t test. The occurrence of factors potentially determining exercise
RV dysfunction was compared using the chi-square
test. Correlation coefficients and regression equations
were obtained using standard formulas. Probability
< 0.05 was considered significant.
Results
Normal Subjects
All 14 normal subjects exercised to moderate
fatigue and none had ischemic electrocardiographic
changes. Their maximal heart rate was 150 ± 6
beats/min. All had augmented RV and LV function
during exercise compared with the resting state. RV
ejection fraction rose significantly, from 54 + 3% at
rest to 68 ± 3% with exercise (p < 0.001). The individual increments in RV ejection fraction ranged
from 7-17%. Similarly, LV ejection fraction rose
significantly, from 67 + 3% at rest to 82 + 4% with
exercise (p < 0.001). The individual increments in LV
1 294
CIRCULATION
RV EJECTION FRACTION
L V EJECT/ON FRAC TION
VOL 60, No 6, DECEMBER 1979
RV EJECT/ON FRACTIOA
LV EJECT/ON FRACTION
90
90
80
80
80
80
70
70
70
70
60
60
60
60
50
50
50
50
40
40
30
30
20
20
REST
EXERCISE
RES T
EXERCISE
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FIGURE 1. Right ventricular (R V) and left ventricular
(L V) ejection fractions at rest and exercise in 14 normal controls. Individual patients are represented by closed circles
connected by solid lines. The open circles at the sides of each
panel are the means. R V ejection fraction increased by at
least 7% and L V ejection fraction by at least 6% in all normal controls.
ejection fraction ranged from 6-26% (fig. 1). Based on
these data and the documented reproducibility of
these radionuclide measurements, a normal response
to exercise (normal exercise reserve) in an individual
patient was considered to be an absolute increment of
at least 5% in either RV or LV ejection fraction.8 12
RV Performance in Coronary Artery Disease
RV ejection fraction was normal (. 45%) at rest in
30 of 32 patients.14 The two patients with an abnormal
RV ejection fraction at rest (40% and 43%) had each
sustained a previous inferior myocardial infarction.
RV ejection fraction either decreased or remained the
same (within 5% of the resting value) with exercise in
19 of 32 patients. In these 19 patients with abnormal
exercise RV reserve, the change in RV ejection fraction with exercise averaged -6% (range 15% to
+2%). In the remaining 13 patients with normal exercise RV reserve, RV ejection fraction increased normally (mean 10%; range 5-16%). For the entire group,
RV ejection fraction was unchanged by exercise (rest
55 ± 1%; exercise 55 ± 2%; p = NS) (fig. 2).
Eighteen patients exercised to an end point of electrocardiographic ischemia (14 had abnormal RV
reserve and four had normal RV reserve), while the
other 14 patients were limited by severe fatigue (five
had abnormal RV reserve and nine had normal RV
reserve) (table 1). The peak heart rate, rate-pressure
product and external work load in patients with abnormal RV reserve were 138 ± 5 beats/min, 224 ± 11
beats/min x mm Hg X 10-2, and 53 35 kpm/min,
respectively. These values were not significantly
different from those in patients with normal RV
reserve (141 ± 5 beats/min, 229 i 14 beats/min X
-
REST
EXERCISE
REST
EXERCISE
FIGURE 2. Right ventricular (R V) and left ventricular
(L V) ejection fractions at rest and exercise in 32 patients
with coronary artery disease. Individual patients are
represented by closed circles connected by solid lines. The
open circles at the sides of each panel are the means. For the
entire group, R V ejection fraction was unchanged by exercise, while L V ejection fraction decreased. Both responses
represent abnormal exercise reserve.
mm Hg X 10-2, and 512
(table 2).
±
21 kpm/min, respectively)
LV Performance in Coronary Artery Disease
LV ejection fraction was normal (. 55%) at rest in
27 of 32 patients. All five patients with abnormal LV
ejection fraction at rest (range 27-53%) had sustained
a previous myocardial infarction (including one with
abnormal RV function). LV ejection fraction either
decreased or remained the same with exercise (abnormal exercise LV reserve) in 26 of 32 patients, including three of five with abnormal resting LV function.
For the group, LV ejection fraction decreased
significantly with exercise, from 65 ± 3% at rest to
59 ± 3% (p < 0.01) (fig. 2). Seventeen of the 18
patients who exercised to electrocardiographic
ischemia had abnormal LV reserve, compared with
nine of 14 who were limited by fatigue. The peak heart
rate, rate-pressure product and external workload in
patients with abnormal LV reserve were 137 ± 4
beats/min, 223 ± 14 beats/min X mm Hg X 10-2,
and 527 ± 26 kpm/min, respectively. These values
were not significantly different from those in patients
with normal LV reserve (147 ± 6 beats/min,
237
±
27 beats/min
X
mm
Hg
X
10-2, and 525
±
34
kpm/min, respectively) (table 2). Of the six coronary
disease patients with normal exercise LV reserve, two
EXERCISE RV FUNCTION IN CAD/Berger et al.
TABLE 1. Clinical, Angiographic and Radionuclide Data
Previous
Coronary artery stenosis
MI
Prox Distal
An- InPt RCA* RCAt LAD LCF
terior ferior
1
+
+
2
+
3
4
+
5
+
+
6
+
7
+
8
9
+
10
+
+
+
+
11
+
+
+
+
12
+
+
+
13
+
14
+
+
+
15
+
+
+
16
+
+
17
+
+
+
18
+
19
+
+
20
+
21
+
22
+
23
_+
24
+
25
26
+
+
27
+
+
28
+
29
+
_
+
+
30
-
-
-
-
-
-
-
-
-
-
+
-
+
-
+
+
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-
-
-
-
-
-
-
+
_
31
-
+
+
-
-
-
-
RV ejection
fraction (%)
Rest
Ex
A
59
+8
48
50
59
67
58
46
49
64
61
63
35
45
67
58
47
43
45
49
71
63
58
53
67
46
57
58
58
53
55
64
64
50
48
59
44
51
54
61
50
47
57
53
52
53
64
54
51
57
64
61
58
50
40
58
45
55
63
60
55
53
55
+7
-8
-12
+14
+14
+6
-18
-7
+14
-6
-7
-8
-12
-15
+10
+5
+8
+13
+9
+1
+2
-7
-2
-2
+2
+9
+16
0
-11
-15
LV ejection
fraction (%)
Rest Ex
A
70
67
-3
61
69
+8
70
69
-1
64
60
-4
75
75
0
68
80
+12
71
69
-3
67
61
-6
74
61
-13
70
92
+22
52
41
-11
-14
83
69
71
-24
47
66
50
-16
74
51
-23
38
43
+5
62
-4
58
27
17
-10
32
43
+11
83
79
-4
64
44
-20
67
69
+2
60
67
-7
-3
59
56
58
50
-8
65
57
-8
71
74
+3
63
74
+11
80
81
+1
80
-33
47
70
52
-18
54
52
-2
1295
Abnormal
exercise
reserve
RV
-
+
LV
+
+
+
-
+
+
-
+
+
+
+
+
+
+
+
+
+
+
+
-
-
+
-
+
+
+
+
+
+
+
-
+
+
+
+
+
+
+
+
+
+
43
41
+
-2
+
+
+
*Supplying the right ventricle.
tPrimarily not supplying the right ventricle.
Abbreviations: Prox = proximal; RCA = right coronary artery; LAD = left anterior descending; LCF = left circumflex;
MI = myocardial infarction; Ex = exercise; A = difference between resting and exercise values; RV = right ventricle; LV =
left ventricle; + = condition present; - = condition absent.
32
had abnormal LV ejection fraction at rest. Although
LV ejection fraction rose by an absolute value of at
least 5% in these patients, it remained in the abnormal
range. Thus, LV function was abnormal at rest or during exercise in 28 of 32 patients. Of the six patients
with normal exercise LV reserve, three had singlevessel disease, two double-vessel disease and one
triple-vessel disease (table 1).
Relationship of Exercise RV and LV Performance
All 19 patients with abnormal exercise RV reserve
also had abnormal exercise LV reserve. No patient
had abnormal exercise RV reserve and a normal LV
response to exercise. Of the 13 patients with normal
RV reserve, six had a normal LV response and seven
an abnormal LV response (fig. 3). In the six patients
with normal LV reserve, RV ejection fraction rose
significantly in each patient (rest 50 ± 3%; exercise
62 ± 3%, p < 0.001). This is in contrast to the results
in patients with abnormal LV reserve, whose RV ejection fraction was unchanged by exercise (rest
56 ± 1%; exercise 54 ± 2%; p = NS). Of the 26
patients with abnormal exercise LV reserve, the
decrease in LV ejection fraction with exercise was
significantly greater in the 19 patients with concomitant abnormal RV reserve than in the remaining seven
1296
CI RCULATION
VOL 60, No 6, DECEMBER 1979
TABLE 2. Physiologic End Potnts Attained with Graded Bicycle Exercise
Pt
1
2
3
Exercise end point
Ischemia*
Fatigue
+
+
4
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5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
+
+
+
+
+
+
+
±
+
+
+
+
+
Maximal
heart rate
(beats/min)
130
140
132
135
119
121
152
168
162
155
110
145
92
105
128
164
125
164
150
112
145
138
142
158
138
120
150
150
165
125
155
150
+
*ST-segment depression > 1 mm.
Abbreviations: + = present; - = absent.
with a normal RV response (-12 ± 2% vs -3 ± 1%,
respectively; p < 0.05). Further, there was a significant linear relationship between the direction and
magnitude of change from rest to exercise of LV ejection fraction and RV ejection fraction (r = 0.77,
p < 0.001) (fig. 4). The presence or absence of abnormal exercise LV reserve was a significant determinant
of the RV response to exercise (X2 = 7.98, p < 0.01)
(table 3). Thus, the concomitant LV response to exercise appears to be a major determinant of abnormal
RV exercise reserve in coronary artery disease.
Relationship of Exercise RV Performance
and Proximal Right Coronary Artery Stenosis
The RV response to exercise was heterogeneous in
Rate-pressure product
(beats/min X mm Hg X 10-2)
210
221
142
176
171
154
281
285
272
232
151
196
167
186
225
311
200
205
188
210
276
262
210
200
275
270
270
315
277
200
230
250
External workload
(kpm/min)
450
450
600
450
600
450
450
450
600
600
300
450
300
450
600
600
450
450
600
450
300
450
600
750
750
450
600
450
600
600
750
750
the 15 patients with proximal right coronary stenosis:
six patients had normal RV reserve and nine abnormal
RV reserve. In these 15 patients, RV ejection fraction
was unchanged by exercise (rest 55 ± 2%; exercise
55 ± 2%; p = NS). Similarly, the RV response was
heterogeneous in the 17 patients without proximal
right coronary stenosis: seven had normal RV reserve
and 10 abnormal RV reserve (fig. 5). RV ejection fraction was unchanged by exercise in these 17 patients
(rest 53 ± 2%; exercise 56 ± 2%, p = NS). In addition, three of six patients with both normal RV and
LV responses to exercise had proximal right coronary
artery involvement. The absolute changes in RV ejection fraction from rest to exercise in patients with or
without right coronary artery stenosis were not
EXERCISE RV FUNCTION IN CAD/Berger
ABNORMAL LV RESERVE
al.
1297
TABLE 3. Relationship of Right Ventricular Response to
Exercise with Exercise Left Ventricular Reserve and Coronary
Anatomy
NORMAL L V RESERVE
N=6
Proximal right
coronary artery
stenosis
Exercise LV reserve
Absent
Normal* Abnormal Present
70
(n= 6) (n
-
2Z
et
60
Normal*
exercise
RV reserve
(n = 13)
Abnormal
exercise
RV reserve
(n 19)
60
(~3
5
2 50
50
=
26) (n
=
15) (n
=
17)
6/13
7/13
6/13
7/13
0/19
19/19
9/19
10/19
=
X2 = 0.09; p = NS
*Increase in ejection fraction (> 5%) with exercise.
Abbreviations: RV = right ventricular; LV = left ventricular.
x2 = 7.98; p <0.01
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40
p
REST
<0.001
Three of four patients with single-vessel disease involving only the proximal right coronary artery had
abnormal exercise LV reserve. Two of these three
patients also had abnormal RV reserve. However, two
patients (nos. 1 and 2) had normal increases in RV
ejection fraction despite proximal right coronary
artery stenosis.
EXERCISE
REST
EXERCISE
FIGURE 3. Right ventricular (R V) ejection fraction at rest
and exercise in 26 patients with abnormal left ventricular
(L V) reserve and six patients with normal L V reserve. The
R V response to exercise was heterogeneous in the group
with abnormal L V reserve; however, RV ejection fraction
increased with exercise in all patients with normal L V
Discussion
First-pass radionuclide angiocardiography is a wellsuited technique for noninvasive assessment of biventricular performance, because of the anatomic and
temporal separation of radioactivity within the two
ventricles during data acquisition.12 Determination of
ejection fraction is based upon changes in regional
count-rates and thus is free of geometric assumptions
concerning the different shapes of the two ventricles.
Radionuclide assessment of RV ejection fraction has
reserve.
significantly different (-1% vs +2%). These data do
a major causal relationship between the
presence or absence of proximal right coronary
stenosis and an abnormal RV response to exercise
(x2 = 0.09, p = NS) (table 3). Further, the incidence
of abnormal RV reserve was not significantly different
in patients with single-vessel and multivessel disease
(x2 = 0.35, p = NS).
not indicate
-,
+20
* With Proximol RCAD
O Without Proximal RCAD
N =32
r = 0.77
0\
*
+ 10
AO
0
(3
a
D
0
FIGURE 4. Relationship of right ventricular (R V) and left ventricular (LV)
response to exercise. Note the linear correlation between the absolute changes (A) from
rest to exercise in R V and L V ejection fractions. The normal responses are indicated by
the thin horizontal and vertical lines at
+5%. RCAD = right coronary artery dis-
O
0~~~~~~
Z
0
0
0
0
(3
M- 10
0
000
0
'-2
'q
*
c0
0
0
*
0
ease.
-20
IIIIIII
-30
-20
A
-10
0
+10
LlV EJECT/ON FRACTION
+20
(%)
+30
CIRCULATION
1298
WITHOUT PROXIMAL
R/GHT CAD
WITH PROXIMAL
RIGHT CAD
0\1
(3i
(3
L4J
L"'
Z"2
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REST
EXERCISE
RES T
FIGURE 5. Right ventricular (R V) ejection fraction at rest
and exercise in 15 patients with proximal right coronary
artery disease (CAD) and in 17 patients without proximal
right CA D. The R V response to exercise was heterogeneous
in both groups.
already shown variable degrees of RV dysfunction at
rest or during exercise in a variety of patients with cardiopulmonary disease.2-4, 14 1-19 The present study extends these findings and demonstrates that abnormal
RV performance occurs frequently during exercise in
coronary artery disease. The RV response to exercise
appears to be primarily dependent upon concomitant
LV function, rather than the presence of proximal
right coronary artery stenosis. Abnormal exercise RV
reserve (no change or fall in RV ejection fraction with
exercise) was shown only in patients with abnormal
exercise LV reserve. In addition, a normal RV
response was found in all six patients with normal LV
reserve. No patient, including those with single-vessel
disease involving only the proximal right coronary
artery, had isolated exercise-induced RV dysfunction.
The significant linear correlation between the
magnitude of change from rest to exercise of LV and
RV ejection fractions further supports the causal
relationship between these two responses. Thus, within
the context of the relatively small patient group
evaluated, proximal right coronary artery stenosis
does not appear to be the primary modulator of the
RV response to stress. However, since the right coronary artery provides the predominant blood supply
to the RV free wall, its anatomic status may influence
and interact with changes in RV afterload induced by
LV dysfunction.
The functional geometry of the right ventricle probably plays a major role in the dependence of the right
ventricle upon the concomitant LV response to
stress.20 The convex interventricular septum and the
VOL 60, No 6, DECEMBER 1979
concave RV free wall form the boundaries of the RV
chamber. These two broad surfaces surround a narrow
space, giving the right ventricle a large surface area
compared with its volume. The inward motion of the
RV free wall toward the septum is the major contractile movement in RV systolic performance. LV contraction increases the curvature of the septum, but this
probably contributes relatively little to RV systolic
performance. Because of its thin free wall and large
surface area, the right ventricle cannot adapt as
readily as the left ventricle to the development of high
intracavitary pressure under comparable loading conditions. In this case, the RV myocardium would need
to develop far greater tension than the LV myocardium as resistance to outflow increases. These
anatomic insights support the concept that RV performance is highly afterload dependent.
The interrelationship of altered RV afterload and
LV dysfunction during stress in coronary artery disease is supported by hemodynamic studies in patients
with angina pectoris. Several investigations have
shown abnormal elevations in LV end-diastolic and
pulmonary artery pressures in response to exercise in
patients with coronary artery disease.2' 24 The frequency and magnitude of these hemodynamic abnormalities were generally greater in patients who had
electrocardiographic evidence of myocardial ischemia.
Further indirect evidence for the occurrence of
pulmonary vascular effects associated with exercise in
coronary artery disease is provided by Nichols et al.,2'
who evaluated changes in pulmonary blood volume
using inhaled "IC-carbon monoxide and a positron
camera. They found that pulmonary blood volume increased significantly in nine anginal patients with an
ischemic response to exercise, but decreased in six
patients without angina or an ischemic response.
Thus, although hemodynamic abnormalities induced
by stress are primarily manifested as LV systolic
dysfunction and altered LV compliance, they also
result in elevated RV afterload. These changes in
pressure-volume relationships would be expected to
occur in patients with abnormal exercise LV reserve as
determined by radionuclide angiocardiography and
would be expected to result in secondary RV dysfunction as a consequence of altered afterload.
Preliminary reports by Johnson et al.26 using a firstpass radionuclide technique and by Maddahi et al.27
using gated cardiac blood pool imaging have described
results that differ somewhat from those in the present
study. They suggest that right coronary artery disease
may play a more important role in determining the
RV response to exercise. The reasons for the apparent
difference are not readily evident but may be due in
the former study to patient selection and in the latter
to methodologic factors.
The radionuclide exercise LV function study has
become a potentially useful clinical examination.8 " In
addition, it provides important physiologic data in
patients with altered cardiac reserve. The present
study offers further pathophysiologic insights into the
RV response to exercise stress in coronary artery disease. These results also indicate that from a diagnostic
EXERCISE RV FUNCTION IN CAD/Berger et al.
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standpoint, assessment of RV reserve in coronary disease does not provide additional advantage over
evaluation of LV function alone. Other studies have
shown that the LV response to exercise is highly
dependent upon the exercise end point achieved, that
is, the presence of electrocardiographic evidence of
myocardial ischemia.i The importance of the exercise
end point in determining the RV response could not be
evaluated from the present study, because right-sided
precordial leads that might detect the presence of RV
ischemia were not monitored.28
Several experimental studies in animals have
evaluated hemodynamic factors that modify RV performance. Brooks et al.29 demonstrated in the canine
open-chest model that incremental pulmonary artery
obstruction caused a corresponding decrease in cardiac output and an increase in RV end-diastolic
pressure, with eventual RV failure and systemic
shock. At normal pulmonary artery pressures, complete occlusion of the right coronary artery caused a
fall in RV contractile force, but no change in RV, LV
or aortic pressures. With superimposed right coronary
artery occlusion, identical degrees of pulmonary
artery occlusion resulted in more pronounced
hemodynamic changes and RV failure at a lower level
of RV stress. RV decompensation induced by
pulmonary artery obstruction could be reduced by
hyperperfusion of the right coronary artery to levels
above normal flow. The inability of the right ventricle
to compensate for acute elevations in pulmonary vascular resistance has been shown by similar studies.30 31
Brooks et al.32 recently presented data involving the
porcine open-chest model that differed somewhat
from their original findings. In the pig, whose coronary anatomy more closely resembles that of man,
total occlusion of the right coronary artery produced
an elevation in RV end-diastolic pressure and a
decrease in RV contractile force. However, they did
not reexamine the critical relationship between coronary flow and RV afterload. These physiologic
studies suggest that afterload is a major factor in
determining global RV performance during stress and
that the presence of right coronary artery stenosis or
occlusion may further alter this response.
Acknowledgments
We thank Dr. Colin White, Professor of Biometry, for assistance
with statistical analysis and Coletta Sawyer for editorial assistance
in preparation of the manuscript.
References
1. Cohn J, Guiha N, Broder M, Limas C: Right ventricular infarction: clinical and hemodynamic features. Am J Cardiol 33: 209,
1974
2. Reduto L, Berger H, Cohen L, Gottschalk A, Zaret B: Sequential radionuclide assessment of left and right ventricular performance after acute transmural myocardial infarction. Ann
Intern Med 89: 441, 1978
3. Tobinick E,Schelbert H, Henning H, LeWinter M, Taylor A,
Ashburn W, Karliner J: Right ventricular ejection fraction in
patients with acute anterior and inferior myocardial infarction
assessed by radionuclide angiography. Circulation 57: 1078,
1978
1299
4. Steele P, Kirch D, Ellis J, Vogel R, Battock D: Prompt return
to normal of depressed right ventricular ejection fraction in
acute inferior infarction. Br Heart J 39: 1319, 1977
5. Rigo P, Murray M, Taylor D, Weisfeldt M, Kelly D, Strauss
H, Pitt B: Right ventricular dysfunction detected by gated scintiphotography in patients with acute inferior myocardial infarction. Circulation 52: 268, 1975
6. Isner J, Roberts W: Right ventricular infarction complicating
left ventricular infarction secondary to coronary heart disease:
frequency, location, associated findings and significance from
analysis of 236 necropsy patients with acute or healed myocardial infarction. Am J Cardiol 42: 885, 1978
7. Wade W: The pathogenesis of infarction of the right ventricle.
Br Heart J 21: 545, 1959
8. Berger H, Reduto L, Johnstone D, Borkowski H, Sands J,
Cohen L, Langou R, Gottschalk A, Zaret B: Global and
regional left ventricular response to bicycle exercise in coronary
artery disease: assessment by quantitative radionuclide
angiocardiography. Am J Med 66: 13, 1979
9. Borer J, Bacharach S, Green M, Kent K, Johnston G, Epstein
S: Effect of nitroglycerin on exercise-induced abnormalities of
left ventricular regional function and ejection fraction in coronary artery disease. Circulation 57: 314, 1978
10. Rerych S, Scholz P, Newman G, Sabiston D, Jones R: Cardiac
function at rest and during exercise in normals and patients with
coronary disease: evaluation by radionuclide angiocardiography. Ann Surg 187: 449, 1978
11. Bodenheimer M, Banka V, Fooshee C, Gillespie J, Helfant R:
Detection of coronary heart disease using radionuclide determined regional ejection fraction at rest and during handgrip exercise: correlation with coronary arteriography. Circulation 58:
648, 1978
12. Berger H, Gottschalk A, Zaret B: First-pass radionuclide
angiocardiography for evaluation of right and left ventricular
performance: computer applications and technical considerations. In Nuclear Cardiology: Selected Computer
Aspects, edited by Bacharach S. New York, Society of Nuclear
Medicine, 1978, pp 29-44
13. Mariott H: Practical Electrocardiography, 5th ed. Baltimore,
Williams and Wilkins, 1972
14. Berger H, Matthay R, Loke J, Marshall R, Gottschalk A,
Zaret B: Assessment of cardiac performance with quantitative
radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary
disease. Am J Cardiol 41: 897, 1978
15. Marshall R, Berger H, Costin J, Freedman G, Wolberg J,
Cohen L, Gottschalk A, Zaret B: Assessment of cardiac performance with quantitative radionuclide angiocardiography: sequential left ventricular ejection fraction, normalized left ventricular ejection rate, and regional wall motion. Circulation 56:
820, 1977
16. Marshall R, Berger H, Reduto L, Gottschalk A, Zaret B:
Variability in sequential measures of left ventricular performance assessed by radionuclide angiocardiography. Am J Cardiol 41: 531, 1978
17. Matthay R, Berger H, Loke J, Fagenholz T, Dolan T,
Gottschalk A, Zaret B: Right and left ventricular performance
in ambulatory young adults with cystic fibrosis. Br Heart J. In
press
18. Matthay R, Berger H, Loke J, Gottschalk A, Zaret B: Effects
of aminophylline on right and left ventricular performance in
chronic obstructive pulmonary disease: assessment by quantitative radionuclide angiocardiography. Am J Med 65: 903,
1978
19. Reduto L, Berger H, Johnstone D,.Whittemore R, Hellenbrand
W, Cohen L, Zaret B: Radionuclide assessment of exercise
right and left ventricular performance following total correction
of tetralogy of Fallot. (abstr) Circulation 58 (suppl II): 11-145,
1978
20. Rushmer R: Functional anatomy and control of the heart. In
Cardiovascular Dynamics, 4th ed. Philadelphia, WB Saunders
Co, 1976, pp 89-99
21. Cohen L, Elliott W, Rolett E, Gorlin R: Hemodynamic studies
during angina pectoris. Circulation 31: 409, 1965
22. Wiener L, Dwyer E, Cox J: Left ventricular hemodynamics in
exercise-induced angina pectoris. Circulation 38: 240, 1968
1300
VOL 60, No 6, DECEMBER 1979
CIRCULATION
23. Parker J, West R, Case R, Chiong M: Temporal relationships
of myocardial lactate metabolism, left ventricular function, and
S-T segment depression during angina precipitated by exercise.
Circulation 40: 97, 1969
24. Sharma B, Goodwin J, Raphael M, Steiner R, Rainbow R,
Taylor S: Left ventricular angiography on exercise: a new
method of assessing left ventricular function in ischemic heart
disease. Br Heart J 38: 59, 1976
25. Nichols A, Cochavi S, Strauss H, Guiney T, Leavitt M, Beller
G, Pohost G: Changes in cardiopulmonary blood volume during upright exercise stress testing in patients with coronary
artery disease. (abstr) Clin Res 26: 255, 1978
26. Johnson L, McCarthy D, Sciacca R, Cabot C, Ruden B, Cannon P: Right ventricular ejection fraction during exercise in
patients with coronary artery disease. (abstr) Circulation 58
(suppl II): 11-61, 1978
27. Maddahi J, Berman D, Matsuoka D, Charuzi Y, Waxman A,
Gray R, Swan H, Forrester J: Right ventricular ejection frac-
28.
29.
30.
31.
32.
tion during exercise in coronary artery disease by multiple gated
equilibrium scintigraphy. (abstr) Circulation 58 (suppl II): II131, 1978
Erhardt L, Sjogren A, Wahlberg I: Single right-sided precordial
lead in the diagnosis of right ventricular involvement in inferior
myocardial infarction. Am Heart J 91: 571, 1976
BTooks H, Kirk E, Vokonas P, Urschel C, Sonnenblick E: Performance of the right ventricle under stress: relation to right
coronary flow. J Clin Invest 50: 2176, 1971
Taquini A, Fermoso J, Aramendia P: Behavior of the right ventricle following acute constriction of the pulmonary artery. Circ
Res 8: 315, 1960
Guyton A, Lindsey A, Gilluly J: The limits of right ventricular
compensation following acute increase in pulmonary circulatory resistance. Circ Res 2: 326, 1954
Brooks H, Holland R, Al-Sader J: Right ventricular performance during ischemia: an anatomic and hemodynamic
analysis. Am J Physiol 233: H505, 1977
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Exercise Cross-sectional Echocardiography
in Ischemic Heart Disease
L. SAMUEL WANN, M.D., JAMES V. FARIS, M.D., RICHARD H. CHILDRESS, M.D.,
JAMES C. DILLON, M.D., ARTHUR E. WEYMAN, M.D., AND HARVEY FEIGENBAUM, M.D.
SUMMARY We performed cross-sectional echocardiograms at rest, during supine bicycle exercise, and
after sublingual nitroglycerin administration in 28 patients suspected of having ischemic heart disease.
Technically adequate exercise cross-sectional echocardiograms were obtained in 20 patients (71%). Ten
patients had new areas of reversible segmental dysynergy, and all 10 had significant stenoses of coronary
arteries supplying areas of the heart corresponding to the location of reversible dysynergy. Six of these 10
patients also underwent exercise thallium-201 perfusion scanning, and all six had reversible perfusion defects
in the area that demonstrated reversible dysynergy on exercise cross-sectional echocardiography. At least two
of the remaining 10 patients who did not have reversible segmental dysynergy on exercise cross-sectional
echocardiography probably experienced myocardial ischemia that we did not detect. We conclude that exercise cross-sectional echocardiography is technically difficult but feasible. The mechanical consequences of
exercise-induced regional myocardial ischemia can be detected noninvasively by real-time, two-dimensional,
cross-sectional echocardiography.
REGIONAL left ventricular dysfunction is a
hallmark of ischemic heart disease. Segmental left
ventricular contraction abnormalities occur within a
few seconds after onset of acute myocardial infarction, and appear transiently during episodes of reversible myocardial ischemia. Noninvasive detection of
these mechanical consequences of myocardial
ischemia and infarction should improve our ability to
diagnose and enhance our understanding of coronary
heart disease.
From the Veterans Administration Medical Center, Wood,
Wisconsin, and the Krannert Institute of Cardiology, Department
of Medicine, Indiana University School of Medicine, Indianapolis,
Indiana.
Supported in part by grants from the Herman C. Krannert Fund,
USPHS grants HL-06308 and HL-05749, the American Heart
Association, Indiana Affiliate, Inc., and the Veterans Administration.
Address for correspondence: L.S. Wann, M.D., Wood Veterans
Administration Medical Center (111C), Wood, Wisconsin 53193.
Received February 22, 1979; revision accepted June 5, 1979.
Circulation 60, No. 6, 1979.
Cross-sectional echocardiography provides realtime, two-dimensional tomographic images of the
heart. The procedure is being used more frequently in
cardiac diagnosis, and has been useful in detecting abnormal left ventricular wall motion during1-3 and
after4' acute myocardial infarction. Although we
have observed transient segmental left ventricular
dysynergy during episodes of variant angina,6 crosssectional echocardiography has not been widely used
to detect wall motion abnormalities dueing exerciseinduced angina pectoris. This study was undertaken to
determine the feasibility of detecting areas of transient
left ventricular dysynergy with cross-sectional echocardiography during exercise-induced myocardial
ischemia.
Materials and Methods
Patient Population
We studied 28 patients who underwent cardiac
catheterization for clinical evaluation of suspected
ischemic heart disease. All patients had experienced
Response of right ventricular ejection fraction to upright bicycle exercise in coronary
artery disease.
H J Berger, D E Johnstone, J M Sands, A Gottschalk and B L Zaret
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Circulation. 1979;60:1292-1300
doi: 10.1161/01.CIR.60.6.1292
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1979 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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