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Assessment of left ventricular function by resting and exercise radionuclide angiocardiography following acute myocardial infarcton
CLINICAL
INVESTIGATIONS
Assessment of left ventricular function by resting and exercise radionuckie angiocardiugraphy following acute myocardial infarcton Left ventricular function was evaluated by first-pass radionuclide angiocardiography in 42 patients at 3 and 8 weeks followtng acute myocardlal Infarction. Left ventricular ejection fraction, diastolic volume, and wall motion were measured at res and submaximal exercise at 3 weeks and at rest, submaximal and maximal exercise at 8 we 9J 8. The mean ejection fraction, end-diastolic volume, and wall motion Index did not change between 3 and 8 weeks in any group either at rest or during submaximal exercise. Ventricular function was decreased at rest in patients with previous and anterior myocardial infarctions, but not in patients with Inferior and subendocardial myocardial infarctions. During maximal exercise at 8 weeks, nine patients (21%) had ST segment depression, whereas 25 patients (80%) had a decrease in ejection fraction or a deterioration in wall motion. These abnormalities of ventricular function during exercise occurred equally among the infarct groups. Radionucllde angiography in patients with recent myocardial infarction demonstrated highly variable ventricular function at rest and/or during exercise in each infarct subgroup. (AM HEART J 104:1232, 1982.)
Mark T. Upton, M.D., Sebastian T. Palmeri, M.D., Robert H. Jones, M.D., R. Edward Coleman, M.D., and Frederick R. Cobb, M.D. Durham, N.C. Previous studies have demonstrated that exercise stress testing with ECG monitoring can be safely performed early after acute myocardial infarction (AMI).‘-’ The results of these tests have been used to identify patients with exercise-induced myocardial ischemia, to provide guidelines for prescribing physical activity,3s 5 and to assist with establishing prognosis.4,6-s The frequency of ECG evidence of ischemia during exercise stress testing in patients with coronary artery disease is reduced in patients with prior infarction and/or ventricular dysfunction.‘-l4 In addition, the ECG does not provide a quantitative measurement of ventricular function, a major determinant of prognosis,15-1s or serial assessment of change in ventricular function following infarction. Electrocardiographic ST segment changes may be influenced by variables other than ischemia includFrom the Departments sity Medical Center; Institute. This work HL 17670, Association Received accepted
was supported in part and by an Established (Dr. Cobb). for publication Nov. 12, 1981.
Reprint requests: ham VA Medical
1232
of Medicine, Surgery, and Radiology, Duke and the Laboratories of the Howard Hughes
July
by Specialized Investigatorship 21, 1981;
revision
Center for Research of the American received
Oct.
Frederick R. Cobb, M.D., Division of Cardiology, Center, 508 Fulton Sk, Durham, NC 27705.
UniverMedical Grant Heart 19, 1981; Dur-
ing digitalis, electrolytes, ventricular hypertrophy, and conduction abnormalities. Radionuclide angiocardiography (RNA) should prove useful in studying postinfarction patients since this method is noninvasive, easy to perform, provides accurate and reproducible quantitative measurements of left ventricular (LV) function,20-26 and appears to be more sensitive and specific than stress ECG in detecting exercise-induced myocardial ischemia.27-2s Accordingly, in this investigation first-pass radionuclide angiocardiograms were performed at rest and exercise during early and late convalescence phases following AMI. The purpose of this study was to define the extent of LV dysfunction and the time course of recovery following AM1 in a prospective group of patients. Individual patients were identified with either severely depressed ventricular function at rest or evidence of myocardial ischemia during exercise who might be expected to have increased morbidity and mortality. METHODS Patients.
Forty-two men with a mean age of 57 years (range 42 to 83) were studied. The diagnosisof AM1 was made when at least two of the following criteria were present: (1) prolonged chest pain consistent with myocar0002~8703/82/121232
+12$01.20/O@
1982
The
C.V.
Mosby
Co.
Volume Number
104 6
Rest/exercise
RNA assessment of LV function
REST HRTb4 ED\.
108
post-AMI
1233
EXERCISE EL169 WMI~
0
HR
125
EDV- 195
EF 30 b&‘M -~6
Fig. 1. Compositeimagesof the left ventricle at rest and during maximal exerciseat 8 weeksin a patient with an inferior myocardial infarction. At rest, left ventricular function is normal. During exercise, the ejection fraction (EF) decreases,the end-diastolic volume (EDV) increases, and global asyneresis develops.HR = heart rate; WMI = wall motion index.
dial &hernia, (2) characteristic evolutionary ECG changes of myocardial infarction, and (3) elevation of total serum creatine kinase with detection of the MB isoenzyme by electrophoretic assay.According to establishedECG criteria, the patients were divided into the following groups: nine anterior (including anteroseptal and anterolateral), 13 inferior (including inferoposterior and true posterior), and 10 subendocardial(Q waves0.04 secondin duration in two or more leads did not develop). Ten patients had documented previous myocardial infarction and were considered as a separate group. No patient had ECG evidence of LV hypertrophy or left bundle branch block. None required permanent pacemaker therapy. Patients with significant pulmonary or valvular heart diseaseor physical handicaps which precluded pedaling a bicycle were excluded. TWO patients with class IV heart failure had radionuclide angiocardiogramsperformed at rest only and were not included in the analysis. One patient died and another underwent coronary artery bypass surgery between3 and 8 weeks,and thesealsowere not included in the analysis. Study design. Patients were evaluated at 3 and 8 weeks following AMI. Each patient was interviewed and examined by a physician and informed consent was obtained. No patient had taken propranolol within 48 hours or nitrates within 2 hours of exercisestresstesting. A 12-lead ECG wasrecorded prior to exercise.During exercise,leads VS.ewere continuously monitored on a two-channel oscilloscope.The limb leads and leads V,., were also recorded at l-minute intervals during exercise and the recovery period. Blood pressurewas measuredby sphygmomanometer every 2 minutes and at peak exercise. At 3 weeksfollowing AMI, an RNA wasobtained at rest in the erect position. Exercise was then begun on an isokinetic bicycle ergometer (Fitron). The work load was
started at 100 kpm/min and increasedby 100 kpm/min every minute. Exercise wasterminated oncethe heart rate reached 120bpm or after the appearanceof one or more of the following: 0.1 mV ST segmentdepression;chest pain suggestive of angina or excessive fatigue. None of the exercise tests were stopped becauseof hypotension or ventricular arrhythmia. An RNA was performed. during exercise at the maximum work load achieved. At 8 weeks postinfarction, an RNA wasobtained at rest and then the sameexercise protocol as before was followed. An RNA was performed during exercise at the identical workload achieved at 3 weeks. In addition, in those patients who were not symptom-limited at this “submaximal” exercise level, the work load wasprogressively increaseduntil the heart rate reached85% of the maximum predicted for age or one of the above endpoints intervened. A second exercise RNA was performed at this “maximal” exercise level. Radionuclide procedure. The resting radionuclide angiocardiogramwasperformed in the anterior projection with the patient sitting on the bicycle ergometer, Ten millicuries of technetium-99m pertechnetate were injected into either the antecubital or the external jugular vein and were flushed with 10 ml of normal saline. Anterior precordial counts were recorded in binary form at 25 msec intervals for 1 minute using a multicrystal gamma camera (Baird-Atomic System Seventy-Seven) equipped with a l-inch parallel hole collimator. The exercisestudieswere performed in the samemanner asthe resting studies except that background counts were collected over the precordium before each additional injection. Data were stored on a magnetic tape for later processing. Data processing. The radionuclide angiocardiograms were analyzed as previously described.22~24,30 Briefly, each
1234 Table
Upton
et al.
American
I. Mean hemodynamic measurementsat rest and during exerciseat 3 and 8 weeks Ejection
fraction
3 weeks Location
Anterior (9) Inferior (13) Subendocardial (IO) Previous (10) R=rest;
December. 1982 Heart Journal
8 weeks
R
SEX
R
35 +lO 51 211
36 +13 50 +15
36 110 53 +11
64
61 k3 23 +9
61 +4 23 +8
kll 26 +I0
SEx=submaximal
End-diastolic
SEX 35 ill 51 +13 63 ~8 28 &lo
volume
3 weeks MEx
SEX
R
SEX
37 ?13 50 *13
209 156 161 +39
234 k66 180 +50
217 +66 156 236
230 k79 184 -r-39
62
141 k23 252 k75
160 -c42 278 r56
142 +30 277 k100
165 +43 282 k73
28 +lO
exercise; MEx=maximal
output
3 weeks
8 weeks
R
kll
Cardiac
MEx
Wall
motion
3 weeks
8 weeks
R
SEX
R
SEX
MEx
232 k78 193 +37
5.6 f1.5 6.1 e2.3
9.3 22.2 10.4 k4.1
5.5 il.1 6.0 +1.8
9.7 rt2.2 10.4 +3.3
167 +40 291 k80
6.5 rt1.2 4.7 21.6
11.7 k3.0 8.6 k2.4
6.2 k1.2 4.9 22.1
11.9 k3.1 8.9 +2.3
index
8 weeks
R
SEX
R
SEX
MEx
10.7 k2.3 12.7 k4.6
6.4 23.6 3.3 k3.0
7.2 ~3.6 4.5 k3.2
6.1 13.6 3.4 k3.0
7.2 k3.5 4.7 +3.2
7.2 23.5 4.8 k3.2
14.5 24.6 9.4 22.2
0.2 k0.4 9.1 k1.7
1.3 k2.1 9.1 f1.7
0.2 kO.4 9.3 k1.3
1.4 1.6 k1.9 k2.3 9.4 9.1 1.4 k1.7
exercise.
study wasfirst corrected for field nonuniformity and dead time; the exercisestudies were alsocorrected for preexisting counts in each crystal. A high frequency time-activity curve was obtained from the LV region of interest, and individual beats were identified. After subtracting background activity, an average cardiac cycle was derived by summingcounts from four to six of these beats. The LV ejection fraction (EF) wasdetermined from the average cycle: EF = (end-diastolic counts - end-systolic count&/end-diastolic counts LV end-diastolic volume (EDV) was calculated in milliliters using the length-area method of Sandler and Dodge? EDV = 0.85 AZ/L, where A is the planimetered area of the left ventricle, and L is the maximal length. Stroke volume (SV) and cardiac output (CO) were derived from the measuredEF, EDV, and heart rate (HR) by the following equations: SV (ml) = EDV (ml) x EF, and CO (L/min) = SV (ml) X HR (bpm). Regional wall motion was assessed by inspecting both dynamic and static imagesof the average cardiac cycle (Fig. 1). The LV outline was divided into three segments: anterior, apical, and inferior. Each segmentwasgraded on a scale of 0 to 6, where 0 = normal, 1 and 2 = mild and severeasyneresis,3 and 4 = mild and severeakinesia, and 5 and 6 = mild and severedyskinesia. “Mild” wasusedto describe an abnormality involving less than half and “severe” to describean area more than half of the segment analyzed. Scores from each of the three segmentswere summed, and a wall motion index (WMI), ranging from 0 (normal) to +18 (total dyskinesis), was assignedto each study. Statistical analysis. The data are expressedas mean f standard deviation. The significance of difference in measurements between groups was assessedusing one-way analysis of variance. Linear regression equations and correlation coefficients were derived by the least squares method. RESULTS
Table I tabulates the mean hemodynamic measurements in each infarct group at rest and exercise
at 3 weeks and at 8 weeks. Table II tabulates the clinical measurements and endpoints of the exercise test at 8 weeks in individual patients. Table III tabulates the hemodynamic measurements at rest and maximum exercise at 8 weeks in individual patients. Clinical characteristics. Patients were categorized clinically at the time of admission according to the criteria of Killup and Kimbal1.32 Thirty were class I (5 anterior, 10 inferior, 10 subendocardial, and 5 previous myocardial infarctions), seven were class II (two anterior, two inferior, and three previous myocardial infarctions), and five were class III (two anterior, one inferior, and two previous myocardial infarctions). At 8 weeks each patient was also classified clinically according to the New York Heart Association criteria for angina pectoris and heart failure (Table II).” Medications at the time of the 8-week evaluation are listed in Table II. Endpoints of exercise. At 3 weeks, 27 patients exercised to a heart rate of 120 bpm without fatigue, ST segment depression, or chest pain. Six patients were limited by fatigue alone prior to reaching a heart rate of 120 bpm, 7 patients developed 0.1 mm ST segment depression, and 2 experienced chest pain but did not develop ST segment depression. At 8 weeks, 26 patients reached a higher work load than at 3 weeks and therefore were studied during two levels of exercise. Nineteen patients achieved a heart rate of 85% maximum predicted for age without fatigue, ST segment depression, or chest pain. Eleven patients were limited by fatigue, nine patients developed ST segment depression, and three experienced chest pain but did not develop ST segment depression. Six of the 10 patients with previous myocardial infarction did not reach the target heart rate at 8 weeks, whereas none developed ST segment depression (Table II).
Volume Number
Table
104 6
Rest/exercise
RNA assessment
of LV function
post-AM1
1235
II. Clinical measurementsand endpoints of exercise test at 8 weeks Endpoints ECG
Age Anterior MI 1 2 3 4 5 6 7 8 9 Inferior MI 10 11 12 13 14 15 16 17 18 19 20 21 22 Subendocardial 23 24 25 26 27 28 29 30 31 32 Previous MI 33 34 35 36 37 38 39 40 41 42
51 53 58 56 42 56 61 53 56
ALMI AM1 ALMI AM1 AMI AM1 ASMI AM1 AM1
66 56 54 57 56 56 72 60 57 54 56 54 55 MI 54 60 59 59 46 51 56 55 68 77
IMI IMI TPMI TPMI IMI IMI IMI IMI IMI IMI, RBBB IMI IMI IMI Tll, aVL WNL WNL Tll, aVL WNL TJ2,3, aVF TJ2, 3, aVF T11, aVL,V,., Tl Vs., WNL
59 55 62 83 53 47 63 57 65 46
AM1 ALMI, IMI AMI, AMI, AM1 AMI, ASMI, AMI, AMI,
MEDS
Dig,
Fur -
IMI IMI IMI IMI IMI IMI IMI
-
-
Quin
HCTZ
Dig, Dig
Fur
Dig Fur
Dig, Fur -
Angina class
Failure class
I I II II I III III III I
I II II II I II I I III
II I I I II I IV III I I I III I
I I I I I I I I I I I I I
I I III I I I III II I II
I I I I I I I I I I
I I I I I II II I I I
II III I II III I I II II I
Angina
+ + -
+ + +
of exercise ST1
Fatigue
-
+ +
+ -
+ -
-I-
+ +
+ +
+
+ -
+
+
+
+ -
+ +
-
-
+ -
+ + +
+ -
-
+ + +
-
+ -
MI = myocardial infarction; ALMI = anterolateral myocardial infarction; AMI = anterior myocardial infarction; ASMI = anteroseptal myocardial infarction; IMI = inferior myocardial infarction; TPMI = true posterior myocardial infarction; RBBB = right bundle branch block; WNL = within normal limits; MEDS = medications; Dig = digoxin; Fur = furosemide; Quin = quinidine; HCTZ = hydrochlorothiazide.
Ejection fraction. The mean ejection fraction in each group was not significantly different at 3 and 8 weeks at rest or during submaximal exercise (Table I). Linear regression analyses demonstrated a close correlation between EF at rest at 3 and 8 weeks (r = 0.96) and the EF during exercise at 3 and 8 weeks (r = 0.94) (Fig. 2). The EF at rest was a
previous infarct had occurred. At 8 weeks mean EF was lowest in the group with previous infarction (23 + 9%) and was decreased also in the group with anterior infarction (36 + lo%), but not in the groups with inferior (53 +- 11% ) and subendocardial infarction (61 +- 3 % ). At both 3 and 8 weeks all patients with subendocardial myocardial infarctions
function of the location of infarction and whether a
had resting ejection fractions above 53%, whereas
1236
Upton et al.
Table
III. Hemodynamic
American
measurements at rest and during maximal exercise at 8 weeks Wall
Patient no. Anterior
Hi2 (bpm)
R
R
R
MEx
EDV
(ml)
R
MEx
CO (Llmin) R
MEx
Rest Ant
Ap
Exercise Znf
Tot
Ant
1
2 0 0 0 2 2 1 0
4 12 2 3 4 10 10 4 6
4 5 2 1 2 4 4 2 4
Ap
Znf
Tot
1 2 0 0 0 2 2 1 1
6 12 3 3 4 11 10 7 9
97 109 102 80 89 80 100 131 97
124 123 117 93 114 113 97 142 95
70 100 72 72 85 70 100 57 54
150 146 100 145 160 130 120 115 125
40 23 52 37 38 29 22 47 36
37 32 53 56 49 23 24 35 25
190 204 171 187 140 193 344 217 307
190 207 179 174 165 202 389 253 329
5.3 4.7 6.4 5.0 4.5 3.9 7.6 5.8 6.0
10.5 9.7 11.4 14.1 12.9 6.0 11.2 10.0 10.3
2 5 2 1 2 4 4 2 2
90 74 94 106 77 76 91 83 83 125 99 87 97
97 89 101 113 100 101 108 93 117 137 105 103 113
54 80 114 80 68 70 90 84 66 64 84 80 65
100 144 148 150 110 144 148 126 142 98 154 132 110
44 45 70 64 54 44 40 69 53 63 44 49 45
42 53 68 72 51 46 35 30 51 69 47 38 44
173 224 137 138 154 199 137 108 162 111 228 128 148
188 191 184 166 186 235 158 195 246 139 272 177 172
4.1 8.1 10.9 7.1 5.6 6.1 4.9 6.2 5.7 4.8 5.7 5.0 4.3
7.9 10.0 18.5 17.9 10.5 15.6 8.2 7.4 17.8 12.6 19.7 8.9 10.1
0 1 0 0 0 0 0 0 0 0 0 0 0
4 5 0 0 1 2 1 0 2 0 1 0 1
0 4 0 0 4 4 4 0 2 0 4 2 2
4 10 0 0 5 6 5 0 4 0 5 2 3
0 1 0 0 1 0 1 2 0 0 0 2 0
4 5 0 0 2 4 2 2 2 0 1 2 1
2 4 0 0 4 4 4 2 2 0 4 2 2
6 10 0 0 7 8 7 6 4 0 5 6 3
90 90 101 73 101 83 90 83 96 108
113 103 125 110 121 103 115 100 101 122
60 82 64 75 70 74 58 75 75 100
150 148 135 150 150 140 122 165 120 158
67 64 57 60 57 62 62 60 57 64
64 63 42 80 71 64 55 61 68 51
185 153 188 122 158 129 136 141 98 105
207 187 216 180 158 160 155 200 109 98
7.9 8.0 6.8 5.4 6.3 5.9 4.9 6.3 4.2 6.7
19.8 17.5 12.3 21.6 16.9 13.4 10.4 15.9 8.9 7.9
0 0 0 0 0 0 0 0 0 0
0 0 1 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 1
0 0 1 0 0 0 0 0 0 1
0 0 0 0 0 0 4 0 0 2
0 0 4 0 0 0 0 0 0 0
0 0 2 0 0 0 0 2 0 2
0 0 6 0 0 0 4 2 0 4
68 100 78 86 107 89 101 77 73 86
84 113 91 100 93 88 107 85 109 114
90 70 84 58 84 66 63 84 90 95
115 144 130 100 126 138 110 150 140 160
20 14 30 36 20 18 38 12 24 22
25 20 38 31 18 24 50 19 32 21
421 286 210 356 455 239 172 229 222 184
382 296 224 425 380 214 240 312 227 213
7.6 2.8 5.3 7.4 7.6 2.8 4.1 2.3 4.8 3.8
11.0 8.5 11.1 13.2 8.6 7.1 13.2 8.9 10.2 7.2
2 2 2 2 4 4 2 2 2 4
5 4 4 4 4 4 4 6 3 2
2 4 2 2 2 2 2 4 3 4
9 10 8 8 10 10 8 12 8 10
2 2 2 2 4 5 2 2 3 4
5 5 4 4 4 4 4 6 3 4
2 4 2 2 2 2 2 4 2 4
9 11 8 8 10 11 8 12 8 12
Subendocardial
23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
MEx
EF(%)
MI
10 11 12 13 14 15 16 17 18 19 20 21 22
Previous
index
MI
1 2 3 4 5 6 7 8 9 Inferior
-motion
--
Mean BP (mm ZW MEn
December, 1982 Heart Journal
MI
MI
MI = myocardial infarction; BP = blood pressure; R = rest; MEx = maximal exercise; HR = heart rate; bpm = beats per minute; EF = ejection fraction; EDV = end-diastolic volume; CO = cardiac output; Ant = anterior; Ap = apical; Inf = inferior; Tot = total.
all patients with previous myocardial infarctions had resting ejection fractions below 39%. The mean EF from rest to exercise did not change in the group with anterior, inferior, or subendocardial infarction at either 3 or 8 weeks; the mean EF increased significantly in the group with previous
myocardial infarction. However, within each group, the responses to exercise in individual patients were heterogeneous. The EF at rest and during maximum exercise at 8 weeks in individual patients is illustrated in Fig. 3 and is tabulated in Table III. Twenty patients had a decrease in EF during maximal
Volume
104
Number
6
Rest/exercise
RNA assessment
REST
of LV function
post-AMI
EXERCISE
100
'1%:
80-
0’
6 20
I 40
a0
60
100
20
% - 8 WEEKS Fig. 2. Correlation between submaximal exercise.
60
80
I
% - 8 WEEKS
3- and &week
values for left ventricular
100
ANTERIOR
IOOr
40
ejection
fraction
at rest and during
INFERIOR
a0 60-
P=NS 0
100
REST
'11
,
P=NS
REST
ME,
SUBENDOCARDIAL
ao-
, ME,
MULTIPLE
a0 60
OL Fig.
3.
Changes
I REST
in left ventricular
P
ejection
fraction
REST
from rest to maximal
ME,
exercise
(ME3
at 8 weeks.
1237
December,
1238
Upton et al.
American
REST 5ool .
400
400 t
.
t
ln
m
TE
300
::
::. 200 I I
100 1 0=
1982 Journal
EXERCISE
5ool-----7
z L!.J 3
Heart
:- *’
. 21.: *: .
100
200
y -e
r zo.94 y=l.l8X-27 SEE= 27
300
I 200
100
400
.. *
300
z
.‘..
. .’
.
.
i
10
500
ml - 8 WEEKS
ml
-
8 WEEKS
Fig. 4. Correlation between 3 and 8 week values for left ventricular end-diastolic d&ng submaximal exercise.
exercise at 8 weeks: three previous, four anterior, eight inferior, and five subendocardial myocardial infarctions. In the 26 patients who had RNA performed during two levels of exercise at 8 weeks, the change in ejection fraction from rest to submaximal to maximal exercise tended to be in the same direction. Only two patients had an increase in EF at submaximal exercise and a decrease at maximal exercise. End-diastolk voiume. The mean diastolic volumes at rest and exercise for the four groups at 3 and 8 weeks are presented in Table I. Linear regression analysis demonstrated a good correlation between end-diastolic volume at rest at 3 and 8 weeks (r = 0.94) and during exercise at 3 and 8 weeks (T = 0.91) (Fig. 4). The end-diastolic volume at rest was significantly larger in the groups with previous and anterior myocardial infarctions than in the groups with inferior and previous myocardial infarctions. The patients with anterior, inferior, and subendocardial myocardial infarctions demonstrated a significant increase in end-diastolic volume from rest to maximal exercise at 8 weeks, whereas the patients with previous myocardial infarctions demonstrated no significant change (Fig. 5). Enddiastolic volume increased more than 25 % from rest to maximal exercise at 8 weeks in eight patients. Wall motion. The wall motion index did not change significantly between 3 and 8 weeks, either at rest or during exercise (Table I). Linear regression analysis demonstrated excellent correlations between WMI at rest at 3 and 8 weeks (r = 9.99) and during exercise at 3 and 8 weeks (r = 0.98). At 8 weeks, the
volume at rest and
WMIs for the four groups at rest were: 9.3 + 1.3 previous, 5.5 f 1.1 anterior, 3.4 & 3.0 inferior, and 0.2 + 0.4 subendocardial myocardial infarctions. Comparison of mean WMIs at rest between groups by analyses of variance demonstrated significant differences between each group with the exception of anterior versus inferior infarction. All patients with anterior and previous myocardial infarctions demonstrated resting wall motion abnormalities at 8 weeks. Four patients with inferior myocardial infarction and eight with subendocardial myocardial infarction did not demonstrate wall motion abnormalities at rest. In general, the wall motion abnormalities corresponded with the ECG location of the myocardial infarction (Tables II and III). The wall motion index at rest and at maximal exercise at 8 weeks is illustrated in Fig. 6. The groups with anterior, inferior, and subendocardial myocardial infarctions had a significant increase in WMI from rest to maximal exercise; no significant change was noted in the group with previous myocardial infarctions. Sixteen patients developed a new or more severe wall motion abnormality during submaximal exercise at both 3 and 8 weeks; an additional two patients had stress-induced wall motion abnormalities during maximal exercise at 8 weeks (Table III). Patients with severely depressed resting function did not usually develop additional wall motion abnormalities during exercise. carc~ac output. The mean cardiac outputs at rest and exercise for the four groups are listed in Table I.
Volume Number
104 6
Rest/exercise ANTERIOR
500-
RNA assessment
of LV function
post-AM
1239
INFERIOR
500-
400-
300-
300-
200-
200-
ml 0 0
loo-
looPC.05
O-
1 REST
P<.OOl O-
MEr
SUBENOOCARDIAL
500-
400
300 -
: 300 -
opo
loo-
m1200-
E=====-
1 REST
0
0
loo-
PC ,005 0
ML
MULTIPLE
500
400-
m'200-
REST
P=NS I MEx
0.
I REST
MEx
Fig. 5. Changes in left ventricular end-diastolic volume from rest to maximal exercise (it4EJ at 8
weeks.
The cardiac outputs at rest and submaximal exercise did not change significantly between 3 and 8 weeks. Excluding the 12 patients who were limited by angina or ST segment depression during maximal exercise at 8 weeks, a weak linear correlation was observed between the resting ejection fraction and the maximal cardiac output (r = 0.74) (Fig. 7). Including all patients in the regression analysis further weakened the correlation. Five patients with resting EFs below 50% were able to achieve cardiac outputs during exercise above 12 L/min. DISCUSSION
LV function was assessed at rest and during exercise by RNA in 42 patients at 3 and 8 weeks following acute myocardial infarction. The results indicate that LV function at rest was influenced by the location of the myocardial infarction and whether previous infarction had occurred, and that LV function at rest and during exercise did not change
between 3 and 8 weeks after infarction. However, within each group ventricular function in individual patients at rest and/or exercise was heterogeneous. In each group there were patients with reduced ventricular function at rest and/or during exercise who could be expected to be at an increased risk for subsequent morbidity or mortality, Utility of exercise stress testing post-AM. Previous studies have demonstrated that in patients who survive acute myocardial infarctions, subsequent risk of cardiac death and recurrent myocardial infarction has been associated with extensive coro34-35depressed resting vennary artery disease, 16-lgs tricular function,15-1g and evidence of myocardial ischemia during exercise.4v6-g Recent studies have shown that exercise testing can be safely performed soon after myocardial infarction.1-g The frequency of ECG evidence of ischemia during exercise stress in patients with coronary artery disease is reduced in patients with prior myocardial infarction and/or
1240
Upton
December,
et al.
American
Heart
1982 Journal
ANTERIOR
0 I REST
PC.05
I MEx
REST
MEx
SUBENDOCARDIAL
16 r
I2 0..=I _
12 1
....-
a
a I
o .. .
0 t REST
Fig.
ME,
I REST
P=NS
I MEx
6. Changes in left ventricular wall motion index from rest to maximal exercise
left ventricular image was divided into approximateIy
(MEJ at 8 weeks.The
equal anterior, apical, and inferior segments. Each segment was graded on a scale of 0 to 6: 0 = normal; 1 and 2 = mild and severe asyneresis; 3 and 4 = mild and severe akinesis; 5 and 6 = mild and severe dyskinesis. Wall motion index represents the sum of wall motion grades in a given patient.
ventricular dysfunction .7-14The reduced frequency of positive exercise stress tests after infarction may be related to reduction in potentially ischemic myocardium and/or masking of ECG evidence of ischemia as a result of ventricular dysfunction.lO-l4 Electrocardiographic ST segments may be influenced by variables other than ischemia or infarction, including digitalis, electrolytes, ventricular hypertrophy, and conduction abnormalities. Utility of exercise RNA post-AM. RNA is potentially an ideal technique for evaluating the patient with prior myocardial infarction. RNA provides measurements of ventricular function including ejection fraction, ventricular volumes, regional wall motion, and cardiac output which correlate well with contrast angiography and dye dilution techniques.20-24~30 The reproducibility of the technique is high.25,26 RNA is easily adapted to exercise stress testing and thus allows assessment of exercise-induced &hernia
by a technique segment shifts. Rest and exercise
which
is not dependent
LV function
stable between
on ST 3 and 8
weeks post-AMI. The results of this investigation are in agreement with other studies which have demonstrated that ventricular function at rest is depressed to a greater extent in patients with anterior and previous myocardial infarctions than in patients with inferior and subendocardial myocardial infarctions.11*3E-38However, considerable overlap existed among patients in the different groups. The mean LVEF, end-diastolic volume, cardiac output, and WMI did not change significantly in any group between 3 and 8 weeks, either at rest or during submaximal exercise. Furthermore, individual variations in these measurements were small, indicating that LV function is relatively stable during this period. Reduto et al.% have previously demonstrated that resting ventricular function remains constant
Volume
104
Number
6
Rest/exercise
i--l10
20
30
40
Resting
Eiection
RNA assessment
50
60
Fraction
- %
of LV function
70
post-AMI
1241
80
Fig. 7. Correlation between resting ejection fraction and maximal cardiac output in 30 patients not limited by angina or ST segmentdepressionduring exercise at 8 weeks.
during the hospital phase of myocardial infarction; Borer et al.3g reported no significant change in the response of EF to submaximal exercise immediately prior to hospital discharge and 8 to 13 months later. Identification of prognostic subgroups. In the present study, only nine patients (21%) had 0.1 mV or greater ST segment depression during maximal exercise at 8 weeks. Therefore our findings are in agreement with previous studies which have demonstrated a low incidence of stress-induced ECG evidence of ischemia in patients with myocardial infarction.7-14 All patients who had ST segment depression during exercise also demonstrated a decrease in EF and an increase in WMI during exercise. Twenty-three patients (53 % ) had either a decrease in EF or an increase in WMI during submaximal exercise at 3 and 8 weeks, and 25 patients (60%) demonstrated these abnormal ventricular responses to maximal exercise at 8 weeks. Recent studies from our laboratory indicate that failure of the global EF to increase or even a decrease in the EF during exercise are not specific indices of coronary artery disease and myocardial ischemia. We have observed that in women with atypical chest pain but normal coronary arteries the EF frequently does not increase, or may even decrease during exercise .40Studies in our laboratory have also demonstrated a linear decline of the changes in EF with increasing age in asymptomatic
volunteers without apparent cardiovascular disease.41 Using a 0.05 increase in EF as a normal response during exercise, the frequency of a subnormal response was 10% in subjects in the fifth decade of life and then progressively increased to 95% of subjects in the eighth to tenth decades of life. In the present study, all patients were male, 11 were L 60 years of age, and a decrease in EF rather than a failure to increase 0.05 was used as a criteria for an abnormal EF response to exercise. Our findings suggest that an RNA evaluation at rest and during upright exercise in the convalescent phase at 3 or 8 weeks following acute myocardial infarction permits the identification of patients with depressed resting ventricular function or exercise-induced myocardial ischemia who may benefit from intensive medical or surgical therapy. In addition, RNA identified patients with normal or mildly reduced function at rest and no decrease in EF or appearance of additional wall motion abnormalities during exercise who may be expected to have a better subsequent prognosis. Location of AMI and exercise LV dysfunction. In the present study there was no relation between the location of the myocardial infarction by ECG and the presence of exercised-induced LV dysfunction. The presence of Q waves, however, did predict resting wall motion abnormalities. In contrast, Pulido et a1.37 reported that patients with anterior myocardial infarctions had a greater incidence of
1242
Upton et al.
abnormal ventricular responses to exercise. The different findings may be explained by the small number of patients with anterior myocardial infarction evaluated in each study. Rest and exercise LV dysfunction. Eleven patients (26 % 1 had resting EF below 35% ; none developed ST segment depression during maximal exercise at 8 weeks, and only one experienced angina. However, six of those patients had either a decrease in EF or a new or more severe wall motion abnormality during exercise, suggesting that these patients still had residual viable myocardium that was supplied by critically stenosed coronary vessels. These patients with both severely depressed resting ventricular function and exercise-induced myocardial ischemia may be a subgroup at high risk for subsequent coronary events. Exercise increased LVEDV. End-diastolic volume increased more than 25% from rest to maximal exercise at 8 weeks in eight patients. This large increase in end-diastolic volume has previously been reported to occur in patients with coronary artery disease and may represent a greater utilization of the Starling mechanism in patients with reduced systolic performance during exercise.22~42 Excluding those patients who were limited by angina during exercise, there was a linear correlation between resting EF and maximal cardiac output at 8 weeks. However, five patients with depressed resting EF (< 50% ) were able to achieve cardiac outputs in excess of 12 L/min. This preservation of exercise capacity despite depressed LV function has previously been reported in other studies.43-45 Conclusions. This study has shown that RNA can be safely performed at rest and during exercise in the early and late convalescent phases following acute myocardial infarction. Patients with anterior and previous myocardial infarctions tended to have lower resting EF, larger end-diastolic volumes, and more wall motion abnormalities than patients with inferior or subendocardial myocardial infarctions. Ventricular function remained relatively stable both at rest and during submaximal exercise between 3 and 8 weeks. Within each group, the ventricular response to exercise was heterogenous. Individual patients were identified who demonstrated significant functional abnormalities during exercise, including a decrease in EF, a large increase in end-diastolic volume, and new or more severe wall motion abnormalities. The prognostic significance of these abnormalities is the subject of ongoing clinical studies. The following persons rendered valuable assistance with carrying out the studies: Jean Wilson, R.N., Research Nurse, and Cathie Collins, Secretary.
American
December, 1982 Heart Journal
REFERENCES
1. Atterhog JH, Ekelund LG, Kaijser L: Electrocardiographic abnormalities during exercise 3 weeks to 18 months after anterior myocardial infarction. Br Heart J 33:871, 1971. 2. Ericsson M. Granath A. Ohlsen P. Sodermark T. Volne U: Arrhythmias and symptoms during treadmill testing Ithree weeks after myocardial infarction in 100 patients. Br Heart J 35:767, 1973. 3. Ibsen H, Kjgller E, Styperek J, Pedersen A: Routine exercise ECG three weeks after acute myocardial infarction. Acta Med Stand 198:463, 1975. 4. Markiewicz W, Houston N, DeBusk RF: Exercise testing soon after myocardial infarction. Circulation 56:26, 1977. 5. Wohl AJ, Lewis HR, Campbell W, Karlsson E, Willerson JT, Mullins CB, Blomqvist CG: Cardiovascular function during early recovery from acute myocardial infarction. Circulation S&931, 1977. 6. Granath A, Sodermark T, Winge T, Volpe U, Zetterquist S: Early workload test for evaluation of long-term prognosis of acute myocardial infarction. Br Heart J 75:787,1973. 7. Sami M. Kraemer H. DeBusk RF: The nrognostic sienificance of serial exercise testing after myocardial infarction. Circulation 60:1238, 1979. 9. Theroux P, Waters DD, Halpen C, Debasieux JC, Mizzala HF: Prognostic value of exercise testing soon after myocardial infarction. N Engl J Med 301:341, 1979. 9. Davidson DM, DeBusk EF: Prognostic value of a single exercise test 3 weeks after uncomplicated myocardial infarction. Circulation 61:236, 1980. 10. Kramer N, Susmano A, Shekelle RB: The “false negative” treadmill exercise test and left ventricular dysfunction. Circulation 57:763, 1978. 11. Castellanet MJ, Greenberg PS, Ellestad MI-h Comparison of S-T segment changes on exercise testing with angiographic findings in patients with prior myocardial infarction. Am J Cardiol 42:29, 1978. 12. Kasser IS, Bruce RA: Comparative effects of aging and coronary heart disease on submaximal and maximal exercise. Circulation 39:759, 1969. 13. Fitzeibbon GM. Bureeraf GW. Groves TD. Parker JO: A double Master’s two-step te& Clinical, angiographic and hemodynamic correlations. Ann Intern Med 74:509, 1971. 14. Weiner DA, McCabe C, Klein MD, Ryan TJ: ST segment changes postinfarction: Predictive value for multivessel coronary disease and left ventricular aneurysm. Circulation S&887, 1978. 15. Oberman A, Jones WB, Riley CP, Reeves TJ, Sheffield LT: Natural history of coronary artery disease. Bull NY Acad Med 48:1109, 1972. 16. Bruschke AVG, Proudfit WL, Sones FM Jr: Progress study of 590 consecutive nonsurgical cases of coronary disease followed 5-9 years. II. Ventriculographic and other correlations. Circulation 47:1154, 1973. 17. Humphries JO, Kuller L, Ross RS, Friesinger GC, Page EE: Natural history of ischemic heart disease in relation to arteriographic findings. Circulation 49:489, 1974. 18. Burggraf GW, Parker JO: Prognosis in coronary artery disease. Angiographic, hemodynamic and clinical factors. Circulation 51:146, 1975. 19. Harris PJ, Harrell FE Jr, Lee KL, Behar VS, Rosati RA: Survival in medically treated coronary artery disease. Circulation 60:1259, 1979. 20. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS: Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease. N Engl J Med 296:839, 1977. 21. Marshall RC, Berger HJ, Costin JC, Freedman GS, Wolberg J, Cohen LS, Gottachalk A, Zaret BL: 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.
Volume
104
Number
6
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Rest/exercise
Rerych SK, Scholz PM, Newman GE, Sabiston DC Jr, Jones RH: Cardiac function at rest and during exercise in normals and in patients with coronary heart disease. Evaluation bv radionuclide angiocardiography. Ann Surg 187:449, 1978. Bodenheimer MM. Banka VS. Fooshee CM. Hermann GA. Helfant RH: Quantitative radionuclide angiography in the right anterior oblique view: Comparison with contrast ventriculography. Am J Cardiol 41:718, 1978. Scholz PM, Rerych SK, Moran JF, Newman GE, Douglas JM, Sabiston DC Jr, Jones RH: Quantitative radionuclide angiocardiography. Cathet Cardiovas Diagn 6:265, 1980. Marshall RC, Berger HJ, Reduto LA, Gottschalk A, Zaret BL: Variability in sequential measures of left ventricular performance assessed with radionuclide angiocardiography. Am J Cardiol 41:531, 1978. Upton MT, Rerych SK, Newman GE, Bounous EP Jr, Jones RH: The reproducibility of radionuclide angiocardiographic measurements of left ventricular function in normal subjects at rest and during exercise. Circulation 62:126, 1980. Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Seides SF, Epstein SE, Johnston GS: Sensitivitv. snecificitv and predictive accuracy of radionuclide cine”angiography during exercise in patients with coronary artery disease; comparison with exercise electrocardiography. Circulation 60~572, 1979. Bodenheimer MM, Banka VS, Fooshee CM, Helfant RH: Comparative sensitivity of the exercise electrocardiogram, thallium imaging and stress radionuclide angiography to detect the presence and severity of coronary heart disease. Circulation 60:1270, 1979. Newman GE, Rerych SK, Upton MT, Sabiston DC Jr, Jones RH: Comparison of electrocardiographic and left ventricular functional changes during exercise. Circulation 62~1204. 1980. Jones RH, Scholz PM: Data enhancement techniques for radionuclide cardiac studies. In Medical radionuclide imaaing. International Atomic Energy Agency 2:255, 1977. Sandler H, Dodge HT: The use of single plane angiocardiograms for the calculation of left ventricular volume in man. AM HEART J 75:325,
35.
36.
37.
38.
39.
41.
42.
43.
44.
45.
of LV function
post-AMI
1243
coronary arteriography. Tram Assoc Am Physicians 83:78, 1979. Webster JS, Moberg C, Rincon G: Natural history of severe proximal coronary artery disease as documented by coronary cineangiography. Am J Cardiol 33:195, 1974. Hamby RI, Hoffman I, Hilsenrath J, Aintablian A, Shanies S, Padmanabhan V: Clinical, hemodynamic and angiographic aspects of inferior and anterior myocardial infarctions in patients with angina pectoris. Am J Cardiol 34:513, 1974. Pulido JI, Doss J, Twieg D, Blomqvist GC, Faulkner D, Horn V, DeBates D, Tobey M, Parkey PW, Willerson JT: Submaximal exercise testing after acute myocardial infarction: Myocardial scintigraphic and electrocardiographic observations. Am J Cardiol 42:19, 1978. Reduto LA, Berger HJ, Cohen LS, Gottschalk A, Zaret BL: Sequential radionuclide assessment of left and right ventricular performance after acute transmural myocardial infarction. Ann Intern Med 89:441, 1978. Borer JS, Rosing DR, Kent KM, Seides SF, Miller R, Cohen H, Holmes D, Donahue D, Stark R, Green MV, Bacharach SL. Baker W. Enstein SE: Natural historv of left ventricular dy$function after myocardial infarction (abstr). Am J Cardiol 43:370,
40.
1968.
Killip T, Kimball JT: Treatment of myocardial infarction in a coronary care unit. Am J Cardiol 20:457, 1967. 33. The Criteria Committee of the New York Heart Association: Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 8th ed. Boston, 1979, Little, Brown & Company. 34. Friesinger GC, Page.EE, Ross RS: Prognostic significance of 32.
RNA assessment
1979.
McEwan P, Newman GE, Portwood J, Port S, Upton MT, Cobb FR, Jones RH: Correlation of rest and exercise radionuelide angiocardiographic ventricular function with the number of significantly stenosed vessels in 230 patients with coronary artery disease. J Nucl Med 20:687, 1979. Port S, Cobb FR, Coleman RE, Jones RH: The effects of age on the left ventricular ejection fraction response to exercise. N Engl J Med 303:1133, 1980. Upton MT, Rerych SK, Newman GE, Port S, Cobb FR, Jones RH: Detection of abnormalities in left ventricular function during exercise before angina and ST segment depression. Circulation 62:341, 1980. Paine TD, Dye LE, Roitman DL, Sheffield LT, Rackley CE, Russell RO Jr, Rogers WJ: Relation of graded exercise test findings after myocardial infarction to extent of coronary artery disease and left ventricular function. Am J Cardiol 42:716, 1978. Benge W, Litchfield RL, Marcus ML: Exercise capacity in patients with severe left ventricular dysfunction. Circulation 61:355, 1980. Franciosa JA, Park M, Levine B, Cohn JN: Lack of correlation between exercise capacity and indices of resting left ventricular performance in heart failure (abstr). Circulation 59(suppl 11):20, 1979.
NOTE:
After December IOth, Address Manuscripts Dean T. Mason, M.D., Editor-in-Chief AMERICAN HEART JOURNAL, Editorial Cardiac Center, Cedars Medical Center Cedars South-Suite 0 1295 N.W. 14th Street Miami, Florida 33125
I
to: Office
INVESTIGATIONS
Assessment of left ventricular function by resting and exercise radionuckie angiocardiugraphy following acute myocardial infarcton Left ventricular function was evaluated by first-pass radionuclide angiocardiography in 42 patients at 3 and 8 weeks followtng acute myocardlal Infarction. Left ventricular ejection fraction, diastolic volume, and wall motion were measured at res and submaximal exercise at 3 weeks and at rest, submaximal and maximal exercise at 8 we 9J 8. The mean ejection fraction, end-diastolic volume, and wall motion Index did not change between 3 and 8 weeks in any group either at rest or during submaximal exercise. Ventricular function was decreased at rest in patients with previous and anterior myocardial infarctions, but not in patients with Inferior and subendocardial myocardial infarctions. During maximal exercise at 8 weeks, nine patients (21%) had ST segment depression, whereas 25 patients (80%) had a decrease in ejection fraction or a deterioration in wall motion. These abnormalities of ventricular function during exercise occurred equally among the infarct groups. Radionucllde angiography in patients with recent myocardial infarction demonstrated highly variable ventricular function at rest and/or during exercise in each infarct subgroup. (AM HEART J 104:1232, 1982.)
Mark T. Upton, M.D., Sebastian T. Palmeri, M.D., Robert H. Jones, M.D., R. Edward Coleman, M.D., and Frederick R. Cobb, M.D. Durham, N.C. Previous studies have demonstrated that exercise stress testing with ECG monitoring can be safely performed early after acute myocardial infarction (AMI).‘-’ The results of these tests have been used to identify patients with exercise-induced myocardial ischemia, to provide guidelines for prescribing physical activity,3s 5 and to assist with establishing prognosis.4,6-s The frequency of ECG evidence of ischemia during exercise stress testing in patients with coronary artery disease is reduced in patients with prior infarction and/or ventricular dysfunction.‘-l4 In addition, the ECG does not provide a quantitative measurement of ventricular function, a major determinant of prognosis,15-1s or serial assessment of change in ventricular function following infarction. Electrocardiographic ST segment changes may be influenced by variables other than ischemia includFrom the Departments sity Medical Center; Institute. This work HL 17670, Association Received accepted
was supported in part and by an Established (Dr. Cobb). for publication Nov. 12, 1981.
Reprint requests: ham VA Medical
1232
of Medicine, Surgery, and Radiology, Duke and the Laboratories of the Howard Hughes
July
by Specialized Investigatorship 21, 1981;
revision
Center for Research of the American received
Oct.
Frederick R. Cobb, M.D., Division of Cardiology, Center, 508 Fulton Sk, Durham, NC 27705.
UniverMedical Grant Heart 19, 1981; Dur-
ing digitalis, electrolytes, ventricular hypertrophy, and conduction abnormalities. Radionuclide angiocardiography (RNA) should prove useful in studying postinfarction patients since this method is noninvasive, easy to perform, provides accurate and reproducible quantitative measurements of left ventricular (LV) function,20-26 and appears to be more sensitive and specific than stress ECG in detecting exercise-induced myocardial ischemia.27-2s Accordingly, in this investigation first-pass radionuclide angiocardiograms were performed at rest and exercise during early and late convalescence phases following AMI. The purpose of this study was to define the extent of LV dysfunction and the time course of recovery following AM1 in a prospective group of patients. Individual patients were identified with either severely depressed ventricular function at rest or evidence of myocardial ischemia during exercise who might be expected to have increased morbidity and mortality. METHODS Patients.
Forty-two men with a mean age of 57 years (range 42 to 83) were studied. The diagnosisof AM1 was made when at least two of the following criteria were present: (1) prolonged chest pain consistent with myocar0002~8703/82/121232
+12$01.20/O@
1982
The
C.V.
Mosby
Co.
Volume Number
104 6
Rest/exercise
RNA assessment of LV function
REST HRTb4 ED\.
108
post-AMI
1233
EXERCISE EL169 WMI~
0
HR
125
EDV- 195
EF 30 b&‘M -~6
Fig. 1. Compositeimagesof the left ventricle at rest and during maximal exerciseat 8 weeksin a patient with an inferior myocardial infarction. At rest, left ventricular function is normal. During exercise, the ejection fraction (EF) decreases,the end-diastolic volume (EDV) increases, and global asyneresis develops.HR = heart rate; WMI = wall motion index.
dial &hernia, (2) characteristic evolutionary ECG changes of myocardial infarction, and (3) elevation of total serum creatine kinase with detection of the MB isoenzyme by electrophoretic assay.According to establishedECG criteria, the patients were divided into the following groups: nine anterior (including anteroseptal and anterolateral), 13 inferior (including inferoposterior and true posterior), and 10 subendocardial(Q waves0.04 secondin duration in two or more leads did not develop). Ten patients had documented previous myocardial infarction and were considered as a separate group. No patient had ECG evidence of LV hypertrophy or left bundle branch block. None required permanent pacemaker therapy. Patients with significant pulmonary or valvular heart diseaseor physical handicaps which precluded pedaling a bicycle were excluded. TWO patients with class IV heart failure had radionuclide angiocardiogramsperformed at rest only and were not included in the analysis. One patient died and another underwent coronary artery bypass surgery between3 and 8 weeks,and thesealsowere not included in the analysis. Study design. Patients were evaluated at 3 and 8 weeks following AMI. Each patient was interviewed and examined by a physician and informed consent was obtained. No patient had taken propranolol within 48 hours or nitrates within 2 hours of exercisestresstesting. A 12-lead ECG wasrecorded prior to exercise.During exercise,leads VS.ewere continuously monitored on a two-channel oscilloscope.The limb leads and leads V,., were also recorded at l-minute intervals during exercise and the recovery period. Blood pressurewas measuredby sphygmomanometer every 2 minutes and at peak exercise. At 3 weeksfollowing AMI, an RNA wasobtained at rest in the erect position. Exercise was then begun on an isokinetic bicycle ergometer (Fitron). The work load was
started at 100 kpm/min and increasedby 100 kpm/min every minute. Exercise wasterminated oncethe heart rate reached 120bpm or after the appearanceof one or more of the following: 0.1 mV ST segmentdepression;chest pain suggestive of angina or excessive fatigue. None of the exercise tests were stopped becauseof hypotension or ventricular arrhythmia. An RNA was performed. during exercise at the maximum work load achieved. At 8 weeks postinfarction, an RNA wasobtained at rest and then the sameexercise protocol as before was followed. An RNA was performed during exercise at the identical workload achieved at 3 weeks. In addition, in those patients who were not symptom-limited at this “submaximal” exercise level, the work load wasprogressively increaseduntil the heart rate reached85% of the maximum predicted for age or one of the above endpoints intervened. A second exercise RNA was performed at this “maximal” exercise level. Radionuclide procedure. The resting radionuclide angiocardiogramwasperformed in the anterior projection with the patient sitting on the bicycle ergometer, Ten millicuries of technetium-99m pertechnetate were injected into either the antecubital or the external jugular vein and were flushed with 10 ml of normal saline. Anterior precordial counts were recorded in binary form at 25 msec intervals for 1 minute using a multicrystal gamma camera (Baird-Atomic System Seventy-Seven) equipped with a l-inch parallel hole collimator. The exercisestudieswere performed in the samemanner asthe resting studies except that background counts were collected over the precordium before each additional injection. Data were stored on a magnetic tape for later processing. Data processing. The radionuclide angiocardiograms were analyzed as previously described.22~24,30 Briefly, each
1234 Table
Upton
et al.
American
I. Mean hemodynamic measurementsat rest and during exerciseat 3 and 8 weeks Ejection
fraction
3 weeks Location
Anterior (9) Inferior (13) Subendocardial (IO) Previous (10) R=rest;
December. 1982 Heart Journal
8 weeks
R
SEX
R
35 +lO 51 211
36 +13 50 +15
36 110 53 +11
64
61 k3 23 +9
61 +4 23 +8
kll 26 +I0
SEx=submaximal
End-diastolic
SEX 35 ill 51 +13 63 ~8 28 &lo
volume
3 weeks MEx
SEX
R
SEX
37 ?13 50 *13
209 156 161 +39
234 k66 180 +50
217 +66 156 236
230 k79 184 -r-39
62
141 k23 252 k75
160 -c42 278 r56
142 +30 277 k100
165 +43 282 k73
28 +lO
exercise; MEx=maximal
output
3 weeks
8 weeks
R
kll
Cardiac
MEx
Wall
motion
3 weeks
8 weeks
R
SEX
R
SEX
MEx
232 k78 193 +37
5.6 f1.5 6.1 e2.3
9.3 22.2 10.4 k4.1
5.5 il.1 6.0 +1.8
9.7 rt2.2 10.4 +3.3
167 +40 291 k80
6.5 rt1.2 4.7 21.6
11.7 k3.0 8.6 k2.4
6.2 k1.2 4.9 22.1
11.9 k3.1 8.9 +2.3
index
8 weeks
R
SEX
R
SEX
MEx
10.7 k2.3 12.7 k4.6
6.4 23.6 3.3 k3.0
7.2 ~3.6 4.5 k3.2
6.1 13.6 3.4 k3.0
7.2 k3.5 4.7 +3.2
7.2 23.5 4.8 k3.2
14.5 24.6 9.4 22.2
0.2 k0.4 9.1 k1.7
1.3 k2.1 9.1 f1.7
0.2 kO.4 9.3 k1.3
1.4 1.6 k1.9 k2.3 9.4 9.1 1.4 k1.7
exercise.
study wasfirst corrected for field nonuniformity and dead time; the exercisestudies were alsocorrected for preexisting counts in each crystal. A high frequency time-activity curve was obtained from the LV region of interest, and individual beats were identified. After subtracting background activity, an average cardiac cycle was derived by summingcounts from four to six of these beats. The LV ejection fraction (EF) wasdetermined from the average cycle: EF = (end-diastolic counts - end-systolic count&/end-diastolic counts LV end-diastolic volume (EDV) was calculated in milliliters using the length-area method of Sandler and Dodge? EDV = 0.85 AZ/L, where A is the planimetered area of the left ventricle, and L is the maximal length. Stroke volume (SV) and cardiac output (CO) were derived from the measuredEF, EDV, and heart rate (HR) by the following equations: SV (ml) = EDV (ml) x EF, and CO (L/min) = SV (ml) X HR (bpm). Regional wall motion was assessed by inspecting both dynamic and static imagesof the average cardiac cycle (Fig. 1). The LV outline was divided into three segments: anterior, apical, and inferior. Each segmentwasgraded on a scale of 0 to 6, where 0 = normal, 1 and 2 = mild and severeasyneresis,3 and 4 = mild and severeakinesia, and 5 and 6 = mild and severedyskinesia. “Mild” wasusedto describe an abnormality involving less than half and “severe” to describean area more than half of the segment analyzed. Scores from each of the three segmentswere summed, and a wall motion index (WMI), ranging from 0 (normal) to +18 (total dyskinesis), was assignedto each study. Statistical analysis. The data are expressedas mean f standard deviation. The significance of difference in measurements between groups was assessedusing one-way analysis of variance. Linear regression equations and correlation coefficients were derived by the least squares method. RESULTS
Table I tabulates the mean hemodynamic measurements in each infarct group at rest and exercise
at 3 weeks and at 8 weeks. Table II tabulates the clinical measurements and endpoints of the exercise test at 8 weeks in individual patients. Table III tabulates the hemodynamic measurements at rest and maximum exercise at 8 weeks in individual patients. Clinical characteristics. Patients were categorized clinically at the time of admission according to the criteria of Killup and Kimbal1.32 Thirty were class I (5 anterior, 10 inferior, 10 subendocardial, and 5 previous myocardial infarctions), seven were class II (two anterior, two inferior, and three previous myocardial infarctions), and five were class III (two anterior, one inferior, and two previous myocardial infarctions). At 8 weeks each patient was also classified clinically according to the New York Heart Association criteria for angina pectoris and heart failure (Table II).” Medications at the time of the 8-week evaluation are listed in Table II. Endpoints of exercise. At 3 weeks, 27 patients exercised to a heart rate of 120 bpm without fatigue, ST segment depression, or chest pain. Six patients were limited by fatigue alone prior to reaching a heart rate of 120 bpm, 7 patients developed 0.1 mm ST segment depression, and 2 experienced chest pain but did not develop ST segment depression. At 8 weeks, 26 patients reached a higher work load than at 3 weeks and therefore were studied during two levels of exercise. Nineteen patients achieved a heart rate of 85% maximum predicted for age without fatigue, ST segment depression, or chest pain. Eleven patients were limited by fatigue, nine patients developed ST segment depression, and three experienced chest pain but did not develop ST segment depression. Six of the 10 patients with previous myocardial infarction did not reach the target heart rate at 8 weeks, whereas none developed ST segment depression (Table II).
Volume Number
Table
104 6
Rest/exercise
RNA assessment
of LV function
post-AM1
1235
II. Clinical measurementsand endpoints of exercise test at 8 weeks Endpoints ECG
Age Anterior MI 1 2 3 4 5 6 7 8 9 Inferior MI 10 11 12 13 14 15 16 17 18 19 20 21 22 Subendocardial 23 24 25 26 27 28 29 30 31 32 Previous MI 33 34 35 36 37 38 39 40 41 42
51 53 58 56 42 56 61 53 56
ALMI AM1 ALMI AM1 AMI AM1 ASMI AM1 AM1
66 56 54 57 56 56 72 60 57 54 56 54 55 MI 54 60 59 59 46 51 56 55 68 77
IMI IMI TPMI TPMI IMI IMI IMI IMI IMI IMI, RBBB IMI IMI IMI Tll, aVL WNL WNL Tll, aVL WNL TJ2,3, aVF TJ2, 3, aVF T11, aVL,V,., Tl Vs., WNL
59 55 62 83 53 47 63 57 65 46
AM1 ALMI, IMI AMI, AMI, AM1 AMI, ASMI, AMI, AMI,
MEDS
Dig,
Fur -
IMI IMI IMI IMI IMI IMI IMI
-
-
Quin
HCTZ
Dig, Dig
Fur
Dig Fur
Dig, Fur -
Angina class
Failure class
I I II II I III III III I
I II II II I II I I III
II I I I II I IV III I I I III I
I I I I I I I I I I I I I
I I III I I I III II I II
I I I I I I I I I I
I I I I I II II I I I
II III I II III I I II II I
Angina
+ + -
+ + +
of exercise ST1
Fatigue
-
+ +
+ -
+ -
-I-
+ +
+ +
+
+ -
+
+
+
+ -
+ +
-
-
+ -
+ + +
+ -
-
+ + +
-
+ -
MI = myocardial infarction; ALMI = anterolateral myocardial infarction; AMI = anterior myocardial infarction; ASMI = anteroseptal myocardial infarction; IMI = inferior myocardial infarction; TPMI = true posterior myocardial infarction; RBBB = right bundle branch block; WNL = within normal limits; MEDS = medications; Dig = digoxin; Fur = furosemide; Quin = quinidine; HCTZ = hydrochlorothiazide.
Ejection fraction. The mean ejection fraction in each group was not significantly different at 3 and 8 weeks at rest or during submaximal exercise (Table I). Linear regression analyses demonstrated a close correlation between EF at rest at 3 and 8 weeks (r = 0.96) and the EF during exercise at 3 and 8 weeks (r = 0.94) (Fig. 2). The EF at rest was a
previous infarct had occurred. At 8 weeks mean EF was lowest in the group with previous infarction (23 + 9%) and was decreased also in the group with anterior infarction (36 + lo%), but not in the groups with inferior (53 +- 11% ) and subendocardial infarction (61 +- 3 % ). At both 3 and 8 weeks all patients with subendocardial myocardial infarctions
function of the location of infarction and whether a
had resting ejection fractions above 53%, whereas
1236
Upton et al.
Table
III. Hemodynamic
American
measurements at rest and during maximal exercise at 8 weeks Wall
Patient no. Anterior
Hi2 (bpm)
R
R
R
MEx
EDV
(ml)
R
MEx
CO (Llmin) R
MEx
Rest Ant
Ap
Exercise Znf
Tot
Ant
1
2 0 0 0 2 2 1 0
4 12 2 3 4 10 10 4 6
4 5 2 1 2 4 4 2 4
Ap
Znf
Tot
1 2 0 0 0 2 2 1 1
6 12 3 3 4 11 10 7 9
97 109 102 80 89 80 100 131 97
124 123 117 93 114 113 97 142 95
70 100 72 72 85 70 100 57 54
150 146 100 145 160 130 120 115 125
40 23 52 37 38 29 22 47 36
37 32 53 56 49 23 24 35 25
190 204 171 187 140 193 344 217 307
190 207 179 174 165 202 389 253 329
5.3 4.7 6.4 5.0 4.5 3.9 7.6 5.8 6.0
10.5 9.7 11.4 14.1 12.9 6.0 11.2 10.0 10.3
2 5 2 1 2 4 4 2 2
90 74 94 106 77 76 91 83 83 125 99 87 97
97 89 101 113 100 101 108 93 117 137 105 103 113
54 80 114 80 68 70 90 84 66 64 84 80 65
100 144 148 150 110 144 148 126 142 98 154 132 110
44 45 70 64 54 44 40 69 53 63 44 49 45
42 53 68 72 51 46 35 30 51 69 47 38 44
173 224 137 138 154 199 137 108 162 111 228 128 148
188 191 184 166 186 235 158 195 246 139 272 177 172
4.1 8.1 10.9 7.1 5.6 6.1 4.9 6.2 5.7 4.8 5.7 5.0 4.3
7.9 10.0 18.5 17.9 10.5 15.6 8.2 7.4 17.8 12.6 19.7 8.9 10.1
0 1 0 0 0 0 0 0 0 0 0 0 0
4 5 0 0 1 2 1 0 2 0 1 0 1
0 4 0 0 4 4 4 0 2 0 4 2 2
4 10 0 0 5 6 5 0 4 0 5 2 3
0 1 0 0 1 0 1 2 0 0 0 2 0
4 5 0 0 2 4 2 2 2 0 1 2 1
2 4 0 0 4 4 4 2 2 0 4 2 2
6 10 0 0 7 8 7 6 4 0 5 6 3
90 90 101 73 101 83 90 83 96 108
113 103 125 110 121 103 115 100 101 122
60 82 64 75 70 74 58 75 75 100
150 148 135 150 150 140 122 165 120 158
67 64 57 60 57 62 62 60 57 64
64 63 42 80 71 64 55 61 68 51
185 153 188 122 158 129 136 141 98 105
207 187 216 180 158 160 155 200 109 98
7.9 8.0 6.8 5.4 6.3 5.9 4.9 6.3 4.2 6.7
19.8 17.5 12.3 21.6 16.9 13.4 10.4 15.9 8.9 7.9
0 0 0 0 0 0 0 0 0 0
0 0 1 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 1
0 0 1 0 0 0 0 0 0 1
0 0 0 0 0 0 4 0 0 2
0 0 4 0 0 0 0 0 0 0
0 0 2 0 0 0 0 2 0 2
0 0 6 0 0 0 4 2 0 4
68 100 78 86 107 89 101 77 73 86
84 113 91 100 93 88 107 85 109 114
90 70 84 58 84 66 63 84 90 95
115 144 130 100 126 138 110 150 140 160
20 14 30 36 20 18 38 12 24 22
25 20 38 31 18 24 50 19 32 21
421 286 210 356 455 239 172 229 222 184
382 296 224 425 380 214 240 312 227 213
7.6 2.8 5.3 7.4 7.6 2.8 4.1 2.3 4.8 3.8
11.0 8.5 11.1 13.2 8.6 7.1 13.2 8.9 10.2 7.2
2 2 2 2 4 4 2 2 2 4
5 4 4 4 4 4 4 6 3 2
2 4 2 2 2 2 2 4 3 4
9 10 8 8 10 10 8 12 8 10
2 2 2 2 4 5 2 2 3 4
5 5 4 4 4 4 4 6 3 4
2 4 2 2 2 2 2 4 2 4
9 11 8 8 10 11 8 12 8 12
Subendocardial
23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
MEx
EF(%)
MI
10 11 12 13 14 15 16 17 18 19 20 21 22
Previous
index
MI
1 2 3 4 5 6 7 8 9 Inferior
-motion
--
Mean BP (mm ZW MEn
December, 1982 Heart Journal
MI
MI
MI = myocardial infarction; BP = blood pressure; R = rest; MEx = maximal exercise; HR = heart rate; bpm = beats per minute; EF = ejection fraction; EDV = end-diastolic volume; CO = cardiac output; Ant = anterior; Ap = apical; Inf = inferior; Tot = total.
all patients with previous myocardial infarctions had resting ejection fractions below 39%. The mean EF from rest to exercise did not change in the group with anterior, inferior, or subendocardial infarction at either 3 or 8 weeks; the mean EF increased significantly in the group with previous
myocardial infarction. However, within each group, the responses to exercise in individual patients were heterogeneous. The EF at rest and during maximum exercise at 8 weeks in individual patients is illustrated in Fig. 3 and is tabulated in Table III. Twenty patients had a decrease in EF during maximal
Volume
104
Number
6
Rest/exercise
RNA assessment
REST
of LV function
post-AMI
EXERCISE
100
'1%:
80-
0’
6 20
I 40
a0
60
100
20
% - 8 WEEKS Fig. 2. Correlation between submaximal exercise.
60
80
I
% - 8 WEEKS
3- and &week
values for left ventricular
100
ANTERIOR
IOOr
40
ejection
fraction
at rest and during
INFERIOR
a0 60-
P=NS 0
100
REST
'11
,
P=NS
REST
ME,
SUBENDOCARDIAL
ao-
, ME,
MULTIPLE
a0 60
OL Fig.
3.
Changes
I REST
in left ventricular
P
ejection
fraction
REST
from rest to maximal
ME,
exercise
(ME3
at 8 weeks.
1237
December,
1238
Upton et al.
American
REST 5ool .
400
400 t
.
t
ln
m
TE
300
::
::. 200 I I
100 1 0=
1982 Journal
EXERCISE
5ool-----7
z L!.J 3
Heart
:- *’
. 21.: *: .
100
200
y -e
r zo.94 y=l.l8X-27 SEE= 27
300
I 200
100
400
.. *
300
z
.‘..
. .’
.
.
i
10
500
ml - 8 WEEKS
ml
-
8 WEEKS
Fig. 4. Correlation between 3 and 8 week values for left ventricular end-diastolic d&ng submaximal exercise.
exercise at 8 weeks: three previous, four anterior, eight inferior, and five subendocardial myocardial infarctions. In the 26 patients who had RNA performed during two levels of exercise at 8 weeks, the change in ejection fraction from rest to submaximal to maximal exercise tended to be in the same direction. Only two patients had an increase in EF at submaximal exercise and a decrease at maximal exercise. End-diastolk voiume. The mean diastolic volumes at rest and exercise for the four groups at 3 and 8 weeks are presented in Table I. Linear regression analysis demonstrated a good correlation between end-diastolic volume at rest at 3 and 8 weeks (r = 0.94) and during exercise at 3 and 8 weeks (T = 0.91) (Fig. 4). The end-diastolic volume at rest was significantly larger in the groups with previous and anterior myocardial infarctions than in the groups with inferior and previous myocardial infarctions. The patients with anterior, inferior, and subendocardial myocardial infarctions demonstrated a significant increase in end-diastolic volume from rest to maximal exercise at 8 weeks, whereas the patients with previous myocardial infarctions demonstrated no significant change (Fig. 5). Enddiastolic volume increased more than 25 % from rest to maximal exercise at 8 weeks in eight patients. Wall motion. The wall motion index did not change significantly between 3 and 8 weeks, either at rest or during exercise (Table I). Linear regression analysis demonstrated excellent correlations between WMI at rest at 3 and 8 weeks (r = 9.99) and during exercise at 3 and 8 weeks (r = 0.98). At 8 weeks, the
volume at rest and
WMIs for the four groups at rest were: 9.3 + 1.3 previous, 5.5 f 1.1 anterior, 3.4 & 3.0 inferior, and 0.2 + 0.4 subendocardial myocardial infarctions. Comparison of mean WMIs at rest between groups by analyses of variance demonstrated significant differences between each group with the exception of anterior versus inferior infarction. All patients with anterior and previous myocardial infarctions demonstrated resting wall motion abnormalities at 8 weeks. Four patients with inferior myocardial infarction and eight with subendocardial myocardial infarction did not demonstrate wall motion abnormalities at rest. In general, the wall motion abnormalities corresponded with the ECG location of the myocardial infarction (Tables II and III). The wall motion index at rest and at maximal exercise at 8 weeks is illustrated in Fig. 6. The groups with anterior, inferior, and subendocardial myocardial infarctions had a significant increase in WMI from rest to maximal exercise; no significant change was noted in the group with previous myocardial infarctions. Sixteen patients developed a new or more severe wall motion abnormality during submaximal exercise at both 3 and 8 weeks; an additional two patients had stress-induced wall motion abnormalities during maximal exercise at 8 weeks (Table III). Patients with severely depressed resting function did not usually develop additional wall motion abnormalities during exercise. carc~ac output. The mean cardiac outputs at rest and exercise for the four groups are listed in Table I.
Volume Number
104 6
Rest/exercise ANTERIOR
500-
RNA assessment
of LV function
post-AM
1239
INFERIOR
500-
400-
300-
300-
200-
200-
ml 0 0
loo-
looPC.05
O-
1 REST
P<.OOl O-
MEr
SUBENOOCARDIAL
500-
400
300 -
: 300 -
opo
loo-
m1200-
E=====-
1 REST
0
0
loo-
PC ,005 0
ML
MULTIPLE
500
400-
m'200-
REST
P=NS I MEx
0.
I REST
MEx
Fig. 5. Changes in left ventricular end-diastolic volume from rest to maximal exercise (it4EJ at 8
weeks.
The cardiac outputs at rest and submaximal exercise did not change significantly between 3 and 8 weeks. Excluding the 12 patients who were limited by angina or ST segment depression during maximal exercise at 8 weeks, a weak linear correlation was observed between the resting ejection fraction and the maximal cardiac output (r = 0.74) (Fig. 7). Including all patients in the regression analysis further weakened the correlation. Five patients with resting EFs below 50% were able to achieve cardiac outputs during exercise above 12 L/min. DISCUSSION
LV function was assessed at rest and during exercise by RNA in 42 patients at 3 and 8 weeks following acute myocardial infarction. The results indicate that LV function at rest was influenced by the location of the myocardial infarction and whether previous infarction had occurred, and that LV function at rest and during exercise did not change
between 3 and 8 weeks after infarction. However, within each group ventricular function in individual patients at rest and/or exercise was heterogeneous. In each group there were patients with reduced ventricular function at rest and/or during exercise who could be expected to be at an increased risk for subsequent morbidity or mortality, Utility of exercise stress testing post-AM. Previous studies have demonstrated that in patients who survive acute myocardial infarctions, subsequent risk of cardiac death and recurrent myocardial infarction has been associated with extensive coro34-35depressed resting vennary artery disease, 16-lgs tricular function,15-1g and evidence of myocardial ischemia during exercise.4v6-g Recent studies have shown that exercise testing can be safely performed soon after myocardial infarction.1-g The frequency of ECG evidence of ischemia during exercise stress in patients with coronary artery disease is reduced in patients with prior myocardial infarction and/or
1240
Upton
December,
et al.
American
Heart
1982 Journal
ANTERIOR
0 I REST
PC.05
I MEx
REST
MEx
SUBENDOCARDIAL
16 r
I2 0..=I _
12 1
....-
a
a I
o .. .
0 t REST
Fig.
ME,
I REST
P=NS
I MEx
6. Changes in left ventricular wall motion index from rest to maximal exercise
left ventricular image was divided into approximateIy
(MEJ at 8 weeks.The
equal anterior, apical, and inferior segments. Each segment was graded on a scale of 0 to 6: 0 = normal; 1 and 2 = mild and severe asyneresis; 3 and 4 = mild and severe akinesis; 5 and 6 = mild and severe dyskinesis. Wall motion index represents the sum of wall motion grades in a given patient.
ventricular dysfunction .7-14The reduced frequency of positive exercise stress tests after infarction may be related to reduction in potentially ischemic myocardium and/or masking of ECG evidence of ischemia as a result of ventricular dysfunction.lO-l4 Electrocardiographic ST segments may be influenced by variables other than ischemia or infarction, including digitalis, electrolytes, ventricular hypertrophy, and conduction abnormalities. Utility of exercise RNA post-AM. RNA is potentially an ideal technique for evaluating the patient with prior myocardial infarction. RNA provides measurements of ventricular function including ejection fraction, ventricular volumes, regional wall motion, and cardiac output which correlate well with contrast angiography and dye dilution techniques.20-24~30 The reproducibility of the technique is high.25,26 RNA is easily adapted to exercise stress testing and thus allows assessment of exercise-induced &hernia
by a technique segment shifts. Rest and exercise
which
is not dependent
LV function
stable between
on ST 3 and 8
weeks post-AMI. The results of this investigation are in agreement with other studies which have demonstrated that ventricular function at rest is depressed to a greater extent in patients with anterior and previous myocardial infarctions than in patients with inferior and subendocardial myocardial infarctions.11*3E-38However, considerable overlap existed among patients in the different groups. The mean LVEF, end-diastolic volume, cardiac output, and WMI did not change significantly in any group between 3 and 8 weeks, either at rest or during submaximal exercise. Furthermore, individual variations in these measurements were small, indicating that LV function is relatively stable during this period. Reduto et al.% have previously demonstrated that resting ventricular function remains constant
Volume
104
Number
6
Rest/exercise
i--l10
20
30
40
Resting
Eiection
RNA assessment
50
60
Fraction
- %
of LV function
70
post-AMI
1241
80
Fig. 7. Correlation between resting ejection fraction and maximal cardiac output in 30 patients not limited by angina or ST segmentdepressionduring exercise at 8 weeks.
during the hospital phase of myocardial infarction; Borer et al.3g reported no significant change in the response of EF to submaximal exercise immediately prior to hospital discharge and 8 to 13 months later. Identification of prognostic subgroups. In the present study, only nine patients (21%) had 0.1 mV or greater ST segment depression during maximal exercise at 8 weeks. Therefore our findings are in agreement with previous studies which have demonstrated a low incidence of stress-induced ECG evidence of ischemia in patients with myocardial infarction.7-14 All patients who had ST segment depression during exercise also demonstrated a decrease in EF and an increase in WMI during exercise. Twenty-three patients (53 % ) had either a decrease in EF or an increase in WMI during submaximal exercise at 3 and 8 weeks, and 25 patients (60%) demonstrated these abnormal ventricular responses to maximal exercise at 8 weeks. Recent studies from our laboratory indicate that failure of the global EF to increase or even a decrease in the EF during exercise are not specific indices of coronary artery disease and myocardial ischemia. We have observed that in women with atypical chest pain but normal coronary arteries the EF frequently does not increase, or may even decrease during exercise .40Studies in our laboratory have also demonstrated a linear decline of the changes in EF with increasing age in asymptomatic
volunteers without apparent cardiovascular disease.41 Using a 0.05 increase in EF as a normal response during exercise, the frequency of a subnormal response was 10% in subjects in the fifth decade of life and then progressively increased to 95% of subjects in the eighth to tenth decades of life. In the present study, all patients were male, 11 were L 60 years of age, and a decrease in EF rather than a failure to increase 0.05 was used as a criteria for an abnormal EF response to exercise. Our findings suggest that an RNA evaluation at rest and during upright exercise in the convalescent phase at 3 or 8 weeks following acute myocardial infarction permits the identification of patients with depressed resting ventricular function or exercise-induced myocardial ischemia who may benefit from intensive medical or surgical therapy. In addition, RNA identified patients with normal or mildly reduced function at rest and no decrease in EF or appearance of additional wall motion abnormalities during exercise who may be expected to have a better subsequent prognosis. Location of AMI and exercise LV dysfunction. In the present study there was no relation between the location of the myocardial infarction by ECG and the presence of exercised-induced LV dysfunction. The presence of Q waves, however, did predict resting wall motion abnormalities. In contrast, Pulido et a1.37 reported that patients with anterior myocardial infarctions had a greater incidence of
1242
Upton et al.
abnormal ventricular responses to exercise. The different findings may be explained by the small number of patients with anterior myocardial infarction evaluated in each study. Rest and exercise LV dysfunction. Eleven patients (26 % 1 had resting EF below 35% ; none developed ST segment depression during maximal exercise at 8 weeks, and only one experienced angina. However, six of those patients had either a decrease in EF or a new or more severe wall motion abnormality during exercise, suggesting that these patients still had residual viable myocardium that was supplied by critically stenosed coronary vessels. These patients with both severely depressed resting ventricular function and exercise-induced myocardial ischemia may be a subgroup at high risk for subsequent coronary events. Exercise increased LVEDV. End-diastolic volume increased more than 25% from rest to maximal exercise at 8 weeks in eight patients. This large increase in end-diastolic volume has previously been reported to occur in patients with coronary artery disease and may represent a greater utilization of the Starling mechanism in patients with reduced systolic performance during exercise.22~42 Excluding those patients who were limited by angina during exercise, there was a linear correlation between resting EF and maximal cardiac output at 8 weeks. However, five patients with depressed resting EF (< 50% ) were able to achieve cardiac outputs in excess of 12 L/min. This preservation of exercise capacity despite depressed LV function has previously been reported in other studies.43-45 Conclusions. This study has shown that RNA can be safely performed at rest and during exercise in the early and late convalescent phases following acute myocardial infarction. Patients with anterior and previous myocardial infarctions tended to have lower resting EF, larger end-diastolic volumes, and more wall motion abnormalities than patients with inferior or subendocardial myocardial infarctions. Ventricular function remained relatively stable both at rest and during submaximal exercise between 3 and 8 weeks. Within each group, the ventricular response to exercise was heterogenous. Individual patients were identified who demonstrated significant functional abnormalities during exercise, including a decrease in EF, a large increase in end-diastolic volume, and new or more severe wall motion abnormalities. The prognostic significance of these abnormalities is the subject of ongoing clinical studies. The following persons rendered valuable assistance with carrying out the studies: Jean Wilson, R.N., Research Nurse, and Cathie Collins, Secretary.
American
December, 1982 Heart Journal
REFERENCES
1. Atterhog JH, Ekelund LG, Kaijser L: Electrocardiographic abnormalities during exercise 3 weeks to 18 months after anterior myocardial infarction. Br Heart J 33:871, 1971. 2. Ericsson M. Granath A. Ohlsen P. Sodermark T. Volne U: Arrhythmias and symptoms during treadmill testing Ithree weeks after myocardial infarction in 100 patients. Br Heart J 35:767, 1973. 3. Ibsen H, Kjgller E, Styperek J, Pedersen A: Routine exercise ECG three weeks after acute myocardial infarction. Acta Med Stand 198:463, 1975. 4. Markiewicz W, Houston N, DeBusk RF: Exercise testing soon after myocardial infarction. Circulation 56:26, 1977. 5. Wohl AJ, Lewis HR, Campbell W, Karlsson E, Willerson JT, Mullins CB, Blomqvist CG: Cardiovascular function during early recovery from acute myocardial infarction. Circulation S&931, 1977. 6. Granath A, Sodermark T, Winge T, Volpe U, Zetterquist S: Early workload test for evaluation of long-term prognosis of acute myocardial infarction. Br Heart J 75:787,1973. 7. Sami M. Kraemer H. DeBusk RF: The nrognostic sienificance of serial exercise testing after myocardial infarction. Circulation 60:1238, 1979. 9. Theroux P, Waters DD, Halpen C, Debasieux JC, Mizzala HF: Prognostic value of exercise testing soon after myocardial infarction. N Engl J Med 301:341, 1979. 9. Davidson DM, DeBusk EF: Prognostic value of a single exercise test 3 weeks after uncomplicated myocardial infarction. Circulation 61:236, 1980. 10. Kramer N, Susmano A, Shekelle RB: The “false negative” treadmill exercise test and left ventricular dysfunction. Circulation 57:763, 1978. 11. Castellanet MJ, Greenberg PS, Ellestad MI-h Comparison of S-T segment changes on exercise testing with angiographic findings in patients with prior myocardial infarction. Am J Cardiol 42:29, 1978. 12. Kasser IS, Bruce RA: Comparative effects of aging and coronary heart disease on submaximal and maximal exercise. Circulation 39:759, 1969. 13. Fitzeibbon GM. Bureeraf GW. Groves TD. Parker JO: A double Master’s two-step te& Clinical, angiographic and hemodynamic correlations. Ann Intern Med 74:509, 1971. 14. Weiner DA, McCabe C, Klein MD, Ryan TJ: ST segment changes postinfarction: Predictive value for multivessel coronary disease and left ventricular aneurysm. Circulation S&887, 1978. 15. Oberman A, Jones WB, Riley CP, Reeves TJ, Sheffield LT: Natural history of coronary artery disease. Bull NY Acad Med 48:1109, 1972. 16. Bruschke AVG, Proudfit WL, Sones FM Jr: Progress study of 590 consecutive nonsurgical cases of coronary disease followed 5-9 years. II. Ventriculographic and other correlations. Circulation 47:1154, 1973. 17. Humphries JO, Kuller L, Ross RS, Friesinger GC, Page EE: Natural history of ischemic heart disease in relation to arteriographic findings. Circulation 49:489, 1974. 18. Burggraf GW, Parker JO: Prognosis in coronary artery disease. Angiographic, hemodynamic and clinical factors. Circulation 51:146, 1975. 19. Harris PJ, Harrell FE Jr, Lee KL, Behar VS, Rosati RA: Survival in medically treated coronary artery disease. Circulation 60:1259, 1979. 20. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS: Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary-artery disease. N Engl J Med 296:839, 1977. 21. Marshall RC, Berger HJ, Costin JC, Freedman GS, Wolberg J, Cohen LS, Gottachalk A, Zaret BL: 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.
Volume
104
Number
6
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Rest/exercise
Rerych SK, Scholz PM, Newman GE, Sabiston DC Jr, Jones RH: Cardiac function at rest and during exercise in normals and in patients with coronary heart disease. Evaluation bv radionuclide angiocardiography. Ann Surg 187:449, 1978. Bodenheimer MM. Banka VS. Fooshee CM. Hermann GA. Helfant RH: Quantitative radionuclide angiography in the right anterior oblique view: Comparison with contrast ventriculography. Am J Cardiol 41:718, 1978. Scholz PM, Rerych SK, Moran JF, Newman GE, Douglas JM, Sabiston DC Jr, Jones RH: Quantitative radionuclide angiocardiography. Cathet Cardiovas Diagn 6:265, 1980. Marshall RC, Berger HJ, Reduto LA, Gottschalk A, Zaret BL: Variability in sequential measures of left ventricular performance assessed with radionuclide angiocardiography. Am J Cardiol 41:531, 1978. Upton MT, Rerych SK, Newman GE, Bounous EP Jr, Jones RH: The reproducibility of radionuclide angiocardiographic measurements of left ventricular function in normal subjects at rest and during exercise. Circulation 62:126, 1980. Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Seides SF, Epstein SE, Johnston GS: Sensitivitv. snecificitv and predictive accuracy of radionuclide cine”angiography during exercise in patients with coronary artery disease; comparison with exercise electrocardiography. Circulation 60~572, 1979. Bodenheimer MM, Banka VS, Fooshee CM, Helfant RH: Comparative sensitivity of the exercise electrocardiogram, thallium imaging and stress radionuclide angiography to detect the presence and severity of coronary heart disease. Circulation 60:1270, 1979. Newman GE, Rerych SK, Upton MT, Sabiston DC Jr, Jones RH: Comparison of electrocardiographic and left ventricular functional changes during exercise. Circulation 62~1204. 1980. Jones RH, Scholz PM: Data enhancement techniques for radionuclide cardiac studies. In Medical radionuclide imaaing. International Atomic Energy Agency 2:255, 1977. Sandler H, Dodge HT: The use of single plane angiocardiograms for the calculation of left ventricular volume in man. AM HEART J 75:325,
35.
36.
37.
38.
39.
41.
42.
43.
44.
45.
of LV function
post-AMI
1243
coronary arteriography. Tram Assoc Am Physicians 83:78, 1979. Webster JS, Moberg C, Rincon G: Natural history of severe proximal coronary artery disease as documented by coronary cineangiography. Am J Cardiol 33:195, 1974. Hamby RI, Hoffman I, Hilsenrath J, Aintablian A, Shanies S, Padmanabhan V: Clinical, hemodynamic and angiographic aspects of inferior and anterior myocardial infarctions in patients with angina pectoris. Am J Cardiol 34:513, 1974. Pulido JI, Doss J, Twieg D, Blomqvist GC, Faulkner D, Horn V, DeBates D, Tobey M, Parkey PW, Willerson JT: Submaximal exercise testing after acute myocardial infarction: Myocardial scintigraphic and electrocardiographic observations. Am J Cardiol 42:19, 1978. Reduto LA, Berger HJ, Cohen LS, Gottschalk A, Zaret BL: Sequential radionuclide assessment of left and right ventricular performance after acute transmural myocardial infarction. Ann Intern Med 89:441, 1978. Borer JS, Rosing DR, Kent KM, Seides SF, Miller R, Cohen H, Holmes D, Donahue D, Stark R, Green MV, Bacharach SL. Baker W. Enstein SE: Natural historv of left ventricular dy$function after myocardial infarction (abstr). Am J Cardiol 43:370,
40.
1968.
Killip T, Kimball JT: Treatment of myocardial infarction in a coronary care unit. Am J Cardiol 20:457, 1967. 33. The Criteria Committee of the New York Heart Association: Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 8th ed. Boston, 1979, Little, Brown & Company. 34. Friesinger GC, Page.EE, Ross RS: Prognostic significance of 32.
RNA assessment
1979.
McEwan P, Newman GE, Portwood J, Port S, Upton MT, Cobb FR, Jones RH: Correlation of rest and exercise radionuelide angiocardiographic ventricular function with the number of significantly stenosed vessels in 230 patients with coronary artery disease. J Nucl Med 20:687, 1979. Port S, Cobb FR, Coleman RE, Jones RH: The effects of age on the left ventricular ejection fraction response to exercise. N Engl J Med 303:1133, 1980. Upton MT, Rerych SK, Newman GE, Port S, Cobb FR, Jones RH: Detection of abnormalities in left ventricular function during exercise before angina and ST segment depression. Circulation 62:341, 1980. Paine TD, Dye LE, Roitman DL, Sheffield LT, Rackley CE, Russell RO Jr, Rogers WJ: Relation of graded exercise test findings after myocardial infarction to extent of coronary artery disease and left ventricular function. Am J Cardiol 42:716, 1978. Benge W, Litchfield RL, Marcus ML: Exercise capacity in patients with severe left ventricular dysfunction. Circulation 61:355, 1980. Franciosa JA, Park M, Levine B, Cohn JN: Lack of correlation between exercise capacity and indices of resting left ventricular performance in heart failure (abstr). Circulation 59(suppl 11):20, 1979.
NOTE:
After December IOth, Address Manuscripts Dean T. Mason, M.D., Editor-in-Chief AMERICAN HEART JOURNAL, Editorial Cardiac Center, Cedars Medical Center Cedars South-Suite 0 1295 N.W. 14th Street Miami, Florida 33125
I
to: Office