Clin. Cardiol. 15, 17-23 (1992)
Orlglnal Contrlbutlons Influence of Exercise Training Soon after Myocardial Infarction on Regional Myocardial Perfusion and Resting Left Ventricular Function GEORGE A. BELLER, M.D.,GARYC. MURRAY, M.D.,SUSANK. ERKENBRACK, R.N.
Division of Cardiology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA
Summary: There is scant information regarding the effect of exercise training begun soon after hospital discharge for myocardial infarction (MI) with respect to subsequent improvement in exercise tolerance, enhancement of regional myocardial perfusion, or left ventricular function. Accordingly, 19 post-MI patients (mean age 53f7 years) underwent treadmill exercise quantitative thallium-201 (Tl-201) scintigraphy and rest radionuclide angiography (RNA) prior to and after 12 weeks of thrice-weekly exercise training which was targeted to 7 0 4 5 % of maximum exercise heart rate achieved. Training was begun at 25 -13 days after hospital discharge. Eight T1-201 scan segments were each scored from 1-6 points based upon uptake and washout criteria with 6 being the most severe defect (>50% reduction in T1-201 events with no delayed redistribution). When matched to the pretraining peak workload on exercise testing, 12 weeks of training significantly lessened heart rate (120+4 to 97+4, pcO.001), peak systolic blood pressure (142+6 to 129-15 mmHg, pcO.Ol), and significantly reduced double product [17.2+ 10.8 to 12.7-19 ( X lo3), p c 0.0011. Training was associated with a reduction of exercise-induced ST depression or angina (42 to 16%) which was not statistically significant. The mean resting by RNA ejection fraction was 50 k 3% prior to training and 51 -13% after training. There was no significant change in overall Tl-201 defect score or the number of defect regions per patient scan comparing pre- and post-
Address for reprints: George A. Beller, M.D. Division of Cardiology Box 158 University of Virginia Health Sciences Center Charlottesville, VA 22908, USA Received: July 2, 1991 Accepted with revision: September 30, 1991
training scintigrams. Of the 5 patients who had elimination of exercise-induced angina or ischemic ST depression after training, none showed an improvement in the T1-201 defect score between the two studies. Thus, 3 months of exercise conditioning begun soon after acute MI is associated with a significant training effect without an improvement in resting left ventricular function or myocardial perfusion at peak exercise.
Key words: exercise therapy, myocardial infarction, thallium-201 imaging, left ventricular function
Introduction Cardiac rehabilitation and exercise training often begins 2-3 months or longer following myocardial infarction when behavior is ingrained and deconditioning problems are compounded. In recent years, clinicians have prescribed early supervised exercise therapy for patients who survive a myocardial infarction without significant complications. There is scanty information regarding the effect of exercise training begun soon after hospital discharge for myocardial infraction with respect to subsequent improvement in exercise tolerance, enhancement of regional myocardial perfusion or left ventricular function. One recent overview of randomized trials of cardiac rehabilitation with exercise indicates a moderate reduction of about 20% in total and cardiovascular-related mortality. I However, in this analysis, the six “exercise only” trials did not show a statistically significant benefit, most likely because of relatively small numbers of patients randomized. In patients with coronary artery disease (CAD), exercise training reduces the product of heart rate and arterial blood pressure at a matched submaximal work l ~ a d . Since ~-~ heart rate and blood pressure are major determinants of myocardial oxygen consumption, training will increase exercise tolerance by improving the balance between myocardial and total body oxygen consumption. Exercise training has also been observed, in some instances, to in-
18
Clin. Cardiol. Vol. 15, January 1992
crease the maximal rate-pressure product at which anginal symptoms develop.6 This change has been attributed to a possible improvement in coronary blood flow perhaps resulting from the effects of exercise training on coronary c~llateralization.~-~ However, it is still unclear whether this improvement in exercise performance in CAD patients results from training effects on the periphery, through central adaptation, or both. Most prior series of the investigation of exercise training on cardiac performance and myocardial perfusion have been heterogeneous in which patients with stable CAD are included with patients with recent myocardial infraction. lo Accordingly, the purpose of the present study was to determine prospectively if exercise training begun soon after myocardial infarction improves exercise tolerance, enhances regional myocardial perfusion at maximal exercise, and improves resting left ventricular function as assessed by resting ejection fraction. A unique feature of this study was the use of quantitative thallium-201 (TI-201) scintigraphy to assess serial changes in myocardial perfusion.
Patient Selection
Nineteen postmyocardial infarction patients comprised the study group. All underwent graded treadmill exercise testing in conjunction with quantitative T1-201 scintigraphy prior to commencing the exercise training program. Their mean age (k SD) was 53.0k6.9 years. The first exercise session for the group began at a mean of 25.3 k3.3 (SE) days following hospital discharge for myocardial infarction. Eleven patients had a transmural inferior myocardial, 5 had a transmural anterior myocardial infraction, and the remaining 3 had non-Q-wave infarction. Exercise Tkaining Protocol
The exercise prescription was derived from the data obtained from the treadmill exercise test performed prior to entry. Of the 19 patients, 10 underwent a submaximal exercise test according to the Naughton or Modified Bruce protocols, and the remaining 9 underwent maximal symptomlimited testing. During the first several weeks, exercise training consisted of a program of thrice-weekly upper and lower extremity conditioning targeted to intensity based on a target heart rate of 70% of the maximum heart rate achieved on the entry exercise test. At 3 4 weeks, a second treadmill test was performed, and the target heart rate was increased to 70-85% of the maximum heart rate achieved. Patients exercised on six stations following a 5-minute warm-up period. In each patient, training comprised of a 12-week period which was followed by an exit treadmill test done in conjunction with TI-201 scintigraphy. For the entire group, exercise training began 38 k3 days after onset of infarction and 25 k 3 days after hospital discharge.
Exercise Testing Protocol
As mentioned above, the 19 patients either underwent submaximal or symptom-limitedtreadmill exercise testing prior to the training program. Following 12 weeks of training, a symptom-limited test was performed in each individual. Blood pressure was measured at least once during each 3-minute stage and for 5 minutes into the recovery period. A 12-lead electrocardiogram (ECG) was recorded in the resting state, during 30 seconds of hyperventilation, and at 1-minute intervals during exercise and in the 5minute recovery period. The ECG was standardized for 1 mm = 1 mV. All of the exercise ECGs were interpreted by two independent reviewers without knowledge of clinical, scintigraphic, or functional data. Symptom-limited exercise such as chest pain, dyspnea, fatigue, lower extremity claudication, and other symptoms were recorded on a data sheet. All of the ECG tracings were interpreted by two independent reviewers without knowledge of clinical, scintigraphic, or functional data. Differences in interpretation were resolved by employing a third reviewer, with the majority opinion prevailing. A positive ECG stress test was defined as 21.O mm horizontal or downsloping ST-segment depression at 80 ms after the J-point in three consecutive beats. Cardiac medications were continued during the course of training, and doses were adjusted as clinically indicated by the primary physicians. Ten patients were receiving beta-blocking drugs at the time of both pre- and posttraining exercise stress testing, 7 patients were on beta blockers only during the posttraining exercise test, and 2 patients never were put on beta-blocking drugs. Quantitative Thallium-201Scintigraphy
An intravenous dose of 2.0 mCi TI-201 was administered at peak exercise in all patients, followed by a 10 cc flush of normal saline. Exercise was continued whenever possible for an additional 60 seconds after T1-201 injection if symptoms, ECG changes and blood pressure response permitted. The TI-201 scintigraphic technique that was employed has previously been described." Imaging commenced 10 minutes after injection, with the patient supine in the anterior projection. This was followed by obtaining a 45" left anterior oblique (LAO) and 70" LAO image. The anterior, the 45" LAO and occasionally the 70" LAO images were repeated at 1 h and 2-3 h after radionuclide administration. All images were recorded for a preset time of 10 minutes on an Ohio Nuclear 420 portable gamma camera using an all-purpose medium sensitivity collimator and a 25% window centered on the 80 keV x-ray peak. In addition to obtaining unprocessed scintiphotos, all studies were stored in an MDS A2 computer for standardized image formation and quantitation of relative T1-20 1 activity in multiple myocardial segments in accordance with methods previously published. After computer quantitation of regional TI-201 uptake and washout, 8 myocardial scan segments were scored
G. A. Beller et al.:Exercise training after MI
from 1 to 6 by two independent investigators who had no knowledge of patient identity, clinical, or exercise electrocardiographic information. A score of 1 was assigned to normal segments which demonstrated normal T1-201 uptake and washout by quantitation of regional activity over time from the 10-minute postexercise scintigram to the final delayed scintigram. A score of 2 was assigned to segments showing a differential washout pattern but in which no initial defect of > 25% with respect to the regional of greatest activity was noted. For this score to be assigned, a normal segment showing a net decrease in T1201 activity over time was required. A score of 3 designated an initial defect of > 25% (or > 35% in the inferior wall on the anterior view image) with subsequent total redistribution.This implied normalization of the initial defect relative to a normal myocardial region. A score of 4 was designated if a significant initial defect was noted but only partial redistribution was observed on the delayed image. A score of 5 reflected a persistent defect in which there was a 2650% reduction in regional T1-20 1 counts with no subsequent redistribution. Finally, a score of 6 was designated if an initial defect demonstrated > 50% reduction in T1-201 counts relative to a normal myocardial segment and no redistribution was noted on the delayed images. Gated Equilibrium Blood Pool Scanning
After completion of the exercise protocol and myocardial T1-201 imaging, resting equilibrium-gated blood pool imaging was performed. Injection of unlabeled stannous pyrophosphate was followed 30 minutes later by injection of 20 mCi of technetium-99m pertechnetate to complete the in vivo labeling of red blood cells. After equilibration of the blood pool tracer, gated images were obtained in the anterior projection, in the 45" left oblique projection (this angle is modified if necessary to achieve the best ventricular separation), followed by a second left oblique projection obtained by rotating 30" beyond the view of best ventricular separation (normally 75"). A large field gamma camera with parallel hole collimator was used with approximately 2X image magnification for gated imaging. Gated images were acquired for an interval of 8 minutes using 16 images per cardiac cycle, with the image sequence being triggered by an electrocardiographic R-wave detector. Global left ventricular ejection fraction was calculated from the 45" LAO projection without caudal angulation using a standard volume count method.12
Results Exercise Test Results
The changes in treadmill time, metabolic equivalents (METs) achieved and the double product attained prior to and after 3 months of exercise training are summarized in Figure 1. As shown, there was a statistically significant
19 p
Orlglnal Contrlbutlons Influence of Exercise Training Soon after Myocardial Infarction on Regional Myocardial Perfusion and Resting Left Ventricular Function GEORGE A. BELLER, M.D.,GARYC. MURRAY, M.D.,SUSANK. ERKENBRACK, R.N.
Division of Cardiology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA
Summary: There is scant information regarding the effect of exercise training begun soon after hospital discharge for myocardial infarction (MI) with respect to subsequent improvement in exercise tolerance, enhancement of regional myocardial perfusion, or left ventricular function. Accordingly, 19 post-MI patients (mean age 53f7 years) underwent treadmill exercise quantitative thallium-201 (Tl-201) scintigraphy and rest radionuclide angiography (RNA) prior to and after 12 weeks of thrice-weekly exercise training which was targeted to 7 0 4 5 % of maximum exercise heart rate achieved. Training was begun at 25 -13 days after hospital discharge. Eight T1-201 scan segments were each scored from 1-6 points based upon uptake and washout criteria with 6 being the most severe defect (>50% reduction in T1-201 events with no delayed redistribution). When matched to the pretraining peak workload on exercise testing, 12 weeks of training significantly lessened heart rate (120+4 to 97+4, pcO.001), peak systolic blood pressure (142+6 to 129-15 mmHg, pcO.Ol), and significantly reduced double product [17.2+ 10.8 to 12.7-19 ( X lo3), p c 0.0011. Training was associated with a reduction of exercise-induced ST depression or angina (42 to 16%) which was not statistically significant. The mean resting by RNA ejection fraction was 50 k 3% prior to training and 51 -13% after training. There was no significant change in overall Tl-201 defect score or the number of defect regions per patient scan comparing pre- and post-
Address for reprints: George A. Beller, M.D. Division of Cardiology Box 158 University of Virginia Health Sciences Center Charlottesville, VA 22908, USA Received: July 2, 1991 Accepted with revision: September 30, 1991
training scintigrams. Of the 5 patients who had elimination of exercise-induced angina or ischemic ST depression after training, none showed an improvement in the T1-201 defect score between the two studies. Thus, 3 months of exercise conditioning begun soon after acute MI is associated with a significant training effect without an improvement in resting left ventricular function or myocardial perfusion at peak exercise.
Key words: exercise therapy, myocardial infarction, thallium-201 imaging, left ventricular function
Introduction Cardiac rehabilitation and exercise training often begins 2-3 months or longer following myocardial infarction when behavior is ingrained and deconditioning problems are compounded. In recent years, clinicians have prescribed early supervised exercise therapy for patients who survive a myocardial infarction without significant complications. There is scanty information regarding the effect of exercise training begun soon after hospital discharge for myocardial infraction with respect to subsequent improvement in exercise tolerance, enhancement of regional myocardial perfusion or left ventricular function. One recent overview of randomized trials of cardiac rehabilitation with exercise indicates a moderate reduction of about 20% in total and cardiovascular-related mortality. I However, in this analysis, the six “exercise only” trials did not show a statistically significant benefit, most likely because of relatively small numbers of patients randomized. In patients with coronary artery disease (CAD), exercise training reduces the product of heart rate and arterial blood pressure at a matched submaximal work l ~ a d . Since ~-~ heart rate and blood pressure are major determinants of myocardial oxygen consumption, training will increase exercise tolerance by improving the balance between myocardial and total body oxygen consumption. Exercise training has also been observed, in some instances, to in-
18
Clin. Cardiol. Vol. 15, January 1992
crease the maximal rate-pressure product at which anginal symptoms develop.6 This change has been attributed to a possible improvement in coronary blood flow perhaps resulting from the effects of exercise training on coronary c~llateralization.~-~ However, it is still unclear whether this improvement in exercise performance in CAD patients results from training effects on the periphery, through central adaptation, or both. Most prior series of the investigation of exercise training on cardiac performance and myocardial perfusion have been heterogeneous in which patients with stable CAD are included with patients with recent myocardial infraction. lo Accordingly, the purpose of the present study was to determine prospectively if exercise training begun soon after myocardial infarction improves exercise tolerance, enhances regional myocardial perfusion at maximal exercise, and improves resting left ventricular function as assessed by resting ejection fraction. A unique feature of this study was the use of quantitative thallium-201 (TI-201) scintigraphy to assess serial changes in myocardial perfusion.
Patient Selection
Nineteen postmyocardial infarction patients comprised the study group. All underwent graded treadmill exercise testing in conjunction with quantitative T1-201 scintigraphy prior to commencing the exercise training program. Their mean age (k SD) was 53.0k6.9 years. The first exercise session for the group began at a mean of 25.3 k3.3 (SE) days following hospital discharge for myocardial infarction. Eleven patients had a transmural inferior myocardial, 5 had a transmural anterior myocardial infraction, and the remaining 3 had non-Q-wave infarction. Exercise Tkaining Protocol
The exercise prescription was derived from the data obtained from the treadmill exercise test performed prior to entry. Of the 19 patients, 10 underwent a submaximal exercise test according to the Naughton or Modified Bruce protocols, and the remaining 9 underwent maximal symptomlimited testing. During the first several weeks, exercise training consisted of a program of thrice-weekly upper and lower extremity conditioning targeted to intensity based on a target heart rate of 70% of the maximum heart rate achieved on the entry exercise test. At 3 4 weeks, a second treadmill test was performed, and the target heart rate was increased to 70-85% of the maximum heart rate achieved. Patients exercised on six stations following a 5-minute warm-up period. In each patient, training comprised of a 12-week period which was followed by an exit treadmill test done in conjunction with TI-201 scintigraphy. For the entire group, exercise training began 38 k3 days after onset of infarction and 25 k 3 days after hospital discharge.
Exercise Testing Protocol
As mentioned above, the 19 patients either underwent submaximal or symptom-limitedtreadmill exercise testing prior to the training program. Following 12 weeks of training, a symptom-limited test was performed in each individual. Blood pressure was measured at least once during each 3-minute stage and for 5 minutes into the recovery period. A 12-lead electrocardiogram (ECG) was recorded in the resting state, during 30 seconds of hyperventilation, and at 1-minute intervals during exercise and in the 5minute recovery period. The ECG was standardized for 1 mm = 1 mV. All of the exercise ECGs were interpreted by two independent reviewers without knowledge of clinical, scintigraphic, or functional data. Symptom-limited exercise such as chest pain, dyspnea, fatigue, lower extremity claudication, and other symptoms were recorded on a data sheet. All of the ECG tracings were interpreted by two independent reviewers without knowledge of clinical, scintigraphic, or functional data. Differences in interpretation were resolved by employing a third reviewer, with the majority opinion prevailing. A positive ECG stress test was defined as 21.O mm horizontal or downsloping ST-segment depression at 80 ms after the J-point in three consecutive beats. Cardiac medications were continued during the course of training, and doses were adjusted as clinically indicated by the primary physicians. Ten patients were receiving beta-blocking drugs at the time of both pre- and posttraining exercise stress testing, 7 patients were on beta blockers only during the posttraining exercise test, and 2 patients never were put on beta-blocking drugs. Quantitative Thallium-201Scintigraphy
An intravenous dose of 2.0 mCi TI-201 was administered at peak exercise in all patients, followed by a 10 cc flush of normal saline. Exercise was continued whenever possible for an additional 60 seconds after T1-201 injection if symptoms, ECG changes and blood pressure response permitted. The TI-201 scintigraphic technique that was employed has previously been described." Imaging commenced 10 minutes after injection, with the patient supine in the anterior projection. This was followed by obtaining a 45" left anterior oblique (LAO) and 70" LAO image. The anterior, the 45" LAO and occasionally the 70" LAO images were repeated at 1 h and 2-3 h after radionuclide administration. All images were recorded for a preset time of 10 minutes on an Ohio Nuclear 420 portable gamma camera using an all-purpose medium sensitivity collimator and a 25% window centered on the 80 keV x-ray peak. In addition to obtaining unprocessed scintiphotos, all studies were stored in an MDS A2 computer for standardized image formation and quantitation of relative T1-20 1 activity in multiple myocardial segments in accordance with methods previously published. After computer quantitation of regional TI-201 uptake and washout, 8 myocardial scan segments were scored
G. A. Beller et al.:Exercise training after MI
from 1 to 6 by two independent investigators who had no knowledge of patient identity, clinical, or exercise electrocardiographic information. A score of 1 was assigned to normal segments which demonstrated normal T1-201 uptake and washout by quantitation of regional activity over time from the 10-minute postexercise scintigram to the final delayed scintigram. A score of 2 was assigned to segments showing a differential washout pattern but in which no initial defect of > 25% with respect to the regional of greatest activity was noted. For this score to be assigned, a normal segment showing a net decrease in T1201 activity over time was required. A score of 3 designated an initial defect of > 25% (or > 35% in the inferior wall on the anterior view image) with subsequent total redistribution.This implied normalization of the initial defect relative to a normal myocardial region. A score of 4 was designated if a significant initial defect was noted but only partial redistribution was observed on the delayed image. A score of 5 reflected a persistent defect in which there was a 2650% reduction in regional T1-20 1 counts with no subsequent redistribution. Finally, a score of 6 was designated if an initial defect demonstrated > 50% reduction in T1-201 counts relative to a normal myocardial segment and no redistribution was noted on the delayed images. Gated Equilibrium Blood Pool Scanning
After completion of the exercise protocol and myocardial T1-201 imaging, resting equilibrium-gated blood pool imaging was performed. Injection of unlabeled stannous pyrophosphate was followed 30 minutes later by injection of 20 mCi of technetium-99m pertechnetate to complete the in vivo labeling of red blood cells. After equilibration of the blood pool tracer, gated images were obtained in the anterior projection, in the 45" left oblique projection (this angle is modified if necessary to achieve the best ventricular separation), followed by a second left oblique projection obtained by rotating 30" beyond the view of best ventricular separation (normally 75"). A large field gamma camera with parallel hole collimator was used with approximately 2X image magnification for gated imaging. Gated images were acquired for an interval of 8 minutes using 16 images per cardiac cycle, with the image sequence being triggered by an electrocardiographic R-wave detector. Global left ventricular ejection fraction was calculated from the 45" LAO projection without caudal angulation using a standard volume count method.12
Results Exercise Test Results
The changes in treadmill time, metabolic equivalents (METs) achieved and the double product attained prior to and after 3 months of exercise training are summarized in Figure 1. As shown, there was a statistically significant
19 p
