Propranolol therapy alters estimation of potential cardiovascular risk derived from submaximal postinfarction exercise testing We studied the effect of propranolol administration on risk assessment based on submaximal exercise testing performed early after myocardial infarction. A total of 70 patients with recent infarction underwent modified Bruce treadmill testing with simultaneous measurement of expired gases in the absence of antianginal agents including @antagonists. Among these, 31 patients -ST depression 21 mm (22 patients), chest who had at least one of the following abnormalities pain (four patients), or treadmill time < 360 seconds (12 patients)-were studied in a randomized double-blind fashion and received either placebo or 240 mg of propranolol/day. A total of 28 patients completed the randomized phase and were able to undergo repeat exercise testing an average of 3.4 f 1.6 days later. Randomized groups were equivalent at baseline except for a higher peak oxygen consumption and carbon dioxide production (p < 0.05) in the propranolol compared with the placebo group; these differences were taken into account in statistical analyses of the study data. Resting heart rate (59 * 1.2 versus 62 + 4.2 beats/min) and peak heart rate X systolic blood pressure (14,206 + 496 versus 20,075 f 1,062) were both significantly less (p < 0.01) after propranolol than after placebo. Eight of nine patients treated with placebo maintained ST depression I 1 mm from the initial to the randomized exercise test, compared with only 4 of 13 receiving propranolol (p < 0.01). In those with continued ST depression, time to positivity was significantly longer in those receiving propranolol compared with those taking placebo (538 + 73 versus 318 f 44 seconds, p < 0.05). In contrast, the peak ratio between carbon dioxide production and oxygen consumption was higher in those receiving propranolol compared with those receiving placebo (0.93 + 0.04 versus 0.81 f 0.03, p < 0.05). We conclude that propranolol therapy reduces evidence of ischemia and changes traditional estimates of potential cardiac risk derived from submaximal postinfarction exercise testing. (AM HEART J 1991;121:1655.)

Jeffery L. Curtis, MD, Jan L. Houghton, MD, J. Herbert Patterson, PharmD, Gary Koch, PhD, Deborah A. Bradley, BSN, and Kirkwood F. Adams, Jr., MD. Chapel Hill, N.C.

Delineation of prognosis remains an important element in the management of patients after myocardial infarction,lm3 and submaximal exercise testing has emerged as the major tool in the assessment of their cardiovascular risk.4-12 Those patients whose exercise test is abnormal are significantly more likely to From the Departments of Medicine and Radiology, School of Medicine, School of Pharmacy, and the Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill. Supported in part by a grant-in-aid from the American Heart Association, North Carolina Affiliate, Inc., and by research grant MO1 RR00046 from the General Clinical Research Centers branch of the Division of Research Resources, IJnited States Public Health Service. Received

for publication

May

3, 1990; accepted

Reprint requests: Kirkwood F. Adams, University of North Carolina at Chapel ack Bldg., Chapel Hill, NC 27599.7075. 4/1/28510.

Oct. 18, 1990.

Jr., MD, Division of Cardiology, Hill, CB No. ‘7075, Burnett-Wom-

experience cardiovascular death, unstable angina, or recurrent myocardial infarction, especially in the first 1 to 2 years of follow-up. Identification of these patients prior to hospital discharge can lead to more aggressive management, including early catheterization and intervention, in an attempt to favorably alter their prognosis. The widespread acceptance that treatment with P-adrenergic blocking drugs after infarction can improve long-term prognosis has complicated the use of exercise testing in the evaluation of patients after myocardial infarction.i3-l6 ,&Adrenergic receptor antagonists are now routinely administered early after this event, with the subsequent performance of the predischarge treadmill test under the influence of these agents. Since these drugs have the potential to influence exercise performance, they may diminish 1655

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et

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the accuracy of risk stratification based on such testing. The present investigation was performed in a randomized, double-blind, placebo-controlled fashion to specifically determine the effect of propranolol on the interpretation of a submaximal treadmill test performed early in the postinfarction period. Patients were selected on the basis of an initial exercise test that demonstrated evidence of cardiovascular risk by standard criteria. To minimize any confounding effect of other medications that influence treadmill performance, all antianginal therapy was withdrawn prior to patient enrollment in the protocol. METHODS Patient population. Subjects for the study were recruited from patients hospitalized for acute myocardial infarction. The diagnosis of infarction was confirmed by the presence of ischemic chest pain lasting longer than 30 minutes, a twofold rise in serum creatine phosphokinase (CK) with at least 20 IUIL of MB fraction, and characteristic electrocardiographic (ECG) changes diagnostic of Q wave or non-Q wave infarction. Patients were excluded from the study if they could not safely undergo exercise testing due to postinfarction angina or persistent heart failure. Patients were not studied if they had left bundle branch block or left ventricular hypertrophy on their ECG, if they refused, or if they were unable to exercise due to weakness, deconditioning, or musculoskeletal problems. Patients were also excluded if they were unable to discontinue all antianginal therapy (nitrates, P-adrenergic blocking drugs, and calcium antagonists) prior to exercise testing. The protocol was approved by the Institutional Review Board of the University of North Carolina. Written informed consent was obtained from all subjects before their participation in the study. Exercise testing. Submaximal exercise treadmill testing was performed 1 to 2 weeks after myocardial infarction, using the modified Bruce protocol.17T’s Standard ECG leads II, Vd, and V5 were monitored continuously throughout exercise and were recorded every 30 seconds during exercise. A full 12-lead ECG was recorded every minute during exercise and every minute after exercise for 5 minutes or until the tracing returned to baseline. Blood pressure was measured by cuff with subjects in the standing position before exercise, every 2 minutes during exercise, and every minute after exercise until the pressure had returned to the preexercise level. An attempt was made to exercise all patients until they reached 70 % of their maximum predicted heart rate or 120 to 130 beats/min, whichever was greater. Otherwise, exercise was terminated if the patient: (1) experienced severe progressive angina; (2) had ST segment depression of 3 mm or more from the baseline value; (3) had hemodynamically significant arrhythmias; (4) had a drop in systolic blood pressure of more than 10 mm Hg from the previous reading; or (5) was too fatigued to continue. The reason for the termination of exercise was documented in each patient. The initial and the final exercise tests in a

given subject were always performed by the same physician. An exercise test was considered positive if the patient had: (1) exercise-induced angina; (2) exercise duration of less than 360 seconds; or (3) ST segment depression, flat or downsloping, at least 0.1 mV in amplitude when compared with the baseline at 0.08 second after the J point, in at least one ECG lead. An exercise duration of