Evaluation of Metoprolol in Suppressing Complex Ventricular Arrhythmias CRAIG M. PRATT, MD, SHEILA C. YEPSEN, RN, CVNS, M. G. KIM BLOOM, MD, ADDISON A. TAYLOR, MD, JAMES B. YOUNG, MD, and MIGUEL A. QUINONES, MD This study documents the extent of suppression of premature ventricular beats which can be achieved with metoprolol, a semiselective beta-adrenergic blocking agent, at doses of 100 to 200 mg daily, utilizing a single-blind placebo-controlled lo-day protocol with continuous ambulatory electrocar- diographic recording of 20 patients with cardiac disease and complex ventricular arrhythmias. Me- toprolol (200 mg/day) resulted in suppression of 60% of total premature ventricular beats, with couplets (pairs) and ventricular tachycardta de- creased 64% and 94%, respectively (all p <O.Ol). Exercise-induced premature ventricular beats, especially ventricular tachycardia, were effectively suppressed. The peak plasma metoprolol level to achieve these results was 72 f 34 ng/ml (mean f 1 standard deviation). At this plasma concen- tration, the mean 24-hour heart rate during normal activity was reduced from 76 f 6 beats/mtn (pla- cebo) to 62 f 4 (metoprolol 200 mg/day)(p <O.OOl). Beta blockade also was demonstrated by a 20% reduction in heart rate during maximal Bruce exercise testing with metoprolol 200 mg/day. Al- though resting left ventricular function was not af- fected by metoprolol, pulmonary function tests show a statistically significant decrease in forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow rates (25-75) reversible with a beta-2 agonist. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP Ventricular rhythm disturbances have prognostic sig- nificance in identifying an increased risk for sudden cardiac death in patients after myocardial infarction.lv2 Beta-adrenergic blocking agents are efficacious in suppressing ventricular arrhythmias, especially in specific clinical settings including catecholamine excess, digitalis toxicity, mitral valve prolapse, and those in- duced by exercise.3-6 Importantly, in numerous pro- spective placebo-controlled randomized clinical trials of beta-blockers in patients after myocardial infarction, cardiac mortality and sudden cardiac death have been reduced. Propranolol, timolol, and metoprolol have From the Section of Cardiology, Baylor College of Medicine and The Methodist Hospital, Houston, Texas. This study was supported in part by Grant HL-17269 from the National Heart, Lung, and Blood Vessel Research and Demonstration Center, Baylor College of Medicine, and Biomedical Research Support Grant P-14, General Clinical Research Center, The Methodist Hospital, Houston, Texas. Computational as- sistance was provided by the CLINFO Project funded by Grant RR- 00350, Division of Research Resources, National Institutes of Health, Bethesda, Maryland. Manuscript received October 19, 1962; revised manuscript received March 21, 1963, accepted March 26, 1983. Address for reprints: Craig M. Pratt, MD, Assistant Professor of Medicine, Section of Cardiology, Baylor College of Medicine, and The Methodist Hospital, 6565 Fannin, MS FlOOl, Houston, Texas 77030. achieved the most significant reduction in mortality and sudden death in these large clinical trials.7-g Although a reduction in mortality and sudden death has been documented, it has not been demonstrated that this reduction is due to suppression of ventricular arrhyth- mias. Despite a substantial experience with beta-blockers, the ventricular antiarrhythmic efficacy of metoprolol is poorly documented. Since the semiselective proper- ties of this beta-blocker may be beneficial to patients with asthma or obstructive lung disease, this study was designed to assess the effect of metoprolol in sup- pressing complex ventricular arrhythmias, with con- comitant measurement of left ventricular function, pulmonary function, and correlation with plasma me- toprolol levels. Methods zyxwvutsrqponmlkjihgfedcba The study population consisted of 20 patients (10 male, 10 female; mean age 57 f 8 years) with screening 24-hour am- bulatory electrocardiograms demonstrating complex ven- tricular rhythm disturbances (frequent premature ventricular beats [PVB] 130 per hour, couplets, ventricular tachycardia [VT]). All 20 patients had documented cardiac disease: 15