Hormone-Electrolyte Interactions in the Pathogenesis of Lethal Cardiac Arrhythmias in Patients with Congestive Heart Failure Basis of a New Physiologic Approach to Control of Arrhythmia MILTON PACKER, M.D. STEPHEN S. GOTTLIEB, M.D. PAUL D. KESSLER, M.D. New York, New York From the Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine of The City University of New York, New York, New York. Dr. Packer is the recipient of a Research Career Development Award (K04-HL-01229) from the Na- tional Heart, Lung, and Blood Institute, Bethesda, Maryland. Requests for reprints should be ad- dressed to Dr. Milton Packer, Division of Cardiol- ogy, Mount Sinai Medical Center, 1 Gustave Levy Place, New York, New York 10029. Congestive heart failure isthe most arrhythmogenic disorder in car- diovascular medicine. As left ventricular performance deteriorates and symptoms of dyspnea and fatigue become progressively more severe, nearly all patients with heart failure experience frequent and complex ventricular tachyarrhythmias and nearly half die suddenly during long-term follow-up. This imminent risk of sudden death appears to be present for a// patients with congestive heart failure; ambulatory electrocardiographic monitoring and programmed elec- trical stimulation are not useful in distinguishing patient subsets that are particularly predisposed to fatal arrhythmic events. Al- though conventional antiarrhythmic agents are widely prescribed as a nonspecific approach to prevent sudden death in these pa- tients, there is little evidence to indicate that these drugs possess clinically important antiarrhythmic activity in patients with conges- tive heart failure, and these agents frequently serve to exacerbate the heart failure state and the underlying ventricular tachyarrhyth- mia. A useful approach to the prevention of sudden death in pa- tients with congestive heart failure addresses the reversible causes of lethal ventricular arrhythmias in these individuals. Both experi- mental and clinical evidence indicates that circulating neurohor- mones and electrolyte deficits (particularly of potassium and mag- nesium) interact to provoke malignant ventricular ectopic rhythms and that the prevention of electrolyte depletion and the use of neu- rohormonal antagonists may exert clinically important antiarrhyth- mic actions. This physiologic approach may prove to be a more effective means of ameliorating the problem of sudden death than the empiric administration of conventional antiarrhythmic drugs. Congestive heart failure is the most arrhythmogenic disorder in cardio- vascular medicine [l]. Although ventricular arrhythmias occur frequently in normal people and in patients with a variety of cardiac diseases, the vast majority of these rhythm disturbances do not compromise circulatory function and are not a harbinger of sudden death [2,3]; hence, these asymptomatic patients should not be the target of therapeutic attempts at arrhythmia control. The prevalence and complexity of ambulatory ventric- ular arrhythmias increase precipitously, however, as left ventricular func- tion deteriorates, and, in a parallel fashion, sudden death becomes an increasingly frequent occurrence [4-91. In patients with a left ventricular ejection fraction of less than 30 percent and symptoms of severe heart failure, complex ventricular arrhythmias are universally present during ambulatory electrocardiographic monitoring [l O-l 81, and nearly half of these patients die suddenly and unexpectedly within two to four years of April 25, 1986 The American Journal of Medicine Volume 80 (suppl 4A) 23