Familial polymorphic ventricular arrhythmias - A quarter century of successful medical treatment based on serial exercise-pharmacologic testing

OBJECTIVES We sought to determine whether objective tests of antiarrhythmic drug efficacy could produce favorable short- and long-term outcomes in a f amily with idiopathic malignant ventricular arrhythmias. BACKGROUND In 1973 a family presented with a history of several generations of syncopal spells and sudden death. Some individuals had nonspecific elec trocardiographic (ECG) changes. Their QT intervals were normal at rest and with exercise. Autopsies in two young family members showed no cardiac abno rmalities, specifically no evidence of arrhythmogenic right ventricular dys plasia, other cardiomyopathy, myocarditis or gross abnormality of the condu ction system. METHODS Available family members had screening ECGs. Symptomatic members ha d a battery of tests, including electrophysiologic studies, ambulatory ECGs , audiograms, exercise stress testing, serum catecholamine levels during re st and exercise and isoproterenol infusion. Serial exercise-pharmacologic t esting was performed in symptomatic family members until induction of an ar rhythmia during exercise required higher work loads or became impossible. RESULTS Arrhythmias were not induced during electrophysiologic studies. In several family members tested, ventricular premature beats and then rapid p olymorphic ventricular arrhythmias occurred whenever the sinus rate exceede d 130 beats/min. Emotional stress, isoproterenol infusion and exercise all elicited similar arrhythmias. Catecholamine levels during exercise were, ho wever, unequivocally normal in two of three family members tested. Beta-blo ckers appeared to be the most effective pharmacologic agent for prevention of these arrhythmias. The efficacy of treatment has been confirmed during a follow-up of 25 years. CONCLUSIONS This family appears to have catecholamine hypersensitivity as t he basis for their ventricular arrhythmias. Guided therapy using serial exe rcise-pharmacologic testing provided reliable protection for this familial ventricular arrhythmia during a 25-year follow-up. (C) 1999 by the American College of Cardiology.