Cardiovascular collapse associated with disopyramide therapy

Five patients with severe left ventricular failure, renal insufficiency, and recurrent ventricular tachycardia had cardiovascular collapse and died eight hours to 23 days after initiation of the usual doses of disopyramide. Three patients had recent myocardial infarction (12 to 33 days), and one had severe congestive cardiomyopathy. ECG changes antedated appearance of cardiovascular collapse and consisted of lengthening of the QRS (0.10 plus or minus 0.02 to 0.22 plus or minus 0.09; P less than 0.025) and the QTc duration (0.44 plus or minus 0.04 to 0.56 plus or minus 0.09; P less than 0.05). Sinus bradycardia or varying degrees of atrioventricular block or both occurred in all patients. Terminal disopyramide blood concentration (4.9 and 8.1 micrograms/ml) were available in two patients. A syndrome of progressive lengthening of ventricular depolarization and repolarization terminating in cardiovascular collapse and death associated with disopyramide is described. In addition, a high incidence of sinus bradycardia, atrioventricular conduction disturbances, or both was also noted. Disopyramide is contraindicated in patients with severe heart failure and renal insufficiency. Progressive widening of the QRS complex or the QT interval may presage appearance of severe myocardial dysfunction.