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Effect of Disopyramide on Left Ventricular Performance: The Relationship of Free and Total Concentrations of the Drug and of Its Mono‐N-dealkylated Metabolite to Noninvasive Indices of Function

Summary We used M-tnode echocardiography and recordings of systolic time intervals to follow changes in left ventricular systolic function of 10 normal subjects during administration of 200 mg oral disopyramide every 8 h. Left ventricular function was significantly depressed (peak rate of change of dimension −17%, p < 0.001; mean velocity of circumferential fiber shortening −15%, p < 0.01; percent fractional shortening −16%, p < 0.05) for as long as 7 h after a dose. These changes could be correlated with those in plasma concentrations of free and total disopyramide, and of its mono-N-dealkylated metabolite (change in peak rate of change of dimension versus levels of disopyramide plus metabolite, r = −0.41, p < 0.03; changes in ratio preejection time/ejection time versus levels of disopyramide and metabolite, r = 0.62, p < 0.002).