EFFECTS OF THE CLASS-III ANTIARRHYTHMIC DRUG DOFETILIDE ON VENTRICULAR MONOPHASIC ACTION-POTENTIAL DURATION AND QT-INTERVAL DISPERSION IN STABLE ANGINA-PECTORIS

The effects of intravenous dofetilide on ventricular monophasic action potential duration and effective refractory period at the right ventricular apex and outflow tract were studied in 18 patients (aged 37 to 70 years) with ischemic heart disease. Six patients received low-dose dofetilide as a 3 mug/kg loading dose over 15 minutes and a 1.5 mug/kg maintenance dose over 45 minutes; 6 received high-dose dofetilide 6 + 3 mug/kg and 6 placebo. During atrial pacing at a cycle length of 800 ms high-dose dofetilide prolonged right ventricular apex monophasic action potential duration by 45 ms (16%) and the effective refractory period by 40 ms (16%). At the right ventricular outflow tract, monophasic action potential duration was prolonged by 45 ms (15%) and effective refractory period by 55 ms (21%). During atrial pacing at a cycle length of 500 ms high-dose dofetilide prolonged the right ventricular apex monophasic action potential duration by 40 ms (18%) and the effective refractory period by 43 ms (21%). The right ventricular outflow tract monophasic action potential duration was prolonged by 33 ms (14%) and effective refractory period by 45 ms (21%). Dofetilide produced no increase in the dispersion of repolarization between the 2 sites. During the maintenance infusion QTc prolongation by high-dose dofetilide averaged 43 ms (10%) with no increase of interlead QT dispersion. The effects of dofetilide on QT interval and effective refractory period are shown to be due to a direct effect on action potential duration with no effect on dispersion. No rate dependence of monophasic action potential prolongation was detected at these cycle lengths.