QUINIDINE PHARMACODYNAMICS IN PATIENTS WITH ARRHYTHMIA - EFFECTS OF LEFT-VENTRICULAR FUNCTION

Objectives. This study was undertaken to determine whether quinidine p harmacodynamics are altered in the presence of left ventricular dysfun ction. Background. Left ventricular function is an independent predict or of antiarrhythmic drug efficacy. However, the effects of left ventr icular dysfunction on the pharmacodynamics of antiarrhythmic drugs hav e not been studied extensively.Methods. Signal averaged electrocardiog rams were obtained and quinidine plasma concentrations measured during 24-h quinidine washout in 22 patients. Results. Linear quinidine conc entration-effect relations were observed for QRS and QT intervals corr ected for heart rate. The slopes of the concentration effect relation describing changes in the corrected QT (QTc) interval were significant ly higher in the group with left ventricular ejection fraction greater than or equal to 0.35 ([mean +/- SD] 29.5 +/- 11.2 ms/mu g per ml) th an in the group with a low left ventricular ejection fraction (15.7 +/ - 9.7 ms/mu g per ml, p = 0.001). The QRS concentration-effect relatio ns were not different in the two groups. A significant linear correlat ion was observed between the slopes of the concentration-effect relati ons describing changes in QTc intervals and left ventricular ejection fraction (r = 0.7, p < 0.001). Nineteen patients with inducible ventri cular tachycardia underwent serial electrophysiologic studies for eval uation of quinidine efficacy. Ventricular tachycardia could not be ind uced during quinidine therapy in eight patients. The slopes of the qui nidine concentration-effect relations for QTc intervals were significa ntly higher in quinidine responders than in nonresponders (p < 0.05). Conclusions. The effects of quinidine on ventricular repolarization ar e linearly related to left ventricular ejection fraction. Quinidine co ncentration-effect relations describing ventricular repolarization are associated with antiarrhythmic efficacy in patients with ventricular tachycardia.