Quinidine pharmacodynamics in patients with arrhythmia: effects of left ventricular function
AM Gillis,
LB Mitchell,
DG Wyse,
M McDonald,
and
HJ Duff
Division of Cardiology, Foothills Medical Centre, Calgary, Alberta, Canada.
OBJECTIVES. This study was undertaken to determine whether quinidine pharmacodynamics are altered in the presence of left ventricular dysfunction. BACKGROUND. Left ventricular function is an independent predictor of antiarrhythmic drug efficacy. However, the effects of left ventricular dysfunction on the pharmacodynamics of antiarrhythmic drugs have not been studied extensively. METHODS. Signal-averaged electrocardiograms were obtained and quinidine plasma concentrations measured during 24-h quinidine washout in 22 patients. RESULTS. Linear quinidine concentration-effect relations were observed for QRS and QT intervals corrected for heart rate. The slopes of the concentration-effect relation describing changes in the corrected QT (QTc) interval were significantly higher in the group with left ventricular ejection fraction > or = 0.35 ([mean +/- SD] 29.5 +/- 11.2 ms/micrograms per ml) than in the group with a low left ventricular ejection fraction (15.7 +/- 9.7 ms/micrograms per ml, p = 0.001). The QRS concentration-effect relations were not different in the two groups. A significant linear correlation was observed between the slopes of the concentration-effect relations describing changes in QTc intervals and left ventricular ejection fraction (r = 0.7, p < 0.001). Nineteen patients with inducible ventricular tachycardia underwent serial electrophysiologic studies for evaluation of quinidine efficacy. Ventricular tachycardia could not be induced during quinidine therapy in eight patients. The slopes of the quinidine concentration-effect relations for QTc intervals were significantly higher in quinidine responders than in nonresponders (p < 0.05). CONCLUSIONS. The effects of quinidine on ventricular repolarization are linearly related to left ventricular ejection fraction. Quinidine concentration-effect relations describing ventricular repolarization are associated with antiarrhythmic efficacy in patients with ventricular tachycardia.
