Author + information
- Received June 20, 1994
- Revision received October 20, 1994
- Accepted December 5, 1994
- Published online April 1, 1995.
- Anne M. Gillis, MD*,1,
- L. Brent Mitchell, MD,
- D. George Wyse, MD, PhD, FACC,
- Margot McDonald, BN and
- Henry J. Duff, MD
- ↵*Address for correspondence: Dr. Anne M. Gillis, Department Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
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 ≥0.35 ([mean ±SD] 29.5 ± 11.2 ms/μg per ml) than in the group with a low left ventricular ejection fraction (15.7 ± 9.7 ms/μg 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.
↵1 Dr. Gillis is a Scholar and Dr. Duff a Medical Scientist of the Alberta Heritage Foundation for Medical Research, Edmonton, Alberta, Canada.
This study was supported by grants-in-aid from the Heart and Stroke Foundation of Alberta and the Medical Research Council of Canada (PG11188), Ottawa, Ontario.
- Received June 20, 1994.
- Revision received October 20, 1994.
- Accepted December 5, 1994.
- North American Society of Pacing and Electrophysiology; American College of Cardiology; American Heart Association, Inc.; and European Society of Cardiology.