Author + information
- Received August 16, 1990
- Revision received December 6, 1990
- Accepted January 5, 1991
- Published online June 1, 1991.
- ↵∗Address for reprints: Jonathan S. Steinberg, MD, St. Luke's-Roosevelt Hospital Center, Arrhythmia Service/Division of Cardiology, Amsterdam Avenue at 114th Street, New York, New York 10025.
The mechanism of action of moricizine, a new antiarrhythmic agent used in the Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because moricizine is extensively metabolized, plasma moricizine concentration has an unknown relation to myocardial drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor moricizine's myocardial effects in 16 patients with frequent ventricular premature complexes taking 600 to 900 mg daily. Three signal-averaged ECG variables were measured: total filtered QRS duration (fQRS), root-mean-square voltage in the terminal 40 ms or the QRS complex (V40) and the terminal low amplitude duration <40 μV (LAS). At steady state, plasma samples were collected and serial recordings of signal-averaged and standard ECGs were taken at 0, 1, 2, 4, 6 and 8 h after moricizine administration. A 24 h ambulatory ECG was recorded throughout the test period.
Moricizine prolonged the fQRS (p < 0.05) and decreased the V40 (p < 0.05) of the signal-averaged ECG and prolonged the QRS (p < 0.05) and corrected JT (JTc) intervals (p < 0.05) of the standard ECG. The time course of the signal-averaged and standard ECG variables paralleled plasma moricizine concentration; that is, the maximal changes occurred at 1 to 2 h and declined to time 0 values at 8 h. The maximal changes were: fQRS (+8%), V40 (−33%), QRS (+8%) and JTc (+4%). Thus, dynamic changes were observed for intraventricular conduction (fQRS, QRS) and ventricular repolarization (JTc) over the dosing interval.
In a subset of seven patients with ≥6 ventricular premature complexes/h at steady state on moricizine, the frequency of ventricular premature complexes related inversely with plasma moricizine concentration and changes on the signal-averaged and standard ECGs. Noninvasive evaluation of moricizine provided insight into the relation between drug concentration and myocardial effect.
☆ This study was supported in part by Grants RR-00645 from the Research Resource Administration, Bethesda, Maryland and HL-07406 from the Department of Health and Human Services, Bethesda; and by Du Pont Pharmaceuticals, Wilmington, Delaware. It was presented in part at the 11th Annual Scientific Session of the North American Society of Pacing and Electrophysiology, San Diego, California, May 1990.
- Received August 16, 1990.
- Revision received December 6, 1990.
- Accepted January 5, 1991.