ELECTROPHYSIOLOGICAL EVALUATION OF MORICIZINE IN PATIENTS WITH SUSTAINED VENTRICULAR TACHYARRHYTHMIAS - LOW EFFICACY AND HIGH-INCIDENCE OF PROARRHYTHMIA

In patients with history of sustained ventricular tachyarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in, hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 +/- 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducible in 27 patients, ventricular fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15-25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 +/- 185 mg) over a period of 2-7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6-24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 +/- 30 msec to 299 +/- 60 msec (P < 0.09). Four noninducible patients, two patients with inducible but slowed VT and one patient who had refused further testing were discharged on moricizine. Among these seven patients, recurrent arrhythmic events occurred in two patients, ventricular proarrhythmia in one patient, complete AV block in one patient, and severe disabling headache in one patient. Only two patients have continued to take moricizine without side effects or recurrent arrhythmic events during a follow-up of 4 months and 9 months, respectively. Moricizine is only rarely effective for long-term treatment of patients with spontaneous sustained ventricular tachyarrhythmias. It renders ventricular tachyarrhythmias noninducible in a small minority (16%) and is associated with a high incidence (23%) of ventricular proarrhythmias.