Electrophysiologic Effects of Intravenous E-4031, a Novel Class III Antiarrhythmic Agent, in Patients with Supraventricular Tachyarrhythmias

Abstract

Summary: The electrophysiologic effects of intravenous (i.v.) E-4031, a new class III antiarrhythmic drug, were evaluated in 15 patients with supraventricular tachyar-rhythmias [11 men, 4 women; mean age 41 ± 19 (SD) years]. Eleven patients had accessory atrioventricular (AV) pathways, and 4 patients with no accessory pathway had paroxysmal atrial fibrillation. Electrophysiologic studies were performed before and after E-4031 administration (loading infusion 9 μg/kg for 5 min + maintenance infusion 0.15 μg/kg/min). QT and QTc intervals were significantly prolonged by E-4031 from 0.40 ± 0.03 (mean ± SD) to 0.46 ± 0.03 s (p < 0.0001) and from 0.43 ± 0.03 to 0.49 ± 0.04 s (p < 0.0001), respectively. No effect was observed on RR interval, PR interval, QRS duration, or AH and HV intervals. The effective refractory periods (ERPs) of the right atrium and ventricle were significantly prolonged from 219 ± 27 to 236 ± 26 ms (p < 0.001) and from 230 ± 12 to 249 ± 11 ms (p < 0.001), respectively. The ERP of the AV node did not change significantly after E-4031 administration. In patients with ventricular preexcitation, E-4031 significantly prolonged the ERP of the antegrade accessory pathway conduction from 340 ± 101 to 362 ± 106 ms (p < 0.001), but not retrograde accessory pathway conduction. AV reentrant tachycardia was induced in 3 of 11 patients with an accessory pathway, and repetitive atrial firing was induced in 3 of 4 patients with paroxysmal atrial fibrillation. E-4031 could prevent repetitive atrial firing in only 1 patient and could not prevent induction of AV reentrant tachycardia. Blood pressure (BP) did not change significantly, and no undesirable side effects were associated with E-4031 administration. That E-4031 prolonged the ERP without affecting conduction time indicates that it possesses pure class III antiarrhythmic properties in patients with supraventricular tachyarrhythmias. Further evaluation of the therapeutic potential of this drug using the higher dosage may be needed.