The Effect of Vernakalant (RSD1235), an Investigational Antiarrhythmic Agent, on Atrial Electrophysiology in Humans

OBJECTIVES: To determine the acute effects of vernakalant (RSD1235) on electrophysiologic (EP) properties in humans. BACKGROUND: Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more "atrial-selective" than available agents. METHODS: Patients (N=19; 53% male; age, 48+/-11 years) underwent EP study before and after 25 minutes of intravenous vernakalant administration: 2 mg/kg over 10 min+0.5 mg/kg/hr for 35 min or 4 mg/kg over 10 min+1 mg/kg/hr for 35 min. EP measurements, including atrial refractory period (AERP) and ventricular refractory period (VERP), were obtained. RESULTS: The lower dose prolonged AERP at 600, but not at 400 or 300 msec paced cycle length. The higher dose significantly prolonged AERP from 203+/-31 msec to 228+/-24 msec at 600 msec, 182+/-30 msec to 207+/-27 msec at 400 msec, and 172 msec+/-24 to 193+/-21 msec at 300 msec. There was no significant prolongation of VERP at either dose or at any cycle length. There was a small but significant prolongation of AV nodal refractoriness; Wenckebach cycle length prolonged by 18+/-12 msec (from baseline 343+/-54 msec) at the higher dose (P<0.05). Sinus node recovery time also increased by 123+/-158 msec (from baseline 928+/-237 msec) at the higher dose (P<0.05). There was a slight prolongation of QRS duration at the higher dose, during ventricular pacing at CL=400 msec (15+/-15 msec, P=0.0547). QT and HV intervals were unchanged. CONCLUSIONS: At doses similar to those tested clinically, vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness.