ANTIARRHYTHMIC ACTIONS OF INTRAVENOUS IBUTILIDE COMPARED WITH PROCAINAMIDE DURING HUMAN ATRIAL-FLUTTER AND FIBRILLATION - ELECTROPHYSIOLOGICAL DETERMINANTS OF ENHANCED CONVERSION EFFICACY

Background The selective class III antiarrhythmic agent ibutilide prol ongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy i n humans has not been fully characterized. This study compared the ant iarrhythmic effects of ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electroph ysiological characteristics of AFL and AF that enhanced pharmacologica l termination were investigated. Methods and Results Right atrial mono phasic action potentials were recorded during 148 episodes of AFL (n=8 9) or AF (n=59) in 136 patients treated with intravenous ibutilide (n= 73) or placebo (n=22) as participant-a in randomized, double-blinded c omparative studies or intravenous procainamide (n=53) in a concurrent open-label study. The conversion rates in AFL with ibutilide, procaina mide, and placebo were 64% (29 of 45 patients), 0% (0 of 33), and 0% ( 0 of 11), respectively, whereas in AF the rates were 32% (9 of 28), 5% (1 of 20), and 0% (0 of 11), respectively. In AFL, ibutilide increase d atrial monophasic action potential duration (MAPD) more (30% versus 18%, P<.001) and prolonged atrial cycle length (CL) less (16% versus 2 6%, P<.001) than procainamide. Ibutilide shortened and procainamide pr olonged action potential diastolic interval during AFL (-12% versus 51 %, P<.001). Ibutilide increased MAPD/CL ratio, whereas procainamide te nded to decrease this ratio (13% versus -6%, P<.01). In AF, ibutilide and procainamide induced similar increases in atrial CL (48% versus 45 %), but ibutilide induced a greater increase in MAPD (52% versus 37%, P<.05). Independent electrophysiological predictors of pharmacological arrhythmia termination were increase in MAPD/CL ratio (P=.005) in AFL and longer baseline mean MAPD (P=.011) in AF. Termination of AFL with ibutilide was characterized by significant increases in beat-to-beat atrial CL, MAPD, and diastolic interval variability. Ibutilide was sig nificantly more effective in converting AF when the mean atrial CL was greater than or equal to 160 ms (64% versus 0%, P<.001) or MAPD was g reater than or equal to 125 ms (57% versus 0%, P=.002) at baseline. Co nclusions Enhanced conversion efficacy of ibutilide compared with proc ainamide in AFL is correlated with a relatively greater prolongation o f atrial MAPD than atrial CL, and termination of AFL by ibutilide is c haracterized by oscillations in atrial CL and MAPD. Conversion of AF b y ibutilide is enhanced by a longer baseline mean atrial CL or MAPD.