Maintenance of Sinus Rhythm and Recovery of Atrial Mechanical Function After Cardioversion With Bepridil or in Combination With Aprindine in Long-Lasting Persistent Atrial Fibrillation

Abstract

harmacological termination by class I antiarrhythmic drugs is usually considered effective treatment for atrial fibrillation (AF) lasting only several days, but of little help for long-lasting AF. As AF progresses from paroxysmal to persistent, changes in the relative importance of AF mechanisms occur such as increasing substratemediated factors and decreasing triggering factors. Hence, in patients with long lasting AF, rhythm control therapy is abandoned and rate control therapy is selected as standard therapy. 1,2 However, we have previously demonstrated that oral administration of bepridil alone or in combination with aprindine restored sinus rhythm in 69% of 32 patients with long-lasting persistent AF (>3 months), 3 and we speculate that bepridil inhibits substrate-mediated factors and aprindine suppresses trigger-mediated factors. Bepridil hydrochloride, a diarylaminopropylamine derivative, was introduced as an anti-anginal agent. In addition to its Ca antagonist properties, it prolongs action potential duration and refractory periods of normal ventricular and atrial myocardium 4 by inhibiting several types of K current including rapid, slow and ultra rapid components of delayed rectifier K current. 5,6 Amiodarone has multi-channel blocking properties similar to bepridil and is effective in not only terminating long-lasting AF, but also maintaining sinus rhythm. 7 In a canine model of AF, amiodarone prevented down-regulation of the L-type Ca channel and increased fibrillation cycle length (FCL) through reversal of atrial remodeling. 8 In our previous study, termination of long-lasting AF with oral administration of bepridil was associated with a 30% increase in FCL, 2 and it is possible that bepridil is effective for not only termination of AF but also perpetuation of sinus rhythm. In the present study, we assessed the efficacy of pharmacological or electrical conversion in patients with long-lasting AF for recovery of atrial mechanical function and maintenance of sinus rhythm with respect to changes in FCL. Methods SubjectsAll 38 patients in the study group had had AF lasting at least 1 month, quantified by ECG, and the median was 5 months (range: 1-84 months). All patients underwent phys- Background The aim of this study was to evaluate pharmacological cardioversion of long-lasting persistent atrial fibrillation (AF) using bepridil in terms of recovery of atrial mechanical function and maintenance of sinus rhythm. Bepridil alone or in combination with aprindine is effective for termination of persistent AF. Methods and ResultsThe study group comprised 38 consecutive patients (24 men, 58.8±9.3 years) with successful conversion of persistent AF lasting >1 month either pharmacologically (Group I) or electrically (Group II). Fast Fourier transform analysis of fibrillation waves was performed and fibrillation cycle length (FCL) was calculated from the peak frequency. In Group I, sinus rhythm was pharmacologically restored in 22 patients after an average 30 days (7-49 days) of bepridil administration, either al...

Dose-Response Effects of Bepridil in Patients With Persistent Atrial Fibrillation Monitored With Transtelephonic Electrocardiograms A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study (J-BAF Study)

“…In the 2000's, several Japanese clinical studies reported that a low-dose bepridil (at 100-200 mg/day) was effective for converting persistent AF to sinus rhythm without causing any arrhythmogenic effects. [20][21][22][23][24] Since then, some Japanese specialists in cardiac electrophysiology gradually began carefully using a low-dose bepridil for persistent AF. However, those previous studies were performed in selected patients in selected institutions, and also in an open-label fashion.…”

Recurrence of Atrial Fibrillation After Internal Cardioversion of Persistent Atrial Fibrillation Prognostic Importance of Electrophysiologic Parameters

“…Fujiki et al 39 and Nakazato et al 40 reported that 83% (18 of 22 patients) and 81% (70 of 86 patients) of PAF patients were free of AF recurrence at 12-months and 18-months of follow-up, respectively. In contract to those studies, the rate of maintaining SR at 12 months of follow-up using the combination of bepridil and carverilol in the present study was lower (21 of 47 patients: 44.7%, Fig 2).…”

“…38 However, we used bepridil and carvedilol for the maintenance of SR after cardioversion. Recent reports have shown that bepridil does not have the adverse effects of amiodarone and has a high rate of conversion of AF to SR and maintenance of SR. 39,40 Furthermore, because bepridil has the electrophysiologic characteristics of class Ib, III, and IV drugs and carvedilol has the electrophysiologic characteristics of class II drugs, 41,42 we expected their combined use to have electrophysiological effects similar to those of amiodarone, except for the effects on the thyroid hormone. We expected the major electrophysiologic effect of bepridil to be prolongation of the atrial ERP or MAPD because AF recurrence correlated with MAPD90 shortening according to our present results.…”

Opposing Effects of Bepridil on Ventricular Repolarization in Humans Inhomogeneous Prolongation of the Action Potential Duration vs Flattening of Its Restitution Kinetics

“…[1][2][3][4][5][6][7][8][9] Despite its usefulness for the treatment of AF, there remains some concern about the drug-induced polymorphic ventricular tachycardia, known as torsades de pointes (TdP), in association with QT prolongation. [10][11][12][13] The QT prolongation is attributable to the blockade of several K + outward currents, including the rapidly and slowly activating delayed rectifier K + currents (IKr and IKs).…”