Serial Cardioversion by Class IC Drugs During 4 Months of Persistent Atrial Fibrillation in the Goat

INTRODUCTION: The success rate of pharmacological cardioversion of atrial fibrillation (AF) in patients depends on the duration of AF. It is unknown to what extent AF-induced structural atrial remodeling contributes to this loss of efficacy. METHODS AND RESULTS: In 10 goats, persistent AF was induced by repetitive burst pacing. During a time period of 16 weeks, the efficacy of flecainide and cibenzoline to cardiovert AF was investigated by serial cardioversion. The drugs were administered intravenously at a rate of 0.1 mg/kg/min. AF cycle length (AFCL) was continuously monitored. Drug infusion was continued until AF was successfully cardioverted or the QRS duration was prolonged about twofold. The average atrial cycle length during persistent AF was 104 +/- 10 msec and did not change during the 16-week period. The success rate of cardioversion by flecainide and cibenzoline decreased with the duration of AF from 60% to 17% and from 80% to 63%. In goats that failed to cardiovert, sinus rhythm was not restored despite a twofold prolongation of the AF cycle length (respectively from 96 +/- 5 msec to 168 +/- 30 msec (flecainide) and 203 +/- 26 msec (cibenzoline)). The sensitivity of AF for Class IC drugs was not altered with time, and the dose-dependent effect on AFCL remained the same (flecainide: 8 +/- 5 vs 7 +/- 2 msec/mg/kg (P = 0.70) and cibenzoline: 13 +/- 3 vs 13 +/- 5 msec/mg/kg (P = 0.95)). In animals in which cardioversion remained possible, the critical AFCL at which cardioversion occurred increased from 96 +/- 5 msec to 211 msec (flecainide) and 189 +/- 24 msec (cibenzoline). CONCLUSIONS: The progressive loss of efficacy of Class IC drugs to cardiovert AF of longer duration is not due to a decrease in the sensitivity of remodeled atrial myocardium for Class IC drugs. Failure of cardioversion was due to an increase in the critical AF cycle length required for pharmacological cardioversion.