Exaggerated QT prolongation after cardioversion of atrial fibrillation

OBJECTIVES The purpose of this study was to test the hypothesis that the extent of drug-induced QT prolongation by dofetilide is greater in sinus rhythm (SR) after cardioversion compared with during atrial fibrillation (AF). BACKGROUND Anecdotes suggest that when action potential–prolonging antiarrhythmic drugs are used for AF, excessive QT prolongation and torsades de pointes (TdP) often occur shortly after sinus rhythm is restored. METHODS QT was measured in nine patients with AF who received two identical infusions of dofetilide: 1) before elective direct current cardioversion and 2) within 24 h of restoration of SR. RESULTS During AF, dofetilide did not prolong QT (baseline: 368 ± 48 ms vs. drug: 391 ± 60, p = NS) whereas during SR, QT was prolonged from 405 ± 55 to 470 ± 67 ms (p < 0.01). In four patients (group I), the SR dofetilide infusion was terminated early because QT prolonged to >500 ms, and one patient developed asymptomatic nonsustained TdP. The remaining five patients (group II) received the entire dose during SR. Although ΔQT was greater in group I during SR (91 ± 22 vs. 45 ± 25 ms, p < 0.05), plasma dofetilide concentrations during SR were similar in the two groups (2.72 ± 0.96 vs. 2.77 ± 0.25 ng/ml), and in AF (2.76 ± 1.22 ng/ml). ΔQT in SR correlated inversely with baseline SR heart rate (r = −0.69, p < 0.05), and QT dispersion developing during the infusion (r = 0.79, p < 0.01). CONCLUSIONS Shortly after restoration of SR, there was increased sensitivity to QT prolongation by this IKr-specific blocker. Slower heart rates after cardioversion and QT dispersion during treatment appear to be important predictors of this response.