Acute conversion of persistent atrial fibrillation during dofetilide initiation

Background: Dofetilide (D) is a highly selective blocker of the rapid component of the delayed rectifier potassium current and was approved for the treatment of atrial fibrillation (AF) based on a satisfactory safety/efficacy profile from trials in patients with left ventricle (LV) dysfunction or heart failure. The dose-dependant acute conversion rates (< 72 hours) were reported to be in the range of 6-30%. We hypothesized that the acute pharmacological conversion rate of D is higher than previously reported if used in a healthier cohort of patients with persistent AF. Methods and Results: Eighty consecutive patients received D dosing per Cockroft-Gault adjustment for creatinine clearance and QTc intervals. Patients were 61 +/- 10 years, 79% male, ejection fraction (EF) 53 +/- 13%, coronary artery disease 20%, and left atrial dimension 4.1 +/- 0.2 cms. The duration of the treated AF episode was a median of 19 days (range 10-113 days). All patients received D while on telemetry for at least six dosing intervals. After 2.2 +/- 1.2 doses, 77% of patients converted to sinus rhythm (SR) and 23% did not and required direct current (DC) cardioversion. Acute pharmacological conversion rates were: 20% for D 125 mcg bid, 44% for 250 mcg bid, and 85% for 500 mcg bid. None of the patients had torsade de pointes and none had to stop D for intolerance. Failure to convert to SR on D alone was associated with larger left atrium (LA) diameter (P = 0.04), longer duration of AF (P = 0.02), and use of lower dosages of D (P = 0.04). Conclusions: D had an unusually high pharmacological conversion rate, demonstrated an incremental dose response, and was well tolerated and safe, in a relatively healthy adult cohort with persistent AF. In addition to D dose, pharmaco-conversion was predicted by LA size and AF duration. D is a desirable alternative for conversion of AF in a variety of clinical settings.