B-po02-146 impact of dofetilide loading during atrial fibrillation on discharge dose and qtc stability over 1-year follow-up

Dofetilide, an IKr blocker suppresses AF in a dose-dependent fashion. The combination of the protective effect of AF against QTc prolongation coupled with transient post-cardioversion QTc prolongation when exposed to IKr blockers may result in Dofetilide under-dosing when loading during AF. Thus, the optimal timing of cardioversion for AF patients undergoing dofetilide initiation in order to maximize discharge dose remains unknown. To evaluate whether Dofetilide loading during AF prior to cardioversion leads to under-dosing and assess the stability of QTc-a (Bazett, Fridericia, Framingham, and Hodges) in Dofetilide loaded patients over 1-year follow-up. Electronic medical records of patients who underwent pre-planned Dofetilide loading at a tertiary care center between January 1, 2017 and January 1, 2019 were retrospectively reviewed. A total of 136 patients, age 66±11 years, 35% females, with a CHADS2 Vasc score of 3 (2-4), LVEF 56±12% and creatinine clearance of 81±18 presented for Dofetilide loading in AF (57%) and SR (43%).Cumulative Dofetilide dose given prior to spontaneous or electrical AF cardioversion moderately correlated (r=0.42; p=0.0001) with discharge dose. Neither the presenting rhythm (AF vs SR), nor spontaneous conversion to SR impacted the discharge dose. Post-cardioversion QTc-a prolongation (p<0.01) prompted discharge dose reduction (902±222 mcg/day vs 544±168 mcg/day; p<0.0001) in 25% patients. All patients displayed QTc-a reduction (p<0.0001) from discharge to 1st (60±47 days) and to 1 year (359±152 days) follow-ups. The QTc-a reduction correlated with discharge QTc-a prolongation (r=0.49-0.61; p<0.0001). In fact, follow-up QTc-a returned to pre-loading baseline in patients who presented in SR. Drug loading prior to AF cardioversion does not under-dose Dofetilide when compared to drug loading in SR. Significant QTc reduction proportional to QTc prolongation at discharge is noted overtime in all Dofetilide patients, such that QTc returns back to pre-loading baseline during follow-up in patients loaded in SR. This is likely due to progressive QT prolongation blunting noted over time for the same daily Dofetilide dose and transient post-cardioversion QT prolongation.