Longitudinal QTc stability and impact of baseline cardiac rhythm on discharge dose in dofetilide‐treated patients

• Published in: Journal of cardiovascular electrophysiology Vol. 33; no. 6; pp. 1281 - 1289
• Main Authors: Khan, Zeryab A., LaBreck, Megan E., Luli, Jordan, Roberts, Chelsea, Smith, Alexander, El‐Zein, Rayan, Tyler, Jaret D., Fu, Eugene Y., Billakanty, Sreedhar R., Amin, Anish K., Chopra, Nagesh
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.06.2022
• Subjects: atrial fibrillation; Cardioversion; dofetilide; Dosage; drug dosing; Fibrillation; follow up; Medical records; Patients; QT interval
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/jce.15483

Introduction Dofetilide suppresses atrial fibrillation (AF) in a dose‐dependent fashion. The protective effect of AF against QTc prolongation induced torsades de pointe and transient post‐cardioversion QTc prolongation may result in dofetilide under‐dosing during initiation. Thus, the optimal timing of cardioversion for AF patients undergoing dofetilide initiation to optimize discharge dose remains unknown as does the longitudinal stability of QTc. The purpose of this study was to evaluate the impact of baseline rhythm on dofetilide dosing during initiation and assess the longitudinal stability of QTc‐all (Bazzett, Fridericia, Framingham, and Hodges) over time. Methods Medical records of patients who underwent preplanned dofetilide loading at a tertiary care center between January 2016 and 2019 were reviewed. Results A total of 198 patients (66 ± 10 years, 32% female, CHADS2‐Vasc 3 [2–4]) presented for dofetilide loading in either AF (59%) or sinus rhythm (SR) (41%). Neither presenting rhythm, nor spontaneous conversion to SR impacted discharge dose. The cumulative dofetilide dose before cardioversion moderately correlated (r = .36; p = .0001) with discharge dose. Postcardioversion QTc‐all prolongation (p < .0001) prompted discharge dose reduction (890 ± 224 mcg vs. 552 ± 199 mcg; p < .0001) in 30% patients. QTc‐all in SR prolonged significantly during loading (p < .0001). All patients displayed QTc‐all reduction (p < .0001) from discharge to short‐term (46 [34–65] days) that continued at long‐term (360 [296–414] days) follow‐ups. The extent of QTc‐all reduction over time moderately correlated with discharge QTc‐all (r = .54–0.65; p < .0001). Conclusion Dofetilide initiation before cardioversion is equivalent to initiation during SR. Significant QTc reduction proportional to discharge QTc is seen over time in all dofetilide‐treated patients. QTc returns to preloading baseline during follow‐up in patients initiated in SR.