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. 2022 Jun;33(6):1281-1289.
doi: 10.1111/jce.15483. Epub 2022 Apr 17.

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

Zeryab A Khan  1 , Megan E LaBreck  2 , Jordan Luli  1 , Chelsea Roberts  2 , Alexander Smith  3 , Rayan El-Zein  1 , Jaret D Tyler  4 , Eugene Y Fu  4 , Sreedhar R Billakanty  4 , Anish K Amin  4 , Nagesh Chopra  4
Affiliations

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

Zeryab A Khan et al. J Cardiovasc Electrophysiol. 2022 Jun.

Abstract

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.

Keywords: QT interval; atrial fibrillation; dofetilide; drug dosing; follow up.

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References

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