Genetic Investigation of Corrected QT Interval Sensitivity to Oral Bepridil Hydrochloride Hydrate in Patients With Atrial Fibrillation

Journal of the American Heart Association, Volume 15, Issue 12 , June 16, 2026. BackgroundBepridil is an antiarrhythmic drug used to treat paroxysmal atrial fibrillation; however, its use is limited by corrected QT interval (QTc) prolongation and the risk of ventricular arrhythmias.

This study aimed to identify genetic variants associated with bepridil‐associated QTc prolongation after catheter ablation for paroxysmal atrial fibrillation.MethodsA total of 523 patients who initiated bepridil therapy after catheter ablation at Hiroshima University between November 2013 and March 2023 were enrolled. Of these, 445 patients were included in a genome‐wide association study, and 78 were used as an independent replication cohort.

QTc was measured 1 month after treatment initiation, with QTc prolongation defined as ≥450 ms in men and ≥460 ms in women. Logistic regression analyses were conducted using additive, dominant, and recessive genetic models.

Variants showing suggestive associations in the genome‐wide association study (P<1.00×10−6) were evaluated in the replication cohort, followed by random‐effects meta‐analyses, with genome‐wide significance defined asP<5.00×10−8.