Factors predisposing to ventricular proarrhythmia during antiarrhythmic drug therapy for atrial fibrillation in patients with structurally normal heart

BACKGROUND Ventricular arrhythmia (VA) can occur during propafenone therapy in atrial fibrillation (AF) patients with structurally normal heart. OBJECTIVE The purpose of this study was to evaluate the incidence and characteristics of propafenone-associated VAs in AF patients with structurally normal heart. METHODS We studied and compared the risk of new-onset VAs between AF patients with structurally normal heart taking and those not taking propafenone in a nationwide longitudinal cohort in Taiwan (n = 127,197 since 2000). We then investigated the association between propafenone and VA in AF patients with structurally normal heart in a single-center database (n = 396). RESULTS In the nationwide cohort, 102 patients (0.008% per patient-year) developed ventricular tachycardia (VT)/ventricular fibrillation (VF) during a follow-up period of 9.8 +/- 3.5 years. After multivariate Cox regression analysis, propafenone treatment was a significant risk factor for new-onset VT/VF with a hazard ratio (HR) of 3.59 (95% confidence interval [CI] 1.30-9.89, P = .0136). Propafenone treatment offered protection against ischemic stroke with HR 0.649 (95% Cl 0.55-0.77, P<.001). In the single-center study using ECG and medical records, the presence of inferior wave, wider QRS, and old age were independent risk factors for VA after adjustment for clinical, biochemical, and echocardiographic variables. CONCLUSION Albeit with low incidence, propafenone therapy for AF was associated with new-onset VA in the nationwide longitudinal cohort study in Taiwan. Old age, presence of inferior Lead 3 wave, and wider QRS on ECG were significant risk factors in our single-center study.