Proarrhythmic Response to Antiarrhythmic Drug as a Risk Factor for Sudden Cardiac Death in Patients with Ischemic Heart Disease

The prognostic significance of arrhythmogenic response to an antiarrhythmic drug was studied. In 782 patients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature beats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) greater than 4-fold increase in VPBs, (2) greater than 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1-49 months (mean 22) patients were treated with antiarrhythmic drugs found to be safe in control Holter monitoring. Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 53 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P less than 0.01) and sudden death rate (P less than 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction less than 40% and QTc greater than 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be an additional predictor of sudden death in IHD.