Propafenone during acute myocardial ischemia in patients: a double-blind, randomized, placebo-controlled study

The proarrhythmic risk of class I antiarrhythmic agents in combination with myocardial ischemia is mainly the result of their effects on ventricular repolarization. This study was designed to evaluate the effect of class Ic antiarrhythmic agents on QT dispersion during myocardial ischemia.

QT interval dispersion on the 12-lead electrocardiogram (ECG) has been suggested as a noninvasive marker of inhomogeneous ventricular repolarization and susceptibility to ventricular arrhythmias.

In a randomized, double-blind study, 98 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were pretreated with propafenone or placebo. QT dispersion was defined as a maximal minus minimal QT interval on the 12-lead ECG before and after PTCA. The power of the study to detect clinically meaningful differences in QT dispersion was 0.75, and a twofold increase in QT dispersion in the propafenone group compared with the placebo group was considered clinically relevant.

The QT and corrected QT (QTc) intervals increased significantly during occlusion of the left anterior descending coronary artery (LAD) (9% and 11%, respectively, p < 0.05), whereas occlusion of the circumflex and right coronary arteries had no effect. QTc dispersion increased significantly in the propafenone group during ischemia (+52%, p = 0.002, vs. +23%, p = 0.15). The most considerable effect on QT dispersion was observed during LAD occlusion and ischemia of the anterior wall (+74%, p = 0.025). Corrected JT dispersion (+57%, p = 0.017, vs. +24%, p = 0.23) and the QT dispersion ratio (+1.6%, p = 0.031, vs. 0.9%, p = 0.34) showed similar effects. Plasma levels of propafenone (522 +/- 165 micrograms/liter) did not influence the results.

During myocardial ischemia, particularly during LAD occlusion, propafenone results in a significant increase in QT dispersion. The results indicate that QT interval prolongation and enhanced QT dispersion reflect inhomogeneous ventricular repolarization generated by the ischemic anterior wall of the myocardium. These observations may demonstrate a clinically important interaction between myocardial ischemia, repolarization variables and propafenone.