Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome

Introduction: Brugada syndrome is characterized by an ST segment elevation in leads V-1-V-3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Naf channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhgthmias in patients with Brugada syndrome. Methods and Results: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12-lead EGG, and ventricular arrhythmias In 12 Brugada and LO control patients. Maximum ST20 observed in the V-2 or V-3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval,were no different between the two groups. Flecainide and disopyramide, but not mexiletine, signiticantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS. Conclusion: Our findings suggest that Na+ channel blockers amplify existing I-Na and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome.