Abstract 5673: Blocking of Sodium Channels reveals the Regional Endocardial Substrate in Brugada Syndrome
Brugada syndrome (BS) is characterized by ST segment elevation in the right precordial ECG leads and sudden cardiac death from ventricular tachyarrhythmias. Blocking of sodium channels is known to influence the mechanisms. Regional epicardial electrical abnormalities, especially those in right ventricular (RV) outflow tract, are likely to be involved in the arrhythmogenic substrates in BS. However, the involvement of endocardial substrate remains to be examined. The purpose of this study was to investigate whether blocking of sodium channels unravels the regional endocardial substrate in patients with BS. 18 patients with suspected BS who underwent programmed ventricular stimulation were studied. Ventricular fibrillation (VF) was induced in 12 patients (all males, 47±13 yrs; VF-induced) but not in the remaining 6 patients (all males, 47±13 yrs; non-VF). We assessed the effects of pilsicainide, a pure sodium channel blocker, (1 mg/kg, IV in 10 min) on endocardial conductions in right ventricular outflow/inflow tract and apex sites. Endocardial conduction was defined as the duration of the onset of the endocardial potential in RV from the earliest QRS, and conduction delay (Δ duration) was calculated as the difference between endocardial conductions in the vicinity of the administration of pilsicainide. Pilsicainide significantly elevated ST levels in the right precordial leads in VF-induced patients more than those in non-VF patients (V2, 0.22±0.06 vs. 0.02±0.11 mV, P<0.001), and delayed endocardial conduction in RV outflow/inflow tract in VF-induced patients compared to in non-VF patients (Δ duration, 20±8 vs. 5±7 msec, P<0.001). Furthermore the endocardial conductions in RV apex were also recorded in 15 out of 18 patients (10 VF-induced patients, 5 non-VF patients). In VF-induced patients, endocardial conduction in RV outflow/inflow was significantly slowed by pilsicainide, compared in RV apex (Δ duration, 19±8 vs. 5±6 msec, P<0.001). This difference in sites was not recognized in non-VF patients. These results suggest that the regional endocardial substrate is also involved in the pathogenesis of BS, which could be distinguished by the response to sodium channel blockers, such as pilsicainide.