Abstract 2822: Impact of Sodium Channel Dysfunction on Arrhythmogenesis in Brugada Syndrome
(Introduction) Although genotype-phenotype correlations have been reported in patients with long QT syndrome, similar observations in patients with Brugada syndrome (BS) are less established. We evaluated the impact of sodium channel (Na-Ch) dysfunction on arrhythmogenesis in patients and in a drug induced BS model.
Clinical study: we evaluated 19BS with prior ventricular fibrillation (VF) and implantation of a cardioverter defibrillator. Patients were divided into 2 groups according to the presence of SCN5A mutation (mutation positive n=4, mutation negative n=15). We compared ECG parameters and recurrent VF episodes between 2 groups.
Experimental study: We optically mapped multisite action potentials (APs) on the transmural surface in 18 arterially-perfused canine right ventricular preparations.
We created 2 models of BS; 1) Na-Ch dysfunction model (Na-model) by pilsicainide (5μM) and pinacidil (5μM) (n=11); and 2) Ca-Ch dysfunction model (Ca-model) by verapamil (10μM) (n=7). We evaluated transmural APs, arrhythmogenesis, and ECGs.
Clinical study. Patients with the SCN5A mutation had a longer PQ interval (202±31 ms) than patients without the mutation (182±31 ms, p<0.05). There were no differences in ST elevation between the 2 groups. Recurrent VF occurred in all patients with the mutation within 11 months after the first VF episode, but in only 47% of the patients without the mutation (p<0.05).
Experimental study. There was no difference in ST elevation between the 2 groups. The Na-model had longer epicardial (EPI) activation time than the Ca-model (50±11, vs 34±10 ms, p<0.01).
The Na-model had prominent EPI AP heterogeneity (difference between maximum and minimum EPI AP durations: Na-model 42±19 ms vs Ca-model 18±9 ms, p<0.01), which promoted the frequent occurrence of ventricular arrhythmias (VA) due to phase 2 reentry (incidence of VAs: at pacing cycle length (CL) 2000ms: Na-model 75% vs Ca-model 0%, p<0.01; at CL=1000ms: Na-model 42% vs Ca-model 14%, p=0.22).
(Conclusion) Conduction disturbances and AP heterogeneity, present in the patients and the BS model with Na-Ch dysfunction, were associated with more frequent occurrence of VAs than patients and canine model without the conduction disturbances.