Mechanism of the Effects of Sodium Channel Blockade on the Arrhythmogenic Substrate of Brugada Syndrome.

Abstract Background The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram substrates of Brugada syndrome (BrS) have not been elucidated. Objectives To determine the effect of ajmaline and high pacing rate on the BrS substrates. Methods Thirty-two BrS patients (age 40 ± 12 years) with frequent ventricular fibrillation (VF) episodes underwent right ventricular outflow tract (RVOT) substrate electroanatomical and electrocardiogram imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies. Results Ajmaline increased the activation time delay in the substrate (33%; p = 0.002), ST elevation in the right precordial leads (74%; p Conclusions INa reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring VF genesis.