Noninvasive assessment of hydroquinidine effect in Brugada syndrome (QUIET BrS)

Hydroquinidine reduces arrhythmic events in patients with Brugada syndrome (BrS). The mechanism by which it exerts antiarrhythmic benefit and its electrophysiological effects on BrS substrate remain incompletely understood.

This study aimed to determine the effect of hydroquinidine on ventricular depolarization and repolarization in patients with BrS in vivo.

Twelve patients with BrS underwent electrocardiography (standard, high-lead, and signal averaged) and electrocardiographic imaging at baseline and "on-treatment" with hydroquinidine 300 mg twice daily. ST-segment elevation, activation time, repolarization time, and activation-recovery interval (ARI) were computed for the ventricles and right ventricular outflow tract (RVOT). Serum hydroquinidine levels were determined, and adverse drug events were captured through a medication survey.

Hydroquinidine increased repolarization time (301.1 ± 24.1 ms vs 348.8 ± 28.3 ms; P<.001), repolarization gradients (1.1 ± 0.4 ms/mm vs 1.6 ± 0.4 ms/mm; P<0.001), and ARI (241.3 ± 18.1 ms vs 284.8 ± 21.5 ms; P<.001) in the RVOT, with a greater change in the RVOT than in the rest of the ventricles. In contrast, activation parameters did not change significantly on-treatment with hydroquinidine, although there was a subtle increase in ST-segment elevation over the RVOT (1.5 ± 0.7 mV vs 1.8 ± 0.8 mV; P<.001). Hydroquinidine levels did not correlate with electrophysiological changes or occurrence of adverse drug reactions. One patient developed frequent nonsustained ventricular tachycardia on-treatment with hydroquinidine.

Hydroquinidine primarily affects ventricular repolarization and action potential duration (indicated by ARI) in patients with BrS and demonstrates regional variation with more significant changes in the RVOT.