Non-invasive Assessment of HydroQUInidine EffecT in Brugada Syndrome (QUIET BrS).

Abstract

Background: 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.

Objective: This study aimed to determine the effect of Hydroquinidine on ventricular depolarisation and repolarisation in patients with BrS in vivo.

Methods: Twelve patients with BrS underwent electrocardiogram (standard, high-lead and signal averaged) and electrocardiographic imaging (ECGi) at baseline and "on-treatment" with Hydroquinidine 300mg twice daily. ST-segment elevation, activation time (AT), repolarisation time (RT) and activation-recovery intervals (ARI) were computed for the ventricles and the right ventricular outflow tract (RVOT). Serum Hydroquinidine levels were determined, and adverse drug events captured through medication survey.

Results: Hydroquinidine increased RT (301.1 ± 24.1ms vs 348.8 ± 28.3ms, p <0.001), repolarisation 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<0.001) in the RVOT, with a greater change in the RVOT compared to 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 ± 0.7mV vs 1.8 ± 0.8mV; P<0.001). Hydroquinidine levels did not correlate with electrophysiological changes or occurrence of adverse drug reactions. One patient developed frequent non-sustained ventricular tachycardia on-treatment with Hydroquinidine.

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