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

Julia C Isbister; Marina Strocchi; Matthew Riedy; Laura Yeates; Belinda Gray; Emma S Singer; Richard D Bagnall; Jodie Ingles; Hariharan Raju; Christopher Semsarian; Steven A Niederer; Raymond W Sy

doi:10.1016/j.hrthm.2024.12.014

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

Heart Rhythm. 2024 Dec 14:S1547-5271(24)03659-2. doi: 10.1016/j.hrthm.2024.12.014. Online ahead of print.

Authors

Affiliations

¹ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
² National Heart and Lung Institute, Imperial College London, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
³ Medtronic Australasia, Sydney, New South Wales, Australia.
⁴ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia; Bioinformatics and Molecular Genetics Group at Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
⁶ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Bioinformatics and Molecular Genetics Group at Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
⁷ Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁸ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.
⁹ National Heart and Lung Institute, Imperial College London, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom; The Alan Turing Institute, London, United Kingdom.
¹⁰ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. Electronic address: raymond.sy01@gmail.com.

PMID: 39675648
DOI: 10.1016/j.hrthm.2024.12.014

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 depolarization and repolarization in patients with BrS in vivo.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Activation-recovery interval; Brugada syndrome; Electrocardiographic imaging; Hydroquinidine; Noninvasive; Ventricular activation; Ventricular repolarization.