Hydroquinidine Hydrochloride

Dilated cardiomyopathy has a diverse aetiology. Around 20% of cases have an underlying genetic cause. A subset of patients with dilated cardiomyopathy is prone to arrhythmia (‘arrhythmogenic’ cardiomyopathy). (Likely) Pathogenic variants of SCN5A, the gene coding for the alpha subunit of the main cardiac sodium voltage-gated channel, are a known cause of this subset.

A 17-year-old male presents with new-onset severe left ventricular systolic dysfunction with atrial flutter and significant ventricular ectopy. Despite medical therapy, his management was challenging. A LifeVest was fitted to allow outpatient optimization of his medications whilst bridging to a decision about implantable cardioverter defibrillator implantation. Specialist genetic testing revealed a pathogenic variant in SCN5A (p.R814W) leading to gain of function. This prompted the use of a sodium channel blocker, hydroquinidine. Hydroquinidine resulted in complete resolution of arrhythmia and improvement of ventricular size and function. Its effect was confirmed on accidental withdrawal of hydroquinidine due to supply issues, resulting in recurrence of atrial arrhythmia.

This atypical presentation of a cardiomyopathy was driven, at least in part, by the patient’s extensive arrhythmia. Previous research has shown variable, short-term effects of sodium channel antagonists in familial p.R814W variants. Contrastingly, in our patient, sustained and long-term improvement was observed with the use of hydroquinidine. Close multidisciplinary team working and early genetic testing facilitated personalized care in our patient’s case, resulting in a favourable outcome.

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.