Resolution of severe dilated cardiomyopathy with significant arrhythmia burden using hydroquinidine, in addition to guideline-directed medical therapy, in a patient with a pathogenic SCN5A variant: a case report

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.