Background: Mutations in the cardiac sodium channel gene, SCN5A, cause a variety of inherited arrhythmic syndromes. However, the relationship between the SCN5A gene mutations and left ventricular (LV) dysfunction is still unclear.
Methods and results: We screened the SCN5A gene in 603 probands associated with phenotypes that indicated sodium channel loss-of-function mutations such as Brugada syndrome (BrS), cardiac conduction disease (CCD), sick sinus syndrome (SSS), idiopathic ventricular fibrillation (IVF) and atrial fibrillation (AF). In this cohort, we identified SCN5A mutations in 41 probands (21 in BrS, 14 in SSS, 4 in AF, 4 in CCD, and 3 in IVF, including overlap syndrome). Four of 41 patients were associated with decreased LV systolic function (R1023C in two patients, D1275N and W1345_F1348del in one patient, respectively).
One of the R1023C mutation carrier was 46 yo male diagnosed with arrhythmogenic right ventricular cardiomyopathy with LV involvement, and the other R1023C carrier was 75 yo female associated with complete atrio-ventricular block and severe LV dysfunction. The patient with a D1275N mutation was 61 yo female suffered from AF and SSS, and her LV function was decreased. The W1345_F1348del mutation carrier was 71 yo male. He received a pacemaker implantation due to SSS, and his LVEF was decreased to 30%.
Conclusions: In this study, approximately 10% (4/41) of the patients with SCN5A mutations who presented with sodium channel loss-of-function phenotypes were associated with LV dysfunction. Further experiments will be needed to reveal the underlying mechanisms of SCN5A-related cardiomyopathy.