**Babken Asatryan**

Department of Cardiology, Inselspital, Bern University Hospital, Freiburgstrasse 10, 3010 Bern, Switzerland; babken.asatryan@insel.ch; Tel.: +41-31-632-84-37; Fax: +41-31-632-42-11

Received: 29 May 2019; Accepted: 9 July 2019; Published: 12 July 2019

**Abstract:** A key emerging theme in translational cardiovascular medicine is the need to identify specific causes of arrhythmias and heart failure, defined by phenotype and/or genotype that will respond to a particular intervention. Unlike other genes implicated in hereditary arrhythmias and cardiomyopathies, pathogenic/likely pathogenic variants in the cardiac sodium channel alpha subunit gene (*SCN5A*) produce a remarkably diverse set of electrical and structural phenotypes, one of them being dilated cardiomyopathy. There has been debate about whether left ventricular remodeling is a bona fide phenotypic feature of cardiac sodium channel dysfunction, or a consequence of tachyarrhythmias or conduction disturbances. In light of recent findings, a critical digest of the available experimental and medical literature is necessary. This paper provides a critical appraisal of the evidence linking a dysfunctional cardiac sodium channel to ventricular dysfunction, and discusses the potential mechanisms involved in shaping this phenotype along with implications for precision therapy.

**Keywords:** *SCN5A*; cardiac sodium channel; cardiac channelopathy; dilated cardiomyopathy; precision medicine
