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. 2019 Jul 12;8(7):1029.
doi: 10.3390/jcm8071029.

Cardiac Sodium Channel Dysfunction and Dilated Cardiomyopathy: A Contemporary Reappraisal of Pathophysiological Concepts

Babken Asatryan  1
Affiliations

Cardiac Sodium Channel Dysfunction and Dilated Cardiomyopathy: A Contemporary Reappraisal of Pathophysiological Concepts

Babken Asatryan. J Clin Med. .

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 channelopathy; cardiac sodium channel; dilated cardiomyopathy; precision medicine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Rare variants in cardiac NaV1.5 voltage-gated sodium channel (SCN5A) reported in association with dilated cardiomyopathy. Two additional variants, c.2550-2551insTG and c.3318dupC, causing truncation of the encoded protein in patients with dilated cardiomyopathy, are not shown. Pathogenic/likely pathogenic variants are shown in red, variants with insufficient evidence of pathogenicity in dilated cardiomyopathy are shown in red/white.
See this image and copyright information in PMC

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