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Editorials

Dilated Cardiomyopathy due to Sodium Channel Dysfunction

What Is the Connection?

Connie R. Bezzina, PhD and Carol Ann Remme, MD, PhD

From the Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands.

Correspondence to Connie R. Bezzina, PhD, Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, Room L2–108-1, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail C.R.Bezzina@amc.uva.nl

Key Words: ion channel • sodium channel • genetics • mutation • dilated cardiomyopathy • arrhythmia

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The cardiac sodium channel mediates the rapid upstroke of the cardiac action potential and thereby constitutes a critical determinant of cardiac excitability and conduction. Mutations in the SCN5A gene encoding the -subunit of this channel have been linked to a broad clinical spectrum of arrhythmia disorders, including long QT syndrome, Brugada syndrome, sick sinus syndrome, conduction disease, and most recently, atrial fibrillation.^1,2 These primary arrhythmia syndromes were originally considered pure electrical entities occurring in the absence of structural heart disease, and the presence of myocardial abnormalities in these disorders was originally actually excluded by definition. Evidence is now accumulating, however, that sodium channelopathy can also be associated with the development of cardiac fibrosis, dilatation, and hypertrophy.^3–8 Such structural changes within the myocardium may in turn further predispose to the development of ventricular arrhythmias. These findings have led to reevaluation of the initial view that mutations in a cardiac ion channel would only lead to pure electrical dysfunction and raised the intriguing possibility that the structural alterations could be a direct consequence of sodium channel dysfunction rather than a consequence of long-standing arrhythmia. The mechanism by which a dysfunctional sodium channel leads to structural changes in myocardial tissue, however, remains unclear.

Article p 83

In this issue of Circulation: Arrhythmia and Electrophysiology, Ge et al⁸ report on a novel SCN5A mutation (A1180V) linked to dilated cardiomyopathy (DCM), expanding the repertoire of SCN5A mutations associated with DCM. Previously, the D1275N mutation was discovered independently by McNair et al⁵ and Olson et . . . [Full Text of this Article]

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