Electrical Ventricular Remodeling in Dilated Cardiomyopathy

Abstract

Ventricular arrhythmias contribute significantly to morbidity and mortality in patients with heart failure (HF). Pathomechanisms underlying arrhythmogenicity in patients with structural heart disease and impaired cardiac function include myocardial fibrosis and the remodeling of ion channels, affecting electrophysiologic properties of ventricular cardiomyocytes. The dysregulation of ion channel expression has been associated with cardiomyopathy and with the development of arrhythmias. However, the underlying molecular signaling pathways are increasingly recognized. This review summarizes clinical and cellular electrophysiologic characteristics observed in dilated cardiomyopathy (DCM) with ionic and structural alterations at the ventricular level. Furthermore, potential translational strategies and therapeutic options are highlighted.

Genome-wide association study of dilated cardiomyopathy-induced heart failure associated with renal insufficiency in a Chinese population

“…According to previous research, mutations in the cardiac sodium channel Na v 1.5 gene ( SCN5A ) are associated with DCM, which is evidence of sodium channel involvement in the pathogenesis of DCM. However, pathways that cause ventricular dilatation and dysfunction associated with SCN5A mutations remain unclear [ 32 , 33 ]. Whether other ion channel pathways are involved in the pathogenesis of RI in patients with DCM-induced HF remains to be further observed in large-scale clinical studies.…”

A Rare Case of Coexisting Mutation in Desmin and Thioredoxin Reductase 2 Genes Causing Dilated Cardiomyopathy

“…These proteins are intermediate filaments that anchor nuclear chromatin and are important for cross-cellular transport [2,5]. LMNA mutations have also been implicated in muscular dystrophies and various arrhythmias, such as ventricular tachycardia and atrial fibrillation, which are common DCM complications [1,[3][4][5]. Aberrations in genes encoding cardiac actin, dystrophin, desmin, and thioredoxin reductase 2 account for a small portion of genetic DCM cases [2,5].…”

“…DCM clinically manifests as a left ventricular ejection fraction of less than 40% with or without heart failure symptoms such as progressive dyspnea, ankle swelling, and exercise intolerance [1,2]. If not managed appropriately, it can lead to severe cardiac complications such as systolic and diastolic heart failure, arrhythmias, thromboembolisms, and cardiogenic shock [1][2][3][4]. DCM has multiple etiologies that involve structural damage and weakening of the myocardium yielding a clinical phenotype that is distinct from ischemic cardiomyopathies.…”

Electrical Remodelling in Cardiac Disease

“…Mutations in a large number of genes that encode not only for ion channels and intercellular junction molecules but also for contractile and cytoskeleton proteins have been identified in patients with dilated cardiomyopathy. In addition, electrical remodelling is affected by chromosomal alterations without changes in DNA sequence, referred to as epigenetic changes [29]. Hypertrophic cardiomyopathy is also burdened with life-threatening ventricular arrhythmias.…”