Pathogenesis of Arrhythmogenic Cardiomyopathy #MMPMID26199027
Asimaki A; Kleber AG; Saffitz JE
Can J Cardiol 2015[Nov]; 31 (11): 1313-24 PMID26199027show ga
Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodeling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation may promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbor mutations in genes encoding desmosomal proteins, which has raised the possibility that defective cell-cell adhesion may play a role in disease pathogenesis. Recent advances have implicated changes in the canonical Wnt/?-catenin and Hippo signaling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. This review summarizes current understanding of the pathogenesis of ACM and highlights future research directions.