Arrhythmogenesis in Fabry Disease

AbstractPurpose of ReviewFabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A. Cardiac sphingolipid accumulation triggers various types of arrhythmias, predominantly ventricular arrhythmia, bradyarrhythmia, and atrial fibrillation. Arrhythmia is likely the primary contributor to FD mortality with sudden cardiac death, the most frequent cardiac mode of death . Traditionally FD was seen as a storage cardiomyopathy triggering left ventricular hypertrophy, diastolic dysfunction, and ultimately, systolic dysfunction in advanced disease. The purpose of this review is to outline the current evidence exploring novel mechanisms underlying the arrhythmia substra te.Recent FindingsThere is growing evidence that FD cardiomyopathy is a primary arrhythmic disease with each stage of cardiomyopathy (accumulation, hypertrophy, inflammation, and fibrosis) contributing to the arrhythmia substrate via various intracellular, extracellular, and environmental mechanisms. It is therefore important to understand how these mechanisms contribute to an individual ’s risk of arrhythmia in FD.SummaryIn this review, we outline the epidemiology of arrhythmia, pathophysiology of arrhythmogenesis, risk stratification, and cardiac therapy in FD. We explore how advances in conventional cardiac investigations performed in FD patients including 12-lead electrocardiography, transthoracic echocardio...
Source: Current Cardiology Reports - Category: Cardiology Source Type: research