Arrhythmogenesis in Fabry Disease

Area of Science:

• Cardiology
• Genetics
• Metabolic Disorders

Background:

• Fabry disease (FD) is a rare lysosomal storage disorder caused by alpha-galactosidase A deficiency.
• Glycosphingolipid accumulation in FD leads to cardiac dysfunction and arrhythmias, a major cause of mortality.
• Traditionally viewed as storage cardiomyopathy, emerging evidence suggests FD is primarily an arrhythmic disease.

Purpose of the Study:

• To review current evidence on novel mechanisms underlying the arrhythmia substrate in Fabry disease.
• To explore the pathophysiology, epidemiology, and risk stratification of arrhythmias in FD.
• To discuss advancements in cardiac investigations and potential therapeutic strategies.

Main Methods:

• Literature review of current evidence on Fabry disease and cardiac arrhythmias.
• Analysis of mechanisms contributing to arrhythmogenesis in FD cardiomyopathy stages.
• Evaluation of conventional cardiac investigations for early detection and risk stratification.

Main Results:

• FD cardiomyopathy stages (accumulation, hypertrophy, inflammation, fibrosis) contribute to arrhythmia substrate.
• Advances in ECG, echocardiography, and cardiac MRI enable early detection of pro-arrhythmic substrates.
• Current investigations allow for appropriate risk stratification of FD patients.

Conclusions:

• Fabry disease cardiomyopathy is fundamentally an arrhythmic disease.
• Understanding arrhythmogenic mechanisms is crucial for risk prediction and therapeutic development.
• Future research should focus on novel therapies and risk models to mitigate arrhythmia burden in FD.