Abstract
Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme α-galactosidase A, leading to the accumulation of globotriaosylceramide in various tissues, including the heart. Cardiac involvement is a prominent feature and a major cause of morbidity and mortality in Fabry disease, manifesting as left ventricular hypertrophy, myocardial ischaemia, heart failure, and arrhythmias. Secondary mechanisms, triggered by lysosomal storage, contribute to myocardial damage, in particular, myocardial inflammation. Early cardiac involvement can be subtle, but with disease progression, it becomes a major determinant of morbidity and mortality. Recent progresses in diagnostic techniques, such as advanced cardiac magnetic resonance imaging with T1 and T2 mapping, have improved early detection of Fabry-related cardiac disease. Enzyme replacement therapy and newer treatments like chaperone therapy have shown potential in managing cardiac manifestations when initiated early, while the progression of cardiac involvement may be difficult to halt in patients diagnosed late in the disease course. Gene therapy and substrate reduction therapy are emerging treatment modalities that hold promise but require further clinical evaluation. The limited efficacy of available therapies and the variability of cardiac response to treatment represent main unresolved issues, together with challenges in monitoring disease progression, and the need for additional therapeutic strategies targeting secondary mechanisms. Unmet needs in clinical practice include the identification of disease-specific and cardiac-specific biomarkers for early detection, staging, and monitoring cardiac damage. Similarly, strategies for prognostic stratification and better prevention of cardiovascular complications are essential to improve the care of these patients.