Risk stratification in Fabry disease: what do current models really tell us?

This invited editorial refers to ‘Prognostic role of myocardial storage, hypertrophy and inflammation/fibrosis in Fabry Cardiomyopathy: a new predictive score including T1 values’, by A. Camporeale et al., https://doi.org/10.1093/ehjqcco/qcaf154. Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene that result in reduced or absent α-galactosidase A (α-Gal A) activity. This in turn causes lysosomal accumulation of glycosphingolipids and a complex cellular pathophysiology that includes mitochondrial and sarcomere disruption, apoptosis, impaired autophagy, and inflammation. The heart, kidneys, and nervous system are the main sites of disease burden. Enzyme replacement therapy has been the standard of care since the early 2000s and most evidence suggests a favourable disease modifying effect.1 Cardiovascular disease remains the primary cause of death in FD and, for this reason, there have been numerous attempts to identify prognostic markers in FD.2–5 Among the many clinical features of the disease, age, a classical phenotype, and renal dysfunction are consistent predictors of poor outcomes.2,4–6 With respect to cardiac risk markers, left ventricular hypertrophy (LVH) is one of the most reproducible.2–5,7 Other imaging variables associated with cardiovascular events include late gadolinium enhancement (LGE), global longitudinal strain, and diastolic indices such as E/e′ and left atrial volume.8,9