Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week

J Am Coll Cardiol. 2021 Feb 23;77(7):922-936. doi: 10.1016/j.jacc.2020.12.024.

PMID: 33602475

Maurizio Pieroni, James C Moon, Eloisa Arbustini, Roberto Barriales-Villa, Antonia Camporeale, Andreja Cokan Vujkovac, Perry M Elliott, Albert Hagege, Johanna Kuusisto, Aleš Linhart, Peter Nordbeck, Iacopo Olivotto, Päivi Pietilä-Effati, Mehdi Namdar

Highlights: The diagnosis and staging of FD-related cardiac diseases have improved thanks to advances in imaging techniques, suggesting that myocardial inflammation plays a significant role in the development of the disease.

Abstract

Background: Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient αgalactosidase. An activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications.

Results: Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research.

Conclusion: With the recent approval of oral chaperone therapy and new treatment developments, the FDspecific treatment landscape is rapidly evolving.

Keywords: Fabry disease, T1 mapping, hypertrophic cardiomyopathy, lysosome function.