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Review Article Volume 19 Issue 2
Fabry cardiomyopathy: pathophysiology, multimodality imaging, and evolving therapeutic strategies
Mehmet Murat Şahin, Abdullah Sarihan, Abdülmelik Birgün, Ömer Burak Çelik, Macit Kalçik, Mehmet Mustafa Yilmaz, Osman Karaarslan, Mucahit Yetim, Muhammet Cihat Çelik, Lütfü Bekar, Yusuf Karavelioğlu
Received: April 02, 2026 | Published: April 16, 2026
Citation: Şahin MM, Sarihan A, Birgü A, et al. Fabry cardiomyopathy: pathophysiology, multimodality imaging, and evolving therapeutic strategies. J Cardiol Curr Res. 2026;19(1):38-53. DOI: 10.15406/jccr.2026.19.00641
Abstract
Fabry disease is an X-linked lysosomal storage disorder caused by deficient α-galactosidase A activity, leading to progressive accumulation of glycosphingolipids in multiple organs. Cardiac involvement, commonly referred to as Fabry cardiomyopathy, represents a major determinant of morbidity and mortality and may occur as an isolated late-onset phenotype. The pathophysiology is characterized by intracellular lipid accumulation, microvascular dysfunction, inflammation, and progressive myocardial fibrosis, ultimately resulting in left ventricular hypertrophy, diastolic dysfunction, conduction abnormalities, and arrhythmias. Early diagnosis remains challenging due to phenotypic heterogeneity and overlap with more common causes of left ventricular hypertrophy. Multimodality imaging, particularly cardiac magnetic resonance with T1 mapping and late gadolinium enhancement, plays a pivotal role in early detection, tissue characterization, and risk stratification. Diagnostic strategies integrate enzymatic assays, genetic testing, and biomarkers such as plasma lysoglobotriaosylsphingosine. Disease-modifying therapies, including enzyme replacement therapy and pharmacological chaperone therapy (migalastat), have significantly improved patient outcomes, particularly when initiated before the development of advanced myocardial fibrosis. However, therapeutic efficacy is limited in later stages, and novel approaches such as gene therapy and substrate reduction therapy are under investigation. Arrhythmias and heart failure remain major clinical challenges, requiring individualized management strategies and, in selected cases, device therapy. Despite substantial progress, important knowledge gaps persist, particularly regarding optimal timing of therapy, management of variants of uncertain significance, and risk stratification for sudden cardiac death. Future directions include precision medicine approaches, advanced imaging techniques, and the development of disease-specific risk models. Early recognition and timely intervention remain critical to improving long-term outcomes in Fabry cardiomyopathy.
Keywords: fabry disease, fabry cardiomyopathy, lysosomal storage disorder, cardiac magnetic resonance imaging, enzyme replacement therapy
©2026 Şahin, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.