Utilization of Transthoracic Echocardiography and Biochemical Markers in Detecting Cardiomyopathy in Fabry Disease.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by α-galactosidase A enzyme deficiency, resulting in multiorgan accumulation of glycosphingolipid. Cardiac accumulation leads to left ventricular hypertrophy, diastolic dysfunction, fibrosis, and sudden cardiac death. Advances in transthoracic echocardiograms (TTEs) have enabled the detection of subclinical atrial and ventricular cardiomyopathy. Until now, studies assessing changes on TTE in FD have been small and cross-sectional. To understand longitudinal changes, our aim was to quantify trends in TTE parameters, linked to relevant physiological and biochemical parameters.

Methods: A single-centre retrospective study was conducted of 75 FD patients who received longitudinal follow-up care (53% female, 57% on enzyme replacement therapy) between 2011 and 2023.

Results: Longitudinal follow-up care demonstrated increasingly impaired left ventricular global longitudinal strain (GLS), tissue Doppler imaging, and right ventricular systolic function. Atrial changes included increasingly impaired left atrial GLS, greater volumes, and reduced left atrial ejection fraction and fractional area change. A sex-specific increase occurred in indexed left ventricular mass in male patients. Biochemical changes included increases in high-sensitivity Troponin-T and N-terminal-pro-B-type natriuretic peptide levels. A sex-specific increase in the urine protein level and the albumin-creatinine ratio in male patients.

Conclusions: TTE and biochemical trends highlight the gradual and insidious nature of FD progression, and stress the importance of considering multiparametric endpoints, including GLS, atrial function, and biomarkers, when assessing outcome in FD.