Effects of enzyme replacement therapy in adult patients with Fabry disease on cardiac structure and function: a retrospective cohort study of the Fabry Münster Study (FaMüS) data

OBJECTIVE Fabry disease (FD) is an X-linked inborn error of glycosphingolipid catabolism caused by deficient lysosomal α-galactosidase A activity. Progressive accumulation of globotriaosylceramide and related glycosphingolipids in vascular endothelial lysosomes of the heart, kidneys and brain is responsible for the main disease manifestations. The aim of our study was to assess short-term and long-term effects of enzyme replacement therapy (ERT) on cardiac mass and function. DESIGN Retrospective cohort study. SETTING Hospital outpatient clinic. PARTICIPANTS 40 FD patients (21 men, 19 women) receiving agalsidase β-ERT. OUTCOME MEASURES The focus at baseline and follow-up examinations was on structural, functional (Doppler-echocardiography) as well as electrical changes (ECG) and blood pressure. RESULTS In the Early Group, systolic and diastolic blood pressures significantly decreased. Left-ventricular (LV) also decreased; however, wall thickness and LV mass index showed no further increase. VE as an indicator for diastolic function significantly improved (64±21 vs 75±27 cm/s, p=0.038). There were no significant changes of ECG parameters. There were few relevant changes in the Late Group, albeit systolic blood pressure significantly decreased and QRS duration significantly increased. In conclusion, echocardiographic left-ventricular mass index, interventricular septum thickness, left-ventricular posterior wall, left-ventricular end-diastolic dimension) and diastolic function parameters are valuable for follow-up and guidance of therapy. CONCLUSIONS The primary positive impact of ERT appears to be an early effect after the start of therapy, and early initiation of ERT should be recommended.