Enzyme replacement therapy improves cardiac features and severity of Fabry disease

Area of Science:

• Cardiology
• Genetics
• Pharmacology

Background:

• Fabry disease (FD) is a rare genetic disorder.
• Left ventricular hypertrophy (LVH) is a common cardiac manifestation in FD.
• Enzyme-replacement therapy (ERT) is a treatment for FD, but its efficacy in improving cardiac features is variable and difficult to predict.

Purpose of the Study:

• To evaluate the long-term effects of ERT on cardiac structure and function in FD patients.
• To identify predictors of ERT response in FD patients with LVH.
• To assess the impact of ERT on electrocardiogram (ECG) abnormalities and overall disease burden.

Main Methods:

• A retrospective analysis of a local registry of 66 FD patients.
• Comparison of baseline ECG, echocardiogram, and Fabry Outcome Survey-Mainz Severity Score Index (FOS-MSSI) data with post-ERT data (median 36 months).
• Logistic-regression analysis to identify predictors of ERT response.

Main Results:

• ERT significantly improved left ventricular mass index (LVMI), maximal wall thickness (MWT), left ventricular end-diastolic diameter (LVEDD), and ejection fraction (EF) in patients with LVH.
• ERT led to significant changes in ECG parameters, including increased PQ interval and P wave duration, and decreased QT(c) interval.
• The median FOS-MSSI score decreased, indicating a reduced disease burden.
• No baseline features (age, gender, LVMI, MWT, LVEDD, aortic diameter, EF, ECG parameters, or FOS-MSSI) predicted improvements in LVH or FOS-MSSI with ERT.

Conclusions:

• ERT effectively improves left ventricular morphology and function in FD patients with LVH.
• ERT also normalizes certain ECG abnormalities and reduces the overall disease burden in FD.
• Predictors for ERT response in cardiac manifestations of FD remain elusive, necessitating further investigation.