Enzyme replacement therapy improves cardiac features and severity of Fabry disease.

ABSTRACT

BACKGROUND: Although left ventricular hypertrophy (LVH) in Fabry disease (FD) can improve with enzyme-replacement therapy (ERT), the response is difficult to predict. Furthermore, the response of other cardiac features such as aortic dilatation and ECG changes are poorly understood. METHODS: A local registry of 66 patients with FD was studied. ECG, echocardiogram and Fabry Outcome Survey-Mainz Severity Score Index (FOS-MSSI) data were compared between baseline and after long-term ERT (median 36 months). RESULTS: In patients with LVH (n=42), left ventricular mass index (LVMI), maximal wall thickness (MWT), left ventricular end-diastolic diameter (LVEDD) and ejection fraction (EF) were all seen to improve after ERT (LVMI 135±13 vs. 133±13 g/m(2), MWT 17±6 vs. 16±5 mm, LVEDD 55±6 vs. 54±6 mm; EF 62±5 vs. 64±3%; p<0.05). In the entire patient group, PQ interval and P wave duration significantly increased with ERT (PQ 131±13 vs. 144±13 ms, P 76±5 vs. 90±6 ms; p values<0.001); QT(c) interval significantly decreased (418±18 vs. 410±15 ms; p<0.001); and median FOS-MSSI score fell from 16 to 14 (p<0.001). On logistic-regression analysis, none of the recorded baseline features (age, gender, LVMI, MWT, LVEDD, aortic diameter, EF, PQ interval, P wave duration, QRS duration, QT interval, Romhilt-Estes score or FOS-MSSI) predicted improvements in LVH or FOS-MSSI with ERT (p>0.05). CONCLUSIONS: ERT improved LV morphology and function in patients with LVH - but there was no relationship between age, gender, FOS-MSSI or baseline ECG/TTE features and the response. ERT also normalised long QTc intervals, short PQ intervals and short P waves; and reduced disease burden (FOS-MSSI).