Enzyme replacement therapy improves cardiac features and severity of Fabry disease

Abstract

BackgroundAlthough 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. MethodsA 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 36months). ResultsIn 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±13g/m2, MWT: 17±6 vs. 16±5mm, LVEDD: 55±6 vs. 54±6mm; 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±13ms, P: 76±5 vs. 90±6ms; p values<0.001); QTc interval significantly decreased (418±18 vs. 410±15ms; 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). ConclusionsERT 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).