Introduction Fabry disease (FD) is an X linked deficiency of α-galactosidase A which leads to an accumulation of globotriaosylceramide (GL-3) throughout the body, particularly in the heart, brain and kidneys. Although left ventricular hypertrophy (LVH) in 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/m2, MWT: 17±6 vs 16±5 mm, LVEDD: 55±6 vs 54±6 mm; EF: 62±5 vs 64±3%; p<0.05) (Abstract 070 figure 1). 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); QTc 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) (Abstract 070 figure 2). 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).
- Fabry disease
- enzyme replacement therapy