Enzyme replacement therapy improves cardiac features and severity of Fabry disease.
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).
Department of Cardiology, Salford Royal Hospital NHS Foundation Trust, Manchester, UK.
Manish
M
Motwani
Sanjay
S
Banypersad
Peter
P
Woolfson
Stephen
S
Waldek
D000328:Adult; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D004452:Echocardiography / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000519:alpha-Galactosidase