Enzyme replacement therapy improves cardiac features and severity of Fabry disease

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• 作者：Manish Motwani ; Sanjay Banypersad ; Peter Woolfson ; Stephen Waldek
• 关键词：Fabry disease ; Enzyme replacement therapy ; Left ventricular hypertrophy
• 刊名：Molecular Genetics and Metabolism
• 出版年：2012
• 出版时间：September-October, 2012
• 年：2012
• 卷：107
• 期：1-2
• 页码：197-202
• 全文大小：283 K

文摘

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 ¡À 13 vs. 133 ¡À 13 g/m², MWT: 17 ¡À 6 vs. 16 ¡À 5 mm, LVEDD: 55 ¡À 6 vs. 54 ¡À 6 mm; EF: 62 ¡À 5 vs. 64 ¡À 3 % ; p < 0.05). In the entire patient group, PQ interval and P wave duration significantly increased with ERT (PQ: 131 ¡À 13 vs. 144 ¡À 13 ms, P: 76 ¡À 5 vs. 90 ¡À 6 ms; p values < 0.001); QT_c interval significantly decreased (418 ¡À 18 vs. 410 ¡À 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 ¡ª 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).