Frank Weidemann1, Markus Niemann1, Frank Breunig1, Sebastian Herrmann1, Meinrad Beer1, Stefan Störk1, Wolfram Voelker1, Georg Ertl1, Christoph Wanner1, Jörg Strotmann1
1From the Department of Medicine, Divisions of Cardiology and Nephrology (F.W., M.N., F.B., S.H., S.S., W.V., G.E., C.W., J.S.) and Department of Radiology (M.B.), University Hospital, Wuerzburg, Germany.
Tóm tắt
Background—
Enzyme replacement therapy with recombinant α-galactosidase A reduces left ventricular hypertrophy and improves regional myocardial function in patients with Fabry disease during short-term treatment. Whether enzyme replacement therapy is effective in all stages of Fabry cardiomyopathy during long-term follow-up is unknown.
Methods and Results—
We studied 32 Fabry patients over a period of 3 years regarding disease progression and clinical outcome under enzyme replacement therapy. Regional myocardial fibrosis was assessed by magnetic resonance imaging late-enhancement technique. Echocardiographic myocardial mass was calculated with the Devereux formula, and myocardial function was quantified by ultrasonic strain-rate imaging. In addition, exercise capacity was measured by bicycle stress test. All measurements were repeated at yearly intervals. At baseline, 9 patients demonstrated at least 2 fibrotic left ventricular segments (severe myocardial fibrosis), 11 had 1 left ventricular segment affected (mild fibrosis), and 12 were without fibrosis. In patients without fibrosis, enzyme replacement therapy resulted in a significant reduction in left ventricular mass (238±42 g at baseline, 202±46 g at 3 years;
P
for trend <0.001), an improvement in myocardial function (systolic radial strain rate, 2.3±0.4 and 2.9±0.6 seconds
−1
, respectively;
P
for trend=0.045), and a higher exercise capacity obtained by bicycle stress exercise (106±14 and 122±26 W, respectively;
P
for trend=0.014). In contrast, patients with mild or severe fibrosis showed a minor reduction in left ventricular hypertrophy and no improvement in myocardial function or exercise capacity.
Conclusions—
These data suggest that treatment of Fabry cardiomyopathy with recombinant α-galactosidase A should best be started before myocardial fibrosis has developed to achieve long-term improvement in myocardial morphology and function and exercise capacity.
