Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy Evidence for a Better Outcome With Early Treatment

Background-Enzyme replacement therapy with recombinant alpha-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 alpha-galactosidase A should best be started before myocardial fibrosis has developed to achieve long-term improvement in myocardial morphology and function and exercise capacity. (Circulation. 2009;119:524-529.)