Enzyme replacement therapy over 3 years significantly reduced left ventricular mass (238 to 202 g, P<0.001) and improved exercise capacity only in Fabry patients without baseline myocardial fibrosis.
Cohort (n=32)
Does enzyme replacement therapy with recombinant alpha-galactosidase A improve myocardial morphology, function, and exercise capacity in patients with Fabry cardiomyopathy over long-term follow-up?
Enzyme replacement therapy in Fabry cardiomyopathy improves myocardial morphology, function, and exercise capacity only if initiated before the development of myocardial fibrosis.
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.
Weidemann et al. (Mon,) conducted a cohort in Fabry cardiomyopathy (n=32). Enzyme replacement therapy with recombinant alpha-galactosidase A was evaluated on Disease progression and clinical outcome (left ventricular mass, myocardial function, exercise capacity). Enzyme replacement therapy over 3 years significantly reduced left ventricular mass (238 to 202 g, P<0.001) and improved exercise capacity only in Fabry patients without baseline myocardial fibrosis.