Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment.

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.
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.
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.
AuthorsFrank Weidemann, Markus Niemann, Frank Breunig, Sebastian Herrmann, Meinrad Beer, Stefan Störk, Wolfram Voelker, Georg Ertl, Christoph Wanner, Jörg Strotmann
JournalCirculation (Circulation) Vol. 119 Issue 4 Pg. 524-9 (Feb 3 2009) ISSN: 1524-4539 [Electronic] United States
PMID19153271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Recombinant Proteins
  • alpha-Galactosidase
  • Adult
  • Cardiomyopathy, Hypertrophic (diagnosis, drug therapy, etiology)
  • Echocardiography
  • Evidence-Based Medicine
  • Exercise Test
  • Fabry Disease (complications, drug therapy)
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Recombinant Proteins (administration & dosage)
  • Treatment Outcome
  • alpha-Galactosidase (administration & dosage)

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