title: Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment.
abstract: 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.
  
  
  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.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinik Würzburg, Josef-Schneider Str 2, Bau 4, 97080 Würzburg, Germany. weidemann_f@medizin.uni-wuerzburg.de
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Markus
authors.initials: M
authors.lastname: Niemann
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herrmann
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Voelker
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Jörg
authors.initials: J
authors.lastname: Strotmann
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D004452:Echocardiography; D019317:Evidence-Based Medicine; D005080:Exercise Test; D000795:Fabry Disease / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000008:administration & dosage*
chemical_list: D011994:Recombinant Proteins; D000519:alpha-Galactosidase