title: Everolimus prevents endomyocardial remodeling after heart transplantation.
abstract: BACKGROUND
  Endomyocardial remodeling is characterized by progressive fibrosis and scars and may develop after heart transplantation. The role of everolimus in preventing this process has not been evaluated as yet.
  
  
  METHODS
  We prospectively studied 132 patients at baseline pretransplant and at 4 weeks, 1 year, and 3 years after heart transplantation. Fibrosis, scars (Zeiss Vision, in Sirius), and acute cellular rejection (hematoxylin-eosin) were studied in biopsy. Transplant vasculopathy was assessed by coronary angiography (focal stenoses, peripheral obliterations, negative vascular remodeling defined by peripheral obliterations, and diffusely narrowed proximal and mid vessel segments).
  
  
  RESULTS
  Patients on everolimus versus patients on mycophenolate mofetil presented with significantly less fibrosis at 4 weeks (3.8%±0.3% vs. 5.5%±0.3%, P=0.007), 1 year (4.1%±0.3% vs. 4.8%±0.3%, P=0.015), and 3 years (4.2%±0.3% vs. 5.5%±0.7%, P=0.049) posttransplant and showed less scarring at 3 years posttransplant (19.9±1.9% vs. 31.9±4.6% vs. baseline biopsy 26.0±2.8%; P=0.017). Angiographic peripheral obliterations correlated with higher amounts of endomyocardial fibrosis. The negative correlation of everolimus and the positive correlation of peripheral obliterations with fibrosis were confirmed by regression analysis. Angiographic stenoses or acute cellular rejection had no effect on the development of fibrosis. Negative vascular remodeling in 1-year follow-up tended to be less frequent in everolimus-treated patients (24% vs. 76%; P=0.053).
  
  
  CONCLUSIONS
  Everolimus prevents endomyocardial remodeling after heart transplantation and might have beneficial effects on vascular remodeling of epicardial coronary arteries too. Angiographic peripheral obliterations correlate with increased amounts of endomyocardial fibrosis, suggesting a relevant effect on microvascular perfusion.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany. hiemann@dhzb.de
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Hiemann
authors.forename: Ernst
authors.initials: E
authors.lastname: Wellnhofer
authors.forename: Hans B
authors.initials: HB
authors.lastname: Lehmkuhl
authors.forename: Christoph
authors.initials: C
authors.lastname: Knosalla
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Meyer
mesh_terms: D017023:Coronary Angiography; D003586:Cytomegalovirus Infections / Q000209:etiology; D000068338:Everolimus; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus