title: Late antibody-mediated rejection after heart transplantation: Mortality, graft function, and fulminant cardiac allograft vasculopathy.
abstract: BACKGROUND
  Late antibody-mediated rejection (AMR) after heart transplantation is suspected to be associated with a poor short-term prognosis.
  
  
  METHODS
  A retrospective single-center observational study was performed. Late AMR was defined as AMR occurring at least 1 year after heart transplantation. The study included all consecutive patients with proven and treated late acute AMR at the authors' institution between November 2006 and February 2013. The aim was to analyze the prognosis after late AMR, including mortality, recurrence of AMR, left ventricular ejection fraction, and cardiac allograft vasculopathy (CAV). Selected endomyocardial biopsy specimens obtained before AMR were also blindly reviewed to identify early histologic signs of AMR.
  
  
  RESULTS
  The study included 20 patients treated for late AMR. Despite aggressive immunosuppressive therapies (100% of patients received intravenous methylprednisolone, 90% received intravenous immunoglobulin [IVIg],85% received plasmapheresis, 45% received rituximab), the prognosis remained poor. Survival after late AMR was 80% at 1 month, 60% at 3 months, and 50% at 1 year. All early deaths (<3 months, n = 8) were directly attributable to graft dysfunction or to complication of the intense immunosuppressive regimen. Among survivors at 3 months (n = 12), histologic persistence or recurrence of AMR, persistent left ventricular dysfunction, and fulminant CAV were common (33%, 33%, and 17% of patients). Microvascular inflammation was detected in at least 1 biopsy specimen obtained before AMR in 13 patients (65%).
  
  
  CONCLUSIONS
  Prognosis after late AMR is poor despite aggressive immunosuppressive therapies. Fulminant CAV is a common condition in these patients. Microvascular inflammation is frequent in endomyocardial biopsy specimens before manifestation of symptomatic AMR.
authors.affiliation: Department of Cardiac and Thoracic Surgery, Cardiology Institute.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Coutance
authors.affiliation: Department of Cardiac and Thoracic Surgery, Cardiology Institute.
authors.forename: Salima
authors.initials: S
authors.lastname: Ouldamar
authors.affiliation: Department of Pathology.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouvier
authors.affiliation: Department of Hemo-biotherapies, Pitié Salpêtrière Hospital, University of Paris VI.
authors.forename: Samir
authors.initials: S
authors.lastname: Saheb
authors.affiliation: Laboratory of Immunology and Histocompatibility-CIB-HOG, Saint Louis Hospital.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: Department of Medical Reanimation.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bréchot
authors.affiliation: Department of Cardiac Anesthesia and Reanimation, Cardiology Institute, Pitié Salpêtrière Hospital, University of Paris VI, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hariri
authors.affiliation: Department of Cardiac and Thoracic Surgery, Cardiology Institute.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lebreton
authors.affiliation: Department of Cardiac and Thoracic Surgery, Cardiology Institute.
authors.forename: Pascal
authors.initials: P
authors.lastname: Leprince
authors.affiliation: Department of Cardiac and Thoracic Surgery, Cardiology Institute. Electronic address: shaida.varnous@psl.aphp.fr.
authors.forename: Shaida
authors.initials: S
authors.lastname: Varnous
mesh_terms: D000328:Adult; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy; D006085:Graft Survival; D006333:Heart Failure / Q000401:mortality* / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors
keywords: antibody-mediated rejection; cardiac allograft vasculopathy; donor-specific anti-HLA antibodies; heart transplantation; survival