title: Allograft rejection of ISHLT grade >/=3A occurring late after heart transplantation--a distinct entity?
abstract: BACKGROUND
  The significance of International Society of Heart and Lung Transplantation (ISHLT) grade >/=3A rejection detected by routine endomyocardial biopsies beyond 2 years post-transplant remains uncertain.
  
  
  METHODS
  We performed a retrospective analysis of our single-institution database consisting of 4,041 biopsies (188 patients) from 1986 to 2001. Incidence, clinical correlates and outcome of ISHLT grade >/=3A rejection beyond 2 years post-transplant were analyzed.
  
  
  RESULTS
  A total of 307 ISHLT grade >/=3A rejection episodes was diagnosed up to 10 years after transplantation, 69 of which occurred later than 2 years post-transplant in 33 of 139 patients ("late rejection") at therapeutic levels of immunosuppression. Late rejection was only marginally correlated with the incidence of moderate rejection within the first 2 post-transplant years (p = 0.09). The incidence of moderate rejection per patient-year decreased from 1.05 in Year 1 over 0.11 in Year 5 to 0.04 in Year 10. The technical failure rate of biopsies remained low throughout the post-transplant period (range 0.7% to 2.4%). Spontaneous resolution of ISHLT grade >/=3A rejection beyond 2 years post-transplant occurred in all 17 patients in whom specific anti-rejection therapy had been electively withheld. Mortality beyond 2 years post-transplant was lower (p = 0.033) in the "late rejecting" group (n = 33) than in the control group (n = 106).
  
  
  CONCLUSIONS
  Endomyocardial biopsy continues to detect episodes of moderate rejection even very late after heart transplantation, without a close correlation with the rejection frequency in the early post-transplant period. Even without specific treatment, late rejection carries a benign clinical prognosis and may represent a separate biologic entity. Potential long-term effects-for instance, on the pathogenesis of transplant vasculopathy-need further elucidation.
authors.affiliation: Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.forename: Achim
authors.initials: A
authors.lastname: Koch
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Rainer
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Falk-Udo
authors.initials: FU
authors.lastname: Sack
authors.forename: Markus
authors.initials: M
authors.lastname: Haass
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D016027:Heart Transplantation / Q000473:pathology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011183:Postoperative Complications; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous