title: Evolution of focal moderate (International Society for Heart and Lung Transplantation grade 2) rejection of the cardiac allograft.
abstract: BACKGROUND
  In the absence of clinical evidence of cardiac allograft rejection, it is still poorly defined whether the International Society for Heart and Lung Transplantation biopsy grade 2 (e.g., focal moderate rejection) should be treated. Aim of the present study was to retrospectively investigate the evolution of focal moderate rejection, diagnosed during the first postoperative year in patients who had undergone orthotopic heart transplantation.
  
  
  METHODS
  A retrospective analysis was conducted on 256 International Society for Heart and Lung Transplantation grade 2 biopsies from 110 orthotopic heart transplantations; 125 episodes occurred within the first 3 months (group 1), 131 later (group 2). For each grade 2 diagnosis, two biopsies, one immediately before and one after, were analyzed and classified as follows: lower (grade 0 or 1), equal (grade 2), or higher (grade 3 or 4).
  
  
  RESULTS
  Evolution of grade 2 rejection was to a lower grade in 66% of cases, an equal grade in 16.8%, and a higher grade in 17.2%, with differences between group 1 and 2 (higher: 25% versus 10%, respectively, p = 0.005). Episodes which progressed into higher grades occurred earlier compared with those which persisted or resolved (9.2 +/- 8.6 weeks versus 20.0 +/- 15.6, p < 0.001). Five-year actuarial survival and incidence of graft coronary disease were similar in patients whose conditions progressed and those whose conditions did not. However, left ventricular ejection fraction at 1 and 2 years was lower in patients whose conditions progressed compared with those whose conditions persisted or resolved (56% +/- 4% versus 66% +/- 2%, p = 0.004; 56% +/- 10% versus 64% +/- 8%, p = 0.02, respectively).
  
  
  CONCLUSIONS
  Progression of grade 2 rejection occurred in a minority of cases and did not affect 5-year survival or incidence of coronary disease, but its relationship with long-term cardiac allograft dysfunction warrants further investigation.
authors.affiliation: Department of Cardiovascular Surgery, University of Padova Medical School, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Milano
authors.forename: A L
authors.initials: AL
authors.lastname: Caforio
authors.forename: U
authors.initials: U
authors.lastname: Livi
authors.forename: B
authors.initials: B
authors.lastname: Bauce
authors.forename: A
authors.initials: A
authors.lastname: Angelini
authors.forename: D
authors.initials: D
authors.lastname: Casarotto
authors.forename: G
authors.initials: G
authors.lastname: Thiene
mesh_terms: D000206:Actuarial Analysis; D000328:Adult; D003327:Coronary Disease / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000145:classification / Q000503:physiopathology*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013318:Stroke Volume; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016277:Ventricular Function, Left
chemical_list: D007166:Immunosuppressive Agents