title: Natural course of moderate cardiac allograft rejection (International Society for Heart Transplantation grade 2) early and late after transplantation.
abstract: BACKGROUND
  The significance of International Society for Heart Transplantation (ISHT) grade 2 cardiac allograft rejection has been questioned, and the medical community is not in complete agreement as to its clinical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 transplant patients since introduction of the ISHT nomenclature at our institution.
  
  
  RESULTS
  Of 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were preceded by intensified immunosuppression and were excluded from analysis. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies performed 7 to 10 days after prior ISHT 2 rejection without change of treatment. Of these, 70 (18.7%) had progressed to > or = ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) resolved. In contrast, follow-up of 2074 biopsies with lower-grade rejection showed graft rejection classified as > or = ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and < or = ISHT 1B in 1681 (81.1%) biopsy samples (P < .0001). In univariate analysis, the odds ratio (OR) of graft rejection > or = ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rejection > or = ISHT 3A were time after transplantation (OR = 0.96 per month, P < .0001), blood group type B (OR = 1.62, P < .005), "Quilty" lesion on previous biopsy (OR = 1.70, P < .005), number of HLA mismatches (OR = 1.27 per mismatch, P < .005), female sex (OR = 1.55, P < .05), and serum creatinine level (OR = 0.93 per 10 mumol/L, P < .005). Young age of recipients was a risk factor during long-term (> or = 2 years) follow-up (P < .002), and lower cyclosporine level was a risk factor during the first month after transplantation (P < .01). In multivariate logistic regression analysis, ISHT 2 rejection on previous biopsy remained the strongest predictor of rejection > or = ISHT 3A (OR = 2.40, P < .0001).
  
  
  CONCLUSIONS
  Several factors independently increase the risk of rejection classified as > or = ISHT 3A. The strongest predictor of a grade of > or = ISHT 3A was ISHT 2 rejection on the previous biopsy obtained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of clinical significance, and short-term follow-up appears to be warranted even late after transplantation.
authors.affiliation: Division of Cardiology, University Hospital, Zurich, Switzerland.
authors.forename: H P
authors.initials: HP
authors.lastname: Brunner-La Rocca
authors.forename: G
authors.initials: G
authors.lastname: Sütsch
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Follath
authors.forename: W
authors.initials: W
authors.lastname: Kiowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection / Q000145:classification* / Q000503:physiopathology*; D016027:Heart Transplantation; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012955:Societies, Medical; D013997:Time Factors