NATURAL COURSE OF MODERATE CARDIAC ALLOGRAFT-REJECTION (INTERNATIONAL-SOCIETY-FOR-HEART-TRANSPLANTATION GRADE-2) EARLY AND LATE AFTER TRANSPLANTATION

Background The significance of International Society for Heart Transpl antation (ISHT) grade 2 cardiac allograft rejection has been questione d, and the medical community is not in complete agreement as to its cl inical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 tran splant patients since introduction of the ISHT nomenclature at our ins titution. Methods and Results Or 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were pr eceded by intensified immunosuppression and were excluded from analysi s. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies pe rformed 7 to 10 days after prior ISHT 2 rejection without change of tr eatment. Of these, 70 (18.7%) had progressed to greater than or equal to ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) reso lved. In contrast, follow-up of 2074 biopsies with lower-grade rejecti on showed graft rejection classified as greater than or equal to ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and less than or equal to ISH T 1B in 1081 (81.1%) biopsy samples (P<.0001). In univariate analysis, the odds ratio (OR) of graft rejection greater than or equal to ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rej ection greater than or equal to ISHT 3A were time after transplantatio n (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 set: (OR=1.55, P<.05 ), and serum creatinine level (OR=0.93 per 10 mu mol/L, P<.005). Young age of recipients was a risk factor during long-term (greater than or equal to 2 years) follow-up (P<.002), and lower cyclosporine level wa s a risk factor during the first month after transplantation (P<.01). In multivariate logistic regression analysis, ISHT 2 rejection on prev ious biopsy remained the strongest predictor of rejection greater than or equal to ISHT 3A (OR=2.40, P<.0001). Conclusions Several factors i ndependently increase the risk of rejection classified as greater than or equal to ISHT 3A. The strongest predictor of a grade of greater th an or equal to ISHT 3A was ISHT 2 rejection on the previous biopsy obt ained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of cl inical significance, and short-term follow-up appears to be warranted even late after transplantation.