A SEMIQUANTITATIVE APPROACH TO THE EVALUATION OF ACUTE CARDIAC ALLOGRAFT-REJECTION AT ENDOMYOCARDIAL BIOPSY

Background: Histopathologic criteria for grading of acute cardiac allo graft rejection are focused on the most severe lesion that is recogniz ed among the myocardial fragments provided by each endomyocardial biop sy specimen. Considering the distribution of rejection lesions among a ll the fragments improved the accuracy in characterizing the severity of rejection in pathologic studies. This study was undertaken to verif y the usefulness of a semiquantitative evaluation of endomyocardial bi opsy specimens, consisting of the calculation of the proportion of fra gments showing rejection in the clinical setting. Methods: Of the 2386 biopsy specimens obtained during the first posttransplantation year i n 168 consecutive cardiac allograft recipients, 290 biopsy specimens c onstituted by greater than or equal to 3 adequate fragments and showin g rejection not followed by treatment (n = 159) or being the first bio psy specimen prompting treatment with augmented immunosuppression for that rejection episode (n = 131) were selected. These biopsy specimens (index biopsy specimens) were grouped according to whether rejection was present in less than or equal to 33%, >33% to less than or equal t o 67%, and >67% of the fragments. The rejection grade (according to th e standardized grading system) and the proportion of fragments positiv e for rejection were correlated with the occurrence of clinical sympto ms and signs of rejection at index biopsy and with the results of the next biopsy. Results: Rejections graded greater than or equal to 3A we re more frequently symptomatic (36% vs 9% for those graded <3, p < 0.0 001), as were those involving increasing proportions of fragments (les s than or equal to 33%: 5 of 124, 4%; >33 to less than or equal to 67% : 13 of 99, 13%; >67%: 19 of 67, 28% [p < 0.0001]). Spontaneous resolu tion after untreated biopsies was more frequent in focal (grade 1A and 2) than in diffuse mild (1B) rejections (68% vs 38% [p < 0.04]), wher eas progression to grade 3A or greater was less frequent (4% vs 27% [p < 0.01]). Increasing proportions of positive fragments were associate d with lower frequencies of spontaneous resolution (p < 0.05) and high er frequencies of worsening (9%, 22%, 43% [p < 0.009]) or progression to grade 3A or greater (2%, 6%, 28% [p < 0.005]). Complete resolution after treatment was less frequent for increasing proportions of positi ve fragments at index biopsy (80%, 66%, 49% [p < 0.05]). Conclusions: Diffuse versus focal rejection pattern and the proportion of positive fragments seem to be clinically relevant in terms of occurrence of sym ptoms? spontaneous evolution, and response to treatment. J Heart Lung Transplant 1997.