Positive C4d Staining In Endomyocardial Biopsies In The Presence Of Donor Specific Antibodies Is Associated With Increased Cardiac Death And Allograft Dysfunction.

C4d immunostaining of endomyocardial biopsies (EMB) is necessary for the pathologic diagnosis of antibody-mediated rejection in heart transplant (HTx) patients. However, prior studies of C4d positive EMBs have shown contradictory findings on clinical outcomes. In this study, we examined whether C4d positive EMBs in the presence of positive donor specific antibodies (DSA) are associated with worse clinical outcomes. C4d and DSA positive HTx patients will have worse clinical outcomes compared to the three other C4d/DSA groups. This was a single center, retrospective study of endomyocardial biopsies (EMB) performed between January 2002 and February 2023 at University of California, San Diego Health. Patient data and clinical outcomes of death, cardiac allograft dysfunction (<50% LVEF), and clinically significant CAV (>CAV ISHLT grade 2) were collected. Categorical variables were expressed as frequency and percentage and compared with the use of either Pearson's chi-square or Fisher's exact test as appropriate. P < 0.05 was considered significant. A total of 6,294 EMBs from 612 adult HTx patients were analyzed. HTx patients were categorized into four groups based on C4d and DSA positivity: C4d+/DSA+ (n=31), C4d+/DSA- (n=35), C4d-/DSA+ (n=100), and C4d-/DSA- (n=386). There was no significant difference in all-cause death in the four C4d/DSA groups. However, C4d+/DSA+ patients showed significantly higher rates of cardiac death (p=0.01; Table) and cardiac allograft dysfunction (p<0.001) compared to the C4d-/DSA- group. There was no significant difference in clinical outcomes in the C4d+/DSA+ group compared to the C4d+/DSA- group in pairwise comparisons. We also did not observe any significant difference in the rate of CAV in the four C4d/DSA groups. The C4d+/DSA+ group demonstrated significantly higher rates of cardiac death and allograft dysfunction compared to the C4d-/DSA- group. [ABSTRACT FROM AUTHOR]