Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation

Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor-recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced ≥2R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8-1003.3] vs. 65.3 [40.2-163.3] pg/mL; p = 0.04). A trend toward lower mtDNA/gDNA ratio was also observed in the same group (10.5 [5.4-24.6] vs. 6.5 [3.3-10.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury.