Abstract

PURPOSE: Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). Human leukocyte antigen (HLA) sensitization increases the risk of rejection and adverse outcomes after HT. We sought to determine the association between pre-transplant HLA sensitization, as measured using the calculated panel reactive antibody (cPRA) value, and the risk of PGD.METHODS: Consecutive adult HT recipients (n=596) from 1/2015 to 12/2019 at two US centers were included. Severity of PGD was based on the 2014 ISHLT consensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor specific antibodies (DSA) were assessed.RESULTS: There were 90 (15.1%) cases of mild-moderate PGD and 37 (6.2%) cases of severe PGD. Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p=0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p=0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and UNOS status 1 or 2 were associated with increased severity of PGD. Presence of DSA to HLA-B was associated with trend toward increased risk of mild to moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p=0.053) but DSA to other HLA loci were not associated with PGD. Neither HLA mismatch nor T- or B-cell crossmatch was associated with PGD.CONCLUSION: Sensitization for all HLA loci and specifically HLA-A are associated with an increased severity of PGD. These factors should be included in pre-HT risk stratification in order to minimize the risk of PGD.

View details for DOI 10.1016/j.healun.2023.09.017

View details for PubMedID 37802261