Are Those with Primary Graft Dysfunction More Likely to Have Acute Cellular Rejection or Donor-Specific Antibodies after Heart Transplantation?

Abstract

<h3>Purpose</h3> Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between PGD and incidence of acute cellular rejection (ACR) and development of <i>de novo</i> donor specific antibodies (DSA) within two years post-HTx. <h3>Methods</h3> Consecutive adult HT recipients (n=351) from 1/2010 to 7/2018 at a single center were included. Multi-organ and re-transplants were excluded. Definition of moderate and severe PGD was based on the 2014 ISHLT consensus, which includes dependence on extracorporeal membrane oxygenation or intra-aortic balloon pump. The primary outcome was the incidence of ACR (ISHLT grade 2R or 3R) and the development of <i>de novo</i> DSA (mean fluorescence intensity >500) within 2 years post-HTx. <h3>Results</h3> The cohort was predominantly male (70.6%), with a mean age of 54.1±12.5 years; 34.6% had a durable left ventricular assist device as a bridge to HTx. There were 33 (9.1%) cases of moderate or severe PGD. HLA was assessed in a mean of 15 and 24 samples per patient in those with and without PGD respectively. At two years, patients with PGD had lower incidence of development of <i>de novo</i> DSA against HLA-C (1.6 vs. 3.2%, p=0.047), DP (1.3 vs. 4.3%, p=0.002), DQ (3.3% vs. 11.8%, p<0.001), DR (4.9 vs. 12.4%, p<0.001) compared to patients without PGD (Table 1). In patients with and without PGD, there were 7 and 8 endomyocardial biopsies performed per patient, respectively within two years post-HTx. Patients with PGD had similar incidence of ISHLT 2R or 3R ACR compared to those without PGD (5.3% vs. 3.1%, p=0.07). Finally, there was no difference in PGD among patients who received empiric treatment for ACR without positive endomyocardial biopsy results (3.1% in PGD vs. 3.7% in no PGD, p=0.47). <h3>Conclusion</h3> Development of <i>de novo</i> DSA was lower in the PGD group and there was no difference in overall incidence of ACR in patients with and without PGD at 2 years post-HTx.