Heightened Immune Response in Heart Transplant Patients Surviving Severe Primary Graft Dysfunction

Abstract

Purpose Primary graft dysfunction (PGD) now has a standard nomenclature as per the International Society for Heart and Lung Transplantation. Severe PGD is defined as significant graft dysfunction within 24 hours of heart transplantation (HTx) requiring mechanical circulatory support. The cause of severe PGD is not clear but may be due to donor, recipient, and peri-operative factors. The long-term outcome of these patients (especially rejection episodes) is not clear. Methods Between 2010 and 2017, we identified 25 heart transplant patients who developed severe PGD supported by extracorporeal membrane oxygenation (ECMO). This group was compared to 670 patients who did not have PGD. Endpoints for both groups included 1-year survival, and 1-year freedom from cardiac allograft vasculopathy (CAV) as defined by stenosis ≥ 30% by angiography, NF-MACE (myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), any-treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR), and biopsy-negative rejection (BNR). This study also assessed whether severe PGD led to increased donor-specific antibody (DSA) development within the first-year post-transplant. Results The severe PGD group had significantly lower first-year survival compared to patients without PGD. The PGD group also had lower freedom from NF-MACE, ATR, AMR, and BNR compared to the control. The development of DSA was numerically lower in the severe PGD group, but this was not statistically significant. Conclusion Severe PGD requiring ECMO support leads to poor outcome after HTx. The lower freedom from ATR, AMR and BNR suggests a heightened immune response in these patients. Further study into the mechanism of PGD is needed to avoid and treat this high-mortality complication.