The Effect of Pre-Transplant Mechanical Circulatory Support Devices on the Post-Transplant dd-cfDNA and GEP in Heart Transplantation

Abstract

Evidence around sensitization and increased risk of rejection from use of pre-transplant mechanical circulatory support (MCS) devices remains conflicting. Some evidence suggests devices cause inflammation and association with increased antibody production, which has been shown to be associated with AMR, CMR, and early onset of microvasculopathy at one year post-heart transplant. However other evidence suggests no difference or increased risk of adverse outcome using pre-transplant MCS devices. dd-cfDNA (AlloSure) has been shown to rise in advance to the new formation of de-novo anti-HLA antibodies, with changes in AlloMap also seen in patients who become newly sensitized. The aim of this study was to review MCS patients post-transplant with AlloSure and AlloMap to assess if they had different patterns from those who had no MCS, to support suggestion of early post-transplant complications. Patients who were enrolled in Outcomes AlloMap® Registry (OAR) and the dd-cfDNA extension (D-OAR) were included in this analysis if pre-transplant MCS history was recorded and signs or symptoms of rejection during a visit with an accompanying blood draw were absent (i.e. no biopsy accompanied the visit or if a biopsy occurred it yielded Grade 0R). A total of 282 patients met these criteria, 130 had pre-transplant MCS and 152 did not. A total of 652 samples were collected where both AlloSure and AlloMap scores were obtained. The cumulative distribution of AlloSure and AlloMap scores were assessed via a two-sample Kolmogorov-Smirnov test to determine if differences were observed that may be attributed to mechanical assist support prior to transplant. No difference in the distribution of AlloMap scores from patients that received pre-transplant mechanical support versus those that did not was observed, similarly for AlloSure measurements, there was no statistically significant difference in the distribution of AlloSure scores between those that receive pre-transplant mechanical assist support versus those that do not receive support. Pre-transplant MCS does not correlate with increased dd-cfDNA or GEP score, suggesting the adverse outcomes seen early post-transplant are unlikely to be due to MCS devices.