Prevalence of Acute Cellular Rejection and Its Impact on Survival Post Heart Transplantation in the Contemporary Era

Purpose Identify the prevalence and associates of ISHLT grade ≥2R acute cellular rejection (≥2CR) and its impact on survival post heart transplantation in a well-phenotyped, modern era Irish cohort all of whom receive induction therapy. Methods Retrospective analysis of 88 patients who underwent heart transplantation between 2014 and 2019 (mean age 49.8 ± 13.02 years; female 29.5%). Data was collected on recipient and donor anthropometrics, HLA profile, panel reactive antibodies (PRAs) ischaemia time, cytomegalovirus (CMV) serostatus and endomyocardial biopsy results over a median follow up of 2.04 years (IQR 3.18). Kaplan Meier survival, univariate and multivariate cox regression analysis were performed. Results Standard immunosuppression was with basiliximab induction, a calcineurin inhibitor, steroid and antimetabolite. All-cause mortality at 1 year was 14%. In those patients surviving to first biopsy (n=82), 55% experienced at least 1 episode of ≥2CR at a median time of 53.5 days (IQR 149) and cumulative survival was reduced in this group (p=0.04). More than 1 episode of ≥2CR was not associated with an incremental mortality risk. Intermediate-high risk CMV serostatus was independently associated with increased mortality on multivariate analysis (HR 3.16; 95%CI 1.04-9.65; p=0.04) but not with an increased risk of ≥2CR. There was no association between ischaemic time, PRAs, other recipient/donor matching characteristics, number of HLA mismatches or mismatches confined to any of the 6 HLA subclasses on survival or development of ≥2CR. Conclusion In a modern era Irish cohort where induction therapy is standard, patients who experienced ≥1 episode of ≥2CR post transplant had reduced survival. Intermediate-high risk CMV serostatus was the only independent associate of increased mortality but not for ≥2CR. Further work in an extended cohort will focus on understanding the mechanisms underpinning rejection in this contemporary population and its consequences.