Acute Cellular Rejection after Heart Transplantation Dramatically Subsequent Risk of Mortality, Particularly among African Americans

Abstract

African Americans (AA) have worse survival compared to Caucasians after heart transplantation (HTx). We assessed whether AA are at higher risk of acute cellular rejection (ACR), graft failure (GF) and cancer when compared to Caucasians and Other races in the modern era. Retrospective study in HTx recipients between 01/2008 and 05/2019 at a single institution. Outcomes included post-transplant mortality, GF, cancer and ACR. Independent estimating equations were used to analyze longitudinal biopsy differences among races. Kaplan-Meier method was used for survival and competing risk model for GF and cancer. Hazard regression was applied to quantify the association of ACR (a time dependent variable) with mortality adjusted for recipients' demographic characteristics. Among 612 recipients, 323 (56.7%) were Caucasian, 63 (11.1%) AA, and 184 (32.3%) Other. The cohort was predominantly male (71.7%), with a median (IQR) age of 55.9 (44.7 - 62.6) years. AA had a trend towards lower 5-year survival (95% CI) (AA vs. Caucasian vs. other: 77.7% [62.7%, 87.3%] vs. 80.9% [75.0%, 85.5%] vs 79.6% [71.2%, 85.7%], p= 0.49) and higher 5-year incidence of GF (AA vs. Caucasian vs. other: 13.3% [2.4%, 23.0%] vs. 8.5% [4.6%, 12.2%] vs. 6.8% [2.2%, 11.3%], p= 0.44). AA had a significantly increased risk of ACR within the first 2 years of HTx (AA vs. Caucasian vs. other (65.4% [36%, 86.4%] vs. 33.3% [25.3%, 42.3%] vs. 29.2% [18.9%, 42.2%], p< 0.001) Figure 1. Multivariable hazard regression showed that moderate and severe ACR was associated with a significant mortality risk by 14.6 [4.66-43.987] and 55.8 [5.23-590.18] fold when controlled for recipient demographics. Compared to Caucasian patients, AA were significantly more likely to have moderate-to-severe acute cellular rejection. In turn, rejection was significantly associated with post-transplant death. AA may benefit from tailored immunosuppression to reduce the risk of rejection and death.