Risk of Early, Intermediate, and Late Rejection Following Heart Transplantation: Trends Over the Past 25 Years and Relation to Changes in Medical Management Tertiary Center Experience: The Sheba Heart Transplantation Registry

Aim To explore the trends in the risk for rejection following heart transplantation (HT) over the past 25 years, and their relation to changes in medical management. Methods The study population comprised 216 HT patients. Rejection periods were defined: 0-3 months (early), 3-12 months (intermediate), 12+ months (late). HT era was dichotomized: 1991-1999 (remote era) and 2000-2016 (recent era). Medication combination was categorized as newer (TAC, MMF, everolimus) vs. older therapies (AZA, CSA). Results Multivariate analysis showed that patients who underwent HT during the recent era experienced a significant reduction in the risk for major rejection. These findings were consistent for early (OR=0.44 [95% CI 0.22-0.88]), intermediate (OR=0.02 [95% CI 0.003-0.11]), and late rejections (OR=0.18 [95% CI 0.05-0.52]). Using the year of HT as a continuous measure showed that each 1-year increment was independently associated with a significant reduction in the risk for early, intermediate, and late rejections (5%,21%,18% respectively). In contrast, the risk-reduction associated with newer types of immunosuppressive therapies was not statistically significant after adjustment for the treatment period. Conclusions Major rejection rates following HT have significantly declined over the past two decades even after adjustment for changes in immunosuppressive therapies, suggesting that other factors may also play a role in the improved outcomes of HT recipients. This article is protected by copyright. All rights reserved.