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 as follows: 0-3 months (early), 3-12 months (intermediate), and 12+ months (late). HT era was dichotomized as follows: 1991-1999 (remote era) and 2000-2016 (recent era). Medication combination was categorized as newer (TAC, MMF, and 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 2 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.