Recurrent acute cellular rejection graded ISHLT 1R early after heart transplantation negatively affects long-term outcomes: The prognostic significance of 1990 ISHLT grades 1B and 2

Purpose: We investigated the implications of early recurrent 1R rejections for long-term outcomes after heart transplantation (HT) and evaluated the prognostic significance of 1990 ISHLT grading 1B/2 versus 1A. Methods: Data on all patients who underwent HT between 1992 and 2017 were reviewed. Patients with ≥2 endomyocardial biopsies graded 1R in the first 3 months were classified as “recurrent 1R.” Those patients were further categorized according to 1A vs. 1B/2. Outcomes (>3 months) were long-term rejections and the combined endpoint of cardiac allograft vasculopathy (CAV) and cardiovascular (CV) mortality. Results: Sixty-nine out of 228 patients were classified as recurrent grade 1R. In the recurrent 1R group, 2R rejection rate was significantly higher (2.6 ± 0.6 vs 1.2 ± 0.4, p = 0.03), while survival free of rejections was lower (5-year: 57.1% vs. 72.3%, p = 0.022). Multivariate analysis showed that early recurrent 1R rejection was associated with a 30% increased risk for subsequent major rejection. Among 28 patients classified as 1B/2 of the recurrent group, rejection scores were higher, while survival free of rejections was lower, compared to 37 patients of the recurrent group classified as 1A (5-year: 57.1% vs. 72.7%, p = 0.013). Kaplan-Meier analysis showed that CAV/CV mortality at 10 years of follow-up was significantly higher among the recurrent 1R group (38% vs. 18% p < 0.05). Multivariate analysis showed that early recurrent 1R rejections were associated with a 2.5-fold increased risk for CAV/CV mortality. Conclusion: Early recurrent grade 1R rejections negatively affect long-term outcomes. The adverse outcomes are experienced mainly by 1R patients subcategorized as1B/2 and not 1A.