Clinical relevance and outcome of routine endomyocardial biopsy to detect rejection after heart transplantation

Background: Endomyocardial biopsy has been the cornerstone of monitoring rejection after heart transplantation for decades. Although recommendations advise routine biopsies during the first 3-12 months, this timeframe is broad, and intercenter variability persists in its application. Here, we report the yield and complication rate of routine endomyocardial biopsies during the past 36 years of post-transplantation care to monitor acute cellular rejection. Methods: In this retrospective, single-center study, we collected all routine biopsy data after transplantation between 1986 and 2022. The total number of biopsies, type of rejection, complications, and survival were analyzed in the total population as well as per different endomyocardial biopsy protocol over time period (Period 1: 1986-1994; Period 2: 1994-2009; Period 3: 2009-2022). Results: In 474 patients (71.1% male, age at transplant 47.7 ± 12.6 years), 8185 routine biopsy procedures were performed: 29.9 ± 11.1 per patient for Period 1 (n = 83), 16.9 ± 3.8 for Period 2 (n = 220) and 11.6 ± 2.4 for Period 3 (n = 171). Complication rate was low (1.7%; n = 139/8185) and 19.8% (n = 94/474) patients experienced clinically-relevant rejection (≥2R) which mainly occurred <6 months post-transplantation (89.4%; n = 84/94). The incidence of rejection decreased over time, leading to an improved rejection-free survival (p < 0.001) with a subsequent increase in Number-Needed-to-Diagnose. Importantly, severe acute cellular rejection did not occur in Period 3 in the first year post-transplantation. Conclusion: Acute cellular rejection, including clinically-relevant rejection, has declined significantly over time and is rare beyond 6 months post-transplantation. A low-frequency approach seems feasible and safe, which is relevant for the transition towards less-invasive protocols to detect rejection, especially early post-transplantation.