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

Abstract Background After heart transplantation (HTx), endomyocardial biopsies (EMBs) are the gold standard to monitor cardiac allograft rejection. However, a clear consensus on the optimal frequency and duration of EMB monitoring is lacking. Purpose Since the first HTx in 1985 in our center, EMB protocols have gradually changed to a low-frequency schedule. We assessed the diagnostic yield and complication rate of the three different EMB protocols used during the past 37 years. Methods In this retrospective, single centre, observational study, all biopsy data of routine EMBs after HTx between 1985 and 2022 were collected for analysis. Patients with symptom-driven biopsies or follow up in another hospital were excluded. The total number of biopsies, type of rejection and complications were evaluated. Results In a total of 431 patients (69.6% male, mean age at transplant 48±13 years), 6692 routine surveillance EMB procedures were performed. The average number of biopsy procedures per patient was 25.1±8.1 for protocol 1 (n=44, 1985-1994), 17.0 ±3.6 for protocol 2 (n= 213, 1994-2009) and 11.3±2.6 for protocol 3 (n=174, 2009-2022). Cellular rejection was detected in 8.93%, of which grade I, II and III cellular rejections were seen in 7.32%, 1.58% and 0.03%, respectively. The frequency of ≥ ISHLT grade 2R requiring additional treatment was 1.61% and decreased over time with each EMB protocol (2.80%, 1.72%, and 0.76%). Complication rate was 1.63%, mainly consisting of puncture of the carotid artery (57.9%). Independent of the EMB protocol used, the majority of rejections occurred within the first six months after HTx (68.7%). Conclusion Complications of EMB after HTx are rare. Cellular rejection mostly occurs within the first 6 months after HTx. The incidence of clinically relevant cellular rejection (≥ISHLT grade 2) has declined over time, partly due to improved immunosuppressive therapy. A conservative approach using a low-frequency EMB schedule seems feasible and safe.Cellular rejection per protocol