The diagnosis of cardiac allograft rejection is based on the histological analysis of a myocardial tissue sample obtained by endomyocardial biopsy (EMB), an invasive procedure at risk of complications. Our aim is to enable the shift from a protocol biopsy approach, to a precision medicine approach, in which the need for EMB is tailored to each patient's individual risk.

To analyze the incidence and the risk factors for biopsy-proven rejections following heart transplantation in a large cohort of highly phenotyped heart-transplant recipients.

We performed a multicenter, retrospective, observational study (Pitié-Salpêtrière, HEGP, 2004–2016). We included all patients with≥1 EMB during the first year (n=1050 patients, 13677 EMB). All EMB performed before 2012 were retrospectively reviewed and graded according to ISHLT guidelines. Rejections were defined as acute cellular rejection (ACR)≥1R1B and/or antibody-mediated rejections (AMR)≥pAMR1. Pre-formed DSA were evaluated using Luminex Single Antigen Assay (MFI≥500). Risk factors for rejection were identified using Cox proportional hazard model.

Biopsy-proven rejections were diagnosed in 489 patients (46.4%) representing 1009 EMB (7.3%, mostly low-grade rejections: ACR 1R1B or 1R2: n=724, see Figure 1). Risk factors for rejection included recipient's age (HR=0.988 per 1-year increment, P=0.002), type of transplantation (combined heart-kidney and heart-liver compared to isolated heart: HR=0.336 and 0.204 respectively, P<0.001), pre-formed DSA (HR=1.422, P<0.001), HLA A-B-DR mismatches (HR=1.129 per 1-mismatch increment, P=0.02) and the type of induction (basiliximab compared to anti-thymocyte globulins: HR=1.725, P=0.008).

We identified five independent risk factors for biopsy-proven rejection during the first-year post-heart transplantation. Our findings might help clinicians to customize post-transplant endomyocardial biopsies monitoring.