Incidence and risk factors for biopsy-proven heart allograft rejection during the first-year post heart transplantation

Abstract

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 Fig. 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.