Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in immunologically high-risk heart transplant recipients. We previously reported favorable 1-year outcomes of this strategy.

The aim of the current study was to report 5-year outcomes.

We performed a single-center, single-arm, open-label trial (DUET trial, NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre-formed donor-specific antibodies (DSA) ≥5,000 MFI were eligible. In addition to standard of care, patients received 9 infusions of eculizumab during the first two months post-transplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection and patient survival. A matched control group at equivalent immunologic risk and treated with perioperative plasmapheresis and intravenous immunoglobulins was retrieved from the Paris Transplant Group reference set (propensity score matching).

Twenty patients were included in the treatment group. Median post-transplant follow-up was 4.8 years. Beyond the first year post-transplant, there were no episodes of pAMR2 or greater and no LV dysfunction. Primary endpoint free-survival was 79.0% at 3- and 5-year post-transplant. Overall survival was 90% and 83.1% at 3- and 5-year post-transplant. Beyond the first year post-transplant, one episode of pAMR1 was diagnosed and one patient had minimal de novo cardiac allograft vasculopathy. Compared to a matched-control group, we observed a non-statistically significant benefit of eculizumab with a lower incidence of primary endpoint or death (primary endpoint: HR=0.50, 95%CI=0.15–1.67, P=0.26, Fig. 1A; mortality: HR=0.51, 95%CI=0.13–2.07, P=0.35, Fig. 1B).

We report favorable 5-year outcomes of a complement inhibition-based strategy for the management of immunologically high-risk HTx. Chronic antibody-mediated allograft injuries were uncommon. Our results support the utility of complement inhibition for immunologically high-risk heart transplantation.