Sensitization in adults with congenital heart disease evaluated for heart transplantation: prevalence and impact on 1-year post-transplant outcomes

Introduction Adults with congenital heart disease (ACHD) are considered at higher risk of sensitization due to prior surgeries and peri-operative transfusions, though evidence is limited. This may restrict donor compatibility and worsen heart transplant (HTx) outcomes. Purpose To describe the prevalence of sensitization in ACHD patients undergoing HTx evaluation and to compare 1-year post-transplant outcomes focusing on antibody-mediated rejection (AMR) with non-ACHD controls. Methods We retrospectively analysed consecutive ACHD patients evaluated for HTx at a specialized ACHD center between June 2018 and February 2024. Medical history and Luminex single-antigen bead (SAB) assay results were reviewed. Panel-reactive antibody was calculated (cPRA), considering only antibodies with a mean fluorescence intensity (MFI) > 4000 as unacceptable. ACHD patients who underwent isolated HTx were compared to non-ACHD HTx controls, matched 2:1 for age (±8 years), sex, and HTx date (±5 years), from a transplant center affiliated with the same immunology laboratory. Results Of the 63 patients evaluated for HTx (mean age 39.7±11.0; 26 [41.3%] women), 19 (30.2%) had circulating antibodies detectable by Luminex SAB. Fifteen (23.8%) patients had a a cPRA >10%, 12 patients (19.0%) had cPRA > 50% and 6 (9.5%) had cPRA> 90%. Patients with homografts were more frequently sensitized (5/5 (100%) versus 14/58 (24.1%), p<0.001), as were women with prior pregnancies (3/4 (75.0%) versus 4/22 (18.2%), p=0.05). No significant differences were observed regarding age, the number of previous surgeries or the presence of other exogenous implanted materials. The flow-chart of evaluated ACHD patients is shown in Figure 1; patients with cPRA > 10% had a tendency of being more frequently declined for HTx (6/15 (40%) versus 6/46 (13%), p=0.09). Twenty-eight ACHD patients underwent isolated HTx during the study period: 6(21.4%) had anti-HLA antibodies and 2 underwent desensitization as cPRA > 90%, with no significant differences when compared to non-ACHD controls (10/56, 17.9%, p=0.69, 1 desensitization). However, ACHD patients had more frequently donor-specific antibodies and AMR requiring treatment in comparison to non-ACHD patients during 1-year post-HTx (Figure 2). Conclusions Sensitization is common among ACHD patients evaluated for HTx, particularly in those with homografts or a history of pregnancy, and may limit access to transplantation. Notably, ACHD patients undergoing HTx appear to be at higher risk of DSA detection and AMR within the first year post-HTx compared to apparently similarly pre-sensitized non-ACHD controls, possibly due to alloimmune memory recall responses.