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Patients with congenital cardiac defects often require multiple surgeries during childhood and sometimes cardiac transplantation (HTX) as adults. This represents a challenge from a surgical and an immunological point of view. At age 27, our patient was diagnosed with a bicuspid aortic valve and mechanical valve replacement was performed. Five years later, due to biventricular outflow tract obstruction and severe patient-prosthesis mismatch, a reoperation with enlargement of the LVOT and RVOT (Konno-Repair) was performed, followed by several revisions for an iatrogenic septal defect and sternum instability. In 2021, the patient was listed for HTX after continuous deterioration of exercising capacity and progression to severe diastolic heart failure. The patient was highly HLA-sensitized with a virtual Panel Reactive Antibody (vPRA) of 100%. An initial treatment with Rituximab followed by two immunoadsorption sessions (IA) led to adequate B lymphocyte depletion (Panel A, B, E); however, HLA antibodies remained high (Panel D). Escalation with an Anti-CD-38 antibody (Daratumumab) to eradicate the plasma cells, followed by another cycle of IA was effective. Under these conditions, an HLA-matched donor was found within three weeks of the last IA (Panel D, thick lines). On the day of transplantation, the patient received a final IA and a dose of Eculizumab (Anti-C5). To minimise the cold ischemic time (CIT), we use the Organ Care System (OCS) for the first time in Switzerland. The CIT during organ procurement was 88 min (30 min preparation for OCS and 58 min for implantation), while ex-vivo perfusion time was 4 hours. The immediate postoperative course was uneventful. However, the patient suffered an antibody-mediated rejection during the second postoperative week, and desensitisation therapy had to be restarted. In pre-operated, highly immuno-sensitized patients, monoclonal antibody therapy and OCS allowed transplant patients who, a few years prior, would not have been transplantable. [ABSTRACT FROM AUTHOR]