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Approximately 30% of patients (pts) awaiting heart transplantation (HT) develop anti-HLA antibodies (Abs) due to sensitizing events. Highly sensitized pts have peak Panel Reactive Antibody (PRA) levels≥80%. We assessed the efficacy of desensitization therapy (DTx) on these pts awaiting HT. Between 2010-19, we assessed 78 pts awaiting HT with peak PRA≥80% (mean peak PRA 91.6%, range 80-100%). These pts received DTx with intravenous immunoglobulin (IVIG) alone (n=18), rituximab-based therapy (n=5), plasma exchange (PE) alone (n=15), bortezomib-based therapy (BTZ)(n=30), and finally combination therapy with rituximab/BTZ (n=-10). Peak PRAs (mean fluorescent intensity, MFI) were obtained before and after treatment. All pts received ATG induction and IVIG with eculizumab given to pts crossing high level donor-specific Ab (DSA). 3-year outcomes including survival, freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30%), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new onset heart failure, percutaneous coronary intervention, cardioverter defibrillator/pacemaker implant, stroke), and 1-year freedom from rejection [acute cellular rejection (ACR), Ab-mediated rejection (AMR)] were obtained. A group of non-sensitized pts without pre-HT anti-HLA Abs was used as control. With each DTx, peak PRA was reduced (table). Post-HT, there was lower freedom from 1-year AMR in the highly sensitized pt groups compared to the control group. 3-year survival, freedom from CAV and NF-MACE were similar among all groups. 26 highly sensitized pts received eculizumab perioperatively for crossing high level DSA. Although there is variability in how highly sensitized pts respond, pre-HT DTx appears beneficial and enables pts to undergo successful HT. Further studies and longer follow-up are needed to identify the optimal therapy for each highly sensitized individual. [ABSTRACT FROM AUTHOR]

Heart-liver transplant (HLvTx) has been demonstrated to show an immune protective effect with the transplanted liver protecting the heart. There are several reports suggesting less rejection in the HLvTx group. It has not been established whether this benefit is present in the current era. Between 2007 and 2017, we assessed 13 HLvTx patients compared to heart alone patients (HATx, n=758). Patients were assessed for freedom from 1-year rejection [acute cellular rejection (ACR) and antibody-mediated rejection (AMR)] and donor-specific antibodies (DSA). Other endpoints included 5-year survival and freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography) and non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). HLvTx compared to HATx showed similar freedom from 1-year rejection (ACR, AMR) and DSA. 5-year survival, freedom from CAV and NF-MACE were also similar between the two groups (see table). In the current era, HLvTx does not appear to provide immune protection in either rejection or CAV. A larger number of heart-liver transplant patients will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]