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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 transplant patients develop many opportunistic infections due to chronic immunosuppression. One of the more common complications is that of Clostridium difficile (CDif) causing gastroenteritis, usually represented as diffuse diarrhea. It appears that these opportunistic infections such as CDif may have an impact on the immune system via the microbiome. It has not been demonstrated whether patients who develop CDif are at higher risk for the subsequent development of rejection or chronic rejection known as cardiac allograft vasculopathy (CAV) years after the event. Between 2010 and 2018, we assessed 69 heart transplant patients who developed CDif within the first year post-transplant. These patients were assessed for subsequent 3-year survival, 3-year freedom from CAV (stenosis ≥30% by angiography), 3-year freedom from non-fatal major adverse cardiac event (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), and 1-year freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR). These patients were compared to a group (case controlled for time from transplant, age, gender) who did not develop CDif. The average time of infection following transplant was 2.2 ± 3.0 months. The heart transplant patients who developed CDif had significantly lower subsequent 3-year survival, 3-year freedom from NF-MACE, and lower 1-year freedom from AMR compared to the control group. There was no significant difference in the development of CAV (see table). Assessment of specific immunosuppression, antibiotic prophylaxis, and specific CDif treatment did not have an impact on outcome. Heart transplant patients who developed first-year CDif appeared to have immune modulation that adversely affects subsequent outcome. Further investigation to study the microbiome is needed in order to elucidate the mechanisms that are in process. [ABSTRACT FROM AUTHOR]