Search

The donor shortage in heart transplantation (HTx) has led to programs accepting older donors. Coronary calcification is common in older people and is known to correlate with underlying coronary artery disease. It is not known whether these donors with coronary calcification impart an increased risk for the recipient to develop cardiac allograft vasculopathy. Between 2010 and 2017, we assessed 31 heart transplant patients who were found to have coronary calcification within the first 3 months after heart transplantation, either by coronary angiography or chest CT scans. These patients were compared to a contemporary cohort of 192 patients (transplanted with donors >30 years old) without coronary calcification for the following outcomes: 3-year survival, 3-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), 3-year non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Those patients with donor coronary calcification compared to those without had a significantly lower 3-year freedom from CAV (64.5% vs 85.9%, P=0.001). There was no significant difference in 3-year survival, freedom from NF-MACE, and 1-year rejection episodes. The severity of CAV observed in the donor coronary calcification group included: CAV1 = 13, CAV2 = 1, CAV3 = 0. Donor coronary artery calcification appears to be a marker for greater risk for developing CAV after heart transplantation. Caution must be taken to accept these organs and if accepted, early modification of immunosuppression with a proliferation signal inhibitor may be indicated. [ABSTRACT FROM AUTHOR]

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]

Cyclosporine (CsA) became available in the US in 1983 and improved clinical outcomes. Another calcineurin inhibitor, tacrolimus (TAC), became available in the 1990s and demonstrated benefit in further reducing rejection. In most heart transplant (HTx) programs, TAC is currently the drug of choice for immunosuppression. However, a switch to CsA does occur due to adverse effects from TAC. It is not well-established that this switch to CSA results in subsequent non-inferior outcomes. Therefore, we reviewed our single center experience to assess for real world potential outcomes. Between 2010 and 2017, we identified 58 HTx patients who were administered CsA in place of TAC mostly due to neurologic adverse effects from TAC. For comparison, a TAC group was matched based on age, sex, baseline renal function and time from transplant. The average time of this switch occurred at 6.6 ± 1.1 months post-transplant. Outcomes included subsequent 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR) and 3-year subsequent survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), and freedom non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). The CsA/MMF group compared to the TAC/MMF group had significantly lower subsequent 3-year survival and worse renal function at 1-year (after the switch to CsA). There was similar subsequent 3-year freedom from CAV and NF-MACE and 1-year rejections between the two groups. (see table) In the current era in a large, single center study there are indications that a switch to CsA from TAC may be inferior in heart transplant recipients. Further investigation with larger numbers is needed to confirm these findings. [ABSTRACT FROM AUTHOR]