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Because the half-life of the transplanted heart is approximately 14 years, re-transplantation may be necessary. Patients requiring redo heart transplant (HTx) may also have developed chronic kidney disease due to calcineurin inhibitor nephrotoxicity or progression of pre-existing renal dysfunction. Therefore, combined kidney transplant may be indicated. We evaluated outcomes following redo HTx with combined kidney transplant. A prospective institutional registry identified 1075 HTx cases between 1/1/2010 and 9/1/2020. Twenty-two patients undergoing redo HTx with kidney transplantation were compared to 55 patients undergoing redo HTx alone. Post-transplant outcomes included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Delayed graft function of the transplanted kidney was also evaluated and compared to 16540 patients identified from the national United Network for Organ Sharing database who underwent isolated kidney transplant between 2015 and 2020. Patients undergoing redo HTx with combined kidney transplant had higher incidence of post-operative dialysis and longer hospital length of stay. One-year outcomes were similar compared to patients undergoing redo HTx alone (Table). Delayed graft function of the transplanted kidney occurred in 12 patients (54.5%) after redo HTx with combined kidney transplant and 7112 patients (43.0%) after isolated kidney transplant (p=0.274). Redo HTx with combined kidney transplant has acceptable one-year outcomes. Significant renal disease in patients requiring redo HTx should not be a contraindication to re-transplantation. [ABSTRACT FROM AUTHOR]

Patients who undergo heart transplantation may be in need of a second heart transplant if they develop severe graft dysfunction. Due to the long periods of time that these patients have been on calcineurin inhibitors, chronic kidney disease may ensue. These patients who need a second heart transplant may also need a combined kidney transplant. It has not been established in these redo heart transplant patients as to what GFR places them at risk for chronic dialysis post redo heart transplant. Between 2010 and 2021, we assessed 41 heart transplant patients who underwent redo heart transplant alone. These patients were divided into GFR quintiles (<42, 42 to <52, 53 to <61, 61 to <80 and ≥80 cc/minutes) to assess subsequent need for chronic kidney dialysis post-redo heart transplant. A group of 22 combined heart-kidney transplant patients were also included for comparison. Other endpoints included post-transplant 1-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from acute cellular rejection (ACR) and freedom from antibody mediated rejection (AMR). Redo heart transplant patients undergoing a heart transplant alone in the lowest quintile had a trend toward increased need for chronic hemodialysis post-transplant. At 1-year post-transplant, GFR remained low for those redo heart patients with baseline GFR <52cc/minute. Among the GFR quintile groups, there was no significant difference in post-transplant 1-year survival, freedom from CAV, freedom from ACR and freedom from AMR. In comparison, the redo heart transplant with combined kidney transplant patients appeared to have good outcome. (see table) Redo heart transplant patients with GFR < 42 cc/min appear to be at high risk for chronic hemodialysis post redo heart transplant. These patients might be considered for a combined redo heart transplant with kidney transplantation. Larger number of patients are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The number of homozygous human leukocyte antigen (HLA) loci has been associated with the risk of HLA sensitization in kidney transplant candidates, which is a risk factor for antibody-mediated rejection (AMR). We assessed the relationship between HLA homozygosity and sensitization and AMR in heart transplant (HT) recipients. The study cohort comprised 1238 HT recipients transplanted 2012 - 2019 (622 Paris, 616 Los Angeles). Calculated panel reactive antibody values were determined with a threshold of mean fluorescence intensity >= 2500 (Los Angeles) or 3000 (Paris) using an 11-locus CPRA calculator based on National Marrow Donor Program HLA genotype frequencies. Split antigens were mapped to the corresponding broad antigen. HLA genotypes were used to assess homozygosity for HLA-A, -B, -DR, and -DQ. "Low" or "high" HLA homozygosity was defined as 0/1/2 or 3/4 homozygous loci. Cox modeling was performed with biopsy-proven AMR by 3 years post-HT as the endpoint. 525 (42%) recipients had CPRA >=1% and 173 (14%) had CPRA >=50%. Homozygosity at HLA-A, -B, -DR, and -DQ occurred in 20%, 8%, 14%, and 29% of candidates, respectively. The number of homozygous HLA loci was associated with increasing CPRA in a linear model (β=2.39/homozygous locus, p=0.008) and in a stepwise fashion (FIG 1). Only the group with CPRA 50-100% and low homozygosity experienced an increased risk of AMR (HR 4.1, 95% CI 2.8-6.2, p<0.001, FIG 2). Homozygosity at multiple HLA loci is associated with an increased risk of sensitization but decreases the risk of AMR in sensitized candidates. Although the mechanism is unknown, we speculate that HLA homozygosity may limit the repertoire of alloreactive T cells. [ABSTRACT FROM AUTHOR]

Calcineurin inhibitors (CNIs) tacrolimus and cyclosporine, have improved outcomes of heart transplant (HTx) patients but unfortunately have many side effects which include nephrotoxicity, hypertension, and malignancy. CNI-free regimens may protect the kidneys but at the risk of rejection. The purpose of this study was to assess our center's experience with CNI minimization and discontinuation. We assessed 34 HTx patients transplanted between 2010-2020, who transitioned to CNI-free regimens 6m-2 years post HTx and 2-5 years post HTx. Outcomes assessed were any treated rejection (ATR; including acute cellular rejection [ACR], antibody-mediated rejection [AMR], and biopsy-negative rejection [BNR]), survival, cardiac dysfunction (ejection fraction ≤40%) in the 1 year following CNI-free initiation. We also assessed the need for antihypertensive medications, HgbA1c, and estimated glomerular filtration rate (eGFR). Of 34 HTx recipients, 89% of patients were successfully weaned off CNI at <2 years and 94% at 2-5 years after transplant. eGFR for both groups was markedly improved at 1-year post CNI-free initiation. There was no difference between groups in anti-hypertensive medications or HgbA1c. However, CNI had to be restarted in 50% of the CNI-free in <2 years group and in 31% of the CNI-free at 2-5 years group. Return to CNI was for: rejection, medication intolerance, and death. (Table). CNI-free regimens are safe and efficacious for select patients but may not be sustainable. Additional strategies for renal protection and immunosuppression optimization are warranted. [ABSTRACT FROM AUTHOR]