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Heart-kidney transplant (HKTx) is limited by donor availability, and research has suggested that older recipients have less favorable outcomes. However, it is not well established if older recipients of HKTx versus heart transplant alone (HATx) have acceptable post-transplant outcomes. Therefore, we sought to answer this question in our large single center program. Between 2010 and 2018, we assessed 50 HKTx patients 60 years of age and older. We compared these to older patients undergoing HATx in a contemporaneous era. Endpoints included 5-year survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30%), freedom from 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 rejection [any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR)]. Development of delayed graft function, defined as the need for temporary hemodialysis within the first 2 weeks after transplant, was evaluated for the HKTx group. Older patients who underwent HKTx compared to older patients who underwent heart HATx had similar 5-year survival and freedom from CAV and NF-MACE and 1-year freedom from rejection (see table). The older heart-kidney group had 19/50 patients (38%) develop delayed graft function with all but 1 patient recovering renal function. Older HKTx recipients have acceptable outcomes compared to older recipients of HATx. Older age (>60yo) should not be a contraindication to HKTx. [ABSTRACT FROM AUTHOR]

In heart transplantation, donor-to-recipient (D-R) size matching has been done by height and weight. Recently, predicted heart mass (PHM) has been found to be more clinically useful to predict outcome. Using PHM, under-sizing a donor heart for a larger recipient with high pulmonary artery pressures leads to increased mortality. It has recently been noted in the ISHLT registry that there may be increased risk in placing an oversized donor heart using weight into a smaller recipient. This clinical outcome has not been established using PHM. We sought to address this question in our large, single center experience using PHM. Between January 2010 and June 2020, we assessed 588 D-R heart matches. We used PHM to assess outcome differences when the donor hearts were oversized. We divided the D-R ratio by PHM into two categories: Normal (N: 90-110%, n=524), and markedly oversized (MO: greater than 140%, n=64). Outcomes included 1-year survival, freedom from 1-year rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), freedom from cardiac dysfunction (LVEF ≤40%), and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). MO (n=64) compared to N (n=524) using PHM showed no difference in 1-year survival, freedom from ACR, freedom from CAV, freedom from NF-MACE, and freedom from cardiac dysfunction. There was a significantly lower freedom from 1-year AMR in the MO group due to more female recipients (sensitized due to previous pregnancies) in this group (71% MO group vs 20% N group). Markedly oversized donor to recipient matching using PHM does not result in poor outcomes after heart transplantation. This has potential to expand the donor pool, particularly for smaller patients. [ABSTRACT FROM AUTHOR]

The development of donor specific antibody (DSA) has been reported to have poor outcome after heart transplantation (HTx). DSA particularly class II, may result in graft dysfunction, increased mortality, development of cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). These class II DSA appear to form later after heart transplant. It is not firmly established whether early class II DSA (within the first year after transplant) has adverse clinical effects. Between 2010-15, we assessed 35 HTx patients (pts) who developed de novo class II DSA in the 1 year after HTx. Each pt had subsequent follow up of 5 years for mortality, development of CAV, as defined by stenosis ≥30% by angiography), and development of NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke). In subgroup analysis, class II DSA was divided into those DSA that were complement-binding (C1q+) compared to those without complement-binding. All DSA pts were compared to pts without DSA (n=413). At 5 years after HTx, there appeared to be no difference between groups in 5-year survival, 5-year freedom from CAV and NF-MACE. Those DSA that were C1q+ had significantly lower 5-year survival and freedom from NF-MACE compared to DSA pts without C1q+ and to the control group. (see table) Early de novo class II DSA that are not complement-binding do not appear to result in increased mortality or development of CAV or NF-MACE. However, early class II DSA that are complement-binding, appear to impact outcome. [ABSTRACT FROM AUTHOR]

Anti-thymocyte globulin (ATG) has been used as an induction agent in heart transplant (HTx). Early studies suggest that ATG can decrease de novo donor specific antibody (DSA) production after HTx. It has not been established as to the efficacy of ATG in various levels of sensitized pts undergoing HTx. Between 2010-18, we assessed 370 sensitized pts who were divided into panel reactive antibody (PRA) groups including a control group without sensitization but who received ATG: Group A: 0% (control); Group B: 1-25%; Group C: 26-50%; and Group D: >50%. Pts received ATG immediately post-transplant x5 days. Blood was drawn for antibody detection at baseline, 1, 3, 6, and 12 months after HTx. Groups were assessed for freedom from 1-year survival, rejection (any treated rejection (ATR), acute cellular rejection (ACR), and antibody mediated rejection (AMR)), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and freedom from cardiac allograft vasculopathy (CAV). Pts in Groups C and D had decreased freedom from DSA compared to the Control. Furthermore, there was lower freedom from AMR in pts in Group D compared to Control. There were no differences in outcome between each Group and the Control in 1-year survival, freedom from CAV, freedom from NF-MACE, freedom from any treated rejection, and freedom from ACR (see Table). ATG induction may be beneficial in sensitized patients with PRA under 50% but did not appear to decrease the development of AMR and DSA in those pts with PRA >50% compared to control. Larger studies and longer follow-up will need to be performed to assess ATG's impact on antibodies and the development of chronic rejection (CAV). [ABSTRACT FROM AUTHOR]

The development of donor specific antibody (DSA) after heart transplantation has been associated with increased development of cardiac allograft vasculopathy (CAV). Steroid weaning has been popular among heart transplant programs, however, it is not known whether steroid free regimens present an increased risk of the development of DSA. Therefore, we sought to address this question. Between 2010 and 2013 we assessed 229 heart transplantation patients who survived the first year after heart transplantation. Patients were divided into those that were maintained on prednisone (n=120) and those that were weaned off (n=109) at 1-year post-transplant. Subsequent freedom from DSA in the ensuing 5 years was then assessed between these two groups. In addition, we assessed 5-year subsequent outcomes of survival, freedom from CAV, freedom from 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 rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR)). There were no significant difference between the two groups in subsequent 5-year freedom from DSA, survival, freedom from NF-MACE, and freedom from rejection. Weaning of corticosteroids from maintenance after heart transplantation does not appear to increase risk for the development of DSA or other clinical longer-term outcomes. The ability to wean corticosteroids in individual patients after transplant may represent an immune-privileged state. [ABSTRACT FROM AUTHOR]

It has been reported from the ISHLT registry that women have less optimal outcome after heart transplantation (HTx) compared to men. It is not known whether this difference is due to rejection, NF-MACE, or decreased survival. Between 2010 and 2020, we assessed 1071 HTx patients and divided them by male and female sex. 309 females and 762 males were included in the study. Post-transplant outcomes included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), 1-year freedom from rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), and 1-year freedom from de novo DSA production. Women were divided into two groups, sensitized (PRA >10%) or non-sensitized. When comparing women to men, women had similar survival, freedom from CAV, and freedom from NF-MACE, but significantly lower freedom from ATR, AMR, and de novo DSA production. Women who were sensitized had similar survival but lower freedom from rejection and DSA production compared to non-sensitized women. 26% of our female patients were sensitized. Major post-transplant outcomes are similar for women and men. However, sensitization may be the reason for more AMR in women but it does not affect short-term major outcomes. Longer follow-up and impact of these outcomes need to be assessed. [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]

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]

Primary graft dysfunction (PGD) is observed in approximately 7% of all heart transplant (HTx) patients (pts). According to the International Society for Heart and Lung Transplantation (ISHLT), a new PGD scale includes left ventricular (PGD-LV), or right ventricular (PGD-RV). PGD-LV when severe is noted to have increased mortality. PGD-RV has been described as hemodynamics with RAP >15 mmHg, PCWP <15 mmHg, CI < 2.0 L/min/m2, or need for RV temporary support. PGD-RV has not been well studied. Between Dec 2013 and Dec 2018, we assessed 13 HTx pts who developed PGD-RV within 24 hours after HTx and compared them to pts without PGD. Endpoints included 1-year survival, need for temporary kidney dialysis, need for RV unloading with sildenafil, first year rejection including any treated rejection (ATR), 1-year freedom from cardiac allograft vasculopathy (CAV), and 1-year freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke). Pts with PGD-RV compared to pts without PGD had similar 1-year survival, freedom from CAV, freedom from NF-MACE, and rejection. 90% of pts with PGD-RV required RV unloading therapy which may have affected outcome. There was a trend for a lower freedom from temporary kidney dialysis in the PGD-RV group. PGD-RV after HTx appears to have acceptable outcome with good recovery. RV unloading therapy may be helpful. However, there was an associated increased need for temporary kidney dialysis within the first year after HTx. Larger numbers are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Sensitized patients awaiting heart transplantation (HTx) are at increased risk for mortality as their waitlist time is lengthened due to incompatible donors and a subsequently narrowed donor pool. Therefore, these patients undergo desensitization therapies to lower circulating antibodies and to restore the donor pool for these patients. These patients subsequently undergo HTx; however it has not been well established as to their longer-term outcome following HTx. Between 2010 and 2014 we assessed 42 patients awaiting HTx who were sensitized (average cPRA 84%) and subsequently underwent desensitization therapy prior to HTx. These patients then underwent HTx and were followed for 5-year outcome. Endpoints post-HTx included 5-year survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, stroke), and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients were compared to a contemporaneous group of HTx patients that did not receive desensitization therapy prior to HTx conditional to 1-year survival (n=329) for the same endpoints. Sensitized patients that received desensitization therapy prior to HTx had significantly lower freedom from AMR. There is a trend for increased freedom from NF-MACE in this desensitized group. There were no differences between the two groups in terms of survival, freedom from CAV, and freedom from ACR. Sensitized patients awaiting HTx who undergo desensitization therapy appear to have decreased freedom from first-year AMR. However, these patients appear to have comparable outcome (ie survival and CAV) at 5-years post-HTx to HTx patients that do not undergo desensitization therapy. [ABSTRACT FROM AUTHOR]

Purpose Extracorporeal photopheresis (ECP) is an apheresis and photodynamic therapy that uses 8-methoxy-psolaren and ultraviolet light to modulate T-cell activity. Research has shown that ECP is an effective treatment for patients (pts) with recurrent acute cellular rejection (ACR) and antibody-mediated rejection (AMR) post-heart transplantation (HTx). We sought to assess the long-term outcome of pts placed on ECP at our single center. Methods Between 2010-2012, we assessed 235 HTx pts, 10 of which were initiated on ECP. ECP was administered for 2 days, weekly x 4 and once monthly x 5 for 6 months total therapy. Endpoints included subsequent 5-year survival, 5-year freedom from cardiac allograft vasculopathy (CAV) as defined by stenosis ≥ 30% by angiography, 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: defined as myocardial infarction, congestive heart failure, percutaneous cardiac intervention, placement of pacemaker/defibrillator, stroke), 5-year freedom from any-treated rejection (ATR), ACR, and AMR. A control group that was not treated with ECP (n=225) was included. Results The average time to ECP initiation was 1.6 years post-transplant. The ECP group had an average LVEF of 40% (range 23% to 63%) pre-treatment. 8/10 patients were sensitized with a PRA ≥ 10% (range 13% to 90%). The ECP group compared to the control group had a significantly lower subsequent 5-year survival (40.0% vs 79.0%, p=0.001). 6 out of 10 pts on ECP died within 5 years. There was no difference in subsequent 5-year freedom from CAV, NF-MACE, ATR, ACR, and AMR between the groups (see table). Conclusion Heart transplant pts treated with ECP due to high risk factors have reduced long-term survival. It is not clear how much ECP benefited these pts or whether earlier treatment may have been of more benefit. The selection of pts for ECP may be key to improved outcome. Further studies are needed. [ABSTRACT FROM AUTHOR]