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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]

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]

Hemodynamic compromise rejection (HCR) is seen <5% of heart transplantation (HTx) patients. HCR is defined as echocardiographic left ventricular ejection fraction ≤40% and pulmonary capillary wedge ≥15, cardiac index ≤2.0 and the requirement of inotropic support. Endomyocardial biopsy (EMB) done at the presentation of HCR does not always show biopsy proven rejection. With newer modalities of treatment in the current era, we sought to assess if there is now a different outcome in patients (pts) with HCR. Between 2010-15, among 589 heart transplants, we identified 15 HTx pts (2.5%) who developed HCR. At the time of presentation of HCR, results of EMB were reviewed. Outcomes of these pts included subsequent 1-year survival, freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), freedom from non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, defibrillator/pacemaker implant, stroke), and freedom from subsequent recurrence of rejection episodes, including any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). The HCR group was compared to a case-controlled group with similar age, sex, time from transplant (n=39). HCR did not consistently show rejection with 64% revealing neither ACR nor AMR on biopsy slides. 27% showed ACR, 9% showed AMR and the remainder showed no rejection. In the HCR group, subsequent 1-year survival and freedom from NF-MACE was significantly compromised compared to the control group. Subsequent 1-year freedom from CAV and recurrent rejections were not significantly different. (table) In a majority of HCR cases, EMB findings reveal no rejection which may be due to an atypical immune process. In the current era, outcomes from HCR continue to be compromised which suggest the need for a more aggressive approach to immunosuppression and management. [ABSTRACT FROM AUTHOR]

In many heart transplant (HTx) programs, patients greater than 65 years of age who have had a previous left ventricular assist device (LVAD) are not candidates for HTX. They are kept at destination therapy. It is believed that these patients will have complications if transplanted. It has not been well established as to the outcome of these older LVAD patients undergoing HTx. Between 2010 and 2021, we assessed 35 patients who underwent a previous LVAD placement and subsequently underwent HTx at ≥65 years of age (range 65 to 70). A control group was comprised of patients (≥65 years) who underwent HTx without LVAD support. Post-transplant outcomes included 30-day and 1-year survival as well as 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), cardiac allograft vasculopathy (CAV: stenosis ≥30%), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). LVAD patients who underwent HTx at the age ≥65 years appear to have comparable outcomes compared to patients who underwent HTx without LVAD support ≥65 years. 1-year survival, freedom from NF-MACE, CAV, ACR, AMR were not significantly different. Older patients (≥65years) supported on an LVAD do not have compromised post-HTx outomes. These patients do not necessarily need to be committed to destination therapy. [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]

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]

Diastolic dysfunction in the first year post-heart transplantation (HTx) is not uncommon. This can be due to hypertension, rejection, or calcineurin inhibitor therapy treatments. It has not been well established whether this first-year diastolic dysfunction affects outcome post-HTx. Between 2010 and 2016, we assessed HTx patients who developed diastolic dysfunction by echocardiography in the first year post-HTx. Patients with diastolic dysfunction were further divided into groups with mild, moderate, and severe diastolic dysfunction as determined by echo parameters. These patients were compared to patients who survived the first year who had no evidence of diastolic dysfunction. Subsequent 5-year survival, cardiac function (echocardiogram ejection fraction), cardiac allograft vasculopathy (CAV: stenosis ≥30% by angiography), and non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke) were assessed for the patient groups. Patients with diastolic dysfunction had significantly lower 5-year survival and freedom from NF-MACE compared to the control group. The development of CAV at 5 years post-HTx was not significantly different among the study groups. There was not a linear correlation of worsening diastolic dysfunction to poorer outcomes. (See table.) Any diastolic dysfunction appears to be a risk factor for poor outcomes post-HTx and should be addressed in terms of comorbid problems. [ABSTRACT FROM AUTHOR]

Patients with severe heart failure who have undergone placement of a mechanical circulatory support (MCS) device do develop renal dysfunction. This renal dysfunction is not severe enough to necessitate the use of combined heart transplantation (HTx) and kidney transplantation. However, it has not been firmly established whether kidney dysfunction does add to increased morbidity or mortality after HTx in these device patients. Between 2012 and 2019, we assessed 79 patients who have undergone MCS, either with total artificial heart (n=22) or left ventricular assist device (n=53). Baseline creatinine/glomerular filtration rate (GFR) was measured and patients were divided into GFR categories which include 30-39 mL/min, 40-49 mL/min, 50-59 mL/min, and greater than or equal to 60 mL/min. All patients underwent HTx alone. The need for temporary dialysis was recorded, as well as peak creatinine in the first 3 months after HTx and serum creatinine at 1 year compared to baseline. Further outcomes include subsequent 1-year survival, freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30%), and freedom from non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). There was no significant difference in 1-year survival, CAV, and NF-MACE or the need for temporary dialysis amongst all groups. Furthermore, no patient in any group needed chronic dialysis. In the GFR 40-49 group compared to the other groups, there was a trend for higher creatinine at 1 year but the baseline was high. Baseline lower GFRs between 30-39 and 40-49 mL/min in MCS patients do not appear to be a predictor of poorer outcomes after HTx in patients. These patients do not appear to require combined heart and kidney transplantation. [ABSTRACT FROM AUTHOR]

Heart-kidney transplant (HKTx) patients have acceptable outcomes post-transplant. Patients on mechanical circulatory support (MCS) devices who undergo heart transplantation have the potential of several complications such as longer cold ischemic time due the time relegated to explant these devices due to extensive scar tissue and bleeding. In addition, many of these patients receive a significant number of blood products for bleeding episodes which can cause right ventricular dysfunction of the donor heart. Time in the intensive care unit (ICU) is also potentially increased due to the various complications that may occur. This would also include takebacks to the operating room (OR) for extensive bleeding. We reviewed our database to illuminate differences in patients with and without MCS undergoing HKTx. Between 2017 and 2019, we assessed 43 patients undergoing HKTx and divided them into MCS (n=7) versus non-MCS patients (n=36). Endpoints included cold ischemic time, time in the ICU, number of blood products administered, takebacks to the OR for bleeding, 30-day survival, 1-year survival, 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 cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), and the development of severe primary graft dysfunction (PGD). Heart-kidney transplant patients with MCS versus those without MCS had significantly greater packed red blood cells needed and prolonged ICU length of stay. There were no differences between the 2 groups in 1-year survival, freedom from CAV, NF-MACE, and PGD. Heart-kidney transplant candidates on MCS do not appear to have worse 1-year outcomes. Excess bleeding and prolonged ICU stay are the only adverse complications noted. These patients on MCS should be considered for HKTx. [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]

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]

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]

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]

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]