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We have recently reported on a CAV score after HTx to predict the development of this complication. The discovery phase of this trajectory score was developed by the Paris Transplant Group with validations at Leuven University Hospital (Belgium) and Cedars-Sinai Heart Institute (USA). The CAV trajectory score was validated to predict outcomes (CAV and survival) after HTx. We now present our real-world experience using the CAV trajectory score for our patient population. For our clinical application of the CAV trajectory score, we used a 70% or greater prediction of either Trajectory 1 or Trajectory 2 to merit the avoidance of annual coronary angiograms. At this selected threshold, there would be a 0.07% chance of any patient developing CAV within 10 years. For these patients, we reduced angiograms to 5-year intervals. We prospectively assessed 19 HTx patients transplanted between 2011 and 2017 who were given CAV trajectory scores which resulted in a prediction of 70% or greater for CAV Trajectories 1 and 2. CAV trajectory scores were calculated in 2020 according to each patient's first-year angiogram results. These patients were followed with at least 1 angiogram avoided prior to their 5- or 10-year angiograms. Patients with new onset LV dysfunction, DSA, and ACR after the first year were deleted from this study as they could no longer be in Trajectory 1 or 2. Those patients with predicted CAV Trajectories 1 and 2 at the first-year post-transplant were entered in a cross-sectional pattern, but all had angiograms at 5- or 10-year post-transplant. 100% of patients at their 5- or 10-year angiogram showed no evidence of CAV, consistent with the predictive model. Furthermore, all patients had no cardiac dysfunction, no rejection, and no abnormal hemodynamics at the time of the angiogram. The mean predicted score for trajectory 1 and 2 was 76% ± 11% (range 71-91%). The CAV trajectory score with 70% or greater prediction of CAV Trajectory Score 1 and 2 appears to be valid in avoiding annual angiograms as no significant clinical presentation for concern occurred in these patients. [ABSTRACT FROM AUTHOR]

Rabbit anti-thymocyte globulin (ATG) therapy has been used for induction to allow delay of initiation of calcineurin inhibitor (CNI) immediately post-heart transplant (HTx) in patients with moderate to severe renal insufficiency. In our program, this approach has been routine for patients with serum creatinine >2.0 mg/dL. Although this mode of therapy has been shown to be effective for renal protection, its benefit has not been established for patients with less renal insufficiency, in the 1.5-2.0 mg/dL range. Therefore, we reviewed our patient population to assess whether ATG induction was renal-protective for these patients. Between 2010 and 2020, we assessed 84 patients with baseline creatinine in the 1.5-2.0 mg/dL range who underwent HTx, and divided them into those who underwent ATG with delay of initiation from CNI to those patients who did not. Patients given ATG (x 5 days) had delayed CNI beginning on days 3-5 post-operatively once urine output was established. Endpoints included comparison of glomerular filtration rate (GFR) at baseline, with change at 6- and 12-months for each group. In addition, 1-year freedom from temporary and chronic dialysis (occurring greater than 30 days postop) and freedom from rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody mediated rejection [AMR]) was assessed. There was no significant difference in the ATG induction compared to control in renal function (creatinine/GFR) at baseline and change in GFR at 6 months and 1 year post-HTx. In addition, there was no difference between groups in 1-year freedom from temporary or chronic dialysis, and freedom from ATR, ACR, or AMR. ATG induction with delay of CNI does not appear beneficial for kidney function in patients with mild renal insufficiency. Larger studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Hyperlipidemia has been associated with the development of atherosclerotic cardiovascular disease in non-transplant patients. More recently, first-year LDL cholesterol was found to be a significant risk factor for the development of cardiac allograft vasculopathy (CAV) in a paper by Loupy and colleagues. Previous randomized clinical trials have demonstrated that statins can lower LDL cholesterol as well as decrease the development of CAV. Thus, most heart transplant patients are on statin therapy. In the current era with newer immunosuppressive agents, we sought to confirm that first-year lipid levels have an impact on outcome. Between 2010 and 2017 we assessed 260 HTx patients who survived to 1-year, where we assessed first-year lipid levels (where available) to include high vs low levels of total cholesterol (>200 vs <100mg/dl), LDL-cholesterol (>135 vs <70mg/dl), HDL-cholesterol (>60 vs <40mg/dl) and triglycerides levels (>200 vs <150mg/dl). The percent of patients on statin therapy for each group was included. The outcomes included 5-year survival and 5-year freedom from cardiac allograft vasculopathy (CAV: new stenosis ≥30%). High first-year HDL cholesterol levels compared to low levels had significantly greater 5-year survival although there was no significant difference in 5-year freedom from CAV. There was a trend for low LDL-cholesterol levels compared to high levels to have greater freedom from 5-year CAV. There were no significant differences in outcome in high vs low total cholesterol or high vs low triglyceride levels. There were less patients on statins in the high LDL vs low LDL-cholesterol groups. (See Table) HTx patients with high HDL may have survival benefit but CAV remains same. Further studies into the reason for this finding are being pursued. Low LDL levels appear to have benefit in 5-year outcome. [ABSTRACT FROM AUTHOR]

A subset of patients with Takotsubo Cardiomyopathy (TCM) develops hemodynamic instability requiring temporary mechanical circulatory support (tMCS). We examined the National Inpatient Sample (NIS), a large national registry of hospitalized patients in the United States, to identify temporal trends in the utilization of tMCS in TCM patients along with clinical outcomes and cost. All adult hospitalizations of TCM from the National Inpatient Sample Database between 2007 to 2015 using ICD-9-CM codes were identified. We compared baseline characteristics, co-morbidities, mortality, length of stay and hospitalization costs among TCM patients with and without the need for tMCS. Propensity score matching to mitigate the differences was used. SAS 9.4 software was used for statistical analysis. Of 44,842 TCM hospitalizations, 1,120 (2.5%) received tMCS. Table 1 summarizes the baseline characteristics of this study population. Intra-aortic balloon pump (IABP) (1049/1120, 94%) was the most commonly utilized followed by extracorporeal oxygenation (66/1120, 5.8%) and paracorporeal ventricular assist device (20/1120, 0.2%) without any temporal trend in utilization pattern during the study period. After propensity matching, patients requiring tMCS for TCM as primary diagnosis were significantly younger (64.1±12.2 vs 66.3 ±12.9, P<0.0001) and more likely to be male. In-hospital mortality (9.3 % vs. 8.4 %; P = 0.73) was indifferent between the groups. However, the cost incurred during hospitalization and length of stay were higher in patients who underwent tMCS. The use of tMCS in patients with TCM and hemodynamic instability resulted in significantly higher cost, and length of hospital stay without positive impact on survival. This may be secondary to higher utilization of IABP contributing to worsening dynamic left ventricular outflow obstruction, systemic studies are needed. [ABSTRACT FROM AUTHOR]

Bortezomib, a proteasome inhibitor, offers effective desensitization in heart transplant candidates.. We reviewed our center's experience using bortezomib as desensitization therapy for highly sensitized patients to assess pre- and post-transplant outcomes. We assessed 43 HTx candidates 2010-2021 who were highly sensitized with cPRA greater than 50%, underwent bortezomib desensitization, and were subsequently transplanted. Enrolled patients received a course of up to four doses of bortezomib (1.3 mg/m2) over 2 weeks in conjunction with plasmapheresis. The efficacy of bortezomib was assessed by comparing the pre- vs post-desensitization therapy in cPRA, panel reactive antibodies to HLA Class I or Class II antigens, and reduction in immunodominant DSA via MFI. 1-year survival, 1-year freedom from antibody-mediated rejection (AMR), 1-year freedom from hyperacute rejection, 1-year freedom from hemodynamic compromise rejection, and 1-year freedom from the development of de novo DSA were also assessed. The average cPRA prior to bortezomib treatment was 94.5%. Bortezomib did not lower cPRA, Class I or Class II antibodies or lower the immunodominant antibody. However, these highly sensitized patients who underwent HTx had 95% 1-year survival, 76% freedom from 1-year AMR and 65% freedom from 1-year de novo DSA development. Side effects of bortezomib included thrombocytopenia and/or pancytopenia (43%), treated infection (28%) and self-limited neuropathy (12%). The use of bortezomib in highly sensitized patients does not appear to be clinically effective in lowering circulating antibodies prior to heart transplantation. However, its use may have contributed to acceptable post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Sensitized patients undergoing HTx have greater risk of antibody mediated rejection (AMR), cardiac allograft vasculopathy (CAV), and decreased survival. A prospective crossmatch is performed on highly sensitized patients pre-HTx. While a cytotoxicity-positive complement test may be prohibitive for HTx, patients with flow-positive but cytotoxicity-negative crossmatch undergo HTx at our program. We reviewed outcomes of these patients. 60 highly sensitized patients with flow-positive yet cytotoxicity-negative prospective crossmatches 2010-2021 were evaluated. Outcomes assessed: 5-year survival and 5-year freedom from CAV (stenosis ≥40% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous intervention, pacemaker, or stroke), and 1-year freedom from rejection [any treated rejection (ATR), acute cellular rejection (ACR), and AMR]. A subgroup was analyzed for the impact to outcome of T-cell and B-cell flow positivity (median channel shifts, MCS >200 and <200) and for Class I vs Class II donor-specific antibodies (DSA). A control group consisted of non-sensitized patients (n=540). 5-year survival, freedom from CAV and NF-MACE were comparable between flow-positive cytotoxicity-negative patients and controls. These patients, however, had lower freedom from ATR/AMR (Table). There was also lower freedom from ATR/AMR in those with higher flow MCS though no difference based on Class I vs II DSA. Patients with flow-positive cytotoxicity-negative prospective crossmatches have comparable 5-year outcomes to nonsensitized patients. Despite increased ATR, there is no impact on survival or CAV development. These findings support proceeding with transplantation in this high-risk group. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is seen in approximately 50% of heart transplant (HTx) recipients within 8 to 10 years. CAV may be focal and amenable to percutaneous cardiac intervention (PCI) with stent placement though the re-stenosis rate is not well established. We reviewed our experience with CAV post PCI. We assessed 40 HTx recipients transplanted 2010-2017 who underwent PCI. The impact of statin and mTOR inhibitors on in-stent re-stenosis (≥50% stenosis) after 1 and 5 years was assessed. Other outcomes post PCI included survival and development of non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, coronary intervention, defibrillator/pacemaker, stroke). In the 40 patients who underwent PCI, in-stent re-stenosis at 1- and 5-years post-PCI was 0% and 7.5% (n=3). There was no difference in restenosis based on statin use, mTOR use, or both. There was also no difference in 1- and 5-year survival or 5-year freedom from NF-MACE between groups. (Table) The occurrence of in-stent re-stenosis is very low in heart transplant patients in the current era. Whether they are on statins, statins and mTOR inhibitors, or neither does not appear to affect in-stent re-stenosis, survival and freedom from NF-MACE in this small sample. A larger set of data and further follow up will be important to confirm these findings. [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]

Hemodynamic compromise rejection (HCR) after heart transplantation (HTx) historically is seen in approx. 5% of our HTx patients (pts). HCR is a form of severe rejection, defined as pulmonary capillary wedge ≥15, cardiac index ≤2.0, and requirement of inotropic support. In the current era of tacrolimus, mycophenolate mofetil, and corticosteroids, incidence of HCR has not been firmly established. Further, it is not known whether treatment for these pts affects outcomes and whether there are significant sequelae in terms of cardiac dysfunction, reduced survival, or development of cardiac allograft vasculopathy (CAV). We sought to answer these questions in a review of our large single center. Between 2010 and 2017, we assessed 20 HTx pts who developed HCR. Pts who developed primary graft dysfunction immediately post-HTx were excluded. Treatment at the time of HCR was characterized as well as the long-term sequelae of HCR. Long-term sequelae included 5-year survival, freedom from cardiac dysfunction (defined as LVEF ≤40% by echo), and development of CAV. Type of rejection was also characterized. These pts were compared to a contemporaneous case-control of pts (3:1) matched for age, gender, time from HTx and era who did not develop HCR. The incidence of HCR over this study period was 3.0%. Pts developed HCR at an average of 576 ± 385 days post-Htx and majority were treated with combinations of high dose steroids, ATG, plasmapheresis, and IVIg. HCR pts compared to controls had significantly lower survival at 5 years after HTx and a significantly lower 5-year freedom from cardiac dysfunction and freedom from CAV. At biopsy, 40% had acute cellular rejection, 5% had antibody-mediated rejection, 5% had mixed rejection and 50% had no rejection (biopsy-negative rejection). See table. In the current era, pts with HCR after HTx continue to have significant morbidity and mortality following an HCR event. These pts require intensive follow-up and a search for a more effective treatment. [ABSTRACT FROM AUTHOR]

Patients with severe heart disease may develop end-stage biventricular heart failure. These patients may require the placement of a total artificial heart (TAH). In many programs, chronic kidney disease (CKD) has been a relative contraindication for those patients with severe biventricular heart disease needing a total artificial heart. For these patients, kidney dialysis (if needed) is not available for outpatients. Furthermore, it is not known if CKD in TAH patients compromises post-transplant outcomes. Between 2011 and 2019, we assessed 20 TAH patients who developed CKD defined as GFR less than 60 mL/min 90 days apart prior to transplant listing. At transplant listing, these patients have GFR less than 30 mL/min. These patients would be listed for combined heart-kidney transplantation (HKTx) being on the TAH. Study endpoints included: 3- and 6-month waitlist mortality and 30-day and 1-year post-transplant survival were recorded. A control group was comprised of patients with TAH placement listed for transplant with heart alone. 3- and 6-month waitlist mortality were similar for TAH patients with CKD compared to TAH patients without CKD. Post-transplant, the two groups had similar survival at 30 days and 1 year. Patients needing chronic dialysis in the first-year post-transplant was similarly observed in 13.3% of TAH patients with CKD and 8.1% of TAH patients without CKD. (See table) Chronic kidney disease is not a contraindication for TAH or subsequent heart 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 new donor heart allocation policy change occurred in October 2018. At that time, the waiting list statuses changed from 3 statuses to 6 statuses. In the old donor heart policy, Redo heart transplants (HTx) were listed as stable patients waiting at home, which were usually status 2 (old policy). After 2018, redo heart transplants are now status 4 which is a higher listing status compared to the old policy. Redo HTx patients may have higher mortality due to the fact that many have sudden death due to pulseless electrical activity arrest. It has not been established whether waitlist mortality for redo HTx as status 4 patients on the waitlist is greater than other status 4 patients. We wish to establish this waitlist mortality rate in terms of perhaps higher priority listing for these patients. : Between October 18, 2018, and December 31, 2021, we assessed 33 redo HTx patients who were accepted onto the HTx waiting list in our program. These redo HTx patients were compared to 89 non-redo HTx patients listed as Status 4 at our institution. All patients were assessed for 1-year survival on the waitlist and the percentage of patients upgraded to a higher status due to worsening heart failure. : Redo heart transplant patients listed at Status 4 compared to non-redo heart transplant patients had no significant difference for time on the waitlist, time to transplant, percent transplanted and 1-year waitlist survival. The percent of patients switched to a higher status was similar between groups (72.7% vs 68.5%). For this subgroup of patient, there was no difference for the same waitlist outcomes as above. (see table) : Waitlist status 4 for redo heart transplant patients on the heart transplant waitlist appears appropriate. More urgent listing is not indicated for these patients. [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]

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]

Smoking in the potential donor may be a risk factor for the development of cardiac allograft vasculopathy (CAV) following heart transplantation. It has been demonstrated by Loupy and colleagues using the cardiac iBox that donor smoking was an independent factor leading to a high trajectory for developing CAV by coronary angiography. It has not been well established how much donor smoking attributes to this problem. Therefore, we reviewed our experience with donors and their smoking history to assess this post-transplant complication. Between 2010 and 2017, we assessed 678 donors whose heart underwent heart transplantation. Donors were separated into those with smoking history >20 pack-years and continued cigarette use in the past 6 months (data provided from UNOS). Each group was assessed for 1-, 2-, 3-year survival and freedom from the development of coronary angiography-proven evidence of CAV (defined as coronary lesion ≥30% stenosis). This study group was compared to a control group with no donor smoking history. Donors with a current 20 pack-year smoking history compared to those donors without smoking had a trend for an increased risk for the development of CAV on coronary angiography over 3 years. 1-, 2-, 3-year survival was similar in both groups. Active donor smoking history appears to be a potential risk factor for the development of CAV. Longer follow-up is needed to further define this risk. [ABSTRACT FROM AUTHOR]

An acute abdomen (AA) may occur following heart transplantation (HTx). Patients (pts) with atherosclerotic vascular disease may also have risk for ischemic bowel associated with their surgeries. In addition, pts with gallstones are at increased risk for cholecystitis immediately following cardiac surgery. The frequency and outcomes of these abdominal complications that warrant urgent abdominal surgery after HTx has not been well established. Furthermore, the presence of increased inflammation in abdominal surgery may trigger an immune response and thereby cause rejection. We sought to evaluate these complications in our large, single center experience. Between 2010 and 2021, we assessed 1154 pts who underwent HTx and reviewed frequency of AA requiring surgical intervention (n=11) in the first month following HTx surgery. These pts were assessed for 30-day and 1-year survival, allograft rejection, and infectious complications requiring intravenous antibiotics and/or readmission in the ensuing 3 months. The AA pts were compared to a case-controlled group (n=22) matched for age, sex, and time of transplant. 11 of 1154 pts (1.0%) of our HTx pt population developed an AA and required surgical intervention within the 30 days following HTx. Surgical interventions included hemicolectomy, cholecystectomy, and exploratory laparoscopy. Compared to the control group, the AA group had significantly worse 30-day and 1-year survival. In the study group, further infectious complications occurred, with 36.4% requiring rehospitalization for intravenous antibiotics. Rejection episodes following these events were not different from the control population. Acute abdomen immediately post-HTx resulting in urgent abdominal surgery requiring hemicolectomy and/or cholecystectomy is rare but has significant morbidity/mortality. For pts awaiting HTx with gallstones, prophylactic laparoscopic cholecystectomy might be considered. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infections have been associated with the subsequent development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). This is most prominent with patients receiving a donor with positive CMV serology when the patient is CMV serology negative. This mismatched patient cohort was subsequently reviewed for the development of CMV serology positivity, CMV syndrome, and CMV disease (specific organ involvement). Between 2010 and 2016, we assessed 138 HTx patients who had CMV mismatch (donor positive/recipient negative). Patients were treated with CMV prophylaxis with Valcyte for 1 year. CMV patients were then divided (data at 1-year) into those that developed serology positive CMV on IgG, CMV syndrome (who presented with fever, chills, and sweats), CMV disease (organ specific disease, such as retinitis, peritonitis, gastroenteritis). All groups were then assessed for 5-year survival and the development of CAV by angiography. In CMV mismatched patients, there was no significant difference in 5-year survival or freedom from angiographic CAV in those patients with clinical CMV (asymptomatic IgG positive, CMV syndrome, CMV disease groups) compared to the asymptomatic IgG negative group. In the current era, CMV mismatch patients (donor positive/recipient negative CMV serology) do not appear to be at increased risk for poor outcome. Valcyte prophylaxis for 1 year may be beneficial. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygen (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with a transfusion-independent increase in calculated panel reactive antibodies (CPRA), it is unknown whether ECMO is a sensitizing exposure. In this single center retrospective cohort study of lung transplant candidates between 5/1/2015-6/30/2021, antibodies against human leukocyte antigens (HLA-Ab) were evaluated at the time of ECMO initiation and weekly thereafter. Multivariate logistic regression was used to evaluate associations between CPRA increase and ECMO exposure adjusting for a history of any packed red blood cell (PRBC) transfusion and female gender. Sixty-two candidates were placed on ECMO as a bridge to transplant. Of these, 39 (62.9%) either had available HLA-Ab screens from pre- and post-ECMO initiation or multiple HLA-Ab screens post-ECMO. Of the 250 non-ECMO exposed recipients, 224 (89.6%) had multiple pre-transplant screens and served as the comparison cohort. Nine (23.1%) ECMO bridged recipients had an increase in CPRA, compared to 16 (7.1%) of non-ECMO exposed recipients (Fisher's exact p=0.005). Among those with increased CPRA, the median increase was 6% in ECMO bridge patients and 9% in non-ECMO exposed patients. After adjusting for covariates, however, ECMO bridge was not an independent risk factor for increased CPRA (OR=1.85, 95% CI 0.58-5.95, p=0.30). A history of PRBC transfusion trended toward an association with increased CPRA (OR=2.93, 95% CI 0.98-8.78, p=0.06). Pre-lung transplant ECMO was not independently associated with an increase in CPRA when adjusting for PRBC transfusion, although the study was underpowered for small or moderate effect sizes. Where clinically appropriate, PRBC transfusions should be limited in these patients. [ABSTRACT FROM AUTHOR]

Simultaneous heart-kidney transplantation (HKTx) has been increasing over the past 10 years with approximately 5.5% of heart transplants (HTx) being HKTx. Due to the heart being transplanted first and then the kidneys, there is question regarding the incidence and degree of delayed graft function (DGF) in the kidney. In HKTx, it is not uncommon to have fluid shifts and labile hemodynamics perioperatively post-HTx that may require the support of inotropes and vasopressors. It is not known whether these agents can affect the donor kidney which is transplanted immediately after HTx. This may result in varying degrees of DGF and the need for dialysis. Therefore, we reviewed our experience of DGF and compared this to a cohort of patients who underwent kidney transplant (KTx) alone from the UNOS database. Between 2010 and 2020, we assessed 134 HKTx patients. These patients were assessed for DGF (need for dialysis within the first 7 days post-operatively). This study group was compared to a control group of patients who received KTx alone (n=192,134 from the UNOS database) during the same period. In addition, post-transplant outcomes included 1-year survival and patients who resumed chronic dialysis for failed donor kidney. Patients who underwent simultaneous HKTx compared to patients who underwent KTx alone had a significant increase in the development of DGF. However, post-transplant 1-year survival and the percent of patients that resumed chronic dialysis was similar between groups. (see table) Simultaneous HKTx has increased risk for DGF which is most likely related to intraoperative labile hemodynamics commonly requiring the use of inotropes/pressors. However, despite higher incidence for DGF, HKTx has comparable outcomes. [ABSTRACT FROM AUTHOR]

One of the most concerning issues immediately post-heart transplant (HTx) is the development of primary graft dysfunction (PGD) and/or vasoplegia. It has been suggested that patients on angiotensin-converting enzyme inhibitors (ACEi) are at risk for the development of PGD and vasoplegia due to activation of the kallikrein pathways which can activate bradykinin (vasodilator). It is not known whether ACEi with low systolic blood pressure (SBP) prior to HTx is associated with the development of PGD and vasoplegia. We sought to answer this question in our large, single center patient population. Between 2017 and 2020, we assessed 189 patients awaiting HTx treated with ACEi (n=19) who had SBP less than 100 mmHg at the time of HTx and those patients without ACEi (n=170) but also with SBP less than 100 mmHg. Endpoints included the development of PGD (ISHLT grading scale) and vasoplegia (defined as requiring more than 2 vasoconstricting drugs with SBP still < 90 mmHg). A control group (n=176) of patients with SBP > 100mmHg was included for comparison. Patients treated with ACEi and with low SBP at the time of HTx appear to have significantly increased risk of PGD and vasoplegia development post-HTx. However, their 30-day and 1-year survival was no different compared to those patients not on ACEi (with low SBP) and those with normal blood pressure. (See table.) ACEi and lower SBP at the time of heart transplantation may be a significant risk factor for the development of PGD and vasoplegia. Stopping ACEi prior to heart transplant may be warranted but requires further study. [ABSTRACT FROM AUTHOR]

For patients awaiting heart transplantation (HTx), who have high levels of circulating antibodies (greater than 70% PRA) desensitization therapy may be indicated. This will allow expansion of the donor pool for a compatible donor. As women appear to be more highly sensitized (due to multiple pregnancies), it is not clear as to whether women compared to men can benefit from desensitization therapy. We sought to answer this question with review of our large, single center database. Between 2008 and 2020, we assessed 49 patients awaiting HTx who underwent desensitization therapy. These patients were divided into groups by sex to evaluate their response to desensitization therapy. Our desensitization protocols consist of regimens including intravenous immune globulin, anti-CD20 monoclonal antibody, plasmapheresis, proteosome inhibitors. A response to desensitization therapy was assessed by the decline of the dominant circulating antibody determined by mean fluorescence intensity (MFI). Post-HTx data was assessed for 1-year survival and freedom from rejections (acute cellular rejection [ACR], antibody-mediated rejection [AMR]). Rejection episodes were compared to a control group of non-sensitized patients transplanted during the same period (n=771). Desensitization therapy in women appeared to be comparable to men considering similar desensitization protocols. There were no significant differences in waitlist mortality, time on the waitlist, or 1-year post-transplant survival, 1-year freedom ACR or AMR, between the two groups. Compared to non-sensitized patients, freedom from AMR was significantly lower in both sensitized men and women (72.7% men and 78.9% women vs. 96.5% control group). Sensitized women awaiting HTx compared to men appear to have similar response to various desensitization regimens. Post-HTx, there was more AMR in both groups, suggesting sensitization may be responsible. [ABSTRACT FROM AUTHOR]

Leukocytosis following heart transplantation (HTx) is common and most likely is due to high dose corticosteroid therapy immediately post-HTx. However, infection must be excluded with pan cultures. The use of anti-T lymphocyte globulin (ATG) induction may also cause leukocytosis due to an inflammatory reaction. We sought to determine whether culture negative leukocytosis in the first week after HTx has deleterious consequences. Between 2010 and 2020, we assessed 114 patients who developed leukocytosis within the first week following HTx. Patients were divided into groups by the severity of leukocytosis (WBC 11-14.9 x 109/L, 15-19.9 x 109/L, ≥20 x 109/L). Patients were asymptomatic, had negative cultures, and were not treated with antibiotics. The study population was compared to patients without leukocytosis following HTx. Development of infections in the ensuing 1-6 weeks postoperatively were assessed. Furthermore, 1-year outcomes including survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR]) were evaluated. Higher levels of asymptomatic leukocytosis (>15 x 109/L) immediately after HTx appears to signal possible subsequent infection. However, it does not lead to unacceptable 1-year outcomes including survival, or freedom from CAV, NF-MACE, or rejection. Induction therapy with ATG does not contribute to the leukocytosis. (See table.) Continued monitoring should be pursued for asymptomatic culture negative leukocytosis immediately after heart transplantation. [ABSTRACT FROM AUTHOR]

The COVID pandemic has affected the management of heart transplant (HTx) patients. Patients were seen virtually via telemedicine and patients self-isolated at home. We assessed the impact of telemedicine and isolation during the COVID pandemic on HTx outcomes at our center. We assessed 55 HTx patients who were transplanted March - September 2020 and followed for 6 months. Patients were self-isolating and only had every other clinic visit in-person after the first month. Outcomes included 6-month survival, re-hospitalization, non-COVID infections (defined as requiring intravenous antibiotics), any treated rejection (ATR), and maintenance of therapeutic immunosuppressive blood levels. The study patients were then compared to a control group of HTx patients evaluated during March of the previous three years. The study group (during the COVID pandemic) demonstrated a significant decrease in re-hospitalization in the first 6 months following HTx compared to the control group. There was a numerical decrease in non-COVID infectious complications. There was no difference in survival or freedom from treated rejection episodes between the two groups. Reasons for rehospitalization included infections, cardiac and renal issues, malaise, and fever. Of note, 2 patients in the study group developed COVID subsequently after HTx but were not hospitalized. The COVID pandemic demonstrated that self-isolation and virtual visits resulted in less hospitalizations, possibly due to fewer infectious complications. This implies that perhaps stricter restrictions for community exposure might benefit HTx patients in the 6 months following transplantation. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury after heart transplant is not uncommon. This may lead to rejection and endothelial cell dysfunction with subsequent development of cardiac allograft vasculopathy (CAV). It has been reported that the use of anti-thymocyte globulin (ATG) as induction therapy post-transplant may lessen the ischemia reperfusion injury that occurs to donor hearts. This has not been confirmed. Between 2010 and 2020, we assessed 1082 heart transplant patients and divided them into those who received induction with ATG versus those who did not. In our program, ATG is given to patients who are sensitized or have baseline serum creatinine >2.0 mg/dL to delay initiation of tacrolimus. Weekly endomyocardial biopsy samples were reviewed for the first month after heart transplantation for ischemia reperfusion injury. First year outcomes included survival and freedom from CAV (stenosis ≥30%). Patients who underwent induction therapy with ATG had significantly greater freedom from any ischemia reperfusion injury noted on weekly endomyocardial biopsies in the first month post-transplant. There was no difference between the two groups in first-year survival and freedom from CAV. ATG as induction therapy appears to provide protection against ischemia reperfusion injury in donor hearts. Longer follow-up is needed to show potential outcomes benefit. This finding should be confirmed in a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Sensitization in patients (pts) awaiting heart transplantation (HTx) can be refractory to conventional therapies such as plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and bortezomib, particularly for Class II antibodies. Pts refractory to these initial therapies may require more advanced therapies. Tocilizumab is an anti-interleukin-6 monoclonal antibody found to significantly reduce dominant HLA antibodies prior to kidney transplantation. We report here our experience with tocilizumab in refractory sensitized pts awaiting HTx. Between 2008 and 2020, we assessed 7 HTx pts who were initially treated with conventional desensitization therapies, including plasmapheresis, IVIG, rituximab, and bortezomib. Pts were then treated with tocilizumab at 8 mg/kg monthly for 6 months. Endpoints included change in calculated panel reactive antibodies (CPRA) determined just prior to the administration of tocilizumab, and 2 weeks after completion of the 6-month therapy. Antibodies were further classified into Class I and Class II to assess efficacy in each of these subgroups. 1 year post-HTx antibody mediated rejection (AMR) and survival was assessed and compared with pts transplanted without desensitization therapy in the same period (N=302). 6 of 7 sensitized pts treated with tocilizumab had a decrease in their immunodominant antibody with an average 31% reduction. For the CPRA level, 4 of 7 patients had a predominant decrease in Class II circulating antibodies. Post-HTx, compared to pts who did not receive desensitization therapies, 1st year AMR episodes were increased in the tocilizumab group (2.0% vs 14.3% respectively; p=0.032) but this did not affect survival at 1 year (92.1% vs 100% respectively; p=0.447). Highly sensitized pts on the heart transplant waitlist who are refractory to conventional desensitization therapy appear to be responsive to tocilizumab therapy. Although these pts have more AMR post-transplant, survival is comparable. [ABSTRACT FROM AUTHOR]

There are many reports in solid organ transplantation that demonstrate that there are sex discrepancies in waitlist urgent status, time on the transplant waitlist, and waitlist mortality. There should be no differences in men versus women in the percent of patients with severe heart disease. The new donor heart allocation policy change took place in October 2018, and provided the sickest patients with the highest priority for donor hearts. We chose to assess our male and female patients to establish whether there exists a difference in patients listed as urgent status on the heart transplant (HTx) waitlist. Between November 2018 and December 2020 (after donor heart allocation change in October 2018), we assessed 276 patients on our HTx waitlist. Patients on the HTx waitlist were followed for 6 months and censored after they were transplanted or removed from the waitlist. Percent of patients of each sex listed as urgent status (status 1, 2, 3) was recorded. Mortality on the waitlist, waitlist time, and removal from the waitlist due to being too sick were secondary endpoints. After the donor heart allocation policy change in October 2018, women were significantly less likely to be listed as urgent status compared to men. For those patients listed as urgent status, there was no significant difference in mortality for women versus men on the HTx waitlist. Average waitlist time was similar between the 2 groups. (see table) There appears to be a sex disparity for women being less likely to be listed as urgent status on the HTx waitlist. Further studies are needed to determine whether this difference has a biologic mechanism or whether there is selection bias and/or treatment bias present in their care. [ABSTRACT FROM AUTHOR]

The donor heart allocation policy was changed in October 2018, allowing priority for waitlist candidates with intra-aortic balloon pump (IABP) support over those with inotropic support. The use of IABP has increased several-fold since the donor heart policy was put into effect in October 2018. We assessed the UNOS registry to determine if this increase was due to a shift in practice or due to increased patient instability. We reviewed 128 patients in UNOS on IABP awaiting HTx April 1, 2017 - April 1, 2018, and compared them to the 446 patients in UNOS on IABP awaiting HTx November 1, 2018 - November 1, 2019. The patients were further divided into groups based on concomitant use of inotropic support and compared pre- and post-allocation change. 30-day and 1-year survival post-HTx were assessed. In the post-policy era period of 2018, the placement of IABP without inotropes increased by 3.4-fold compared to 1 year prior to the policy change. For all patients with IABP placement, time from listing to transplant was significantly shorter after the policy change. There was no difference in 30-day and 1-year survival (Table 1). There appears to be a shift in practice where IABP support is used without inotropic support after the donor heart allocation policy change. This suggests that physicians are using IABP in place of intravenous inotropes to advocate for their patients for a higher urgency status and donor availability. This should be taken into account in the revision of future donor heart allocation policies. [ABSTRACT FROM AUTHOR]

Candidates for heart transplantation may be placed on durable left ventricular assist devices as bridge to transplantation. These patients are known to develop circulating antibodies mainly due to blood transfusion. It has been reported that up to 30-40% of these patients develop circulating antibodies which may limit the donor pool. It has not been established whether temporary mechanical circulatory support (tMCS) devices result in similar sensitization. Between 2016 and 2021, we assessed 16 patients waiting for heart transplantation who required temporary left ventricular support. tMCS included Impella (n=11) and IABP (n=5). Only patients who had no circulating antibodies at the time of tMCS were entered into this study. Blood samples were drawn beginning at 2 weeks following placement of the temporary device. Freedom from development of circulating antibodies was determined at 2-4 weeks following placement of tMCS. Only 1 of these 16 patients (6%) developed circulating antibodies just prior to heart transplantation while on tMCS. The mean time on tMCS devices prior to transplant was 22 days, and 10 of these 16 patients (63%) received packed red blood cells either during or after tMCS placement but prior to transplant. Patients placed on tMCS have a low likelihood of developing circulating antibodies despite receiving blood transfusions. tMCS does not appear to activate sensitization pathways. [ABSTRACT FROM AUTHOR]

Extended criteria of donors for heart transplant (HTx) include many factors, such as left ventricular hypertrophy (LVH), decreased LVEF, older donor age, inotrope dependence, as well as gender and size mismatch. It has also been reported that various combinations of extended criteria risk factors appear to have worse outcomes depending on severity of the extended criteria characteristic. We sought to assess if severity of LVH with acceptable donor age and ischemic time is associated with increased mortality. Between 2010 and 2020, we assessed 156 donor hearts with varying degrees of LVH defined as left ventricular septal thickness greater than 1.2 cm. Donor hearts were then divided into those that had IVS between 1.2 to <1.3 cm, 1.3 to <1.5 cm, ≥1.5 cm. In addition, an assessment was made for the same LVH groups versus donor age categorized as donor age ≥50 years old and donor ischemic time >240minutes. Severity of LVH with donor age <50 years and ischemic time <240 min appear to have acceptable 1-year survival. However, older donor age/long ischemic time with LVH are higher risk for 1-year mortality. (see table) Severe LVH (IVS >1.5 cm) in donor hearts appears to be acceptable with donor age <50 years and ischemic time <240 minutes. [ABSTRACT FROM AUTHOR]

In the past, light chain (AL) amyloid has been associated with poor outcomes after heart transplantation (HTx), mainly due to its complicated course. Many AL amyloid patients will require stem cell transplant following HTx. It is not known whether these patients have acceptable outcomes after HTx. Between 2008 and 2020, we assessed all AL amyloid patients undergoing HTx. Patients were divided into those that required stem cell therapy and those that did not. Both groups were compared to age-matched control that did not have amyloid. Endpoints included 1-year survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejection (any treated rejection [ATR], acute cellular rejection [ACR], antibody-mediated rejection [AMR], biopsy-negative rejection [BNR]). There was no difference between AL amyloid patients with and without stem cell therapy in 1-year survival, or freedom from CAV, NF-MACE, or ATR. Compared to matched controls, post-transplant outcomes were similar. (See table.) In the current era, therapies for AL amyloid post-heart transplant appear successful with acceptable outcome compared to non-amyloid patients. AL amyloid is not a contraindication for heart transplantation. [ABSTRACT FROM AUTHOR]

West Nile Virus after heart transplant (HTx) is rare. However, it has occurred in our large, single-center heart transplant program. West Nile Virus is reportedly spread by mosquitoes and has been seen in various areas within the United States. We now report on our experience. Between 2013 and 2017, we assessed 5 HTx patients found to have acquired West Nile Virus after HTx. The outcomes of these patients are now assessed. Endpoints included 1-year subsequent survival, neurologic status, rejections, cardiac function, cardiac allograft vasculopathy (CAV, stenosis ≥30%), and non-fatal major adverse cardiac events (NF-MACE). Mortality in this population is 100%. Patients were severely neurologically compromised and completely dependent on 24/7 care. One patient was alert and ambulatory but aspirated on soup, thought to possibly be due to suppressed gag/cough reflex. The patient subsequently died. The other four patients were severely neurologically comprised—all with flaccid paralysis/quadriplegia, although able to communicate by moving eyes, facial gestures, and/or head and lip movement. All patients were able to communicate but were dependent on external feeding. West Nile Virus is devastating post-HTx with high mortality and significant morbidity which has left these patients in almost a comatose state. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic infected large portions of the US community and infected many heart transplant (HTx) patients but in distinct geographical patterns. HTx programs have reported mortality in the range of 23-29% (East Coast of the US) and in non-transplant patients in the range of 15-17%. The impact of hospitalized HTx patients with COVID-19 infection in a large West Coast heart transplant program has not been reported. We now report our outcomes for hospitalized patients with COVID-19. Between March 2020 and March 2021, we assessed 22 HTx patients who were admitted to the Cedars-Sinai Medical Center (CSMC) for COVID-19 infections. COVID-19 is known to affect many systems within the body, and we report the effects on lungs, heart, and kidney. Morbidity and mortality, including risk of death, were included within 90 days post-infection. Of the 22 HTx patients hospitalized at the CSMC, 7 patients died (31.8%). All patients had COVID-19 pneumonia requiring supplemental oxygen and 5 patients required ventilatory support. The mean peak FiO2 of the patients was 79.7%. 16 of these patients also were noted to have an increase in serum creatinine, with 6 patients requiring kidney dialysis. Cardiac function was maintained in all patients with COVID-19 and no myocarditis or cardiac dysfunction was observed. 9 patients received remdesivir and 19 patients received corticosteroids. 4 patients received tocilizumab anti-inflammatory therapy. COVID-19 resulted in significant morbidity and mortality in hospitalized heart transplant patients. Outcomes on the West Coast of the US were similar to the East Coast. The immunosuppressed state appears to be a risk factor for poor outcome and is higher compared to non-transplant hospitalized patients. [ABSTRACT FROM AUTHOR]

Seizures may occur following heart transplantation (HTx), especially since tacrolimus can lower a seizure threshold. HTx recipients are also at high stroke risk given many patients have existing cerebrovascular disease. The purpose of the study was to assess the prevalence and risk factors for seizures in HTx recipients at our center. We assessed 560 patients who underwent HTx between 2015-2020 for the development of seizures within the first month post HTx. We assessed impact of putative risk factors on early post transplant seizures, including prior stroke, atherosclerotic vascular disease, prior seizures, diabetes, prior smoking, and male sex. 40 of 560 HTx patients (7.3%) developed seizures in the first post-transplant month. The seizure group was compared to the control group (n=520) for risk factors for seizures (see table). Univariate analysis found that hypertension, history of atherosclerosis, and history of previous seizures were significant risk factors to develop seizures in the first postoperative month. Multivariate analysis found that only hypertension and history of previous seizures were significantly associated with early seizures post-HTx. All patients with seizures were placed on anti-seizure medications and had tacrolimus switched to cyclosporine. Seizures in the first post-transplant month occur in a significant minority of patients. Patients undergoing heart transplant with both history of hypertension and seizures are at risk to develop seizures in the early postoperative period. These patients might be considered for prophylactic anti-seizure therapy in the first 30 days following HTx surgery. [ABSTRACT FROM AUTHOR]

The calcineurin inhibitors (CNIs), including tacrolimus and cyclosporine, have revolutionized heart transplantation (HTx) in terms of maintaining low rejection rates. However, CNIs have significant side effects, such as nephropathy, hypertension, malignancy, and hypomagnesemia. It is this hypomagnesemia that has not been addressed as to whether this has an impact on outcome after HTx. Hypomagnesemia has been involved in muscle cramping and cardiac arrhythmias. Therefore, we reviewed our HTx patients and their magensium (Mg) levels to assess outcome in the first 6 months after HTx. Between 2010 and 2020, we assessed 956 HTx patients and recorded their Mg levels in the first 6 months after HTx. Patients with low Mg levels less than or equal to 1.8 mg/dL were assessed for complications including muscle cramping, cardiac arrhythmias, rehospitalization, and rejection episodes. Patients with low Mg levels were grouped into mildly low Mg levels (1.7-1.8 mg/dL) and moderately low Mg levels (1.4-1.7 mg/dL). Patients were compared to control patients who had normal Mg levels (>1.8 mg/dL) during this period of time. Patients with mildly or moderately low Mg levels compared to patients with normal Mg levels had no difference in muscle cramping, rejection episodes, cardiac arrhythmias, or use of antihypertensive medications. Kidney function was clinically similar in all groups. There were more arrhythmias in the normal Mg group. Patients had an average of 32 blood draws to assess Mg levels. Mildly to moderately low hypomagnesemia did not have significant adverse effects in heart transplant patients. Aggressive Mg replacement may not be essential. [ABSTRACT FROM AUTHOR]

Pre-transplant antiphospholipid antibodies (aPLab), including anticardiolipin (aCL) and anti-B2 glycoprotein-I (aB2GPI), may be associated with thrombotic complications and graft loss in kidney and liver transplant recipients. The objective of this study was to evaluate the prevalence and impact of aPLab on post-operative thrombotic and bleeding complications in lung transplant recipients. This was a single center retrospective cohort study of patients who were evaluated and transplanted between 1/1/2018-11/30/20. All candidates were screened for aPLab. We compared post-operative arterial and venous thrombotic events, treated as a combined endpoint, in recipients with and without aPLab (Fisher's exact test). Among recipients with aPLab, we recorded major bleeding events—defined as requiring blood transfusion or surgical exploration—while on therapeutic or prophylactic dose anticoagulation (AC). There were 100 patients who were evaluated and transplanted during the study period, 19 (19.0%) of whom had aPLab (Figure 1). Among these, 7 (36.8%) had pre-transplant deep vein thrombosis (DVT) or arterial thrombotic events. After transplant, 7 (36.8%) had new symptomatic DVT or arterial thromboses compared to 20 (24.7%) recipients without aPLab (p=0.39). Ten patients with aPLab were fully anticoagulated post-transplant, either because of prior or new thrombotic events. Of these, 6 (60.0%) had major bleeding. One aPLab patient had major bleeding on prophylactic AC. The majority (85.7%) of patients with major bleeding were on renal replacement therapy or had an eGFR <30. The one-year survival rate among recipients with aPLab was 89.5%. The presence of a pre-transplant aPLab was not associated with an increase in new symptomatic DVT or arterial thrombotic events following lung transplant although the study was underpowered for small or moderate effects. The decision to anticoagulate patients with aPLab should account for other risk factors for bleeding including renal insufficiency. [ABSTRACT FROM AUTHOR]

Obesity has been noted as a risk factor for poor outcome after heart transplantation (HTx). Cardiac cachexia has also been reported to be a risk factor for poor outcome, however no threshold has been noted for this patient population. Body mass index (BMI) greater than 35 kg/m2 is a noted threshold for declined patients for HTx, but a lower BMI has not been established. In this study, we reviewed the UNOS database to evaluate underweight patients awaiting HTx to assess whether there is a risk for poor outcomes post-HTx. Between 2000 and 2020, we assessed 16,457 patients from the UNOS database and divided the patients according to BMI groupings below. Patients were divided by CDC BMI definitions: severely underweight (BMI less than 15.0 kg/m2), moderately underweight (15.0 to 16.0 kg/m2), mildly underweight (16.0 to 18.5 kg/m2), and healthy weight (18.5 to <25.0 kg/m2). Endpoints included 1-year survival and freedom from graft failure. There was no significant difference in BMI underweight groups compared to healthy weight group in 30-day, 6-month, and 1-year survival or freedom from graft failure. (see table) There does not appear to be decreased post-heart transplant outcome for mild, moderate, or severely underweight patients. Being severely underweight should not be an absolute contraindication for heart transplant. However, larger number of severely underweight patients are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is seen in 7-29% of heart transplant (HTx) patients. Many of these patients with PGD also develop significant vasoplegia which requires high doses of intravenous vasoconstrictors. Outcomes of these patients with severe PGD is compromised within 30 days after HTx. Risk factors for the development of severe PGD have included angiotensin-converting enzyme inhibitors (ACEi). There may be a connection between ACEi and the kallikrein-kinin system whereby bradykinin is increased, thus resulting in more vasoplegia and PGD. It is not known whether the new drug, sacubitril/valsartan (S/V), is also a risk factor for the development of vasoplegia/severe PGD as bradykinin is also increased with sacubitril. Therefore, we reviewed our large HTx program to see if there is a correlation with S/V as a risk factor for this complication. Between 2015 and 2020, we assessed 65 HTx patients who were on S/V at the time of transplantation. Vasoplegia was defined as requiring more than 2 vasoconstricting drugs with systolic blood pressure still <90 mmHg. PGD was defined as per the ISHLT classification scheme (within 24 hours post-transplant). These patients on S/V were compared to patients on ACEi/ARB (1:1 control for age, sex, transplant year). Outcomes included survival, freedom from cardiac dysfunction, and freedom from non-fatal major adverse cardiac events in the first year after HTx. Compared to ACEi/ARB, S/V had similar risk for the development of vasoplegia or severe PGD. Furthermore, 1-year survival, freedom from cardiac dysfunction, and freedom from NF-MACE were not significantly different between groups. (see table) Patients undergoing HTx on S/V do not appear to be at risk for vasoplegia or severe PGD. [ABSTRACT FROM AUTHOR]