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Patients with severe heart disease may require hemodynamic support with a durable left ventricular assist device (LVAD) as a bridge to heart transplantation (HTx). Techniques to implant these durable LVADs do vary from institution to institution. Use of various materials to separate tissues also vary amongst implanting institutions. When these patients move to another facility, explanting these LVADs may be more problematic when undergoing HTx. It is not known whether explantation of an LVAD performed at another institution is fraught with more complications. Between January 2010 and June 2021, we evaluated 176 patients who had durable LVAD explanted at the time of HTx. Patients were separated into those that had durable LVAD performed at our transplant hospital versus those that were placed at an outside facility. The following endpoints were obtained: number of blood products administered, primary graft dysfunction, vasoplegia, intraoperative vascular complications, time in the operating room (OR), and 30-day post-HTx survival. Durable LVADs placed at an outside facility compared to those placed internally led to a trend in increased intraoperative complications during HTx surgery. However, there was no significant difference in blood products used, OR time, primary graft dysfunction, vasoplegia, and 30-day survival between the 2 study groups. Durable LVADs placed at an outside institution poses an increased risk for peri-operative complications when bridging to HTx. Extra time should be afforded to compensate for these potential problems. [ABSTRACT FROM AUTHOR]

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

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]

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]

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]

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]

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]

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]

The use of eculizumab, which is a complement blockade inhibitor, has been demonstrated to be efficacious in highly sensitized patients undergoing heart transplantation (HTx). The hypothesis is that the complement blockade protects the heart from hyperacute rejection and from other potential adverse responses. It is postulated that the complement blockade may downregulate antibody production. We reviewed our single center study using eculizumab for highly sensitized patients to assess for post-transplant outcomes. Between 2013 and 2020, we assessed 29 HTx patients who are highly sensitized, defined as calculated panel reactive antibody (cPRA) greater than 70% who underwent HTx with eculizumab therapy perioperatively. In all cases, donor-specific antibody (DSA) was crossed at the time of transplant but with a negative CDC prospective crossmatch. Eculizumab was given intraoperatively, post-op day 1, post-op day 7, and then given weekly for the first month and monthly for the second and third months post-transplant. The development of hyperacute rejection, antibody-mediated rejection, hemodynamic compromise rejection, and development of de novo DSA in the first-year post-transplant were assessed. Eculizumab use in highly sensitized patients resulted in 93.1% 1-year survival and no patient developing hyperacute rejection. There were 11 first-year AMR episodes noted, with one episode associated with hemodynamic compromise. All antibody levels began to wane in the first-year post-transplant. The use of eculizumab in highly sensitized patients (crossing DSA at transplant) appears to be effective in allowing these patients to undergo safe heart transplantation. [ABSTRACT FROM AUTHOR]