Search

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]

Implantation of a wireless pulmonary artery pressure monitoring device [CardioMEMS] has been shown to reduce heart failure hospitalization but safety profile and peri-procedural complications have not been well described in real world practice in a Veterans Affairs (VA) patient population. Electronic medical records of our single VA institution were retrospectively evaluated for device implantation procedure data and follow up clinic visits between 2017 and 2020. 63 patients with NYHA Class 3 heart failure were implanted with the device (Table 1A). Average procedure time was 48 minutes with average fluoroscopy time of 13 minutes. Average total volume of contrast used was 23 mL. Estimated blood loss was 10 mL. At device implantation, average right atrial mean pressures were 11 mmHg and pulmonary artery systolic, diastolic, and mean pressures were 51/24/34 mmHg. There were three peri-procedural complications. One patient developed an access related pseudoaneurysm successfully treated with surgical intervention. One patient developed a 2 cm hematoma at the access site managed conservatively. One patient developed proximal sensor migration following device deployment which was re-advanced using a Swan wedge balloon catheter and position was confirmed with chest radiograph and proper waveform analysis on device interrogation. All implants were successful and no patients were lost to follow up at clinic visits. There were no major adverse cardiovascular events (stroke, myocardial infarction and cardiovascular death) in hospital or at 30-day follow up. Procedural complications are summarized in Table 1B as compared to previously published data in the CHAMPION Trial. This real world study demonstrates that the safety profile of pulmonary artery pressure monitoring device implantation in a single VA healthcare center serving a VA patient population is a feasible and safe management approach to patients with NYHA Class 3 heart failure. [ABSTRACT FROM AUTHOR]

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]

Patients with existing Left Ventricular Assist Device (LVAD) who undergo non-cardiac surgery have a 9% risk of surgical site infection and up to a 44% chance of peri- and post-operative bleeding. This, along with the hemodynamic compromise of advanced heart failure, often makes LVAD patients prohibitively high risk for non-emergent surgeries. We present a successful case of an LVAD implanted into a patient with prior colostomy, who then later underwent a technically difficult colostomy reversal and parastomal hernia repair, without any of the aforementioned complications. A 44-year-old male with a history of non-ischemic cardiomyopathy (LVEF 20%) subsequently suffered perforated diverticulitis which was treated with a sigmoid colon resection with end colostomy. Later that year, he required LVAD (HeartMate 3™ Abbott) placement for cardiogenic shock requiring chronic inotropic support. Prior to his LVAD placement, colostomy reversal was considered to reduce the risk of post-operative LVAD driveline infection. Ultimately, colostomy reversal was deferred due to concern that a colorectal anastomosis may leak due to poor perfusion. However, he then developed a parastomal hernia with loss of domain which hindered colostomy care. Because he was weaned off inotropes and had clinically improved after his LVAD placement, it was felt he would be hemodynamically stable to tolerate colostomy reversal and subsequent parastomal hernia repair. His anticoagulation with warfarin was held for bridging enoxaparin one week before surgery. The colostomy site fascial defect was closed primarily and a sublay of synthetic mesh was placed. The surgical dissection at the old colostomy site was done to ensure there was adequate distance between the surgical field and LVAD driveline. The presence of the LVAD driveline along the right abdominal wall limited the ability to perform a right sided component separation but it was done on the left side to gain intra-abdominal domain. He remained stable during and after the procedure. Warfarin was re-started post-operative day one. This demonstrates feasibility to receive an LVAD with an existing colostomy, despite risk of infection. It also highlights that patients with an LVAD can undergo colostomy reversal and parastomal hernia repair, despite risk of poor anastomosis healing, bleeding, subcutaneous infection, and LVAD driveline infection. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of late graft dysfunction and mortality after heart transplantation. The pathophysiology of CAV consists of a complex interplay between donor risk factors, recipient comorbidities, and immune-mediated processes. Despite many studies showing a correlation between donor-specific antibodies (DSA) and CAV, the effects of different DSA types on the severity of CAV remains elusive. This study investigates the characteristics of DSA amongst different CAV severity groups. We evaluated 526 adult heart transplant recipients at a single tertiary medical center between January 2010 and August 2015. Subjects were screened for DSA at the time of transplant, 1 month, 3 months, 6 months, 1 year, and then annually thereafter. CAV screening was performed with annual angiography. Subjects were divided into those with DSA (n= 143) and those without DSA (control group, n =383). Subjects with DSA were further categorized into those with persistent DSA (n=34), transient DSA (n=106), 1:8 dilution positive DSA (n=45), complement-binding (C1q) DSA (n=36), Class I DSA (n=36), and Class II DSA (n=106). The mean duration of follow up was 3.6 years. The outcomes are the incidence of CAV based on the ISHLT grading scale. Subjects with persistent DSA were found to have higher incidence of moderate-to-severe CAV (CAV2/3) compared the control group (p = <0.001). On the contrary, there was no difference in the incidence of CAV2/3 between subjects with transient DSA and the control group (p =0.873). Subjects with 1:8 dilution positive DSA and C1q positive DSA also had a higher incidence of CAV2/3 when compared those without DSA (p =0.001, p =<0.001). Between subjects with Class I and Class II DSA, only subjects with Class II DSA had higher incidence of CAV 2/3 compared to the control group (p =0.042). DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. Given CAV2/3 is linked with higher mortality post-transplantation, these DSA characteristics may serve as prognostic markers of disease and may warrant consideration for treatment. [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]

Coronavirus disease-2019 (COVID) in patients with advanced heart failure presents unprecedented challenges in management of cardiogenic shock. Recommendations for perioperative triaging of cardiac surgery have been proposed but none regarding LVAD implantation. To our knowledge, we are the first to report on LVAD implantation in a patient with COVID and cardiogenic shock A 37-year-old-male with Stage D, NYHA class IV heart failure on chronic milrinone was admitted for cardiogenic shock. Despite uptitration of milrinone and addition of dobutamine,the patient remained in cardiogenic shock. Our Selection Committee discussed and approved him for an LVAD. Institutional protocol required COVID screening prior to surgery and returned positive. Given the absence of clinical signs of COVID infection contrasted with the severity of shock, the decision was made to proceed with implantation. Temporary mechanical support was considered but not thought to mitigate risks of thrombosis rather adding procedural risk with ECMO cannulation and left ventricular unloading. He successfully underwent LVAD implantation as INTERMACS 1. He required high doses of heparin to achieve ACT for cardiopulmonary bypass. On day 2, he developed left-sided weakness with imaging revealing multifocal acute cerebral infarcts. Despite normal LVAD function, the embolic infarcts to multiple organs led to further deterioration and death LVAD implantation in COVID patients appears inevitable. Centers must risk stratify this cohort to reduce susceptibility to thrombosis and improve outcomes. We propose an algorithm that triages patients for elective and urgent LVAD implantation based on specific coagulation and inflammatory markers (figure 1) and have successfully implanted an LVAD in a COVID patient using this. We acknowledge this method has not been validated in a large cohort and are unable to recommend anticoagulation protocols. Further research is necessary to address safety of LVAD implantation in COVID patients [ABSTRACT FROM AUTHOR]

Hypertension after heart transplantation (HTx) is noted in a majority of HTx patients due to the side effects of calcineurin inhibitors (CNI). The use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are effective anti-hypertensive agents and may have longer term clinical benefits. We assessed our patients on ACEI/ARBs versus others in the first year post-HTx and followed them for 5-year outcomes. Between 2010 and 2015, we assessed 101 HTx patients who were on ACEI/ARBs only in the first year for more than 6 months. Those patients were then followed for 5 years. Likewise, a group of patients who were placed on non-ACEI/ARBs blood pressure medications, such as calcium channel-blockers, beta blockers, and diuretics, in the first year for more than 6 months were the control group. Outcomes included 5-year survival, 5-year freedom from non-fatal major adverse cardiac event (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), freedom from cardiac allograft vasculopathy (CAV: angiographic stenosis >30%), freedom from left ventricular dysfunction (left ventricular ejection fraction ≤40%) and freedom from left ventricular hypertrophy (LVH), defined as intraventricular septum or posterior wall ≥1.3cm. The patients treated with ACEI/ARBs in the first year post-HTx compared to those without had significantly lower 5-year survival but a trend for greater 5-year freedom from CAV. There was no significant difference between the two study groups in 5-year freedom from NF-MACE, left ventricular dysfunction and LVH (see table). Baseline demographics between groups were similar for recipient age, % female, pre-transplant diabetes and renal dysfunction (creatinine >1.5mg/dl) (data not shown). The use of ACEI/ARBs in the first year post-HTx is associated with lower survival but other factors may be involved. A possible lower development of CAV from ACEI/ARBs may be a benefit to be explored. [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]

Diversity in the United States is a point of keen interest within the communities. In the heart transplant selection committees, most programs believe they have no bias in accepting patients for heart transplantation. However, there may be some inherent biases that are not due to the program's decisions, but rather institutional decisions or limitations. Such limitations may include lack of medical insurance, gender, age or geography that may be present without foreknowledge. Therefore, we assessed our heart transplant selection committee decisions to assess whether there is any inherent, institutional or voluntary bias within committee decisions. Between 2016 and 2020 we assessed 296 heart transplant candidates that were presented to the heart transplant selection committee. We assessed for various factors that may be associated with patients declined for transplant for age, gender, race, social support (SIPAT score), health insurance (Medicaid), and state of residence. The standard for comparison included a Caucasian with non-Medicaid health insurance, social support, and ability to travel. The declined patients compared to the accepted patients were significantly older (64.4 vs 54.6 years) and had a higher SIPAT score (13.7 vs 11.2). There was no difference between groups in % female, % non-Caucasian, % w/non-Medicaid health insurance and % from outside California. (see table) Inherent bias within a selection committee is difficult to interpret as older patients are held to a higher standard as older age is a risk factor for lower post-transplant survival. Higher SIPAT scores are also known to be a risk for lower survival due to higher psychosocial risk. It is comforting to appreciate that there does not appear to be inherent bias in gender, race, type of health insurance and region. Larger studies are needed. [ABSTRACT FROM AUTHOR]

Chronic kidney disease after heart transplantation is not uncommon due to the nephrotoxicity of calcineurin inhibitors (CNIs). It is well established that kidney dysfunction does impact post-transplant survival. What is not known is whether early or later development of kidney dysfunction has greater impact on outcomes. Between 2010 and 2017, we assessed 130 heart transplant patients and followed their course over the first 5 years. Patients were categorized as having kidney dysfunction detected with creatinine > 1.5 mg/dL at 1-year, 3-years, and 5-years after heart transplant. These patients were subsequently followed for 5 years to assess for subsequent 5-year survival, subsequent 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), subsequent 5-year freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30%), and 5-year freedom from left ventricular dysfunction (LVEF ≤ 40%). Patients who developed kidney dysfunction at 1-year post-heart transplant appear to have similar subsequent 5-year survival compared to those with kidney dysfunction at 3 and 5 years after heart transplant. However, significantly more patients with kidney dysfunction at 1-year required subsequent kidney dialysis. (See table) Early development of kidney dysfunction appears to lead to more patients needing kidney dialysis compared to those patients that develop kidney dysfunction later post-heart transplant. Renal sparing protocols or CNI minimization should be aggressively approached in these early patients to prevent worsening of kidney dysfunction. [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]

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]

The 99mTc-pyrophosphate (PYP) scan for the diagnosis of Transthyretin Related Cardiac Amyloidosis (ATTR) may be used in an inappropriate context or with incorrect interpretation, leading to misdiagnosis and futile financial burden. Here we report the use of PYP scans at our institution. We retrospectively reviewed 99 consecutive patients' data who underwent PYP between May 2018 and June 2020. ATTR diagnostic criteria were defined as any of: 1) cardiac biopsy-proven ATTR; 2) non cardiac biopsy-proven ATTR with evidence of echocardiographic features (unexplained left ventricular hypertrophy or apical sparing); 3) ATTR mutation with echocardiographic features and no evidence of plasma cell dyscrasia; 4) MRI suggestive of cardiac amyloidosis and no evidence of plasma cell dyscrasia. Comparisons between ATTR and non-ATTR were made using Chi-square, Fisher's Exact or Wilcoxon rank-sum tests. Sensitivity and specificity of PYP scan were estimated with Clopper-Pearson confidence intervals (CI). 48 (48%) patients had adequate data to evaluate diagnostic ATTR criteria. These patients were male (73%), African American (44%), with median age of 68 yrs, NYHA class ≥ 3 (50%), NICM (62%), neuropathy (44%) and orthopedic manifestations (31%). PYP scan (100%), cardiac MRI (44%), cardiac biopsy (31%), genetic testing (58%) and other organ biopsy (21%) were used to diagnose ATTR. The sensitivity of PYP scan for cardiac ATTR was 100% (95% CI: 78-100) and the specificity was 58% (95% CI: 41-74). All indeterminate PYP scans (17%) were negative for ATTR. On TTE, median septal wall thickness was 1.7 mm in those with cardiac ATTR compared to 1.2 mm in those without (p=0.002); median posterior wall thickness was 1.6 mm and 1.1 mm, respectively (p=0.007). 88% of patients who did not have adequate data to evaluate for ATTR had normal or indeterminate PYP scans. In our center representing real world data, PYP scan had similar sensitivity but reduced specificity compared to previously reported data. Our data shows the need for more selective use of PYP scan and reiterates need for ruling out plasma cell dyscrasia if only imaging is used to diagnose ATTR. [ABSTRACT FROM AUTHOR]

Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR. [ABSTRACT FROM AUTHOR]

Monotherapy with tacrolimus alone (TAC-A) was found to be safe and effective in the TICTAC Trial. However, in that trial, tacrolimus levels were maintained at 10-12 ng/mL over the first year which resulted in a higher serum creatinine level compared to those left in combination. We have been using TAC-A at lower doses in patients who have developed leukopenia or thrombocytopenia due to immunosuppression or a natural state. The presence of cytomegalovirus infections and other viruses excluded those patients from being administered monotherapy. It has not been established whether low dose TAC-A is safe and effective. Between 2010 and 2017 we assessed 151 heart transplant patients who are maintained on monotherapy with TAC-A. Patients were maintained on a low level of TAC-A between 4-7 ng/ml. These patients were assessed for subsequent 1-year rejection, subsequent 3-year survival, 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: MI, new CHF, PCI, ICD implant, stroke), cardiac allograft vasculopathy (CAV, epicardial disease with angiographic stenosis>30%), and cardiac dysfunction (LVEF ≤ 40%). Furthermore, periodic testing was done with the T-cell immune function test to assess whether these patients were adequately immunosuppressed. Patients who were maintained on TAC-A had comparable outcomes compared to patients left in combination immunosuppression (see table). The T-cell immune function test showed that these patients had adequate immunosuppression (average was 276 ng/mL with a range of 56-794 ng/mL and standard deviation of 137.1 ng/mL) with the therapeutic range being 200-550ng/ml. Patients had an average of 11 Tacrolimus lab tests (range: 4-46). Low dose TAC-A appears safe and effective in select patients after heart transplantation guided by T cell immune function testing. Further studies with larger number of patients will be needed to confirm these findings. [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]