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Background: Patients with cardiogenic shock may require extracorporeal membrane oxygenation (ECMO) prior to durable mechanical circulatory support (dMCS) or heart transplantation (HTx). Methods: We investigated the clinical characteristics and outcomes of adult patients with ECMO support as bridge to dMCS or HTx between 1/1/13 and 12/31/20. Results: Of 57 patients who underwent bridging ECMO, 41 (72%) received dMCS (approximately half with biventricular support) and 16 (28%) underwent HTx, 13 (81%) after the 2018 UNOS allocation system change. ECMO → HTx patients had shorter ventilatory time (3.5 vs 7.5 days; p = 0.018), ICU stay (6 vs 18 days; p = 0.001), and less need for inpatient rehabilitation (18.8% vs 57.5%; p = 0.016). The 1-year survival post HTx was 81.3% in the ECMO → HTx group and 86.4% in the ECMO → dMCS group ( p = 0.11). For those patients in the ECMO → dMCS group who did not undergo HTx, 1-year survival was significantly lower, 31.6% ( p = 0.001). Conclusion: Patients on ECMO who undergo HTx, with or without dMCS bridge, have acceptable post-HTx survival. These findings suggest that HTx from ECMO is a viable option for carefully selected patients deemed acceptable to proceed with definitive advanced therapies, especially in the era of the new UNOS allocation system.

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre-formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%-97%) and 6250 (5000-10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14-0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.

Data are limited on outcomes after heart transplantation in patients bridged-to-transplantation (BTT) with a total artificial heart (TAH-t).The UNOS database was used to identify 392 adult patients undergoing heart transplantation after TAH-t BTT between 2005 and 2020. They were compared with 11 014 durable left ventricular assist device (LVAD) BTT patients and 22 348 de novo heart transplants (without any durable VAD or TAH-t BTT) during the same period.TAH-t BTT patients had increased dialysis dependence compared to LVAD BTT and de novo transplants (24.7% vs. 2.7% vs. 3.8%) and higher levels of baseline creatinine and total bilirubin (all p .001). After transplantation, TAH-t BTT patients were more likely to die from multiorgan failure in the first year (25.0% vs. 16.1% vs. 16.1%, p = .04). Ten-year survival was inferior in TAH-t BTT patients (TAH-t BTT 53.1%, LVAD BTT 61.8%, De Novo 62.6%, p .001), while 10-year survival conditional on 1-year survival was similar (TAH-t BTT 66.8%, LVAD BTT 68.7%, De Novo 69.0%, all p .20). Among TAH-t BTT patients, predictors of 1-year mortality included higher baseline creatinine and total bilirubin, mechanical ventilation, and cumulative center volume20 cases of heart transplantation involving TAH-t BTT (all p .05).Survival after TAH-t BTT is acceptable, and patients who survive the early postoperative phase experience similar hazards of mortality over time compared to de novo transplant patients and durable LVAD BTT patients.

Background Cardiac amyloidosis (CA) has been historically noted with poor outcomes after heart transplant (HTx). However, strict patient selection, appropriate multi-organ transplant, and aggressive post-transplant therapy can result in favorable outcomes. We present the experience in the largest single-center cohort of CA patients post-HTx in the recent era. Methods Between January 2010 and December 2018, 51 CA patients underwent HTx-13 light-chain amyloidosis (AL) and 38 transthyretin amyloidosis (ATTR), 49 were included. Endpoints included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), and freedom from non-fatal major adverse cardiac events (NF-MACE). Results Overall 3-year survival was 81.6% (69.2% for AL and 86% for ATTR) and was comparable to survival for patients transplanted for non-amyloid restrictive cardiomyopathy (RCM) in the same period (89%, p = .46). Three-year freedom from CAV (84% vs. 89%, p = .98), NF-MACE (82% vs. 83%, p = .96), and any-treated rejection (95% vs. 89%, p = .54) were also comparable in both groups. No recurrence in amyloid was noted in endomyocardial biopsies. Six patients (46%) with AL amyloidosis underwent autologous stem cell transplant 1-year post-HTx, and two patients (8%) with variant ATTR-CA underwent combined heart-liver transplant due to cardiac cirrhosis. Conclusion In the current era, both AL and ATTR cardiac amyloidosis patients have acceptable outcomes after heart transplantation.

Mechanical circulatory support has been performed as a bridge to cardiac retransplantation in selected patients with graft failure. However, there is limited published experience on the use and potential benefit of the total artificial heart (TAH) as a bridge to cardiac retransplantation. We report on our institutional experience with 3 patients that received TAH as a bridge to retransplant, with 1 patient surviving post-retransplantation. This case series demonstrates the high-risk nature of this undertaking in cardiac retransplant candidates and highlights the issue of sensitization portending greater risk for poor outcomes after TAH as bridge to retransplantation.

Background Giant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown. Purpose To describe the post-transplant survival of patients with GCM at a large transplant center. Methods Seven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone. Results One patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant. Conclusions Patients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.

BackgroundCardiac Bridging Integrator 1 (cBIN1) is a membrane deformation protein that generates calcium microdomains at cardiomyocyte t-tubules, whose transcription is reduced in heart failure, and is released into blood. cBIN1 score (CS), an inverse index of plasma cBIN1, measures cellular myocardial remodeling. In patients with heart failure with preserved ejection fraction (HFpEF), CS diagnoses ambulatory heart failure and prognosticates hospitalization. The performance of CS has not been tested in patients with heart failure with reduced ejection fraction (HFrEF).Methods and ResultsCS was determined from plasma of patients recruited in a prospective study. Two comparative cohorts consisted of 158 ambulatory HFrEF patients (left ventricular ejection fraction (LVEF) ≤ 40%, 57 ± 10 years, 80% men) and 115 age and sex matched volunteers with no known history of HF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were also analyzed for comparison. CS follows a normal distribution with a median of 0 in the controls, which increases to a median of 1.9 (p < 0.0001) in HFrEF patients. CS correlates with clinically assessed New York Heart Association Class (p = 0.007). During 1-year follow-up, a high CS (≥ 1.9) in patients predicts increased cardiovascular events (43% vs. 26%, p = 0.01, hazard ratio 1.9). Compared to a model with demographics, clinical risk factors, and NT-proBNP, adding CS to the model improved the overall continuous net reclassification improvement (NRI 0.64; 95% CI 0.18-1.10; p = 0.006). Although performance for diagnosis and prognosis was similar to CS, NT-proBNP did not prognosticate between patients whose NT-proBNP values were > 400 pg/ml.ConclusionCS, which is mechanistically distinct from NT-proBNP, successfully differentiates myocardial health between patients with HFrEF and matched controls. A high CS reflects advanced NYHA stage, pathologic cardiac muscle remodeling, and predicts 1-year risk of cardiovascular events in ambulatory HFrEF patients. CS is a marker of myocardial remodeling in HFrEF patients, independent of volume status.

Temporary mechanical circulatory support (MCS) devices are generally used short term to maintain adequate organ perfusion in patients with advanced heart failure and cardiogenic shock. Unacceptably high waitlist mortality in this cohort motivated changes to heart allocation policy, which recognized the severity of illness by prioritization for temporary MCS and broader sharing in the new U.S. donor heart allocation policy. We evaluated the post-heart transplant outcomes for patients bridged with temporary MCS, a control population not bridged with MCS, and a cohort bridged with durable MCS.The heart transplant research database was queried to identify patients bridged with temporary MCS and bridged with durable MCS who went directly to heart transplant in our center. Temporary MCS included Impella, intra-aortic balloon pump, and extracorporeal membrane oxygenation. Post-transplant endpoints were assessed at 30 days, 6 months, and 1 year.From 2010 to 2017, a total of 23 patients were bridged to heart transplant with temporary MCS and 548 were transplanted without MCS bridge. Patients bridged with temporary MCS had younger age, lower body mass index, and higher frequencies of prior blood transfusion and Status 1 (1A/1B) listing at transplant compared to patients not bridged with MCS (all P .001). Despite the severity of illness in patients bridged with temporary MCS, post-transplant outcomes were indistinguishable from those in patients transplanted without MCS bridge, with no difference in 30-day, 6-month, or 1-year survival or 1-year freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any-treated rejection, acute cellular rejection, or antibody-mediated rejection (P = .23-.97). Similarly, compared to 157 patients bridged with durable MCS, no differences in post-transplant outcomes were identified for the temporary MCS cohort (P = .15-.94).Temporary MCS as a bridge to transplant achieves similar post-transplant outcomes at 1 year compared to no MCS and durable MCS. These encouraging findings support recent changes in the Organ Procurement and Transplantation Network | United Network Organ Sharing (OPTN|UNOS) adult heart allocation policy.

Purpose 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. Methods 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. Results 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). Conclusion 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.

Purpose 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. Methods 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). Results 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. Conclusion 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.

Background Cardiac amyloidosis, typically from abnormal deposition of AL or ATTR amyloid protein, can result in heart failure requiring transplantation (HTx). The role of mechanical circulatory support (MCS) is not well-established. The purpose of this study was to present our experience with MCS in patients with cardiac amyloidosis. Methods Consecutive patients with cardiac amyloidosis who received MCS at Cedars-Sinai Medical Center between 2010 and 2018 were reviewed. Clinical characteristics and outcomes were compared to a control group of MCS patients without amyloid matched 2:1 for age and INTERMACS Profile. Results 11 amyloid patients underwent durable MCS, two with paracorporeal biventricular assist devices and 9 with total artificial hearts. No patients received isolated left ventricular assist device support. By 1 year, 9 (82%) of patients in the MCS-Amyloid group had been transplanted and 2 (18%) had died. In the MCS-No Amyloid group, by 1 year, 8 (36%) of patients had been transplanted, 10 (46%) had died, and 4 (18%) were still living with MCS. Conclusions Over a 9-year period, patients with amyloid cardiomyopathy who required MCS at our institution all received durable biventricular MCS. For carefully selected patients, this approach is feasible with acceptable outcomes as bridge to transplantation.

Importance Transverse tubule remodeling is a hallmark of heart failure. Cardiac bridging integrator 1 (cBIN1) is a circulating membrane scaffolding protein that is essential for transverse tubule health, and its plasma level declines with disease. Objective To determine if a cBIN1-derived score can serve as a diagnostic biomarker of heart failure with preserved ejection fraction (HFpEF). Design, Setting, and Participants In this cohort study, the cBIN1 score (CS) was determined from enzyme-linked immunoabsorbent assay-measured plasma cBIN1 concentrations from study participants in an ambulatory heart failure clinic at Cedars-Sinai Medical Center. Consecutive patients with a confirmed diagnosis of heart failure with preserved ejection fraction (HFpEF; defined by a left ventricular ejection fraction ≥50%) were recruited from July 2014 to November 2015 and compared with age-matched and sex-matched healthy volunteers with no known cardiovascular diagnoses and participants with risk factors for heart failure but no known HFpEF. Baseline characteristics and 1-year longitudinal clinical information were obtained through electronic medical records. Data analysis occurred from November 2016 to November 2017. Main Outcomes and Measures The analysis examined the ability of the CS and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results to differentiate among patients with HFpEF, healthy control participants, and control participants with risk factors for heart failure. We further explored the association of the CS with future cardiovascular hospitalizations. Results A total of 52 consecutive patients with a confirmed diagnosis of HFpEF were enrolled (mean [SD] age, 57 [15] years; 33 [63%] male). The CS values are significantly higher in the patients with HFpEF (median [interquartile range (IQR)], 1.85 [1.51-2.28]) than in the 2 control cohorts (healthy control participants: median [IQR], -0.03 [-0.48 to 0.41]; control participants with risk factors only: median [IQR], -0.08 [-0.75 to 0.42]; P

Purpose Patients more than 50 years of age routinely undergo screening colonoscopies. These patients can develop severe end-stage heart disease and may require heart transplantation. Many of these patients present in cardiogenic shock and it is unclear whether the use of colonoscopy is safe and efficacious in the screening of these patients for candidacy for heart transplantation. In our single-center program, we preform colonoscopies routinely on older patients at risk for colon cancer (family history, previous polyps or adenomas, stools heme positive) awaiting heart transplantation. We now report our experience of performing colonoscopes in these patients who are in cardiogenic shock, defined as patients who are on intravenous inotropic or left ventricular assist device (LVAD) support to maintain acceptable cardiac hemodynamics. Methods Between 2014 and 2019, we evaluated 300 heart transplant candidates who developed cardiogenic shock, defined as the need for IV inotropes or LVAD support. 30 of these patients underwent colonoscopy while on IV inotropes (n=27) and LVAD (n=3). All patients had compensated hemodynamics and anticoagulation was held prior to the procedure. Results Of the 30 patients with inotropic/LVAD support who underwent colonoscopy, the average age was 61.5 years and 87% were male. The specific inotrope(s) administered are listed in the table. The following findings at colonoscopy were found: 0 adenomas and 13 benign malignancies. There was no metastatic disease demonstrated. There were no complications arising from this colonoscopy except for bleeding due to biopsies that required hemoclips but no blood transfusions. Inotropic/LVAD support was continued through these procedures. Conclusion Colonoscopies for evaluation of heart transplant candidates who are in cardiogenic shock are acceptable, but caution should be taken in terms of risk for bleeding. Colonoscopies in cardiogenic shock should be limited to patients who are at risk for colon cancer.

Purpose Heart-liver transplant (HLvTx) has been demonstrated to show an immune protective effect with the transplanted liver protecting the heart. There are several reports suggesting less rejection in the HLvTx group. It has not been established whether this benefit is present in the current era. Methods Between 2007 and 2017, we assessed 13 HLvTx patients compared to heart alone patients (HATx, n=758). Patients were assessed for freedom from 1-year rejection [acute cellular rejection (ACR) and antibody-mediated rejection (AMR)] and donor-specific antibodies (DSA). Other endpoints included 5-year survival and freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography) and non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). Results HLvTx compared to HATx showed similar freedom from 1-year rejection (ACR, AMR) and DSA. 5-year survival, freedom from CAV and NF-MACE were also similar between the two groups (see table). Conclusion In the current era, HLvTx does not appear to provide immune protection in either rejection or CAV. A larger number of heart-liver transplant patients will be needed to confirm these findings.

Purpose Patients who are awaiting heart transplantation (HTx) have blood screened for circulating antibodies. Antibodies can sometimes come and go and not be detected at the time of HTx. However, there are instances when the patient has demonstrated donor specific antibodies (DSA) in the past but yet are not present at the time of HTx. It is not known whether these historical DSA have an impact on post-HTx outcomes. Methods Between 2010 and 2019, we assessed 11 patients awaiting HTx who had historical DSA but none detected at the time of HTx. These patients were compared to patients with DSA at the time of HTx and also compared to a non-sensitized group of patients undergoing HTx in a contemporaneous era. Post-HTx detection of DSA was performed and assessed if there was an amnestic response to the historical DSA. DSA are routinely checked post-HTx at 1, 3, 6, 12 months post-operatively. Other endpoints included 1-year freedom from any treated rejection, acute cellular rejection, and antibody-mediated rejection. 1-year survival, 1-year freedom from non-fatal major adverse cardiac event (NF-MACE, defined as MI, new CHF, PCI, ICD/pacemaker placement, stroke) and 1-year freedom from cardiac allograft vasculopathy were also recorded. Results Patients with historical DSA did not have an amnestic response with an increase of that specific DSA post-HTx. The historical DSA group compared to the non-sensitized group had no significant differences in 1-year survival, freedom from DSA, CAV, NF-MACE or rejections. Specifically, the historical DSA group did not appear to have an increase in any type of rejection in the first year post-HTx compared to (crossing) DSA at transplant group or the non-sensitized group. (See table) Conclusion Historical DSA does not appear to be a factor in terms of an amnestic response possibly due to the immunosuppression that is being administered. Therefore, crossing historical DSA at heart transplant does not appear to have adverse sequelae.

Purpose Sensitization occurs with blood transfusions in recipients of left ventricular assist device (LVAD). 30% of LVAD patients develop a panel reactive antibody (PRA) screen of >= 10%. Highly sensitized patients have an increased morbidity and mortality after heart transplantation. Desensitization therapy is considered for patients with PRAs> 50%. Below are the results of desensitization therapies in mechanical circulatory support (MCS) patients. Methods From 2010-2016, 49 MCS patients who underwent desensitization therapy were compared to a control group who underwent desensitization but did not have MCS support. Desensitization therapy used in both groups included combinations of rituximab/IVIG and plasmapheresis/bortezomib. Baseline PRAs prior to desensitization were repeated 2-4 weeks after treatment. For patients who underwent heart transplantation, outcomes included 1-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE, defined as myocardial infarction, percutaneous coronary intervention, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, and stroke), and freedom from any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Results Desensitization therapy was successful in both MCS and control groups, resulting in an average of 12% decrease in PRA. When subgrouped into Class 1 versus Class 2 antibodies, Class 1 antibodies appeared to have a better response after desensitization therapy (PRA decrease of 15% in Class 1 versus a decrease of 9% in Class 2). Patients on MCS support appear to have a numerical lower incidence of AMR with comparable first-year survival, freedom from CAV, NF-MACE, ATR, and ACR. Conclusion Desensitization of MCS patients appeared to be beneficial. Removal of the MCS device at the time of transplant may be a factor in potentially less AMR post-transplant.

Purpose Patients with end-stage heart failure may undergo mechanical circulatory support (MCS) as a bridge to transplant. This strategy may be complicated by sensitization due to blood transfusions as well as driveline infections. As sensitization narrows the donor pool, desensitization may be performed. The purpose of this study was to determine the impact of desensitization therapy on infections in MCS patients with an existing driveline infection. Methods We reviewed 45 MCS patients who developed a driveline infection between 2012-2018. Patients were divided into: sensitized (PRA >10%, n=22) and not sensitized (n=23). Sensitized patients were divided into: desensitization (when CPRA > 50%; n=7) and no desensitization (n=15). Desensitization included IVIG, rituximab, bortezomib and/or plasmapheresis. Outcomes were assessed 1 year after the driveline infection: survival, freedom from readmission, freedom from new driveline infection, and freedom from any infection. Results There was no difference between sensitized and non-sensitized MCS patients with a driveline infection in 1-year survival, freedom from readmissions, or freedom from any subsequent infection. There was no difference in outcomes between sensitized patients who received desensitization therapy and those who did not. Conclusion Desensitization appears to be safe in MCS patients with an existing driveline infection to potentially expand the compatible donor pool.

Purpose Increased perioperative risk has been observed in patients with left ventricular assist devices (LVAD) and total artificial hearts (TAH) undergoing heart transplantation with worse outcomes in TAH patients. The purpose of this study was to review perioperative transplant outcomes in TAH vs LVAD patients at a high-volume transplant center. Methods We reviewed perioperative transplant outcomes of 46 TAH patients and 85 LVAD patients from 2010-2018. Outcomes included perioperative transfusions (units of packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate), time in the operating room (OR), intensive care unit (ICU) days immediately post-transplant, freedom from return to OR for bleeding, freedom from primary graft dysfunction (PGD), and 1-year freedom from temporary dialysis. In addition, 1-year outcomes included survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous intervention, defibrillator/pacemaker implant, stroke), and freedom from first-year rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR)). Results TAH patients had more perioperative blood transfusions, and had decreased freedom from return to the OR for bleeding, temporary dialysis, and NF-MACE. There were no differences between groups in the time in OR, ICU days post-transplant, and freedom from PGD, survival, CAV, and rejection. Conclusion TAH patients appear to have increased perioperative post-transplant risk for some parameters though no difference in PGD or survival compared to LVAD patients. In a high volume center, there can be acceptable post-transplant outcomes in TAH patients.

Cardiovascular disease is the leading cause of death amongst patients with advanced CKD with an age-adjusted mortality 10-15x greater than the general population. CAD screening recommendations in pre-renal transplant patients differ between ACC/AHA and K/DOQI guidelines, are derived primarily from

Objective: We determined, in stable ambulatory heart failure with reduced ejection fraction (HFrEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS), which assesses the health of cardiac muscle, to identify patients with known heart failure (HF) and to prognosticate future hospitalization. Background: Limited clinical tools are available in assessing cardiac muscle health in stable ambulatory patients. Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte t-tubule membrane scaffolding protein which regulates calcium signaling in cardiomyocytes, decreases in failing muscle, and is present in plasma in levels that correlate with cardiac content. We hypothesize that CS, a normalized index of plasma cBIN1 concentration, can function as a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 concentration is measured by an ELISA test, and CS is calculated as the natural log of the ratio of a constant population mean cBIN1 to measured cBIN1 concentration. We determined CS among 125 clinically stable individuals with HFrEF (LVEF ≤ 40%) (mean age 56 ± 10 years old, 79% men) and 125 age, sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and 18-month longitudinal clinical information were obtained through electronic medical records. Results: CS follows a normal distribution with a median of 0 in the control population and median is significantly increased among HFrEF patients to 1.8 (IQR 1.4 – 2.1, p < 0.0001). CS diagnosed HFrEF with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.93 (AUC is 0.98 for NT-proBNP, and combined CS and NT-proBNP AUC is 0.99). Unlike NT-proBNP, CS does not correlate with body mass index (BMI) in either the control or HFrEF population (Pearson’s r = -0.15, p = 0.12; Pearson’s r = 0.003, p = 0.97, respectively). NT-proBNP significantly correlates with renal function (Pearson’s r = -0.37, p = 0.001), while CS also has no correlation (Pearson’s r = 0.03, p = 0.71). During an 18-month follow-up, a high CS ≥ 1.8 at the initial visit predicted future cardiovascular hospitalizations (38% vs. 21%, p = 0.04, hazard ratio 2.0). NT-proBNP did not predict future cardiovascular hospitalizations. Conclusions: Plasma cBIN1 based CS is insensitive to BMI and renal function and differentiates myocardial health between patients with HFrEF versus matched controls. An abnormally high CS reflected poor intrinsic myocardial health and can predict future 18-month cardiac hospitalization in stable ambulatory patients.

Purpose Thymoglobulin (ATG) is commonly used as induction therapy immediately after heart transplantation (HTx). ATG has been associated with an increase in CMV infection when used with maintenance cyclosporine. In the current era, tacrolimus has replaced cyclosporine as the main maintenance immunosuppressive agent. It is not clear whether ATG induction does indeed lead to more CMV infection in the tacrolimus era. Methods Between 2010 and 2016, we assessed 342 patients who received ATG induction therapy and compared them with HTx patients who did not receive ATG (n=312). ATG is routinely administered to patients with renal insufficiency to delay tacrolimus initiation and to sensitized patients (PRA ≥ 10%). Patients treated with ATG were then divided into their donor/recipient CMV serology matching (D+R-, D+R+, D-R+ and D-R-) and analyzed for the development of CMV infection defined as patients presenting with clinical symptoms and detected CMV virus via PCR. Incidence of rejection was also evaluated. Valcyte is routinely administered for CMV prophylaxis. Results There was a trend towards an increase in CMV infection in patients who received ATG induction therapy after HTx (see table). When the ATG population was analyzed by CMV serology, CMV mismatch (D+R-) had a numerical increase in CMV infection but this result was not statistically significant. When compared to the D-R- group on pairwise analysis, there was a trend towards increase in CMV infection and any-treated rejection in the CMV mismatch group (D+R-). (see table). Of note, valcyte induction was similar between groups per the transplant protocol. Conclusion ATG therapy trends towards increased CMV infection post-transplant in the tacrolimus era. Patients who have been treated with ATG and have CMV mismatch (D+R-) may have increased CMV infection risk as well as rejection risk by 2-years after HTx. Larger numbers are needed to confirm these findings.

Purpose Patients with muscular dystrophy may have an associated cardiomyopathy, resulting in advanced heart failure requiring transplantation. However, the skeletal muscle dysfunction can result in respiratory impairment, dysphagia, and inability to participate in rehabilitation after heart transplantation. The purpose of this study was to describe the characteristics and outcomes of muscular dystrophy patients undergoing heart transplantation at our center. Methods We reviewed patients at our center status post heart transplantation between 2010 and 2017. Of the 646 patients, we identified 10 with muscular dystrophy. The demographics, clinical characteristics, and outcomes of these 10 patients with muscular dystrophy were compared to the 646patients without muscular dystrophy transplanted during this time period. Results The muscular dystrophy patients were all deemed acceptable to proceed by a neurologist with expertise in muscular dystrophy. They were younger (45 years vs 56 years; p = 0.006); had younger donors (27 years vs 35 years, p = 0.05); had lower creatinine (0.95 mg/dL vs 1.15 mg/dL; P = 0.01); and less pre-transplant diabetes (13% vs 52%; p = 0.03). There was no difference in sensitization, CMV IgG mismatch status, or Status 1A listing. The muscular dystrophy patients had 100% 1- and 5-year survival (Figure) and there was no difference in the incidence of cellular rejection, antibody-mediated rejection, or allograft vasculopathy between groups. Conclusion Patients with muscular dystrophy-associated cardiomyopathy may require heart transplantation. This analysis indicates that carefully selected patients can have excellent outcomes and therefore should be considered candidates for advanced heart failure therapies.

Purpose Cytomegalovirus (CMV) has been documented as a risk factor for the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). It has not been firmly established whether CMV would cause an increase in first-year intimal thickening via intravascular ultrasound (IVUS) in the current tacrolimus era. First-year maximal intimal thickening (MIT) ≥0.5mm has been found to be predictive of poor outcome (worse survival, CAV) at 5-years post-transplant. In addition, there has not been a differentiation between CMV infection, CMV syndrome, and CMV disease as it applies to IVUS intimal thickening. CMV infection is noted by positive IgG CMV serology only; CMV syndrome refers to patients with documented CMV virus along with a clinical presentation; CMV disease is defined as organ-specific CMV infection i.e. CMV pneumonitis, CMV colitis etc. Therefore, we sought to use first-year IVUS to determine whether CMV infection, syndrome, or disease would lead to more first-year MIT ≥0.5mm. Methods Between 2010 and 2017, 294 heart transplant patients underwent baseline and 1-year IVUS. These patients were then divided into 4 groups: (Group A - no CMV infection (n=108); Group B - CMV infection (n=173); Group C - CMV syndrome (n=9); and Group D - CMV disease (n=3)). Diagnosis of CAV was based on a ≥ 0.5 mm increase in maximal intimal thickness (MIT) from baseline. Results Baseline MIT was similar among all study groups. The percent of patients with first-year MIT ≥0.5mm was also similar among all patient groups. Conclusion The development of CMV infection, syndrome and disease, does not appear to increase CAV risk by first-year MIT obtained by IVUS in the current tacrolimus era. Larger number of patients with longer follow-up studies are warranted to confirm these findings.

Background: Acquired heart failure (HF) originates with failing heart muscle, yet it is currently not possible to assay the biochemical health of cardiomyocytes. A key pathophysiology of HF is weakened calcium transient under the regulation of a membrane deformation protein bridging integrator 1 (BIN1). BIN1 decreases with HF and is blood available. We hypothesized that a recently cloned cardiac BIN1 isoform (cBIN1, BIN1+13+17) can be selectively measured to diagnose heart muscle health. Methods: Expression of cBIN1 in human heart and plasma was determined by immunoprecipitation, western blotting, and mass spectrometry analysis. A cBIN1 specific ELISA was developed using the combination of anti-BIN1 exon 17 (clone 99D from Sigma) and 13 (gift from Sarcotein Diagnostics) antibodies. Plasma cBIN1 concentration was then measured in a large clinical cohort of HFrEF (N=180) patients and compared to a sex and age matched cohort of healthy volunteers. Plasma cBIN1 concentration was also compared to NT-proBNP for its ability to detect patients with HFrEF. Results: Biochemistry and mass spectrometry confirms that cBIN1 is expressed in human myocardium. An ELISA assay selects for the cBIN1 isoform which significantly reduced in HFrEF (3.0±0.3, n=286, mean±SEM, ng/ml, p Conclusions: A cBIN1 specific ELISA can quantify cBIN1 in human plasma. Low plasma cBIN1 diagnoses diseased heart muscle in HFrEF patients and predicts future hospitalization and death.

Purpose Certain donor characteristics after heart transplantation (HTx) may have less optimal outcome post-HTx. One factors leading to worse outcome is female donors to male recipient possibly due to size (height and weight) mismatch relative to male donors. We try to compensate for this size mismatch by using obese female donors into male recipients. However, there have been recent concerns with obese donors, in the sense that there are commonly large fat deposits on the donor heart. It is not known whether short and obese female donors (weight oversizing) results in acceptable outcome after HTx. We sought to assess for this possibility in our large single center. Methods Between 2010 and 2017 we assessed 799 HTx patients and divided them into those male recipients who received female donors (n=246) that were short (≤ 66 inches) and obese (BMI≥30) (n=61) and short and non-obese (BMI major adverse cardiac events (NF-MACE: myocardial infarction , new congestive heart failure , percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and freedom from any-treated rejection, acute cellular rejection , and antibody-mediated rejection . Results There is no significant difference in 1-year outcomes between short and obese female donors, short and non-obese female donors, and male donors of similar heights and weights (see tables). Conclusion Short and stout female donors appear to be acceptable for HTx which increases the donor pool.

Purpose Proliferation signal inhibitors (PSIs) have been shown to decrease the incidence of cardiac allograft vasculopathy (CAV) and rejection in clinical trials when given at the time of heart transplantation. These trials have also demonstrated that patients on PSIs have a reduced risk of CMV infection post-transplant. However, the effect of PSIs on overall infection rates when given later post-transplant has not been clearly delineated. We sought to evaluate the incidence of infection post-PSI initiation at our single center. Methods Between 2010 and 2015 we assessed 550 heart transplant patients, 187 of which were initiated on a PSI (sirolimus or everolimus) over a five-year period after heart transplant. Endpoints included subsequent 2-year survival and subsequent 2-year freedom from infection (including CMV). A control population with patients not initiated on a PSI (n=363) was also included. Results 187/550 (34.0%) of heart transplant patients were initiated on a PSI over a five-year period after heart transplant. Patients were initiated on a PSI due to rejection, malignancy, CMV viremia, CAV, circulating antibodies, renal insufficiency and infection. The average time to PSI initiation was 1.3 years. Patients on a PSI compared to patients on no PSI had significantly reduced subsequent 2-year survival and reduced subsequent 2-year freedom from infection (see table). There was no difference in subsequent 2-year freedom from CMV infection. Conclusion PSI initiation later after heart transplant is associated with less than optimal outcomes. However, as PSI is used in high-risk patients, the outcomes are not unexpected but PSI use may have increased infection risk. PSI should be used with caution in these patients.

Purpose The Model for End-Stage Liver Disease (MELD) has been used to assess risk in patients awaiting liver transplant. More recently, MELD has been applied to patients with end-stage heart disease and has been demonstrated to reveal patients at high risk for mortality after heart transplantation (HTx). It is not known whether MELD score can predict severe PGD as per the new ISHLT scale. Methods Between 2010 and 2017, we identified 25 heart transplant patients who developed severe PGD supported by ECMO. This group was compared to 670 patients who did not have PGD. The pre-transplant MELD score was calculated for each group to see if there was a correlation to PGD. Results The MELD score was similar between patients that developed PGD and those that did not develop PGD (see table). Characteristics of the two groups demonstrated that the MELD individual criteria revealed that pre-transplant creatinine and total bilirubin were higher in the No PGD group but did not result in a difference between group MELD scores. Conclusion The MELD score may predict poor outcome after HTx; however, it does not appear to be a predictor for PGD.

Purpose The waiting time for heart transplantation can be long. Patients that are deemed ineligible for heart transplantation may become candidates due to the beneficial effects of MCS. Choosing to bridge with a short-term temporary device or a long-term durable device is a very important decision. We sought to evaluate the outcome of patients who were bridged with temporary versus durable MCS devices. Methods Between 2010 and 2017, we assessed 52 patients that were placed on temporary MCS devices (IABP, Impella, and ECMO) and 150 patients that were bridged with durable devices (LVAD, BiVAD, and TAH) prior to heart transplantation. A control non-bridged population was included (n=521). Endpoints included 30-day, 6-month and 1-year survival; 1-year freedom from cardiac allograft vasculopathy (CAV) as defined by 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); and 1-year freedom from any-treated rejection, acute cellular rejection and antibody-mediated rejection. Results There was no significant difference in survival, CAV, NF-MACE, or rejection between patients bridged with temporary and durable MCS devices. Conclusion Bridging with either temporary or long-term durable devices appears to have great outcome. A larger sample size is needed to confirm these findings.

Purpose Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival after HTx. The use of angioplasty and drug-eluting stents is common after HTx. CAV of the left main (LM) coronary artery is known to have high mortality risk. The long-term outcome of stenting for LM disease has not been well evaluated in this cohort of patients. Methods Between 2010 and 2013 we assessed 37 heart transplant patients who underwent stenting of the LM coronary artery post-transplant. A non-left main (no LM disease with another coronary artery stented) population was included (n=27) for comparison. Outcomes included 5-year freedom from restenosis (≥50% stent stenosis) subsequent 5-year survival, subsequent 5-year freedom from any myocardial infarction , and subsequent 5-year freedom from further deterioration in left ventricular function by echocardiogram . Results Subsequent 5-year freedom from restenosis and freedom from further deterioration in LV function was significantly lower in the LM stented group (see table). There was no difference in subsequent 5-year survival or freedom from myocardial infarction. Conclusion Patients with left main stenting appear to be have acceptable survival after heart transplantation despite progression to a lower left ventricular function and more restenosis. Alternatives to treatment for significant LM disease such as coronary bypass surgery and re-transplantation are not practical options in this diffuse disease and scarcity of donor hearts.

PCI for cardiac allograft vasculopathy (CAV) is associated with high revascularization rates but acceptable stent and lesion patency and clinical outcomes. The impact of stent characteristics and the use of intravascular ultrasound (IVUS) to optimize lesion patency is not established. Pts who