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Regulatory oversight for heart transplant programs is currently under review by the United Network for Organ Sharing (UNOS). There is concern whether 1-year patient and graft survival truly represent heart transplant center performance. Thus, a forum was organized by the Thoracic and Critical Care Community of Practice (TCC COP) of the American Society of Transplantation (AST) for the heart transplant community to voice their opinions on matters involving program performance monitoring by UNOS. A TCC COP work group was formed to review outcome metrics for adult heart transplantation and culminated in a virtual community forum (72 participants representing 61 heart transplant programs) on November 12-13, 2020. One-year posttransplant survival is still considered an appropriate and important measure to assess program performance. Waitlist mortality and offer acceptance rate as pretransplant metrics could also be useful measures of program performance, recognizing that outside factors may influence these metrics. In depth discussion of these metrics and other issues including auditing thresholds, innovations to reduce risk-averse behavior and personally designed program scorecards are included in this meeting proceedings.

Objectives This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception). Background The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS. Methods Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared. Results A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events. Conclusions The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.

In 2018, the Organ Procurement and Transplantation Network (OPTN) modified adult heart allocation to better stratify candidates and provide broader access to the most medically urgent candidates. We analyzed OPTN data that included waiting list and transplant characteristics, geographical distribution, and early outcomes 1 year before (pre: October 18, 2017-October 17, 2018) and following (post: October 18, 2018-October 17, 2019) implementation. The number of adult heart transplants increased from 2954 pre- to 3032 postimplementation. Seventy-eight percent of transplants in the post era were for the most medically urgent (statuses 1-3) compared to 68% for status 1A in the pre era. The median distance between the donor hospital and transplant center increased from 83 to 216 nautical miles, with an increase in total ischemic time from 3 to 3.4 hours (all P < .001). Waiting list mortality was not different across eras (14.8 vs 14.9 deaths per 100 patient-years pre vs post respectively). Posttransplant patient survival was not different, 93.6% pre and 92.8% post. There is early evidence that the heart allocation policy has enhanced stratification of candidates by their medical urgency and broader distribution for the most medically urgent candidates with minimal impact on overall waiting list mortality and posttransplant outcomes.

Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I-IV), LVAD, and HT.We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing.Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I-III) as well as in patients with LVAD and HT (p0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I-III, p0.05) but not in patients with HT.Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT.

Antibody-mediated rejection (AMR) driven by the development of donor-specific antibodies (DSA) directed against mismatched donor human leukocyte antigen (HLA) is a major risk factor for graft loss in cardiac transplantation. Recently, the relevance of non-HLA antibodies has become more prominent as AMR can be diagnosed in the absence of circulating DSA. Here, we assessed a single-center cohort of 64 orthotopic heart transplant recipients transplanted between 1994 and 2014. Serum collected from patients with ≥ pAMR1 (n = 43) and non-AMR (n = 21) were tested for reactivity against a panel of 44 non-HLA autoantigens. The AMR group had a significantly greater percentage of patients with elevated reactivity to autoantigens compared to non-AMR (P = .002) and healthy controls (n = 94, P .0001). DSA-positive AMR patients exhibited greater reactivity to autoantigens compared to DSA-negative (P .0001) and AMR patients with DSA and PRA 10% were identified as the subgroup with significantly elevated responses. Reactivity to 4 antigens, vimentin, beta-tubulin, lamin A/C, and apolipoprotein L2, was significantly different between AMR and non-AMR patients. Moreover, increased reactivity to these antigens was associated with graft failure. These results suggest that antibodies to non-HLA are associated with DSA-positive AMR although their specific role in mediating allograft injury is not yet understood.

Permanent pacemaker (PPM) implantation is required in a subset of patients (∼10%) for sinus node dysfunction or atrioventricular block both early and late after heart transplantation. The incidence of PPM implantation has decreased to 5% with the advent of bicaval anastamosis transplantation surgery. Pacing dependence upon follow-up has been variably reported. An even smaller percentage of transplantation recipients (1.5% to 3.4%) undergo implantable cardioverter-defibrillator (ICD) placement. Rigorous data are lacking for the use of ICDs in the transplantation population and is largely derived from cohort studies and case series. Sudden cardiac death occurs in approximately 10% of transplantation recipients, but multiple nonarrhythmic factors are believed to be responsible, including acute rejection, late graft failure with electromechanical dissociation, and ischemia due to cardiac allograft vasculopathy. This review provides a comprehensive analysis of the existing data regarding the role for PPMs and ICDs in this population, including leadless PPMs and subcutaneous ICDs, special considerations, and future directions.

Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in advanced heart failure patients. Recent studies suggest that low socioeconomic status (SES) predicts worst survival after heart transplantation. Both individual-level and neighborhood-level SES (nSES) have been linked to cardiovascular health; however, the impact of SES in CF-LVAD patients remains unknown. We hypothesized that SES is a major determinant of CF-LVAD candidacy and postimplantation outcomes. A retrospective chart review was conducted on 362 patients between February 2009 and May 2016. Neighborhood-level SES was measured using the American Community Survey data and the Agency for Healthcare Research and Quality SES index score. Individual-level SES was self reported. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression determined survival statistics. Patients in the highest SES tertile were older (58 ± 13 vs. 53 ± 14; p < 0.001), less likely to be black or Hispanic (26% vs. 70%; p < 0.001), more likely to be married (87% vs. 65%; p < 0.001), more likely to have private insurance (50% vs. 39%; p < 0.001), and more likely to have employment (29% vs. 15%; p < 0.001) compared with patients in the lowest tertile. Low nSES was associated with a decreased risk of death (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.347-0.970; p = 0.038) in comparison to the high nSES. However, after adjusting for baseline clinical morbidities, the relationship was no longer present. When selecting patients for a LVAD, SES should not be thought of as an immutable risk factor. Carefully selected low-SES patients could be safely implanted with CF-LVAD with outcomes comparable to high-SES patients.

Donation after Circulatory Death (DCD) is an alternative to Donation after Brain death (DBD), and is a growing strategy for organ procurement in the United States(US). The purpose of this analysis was to review the number and quality of hearts in one United Network for Organ Sharing (UNOS) Region that were not utilized as a potential consequence of nonheart DCD donation. We retrospectively identified all successful US DCD solid organ donors from 1/2011 to 3/1/2017, defined an ideal heart donor by age and left ventricular ejection fraction (LVEF), and then reviewed the donor charts of unused hearts in New York and Vermont (UNOS Region 9). Of 8302 successful DCD donors across the United States, 5033 (61%) were between 18 and 49 years of age, and 872 had a screening echocardiogram, with 573 (66%) measuring an EF >50%. Of these 573 potential donors, 44 (7.7%) were from Region 9. Detailed donor chart review identified 36 ideal heart donors, 24 (66.7%) with anoxic brain injury. Trends in Region 9 DCD donation increased from 4 unused hearts in 2011, to 13 in 2016. In the context of severe organ scarcity, these data indicate that implementation of DCD heart transplantation in the United States would improve overall donation rates and provide a pathway to utilize these ideal donor hearts.

BACKGROUND: Conditional survival (CS) is a dynamic method of survival analysis that provides an estimate of how an individual’s future survival probability changes based on time post-transplant, individual characteristics, and post-transplant events. This study sought to provide post-transplant CS probabilities for heart transplant recipients based on different prognostic variables and provide a discussion tool for the providers and the patients. METHODS: Adult heart transplant recipients from January 1(st), 2004 through October 18(th), 2018 were identified in the UNOS registry. CS probabilities were calculated using data from Kaplan-Meier survival estimates. RESULTS: CS probability exceeded actuarial survival probability at all times post-transplant. Women had similar short-term, but greater long-term CS than men at all times post-transplant (10-year CS 1.8%−11.5% greater [95% CI 1.2%−12.9%]). Patients with ECMO or a surgical BiVAD had decreased survival at the time of transplant, but their CS was indistinguishable from all others by one-year post-transplant. Rejection and infection requiring hospitalization during the first-year were associated with a persistently decreased CS probability. CONCLUSIONS: In this study, we report differential conditional survival outcomes based on time, patient characteristics, and clinical events post-transplant, providing a dynamic assessment of survival. The survival probabilities, will better inform patients and clinicians of future outcomes.

Background Antibody mediated rejection (AMR) is an increasingly studied cause of graft failure after heart transplantation . AMR diagnosis previously required the detection of circulating donor specific antibodies (DSA); however, the most recent criteria only require pathological findings. This classification defined a subset of patients with AMR, yet without known antibodies. Here, we sought to evaluate differences in the transcriptome profile associated with different types of AMR. Methods RNA sequencing was used on endomyocardial biopsies to analyze and compare transcriptomic profiles associated with different subtypes of AMR defined by immunopathological and histopathological findings, as well as the presence or absence of DSA. Gene expression profiles were characterized for each diagnostic group. Results The most divergent gene expression profiles were observed between patients with or without DSA. AMR subtypes associated with DSA showed expression of signature genes involved in monocyte activation and response to interferon . There was also substantial difference between the transcriptomic profiles of AMR defined by histopathological and immunopathological findings, the latter being associated with expression of mucin genes. In contrast, there was no differential RNA expression between patients with pAMR1i without DSA and those without AMR. Likewise, no differential expression was observed between patients with pAMR1h with DSA and pAMR2. Conclusions Overall, our studies reveal different expression profiles in endomyocardial biopsies in relation to some key criteria used to diagnose AMR. These findings support the view that the diagnosis of AMR encompasses several phenotypes that may rely on distinct mechanisms of injury.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Background: Trimethylamine N-oxide (TMAO)—a gut-derived metabolite—is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I–IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52–1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68–2.30], 1.97 [95% CI, 1.71–2.24], and 2.09 [95% CI, 1.83–2.34] µM, respectively; all P 6 months: 1.99 [95% CI, 1.76–2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66–2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Whether solid organ transplant (SOT) recipients are at increased risk of poor outcomes due to COVID‐19 in comparison to the general population remains uncertain. In this study, we compared outcomes of SOT recipients and non‐SOT patients hospitalized with COVID‐19 in a propensity score matched analysis based on age, race, ethnicity, BMI, diabetes, and hypertension. After propensity matching, 117 SOT recipients and 350 non‐SOT patients were evaluated. The median age of SOT recipients was 61 years, with a median time from transplant of 5.68 years. The most common transplanted organs were kidney (48%), followed by lung (21%), heart (19%), and liver (10%). Overall, SOT recipients were more likely to receive COVID‐19 specific therapies and to require ICU admission. However, mortality (23.08% in SOT recipients vs. 23.14% in controls, P = .21) and highest level of supplemental oxygen (P = .32) required during hospitalization did not significantly differ between groups. In this propensity matched cohort study, SOT recipients hospitalized with COVID‐19 had similar overall outcomes as non‐SOT recipients, suggesting that chronic immunosuppression may not be an independent risk factor for poor outcomes in COVID‐19.

Background: One of the goals of the revised 6-tiered US adult heart allocation policy was to improve risk stratification of patients to lower exception status utilization for transplant listing. We sought to define the characteristics and outcomes of waitlisted patients using exception status and to examine region- and center-level differences in utilization of exception status in the new heart allocation system. Methods: This retrospective cohort analysis of the United Network for Organ Sharing database included adult waitlisted patients for heart transplant between October 18, 2018, and June 30, 2020, in the United States, stratified by use of exception status versus standard criteria. Results: Out of 6351 patients, 1907 (30.0%) were waitlisted under exception status. Patients using exception status were more likely to have a nonischemic cause of heart failure, blood type O, United Network for Organ Sharing status 2 at listing and were less likely to have a durable left ventricular assist device at listing. Exception status utilization varied significantly between and within United Network for Organ Sharing regions. Listing by exception criteria was associated with a significantly higher incidence of heart transplantation compared with listing by standard criteria (hazard ratio, 1.25 [1.15–1.38], P P =0.12) after multivariable adjustment. Conclusions: The status tiers of the new heart allocation system may not fully capture medical urgency and complexity of waitlisted patients as assessed by transplant physicians and review committees and may limit the ability to develop a heart allocation score.

Sudden cardiac death (SCD) is responsible for up to 10% to 35% of deaths after heart transplantation (HT) ([1][1],[2][2]). In the 2017 guidelines, implantable cardioverter-defibrillators (ICDs) may be reasonable in patients with severe allograft vasculopathy with left ventricular dysfunction post-HT

Background: Bridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT. Methods: Using the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan–Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds. Results: Early mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year ( P −1 ·1.73 m −2 (odds ratio, 1.69; P =0.003) and −1 ·1.73 m −2 (odds ratio, 2.16; P =0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m 2 (odds ratio, 1.88; P =0.024) and >30 kg/m 2 (odds ratio, 2.11; P 60 years, estimated glomerular filtration rate −1 ·1.73 m −2 , and body mass index >30 kg/m 2 , there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients. Conclusions: Bridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.

Objectives This study examined sex-related differences in use and outcomes of continuous-flow left ventricular assist devices (CF-LVADs) among individuals awaiting heart transplantation using the United Network for Organ Sharing registry. Background Advanced therapies for heart failure including CF-LVADs remain underused in women. There have been contradictory results regarding sex-specific outcomes. Many studies have been limited by small sample sizes or included pulsatile-flow devices. Methods De-identified patient-level data were obtained from the United Network for Organ Sharing database. The database was queried to identify adult patients (≥18 years of age) who required mechanical circulatory support with HeartWare HVAD (Medtronic, Minneapolis, Minnesota), HeartMate II (Abbott, Lake Bluff, Illinois), or HeartMate 3 (Abbott) as bridge to heart transplantation between 2008 and 2018. Each patient was assigned a propensity score. The primary outcomes of interest were rates of transplantation and death. Results A total of 13,305 patients (2,771 women, 20.8%) received support with CF-LVAD in the study period. There were significant sex disparities in CF-LVAD use in listed patients (29.9% men vs. 18.9% women in 2017). Female patients receiving CF-LVAD support had lower chances of heart transplantation (55.1% vs. 67.5%), increased risk of waitlist mortality (7.0% vs. 4.2%), and delisting for worsening clinical status (8.5% vs. 4.7%) at 2 years post-implantation (all p Conclusions Durable mechanical circulatory support with CF-LVADs remains underused in women. When matched with similar male control subjects, women experienced higher mortality and lower rates of heart transplantation.

There is renewed interest in intra-aortic balloon pump (IABP) use in chronic systolic heart failure (HF) patients with acute decompensation and cardiogenic shock (CS). We sought to identify predictors of early IABP response to guide optimal use in this population.We retrospectively analyzed records of chronic systolic HF patients presenting to our center between 2011-2018 with acute decompensated HF who received IABP for CS. An IABP responder was defined as having both an early cardiac output (CO) increase and mean pulmonary artery pressure (MPAP) decrease above the cohort median values.During this period, a total of 218 chronic systolic HF patients received IABP for acute decompensation with CS. The average CO increase was 0.57 ± 0.85 L/min and MPAP reduction was 5.1 ± 7.6 mm Hg. Fifty-six patients (25.7%) were identified as IABP responders, with mean CO increase of 1.21 ± 0.87 L/min and MPAP reduction of 12.1 ± 5.9 mm Hg. Systemic vascular resistance (SVR)1300 dynes/sec/cm-5 (odds ratio [OR], 5.04; 95% confidence interval [CI], 1.86-13.6; P.01) and moderate-severe mitral regurgitation (OR, 2.42; 95% CI, 1.25-4.66; P.01) predicted robust hemodynamic response.A subset of chronic systolic HF patients had robust hemodynamic response to IABP with significant CO augmentation and MPAP reduction. Higher SVR and moderate-severe mitral regurgitation predicted early hemodynamic response to IABP.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

CRP is an established inflammatory biomarker with prognostic value in patients with chronic heart failure, yet its role in continuous-flow left ventricular assist device (LVAD) patients is largely unknown. 5,183 patients from the INTERMACS registry who underwent durable LVAD between 2008 and 2017 and had preimplant CRP levels were included. The sample was stratified into two groups based on preimplant CRP levels: CRP of 0-10 mg/L (low) and10 mg/L (high). Kaplan-Meier survival estimates were used to assess outcomes at 2 years after LVAD implantation, with log-rank testing used to compare groups. Cox proportional hazard models were used for multivariable adjustment. Patients with high preimplant CRP were younger, more likely to be INTERMACS class I, and had a higher need for temporary mechanical circulatory support before LVAD implant compared to those with lower CRP levels (all P0.001). The high CRP group had higher WBC counts and BNP levels (all P0.001). After adjustment, higher CRP (10 mg/L) was associated with greater risk of mortality, RV failure, and stroke postimplant (P0.001). In addition, elevated postimplant CRP level at 3 months was associated with increased mortality and stroke on LVAD support (P0.001). CRP is a predictor of death and complications on LVAD support. Future studies are necessary to explore the mechanisms underlying this finding and the potential role of antiinflammatory therapies in this population.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

The purpose of this study was to compare outcomes between patients on extracorporeal membrane oxygenation (ECMO) bridged to left ventricular assist device (LVAD) versus heart transplantation (HT) using registry data.Patients with heart failure supported with ECMO represent the highest priority in the new HT allocation system. For patients on ECMO, bridging to LVAD may be non-inferior compared with bridging to HT.Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017 and United Network for Organ Sharing (UNOS) database from 2006 to June 2019 requiring ECMO were included. Cause-specific hazard models were created and cumulative incidence functions were calculated with mortality, transplantation, and re-transplantation as competing events.A total of 906 patients received ECMO as bridge to VAD (n = 587, 64.8%) or as bridge to HT (n = 319, 35.2%). Patients bridged directly to HT were younger (age 46.3 ± 15.4 years vs. 52.1 ± 13.2 years; p 0.001) and more likely to be female (93 [29.2%] vs. 139 [23.7%]; p = 0.022). Patients bridged directly to HT were more likely to have a nonischemic cardiomyopathy, restrictive physiologies, and allograft failure; (p 0.05 for all). ECMO use increased over time in both UNOS and INTERMACS. There was no significant difference in mortality between groups (Gray's p = 0.581). This remained true even when the analysis was restricted to transplant-listed or eligible patients as well as patients with dilated phenotypes (excluding patients with congenital heart disease, restrictive phenotypes, and allograft failure).There was no difference in mortality on pump support compared with posttransplant mortality among those bridged from ECMO to LVAD or HT.

Introduction: Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplant (HT). Inflammation is a known cardiovascular risk factor, with gut derived endotoxemia potentially instigating this process, leading to endothelial damage. Our prior work showed that elevation of biomarkers of inflammation (endothelin-1 (ET-1)) and endotoxemia (lipopolysaccharide (LPS)) persists after HT. We investigated the association of LPS and ET-1 with subsequent development of CAV. Methods: Pts who met the following criteria were included: i) blood sampling ≥6 mo post-HT; ii) no evidence of CAV at the time of sampling. Pts were followed up to 2.3y after sampling. Cox-PH was used to regress freedom from CAV on LPS and ET-1 (≤ vs >median), time from HT to sampling (≤ vs >1y), interaction among variables. Results: 33 HT pts enrolled, mean age 57±11y; 70% male; median time post-HT 1.96(0.5-3.7)y. 17(52%) pts developed CAV at 0.7(0.6-1)y following blood collection. Baseline characteristics of pts who developed CAV vs not were similar, except for longer median time post-HT in pts who developed CAV: 2.4(0.7-5.3) vs 1.05(0.5-2.7)y, p=0.1. Median LPS and ET-1 for the entire cohort were 0.34(0.28-0.45) EU/ml and 1.83(1.26-2.72) pg/ml. Pts with >median LPS or ET-1 values trended towards higher risk of developing CAV: HR 1.79(0.66, 4.85), p=0.3 ( Fig.1A ); HR 2.05(0.71, 5.92), p=0.2 ( Fig.1B ). No association was observed between time post-HT and CAV: HR=0.87 comparing ≤ vs. >1y, p=0.8. Pts with both >median LPS and ET-1 levels (n=7) were at significantly higher risk of CAV: HR 2.96(1.06, 8.27), p=0.039, compared to others ( Fig.1C ). When examining pts sampled within the first year of HT (N=14), pts with >median LPS (N=5) were at particularly increased risk of CAV: HR 9.71(0.97, 96.9), p=0.05, while pts with >median ET-1 were not. Conclusions: Elevated LPS and ET-1 synergistically associate with increased CAV risk post-HT. Further studies are warranted to validate these findings.

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor β chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFβ) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.

Purpose COVID-19 infection might be associated with higher mortality risk for transplanted patients, as a result of their multiple co-morbidities and their immunosuppressed status. We sought to describe the six-month outcomes of heart transplant (HT) recipients infected by COVID-19. Methods We retrospectively analyzed clinical and echocardiographic data from all HT recipients infected with COVID-19 between March and April 2020. All patients were followed for a minimum of 6 months or until death. Results Twenty-eight HT patients were studied, median age was 64 (range 59-69) and 22 were male. Co-morbidities included obesity (25%), diabetes (61%), HTN (71%), CKD (68 %) and chronic lung disease (36%). Eight patients died (29%) (non-survivors) and 20 survived (survivors) COVID-19 infection. All patients who survived the initial hospitalization period remained alive at 6 months (figure 1). There was no difference in the prevalence of co-morbidities between survivors and non-survivors. Survivors had lower peak ferritin (2185 ± 793 vs 18023 ± 16724, p= 0.04) and procalcitonin (0.8 ± 0.3 vs 104 ± 31, p

Purpose Primary Graft Dysfunction (PGD) is a leading cause of short-term mortality after heart transplantation (HT). Available registries lack data to identify PGD based on post-HT hemodynamics and mechanical circulatory support (MCS). Herein, we describe the development of a multicenter International Consortium on PGD: a registry designed to quantify the incidence, risk factors, and impact of PGD, in order to develop contemporary risk prediction models. Methods We are currently collecting data from 10 participating sites in Europe and North America which will include clinical data from an estimated 3,826 HT recipients (Table 1). We defined PGD using the ISHLT 2014 consensus criteria. Our complete consortium will include data on baseline donors and recipients demographics, pre and post-HT hemodynamics, and the type and duration of MCS after HT. We will use regression models and supervised machine learning (ML) algorithms to develop risk prediction models that reflect the contemporary landscape of HT. Endpoints To date, we have collected preliminary data on 2,178 single-organ HT recipients between 2010 - 2020 (57% of the anticipated final sample size). Our consortium cohort consists of patients with age of 54 ± 12 years, of whom 24.7% (n=537) are female. Pre-transplant MCS included IABP in 3.6% (n=80), ECMO in 1.4% (n=30), and durable LVAD in 8.3% (n=181). Donor age was 37 ± 13 years and ischemic time was 3.4 ± 1.0 hours. A total of 167 (7.7%) recipients met criteria for severe PGD and 76 (6.5%) for moderate PGD. One-year survival was 67% (95% CI 59 - 74%) and 93% (95% CI 92 - 94%) in patients with and without severe PGD, respectively. We aim to develop contemporary tools for risk stratification of HT recipients for incident PGD. Our multicenter, international consortium allows for comprehensive phenotyping of HT recipients based upon a standardized definition of PGD to accurately understand PGD incidence, risk factors, and outcomes in the era of MCS. Interim Results To date, we have collected 106 variables on 2,476 single-organ HT recipients from 2010 to 2020 (Figure 1A). Mean age of cohort is 53.9 ± 12.3 years; 25% female, 330 recipients from Canada, 518 from Europe, and 1628 from the US. Pre-transplant MCS included IABP in 8.4% (n=207), ECMO in 1.3% (n=33), and durable LVAD in 32.1% (n=795) (Figure 1B). Average donor age was 36.4 ± 13.0 years with mean ischemic time 3.4 ± 1.1 hours. A total of 214 (8.6%) of recipients met criteria for severe PGD, requiring VA-ECMO (n=186), RVAD (n=28), or both (n=3). Among 1811 patients with adequate follow up data, 1-year survival was 78% (95% CI 72% – 83%) in patients with severe PGD, and 95% (95% CI 94% – 96%) in those without severe PGD (Figure 1C). The previously-published RADIAL PGD risk score performed poorly in our cohort, with an AUC of 0.50 for severe PGD(Figure 1D).

Purpose Heart transplant (HT) recipients require monitoring for allograft rejection with frequent endomyocardial biopsies (EMB). The aim of this study was to evaluate the safety of transitioning heart transplant recipients to a non-invasive monitoring protocol utilizing HeartCare (combination of gene expression profiling [Allomap] and donor derived cell free DNA [Allosure]). Methods This is a prospective single-center cohort study evaluating the utilization of HeartCare from as early as one month post-HT. Positive Allomap test was defined as ≥32 in patients ≤6 months and ≥34 in patients > 6 months post-HT. Positive Allosure test was defined as ≥0.12%. Positive biopsy included ISHLT Grades ≥1B. Results 320 heart transplant recipients enrolled to this study. Mean age was 57.5±14.0, 231 were males (72.0%). There was a total of 523 HeartCare blood tests drawn and 148 biopsies were performed (Figure). Of 82 patients with elevated Allomap and Allosure, only 7 (8.5%) of them had a confirmed rejection episode. Among 71 patients with elevated Allosure with normal Allomap, only 2 (2.8%) patients had confirmed rejection. 2 patients (4.3%) with negative Allomap and Allosure had rejection. During the study period 55 patients (17.2%) were admitted to the hospital for a total of 67 admissions. 17 patients were admitted for rejection (5.3%). None of the patients died during the study period. Conclusion Transitioning from invasive endomyocardial biopsy monitoring to a non-invasive HeartCare protocol in HT recipients seems feasible based on the high negative value of the combined Allomap and Allosure tests. However, further study is needed to follow the long-term outcomes and presence of rejection in patients post-transplant with this protocol.

Purpose Donor-specific antibodies (DSA) develop following heart transplantation (HT), and are associated with antibody-mediated rejection (AMR). However, treatment of persistently elevated DSA levels remains unclear. We aimed to evaluate the use of intermittent intravenous immunoglobulin (IVIg) for the treatment of elevated DSA. Methods We identified all adult HT recipients receiving monthly IVIg infusions between September 2019 and October 2020. Patient information including serial DSA levels, as well as hemodynamic and echocardiographic characteristics, were collected from the electronic health record. Results The cohort included 17 patients with a mean age of 57 +/- 15 years, 65% were male, & median time from HT was 48 months. 7 patients had prior biopsy-proven AMR, 7 had high mean fluorescence intensity (MFI) DSA alone, and 3 had allograft dysfunction without proven etiology. The average left ventricular ejection fraction (LVEF) prior to IVIg was 50% +/- 14%. Prior to intermittent IVIg 12 patients (71%) received an additional immunosuppressive agent (thymoglobulin, bortezomib, rituximab, belatacept), while 11 of them (65%) also received plasmapheresis. The mean duration of IVIg following pAMR was 7.6 +/- 7 months. DSA MFI decreased by 27% in patients with confirmed diagnosis of AMR and by 10% in those with elevated DSA alone after initiating intermittent IVIg (figure). Both LVEF and cardiac index improved in all three groups following initiation of IVIg infusions. Pulmonary capillary wedge pressure (PCWP) decreased in the elevated DSA and allograft dysfunction groups while it increased in the AMR group. Seven patients were admitted for suspected rejection after starting treatment. Conclusion DSA MFI declined and LVEF improved following initiation of intermittent IVIg infusions. Further study is needed to determine whether IVIg can prevent de novo or recurrent AMR.

Background: Advanced heart failure therapies such as left ventricular assist device (LVAD) implantation require intricate follow-up and complex care. We sought to explore the burden of psychosocial risk factors among patients with LVAD and their impact on postimplant outcomes using the Interagency Registry for Mechanically Assisted Circulatory Support. Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support requiring durable LVAD between 2008 and 2017 were included. Individuals were determined to have psychosocial risk if they had one of the following: (1) limited social support; (2) limited cognition; (3) substance abuse (alcohol and drug); (4) severe psychiatric disease (including major depression and other major psychiatric diagnosis); and (5) repeated noncompliance. Univariate and multivariate Cox proportional hazard regression models were used to analyze predictors of survival and complications. Results: A total of 15 403 continuous-flow LVAD recipients were included. A total of 3163 (20.5%) had one or more psychosocial risk factors. The most prevalent psychosocial risk factor was substance abuse in 1941 (12.6%) recipients. Patients with psychosocial risk factors were significantly younger at LVAD implant, less likely to be White, and less likely to be female compared with those without psychosocial risk, P P P Conclusions: Psychosocial risk is an important component of patient selection for advanced heart failure therapies. Addressing these specific components may help improve access to advanced therapies and post-LVAD outcomes.

The coronavirus disease 2019 (COVID-19) pandemic imposed severe restrictions on traditional methods of patient care. During the pandemic, the heart failure program at New York-Presbyterian Hospital in New York, NY rapidly and comprehensively transitioned its care delivery model and administrative organization to conform to a new healthcare environment while still providing high-quality care to a large cohort of patients with heart failure, heart transplantation, and left ventricular assist device. In addition to the widespread adoption of telehealth, our program restructured outpatient care, initiating a shared clinic model and introducing a comprehensive remote monitoring program to manage patients with heart failure and heart transplant. All conferences, including administrative meetings, support groups, and educational seminars were converted to teleconferencing platforms. Following the peak of COVID-19, many of the new changes have been maintained, and the program structure will be permanently altered as a lasting effect of this pandemic. In this article, we review the details of our program’s transition in the face of COVID-19 and highlight the programmatic changes that will endure.