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Competing Interests: Declaration of competing interest Justin Grodin has consulting or advisory relationships with multiple pharmaceutical companies, including Pfizer, Eidos Therapeutics, Alnylam Pharmaceuticals, AstraZeneca, Alexion Pharmaceuticals, and Intellia Therapeutics. Additionally, Justin Grodin has received funding grants from Pfizer and Eidos Therapeutics. W.H. Wilson Tang has similar consulting or advisory relationships with several companies, including Sequana Medical, Cardiol Therapeutics, Genomics PLC, Zehna Therapeutics, WhiteSwell, Kiniksa Pharmaceuticals, Boston Scientific, CardiaTec Biosciences, and Intellia Therapeutics. Nicholas Hendren also has consulting or advisory relationships with Tosoh Corporation and funding grants from Tricog Health. Maryjane Farr reports a consulting or advisory relationship with TransMedics. Other authors declare no known competing financial interests or personal relationships that could influence their work.

Background: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA., Methods: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4., Results: There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers ( p  < .001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers ( p  = .002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage ( p  < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 ( p  < .05)., Conclusions: V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.

Background: Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking., Objectives: The authors sought to develop and externally validate a machine learning-based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency., Methods: Participants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models., Results: Clustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts., Conclusions: The authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality., Competing Interests: Funding Support and Author Disclosures Dr Pandey has received research support from the National Institute of Health (5R01MD017529, R21HL169708) and grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon Therapies, Medtronic, Edward Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, and Emmi Solutions; has received nonfinancial support from Pfizer and Merck; and is also a consultant for Palomarin Inc with stock compensation. Dr Segar has received honoraria from Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Fonarow has done consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Allen reports grant funding from American Heart Association, National Institutes of Health, and PCORI; and consulting fees from Amgen, Boston Scientific, Cytokinetics, Novartis, and WCG ACI Clinical. Dr Pandey has received grant funding from Applied Therapeutics and Gilead Sciences; has received honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Bayer, Edwards Lifesciences, Medtronic, Sarfez Pharmacuticals, Novo Nordisk, and Roche Diagnostics; has received support from Pfizer and Merck; and is a consultant for Palomarin Inc with stock compensation. Dr Khan serves as an advisory board member for Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR] × peak systolic blood pressure [SBP]-[HR at rest × SBP at rest])/(HR at rest × SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO 2 ), VO 2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO 2 parameters for use in treadmill testing without gas exchange capability., Competing Interests: Disclosures Dr. Grodin reports personal fees from Pfizer, Alnylam, Eidos, and Sarepta. Dr. Tang reports personal fees from Sequana Medical AG, Cardiol Therapeutics Inc, Genomics plc, Springer Nature, and the American Board of Internal Medicine for exam writing committee participation - all unrelated to the subject and contents of this study. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant., Objectives: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13 N-ammonia positron emission tomography (PET) myocardial perfusion imaging., Methods: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET., Results: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation., Conclusions: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment., Competing Interests: Funding Support and Author Disclosures Dr Clerkin has been supported by National Institutes of Health K23 HL148528. Dr Topkara has been supported by National Institutes of Health K08 HL146964. Dr Colombo has received consulting fees from Abbott. Dr Einstein has received speaker fees from Ionetix; has received consulting fees from W. L. Gore and Associates; and his institution has grants/grants pending from Canon Medical Systems, GE Healthcare, Roche Medical Systems, and W. L. Gore and Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Genodermatoses are genetically inherited dermatologic conditions. The management of cutaneous findings in genodermatoses is challenging, and first-line therapies, such as steroids and/or retinoids, are often inadequate. In recent years, research on the molecular basis of genodermatoses has led to the use of biologic therapies for intractable disease. Here, we review the evidence regarding the use of available biologic therapies for the management of dermatologic findings in genodermatoses. Biologic therapies appear to be promising therapeutic options for several recalcitrant genodermatoses, especially those with underlying immune dysregulation. However, not all genodermatoses are amenable to biologic therapies, and some have been shown to paradoxically worsen under treatment. Biologic therapies offer a novel avenue to target refractory genodermatoses. However, evidence supporting the use of biologic therapies in the management of genodermatoses is mostly limited to case reports and case series. Further studies are warranted to determine the safety and efficacy of biologic therapies for the management of cutaneous findings in genodermatoses., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in-hospital VTE after heart transplantation and its association with clinical outcomes., Method: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post-transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies., Results: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60-days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in-hospital mortality (P = .010), and worse 5-year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE., Conclusion: The incidence of VTE in heart transplant recipients is high. Post-transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: For patients with advanced heart failure, socioeconomic deprivation may impede referral for heart transplantation (HT). We examined the association of socioeconomic deprivation with listing among patients evaluated at our institution and compared this against the backdrop of our local community., Methods: We conducted a retrospective cohort study of patients evaluated for HT between January 2017 and December 2020. Patient demographics and clinical characteristics were recorded. Block group-level area deprivation index (ADI) decile was obtained at each patient's home address and Socioeconomic Status (SES) index was determined by patient zip code., Results: In total, 400 evaluations were initiated; one international patient was excluded. Among this population, 111 (27.8%) were women, 219 (54.9%) were White, 94 (23.6%) Black, and 59 (14.8%) Hispanic. 248 (62.2%) patients were listed for transplant. Listed patients had significantly higher SES index and lower ADI compared to those who were not listed. However, after adjustment for clinical factors, ADI and SESi were not predictive of listing. Similarly, patient sex, race, and insurance did not influence the likelihood of listing for HT. Notably, the distribution of the referral cohort based on ADI deciles was not reflective of our center's catchment area, indicating opportunities for improving access to transplant for disadvantaged populations., Conclusions: Although socioeconomic deprivation did not predict listing in our analysis, we recognize the need for broader outreach to combat upstream bias that prevents patients from being referred for HT., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: An aging population and improved cancer survivorship have increased the number of individuals with treated malignancy who develop advanced heart failure. The benefits of heart transplantation (HT) in patients with a pretransplant malignancy (PTM) must be balanced against risks of posttransplant malignancy in the setting of immunosuppression., Methods: Adult patients in the United Network for Organ Sharing registry who received HT between January 1, 2010, and December 31, 2020 were included. Trends, patient characteristics, and posttransplant outcomes in HT recipients with PTM were evaluated., Results: From 2000 to 2020, the proportion of HT recipients with PTM increased from 3.2% to 8.2%. From 2010 to 2020, 2113 (7.7%) of 27 344 HT recipients had PTM. PTM was associated with higher rates of 1-year mortality after HT (11.9% versus 9.2%; adjusted hazard ratio, 1.25 [95% CI, 1.09-1.44], P =0.001), driven by increased mortality in patients with hematologic PTM (adjusted hazard ratio, 2.00 [95% CI, 1.61-2.48]; P <0.001). For recipients who survived the first year, 5-year survival was similar between patients with and without PTM. Rates of malignancy at 5-years posttransplant were higher in the PTM group (20.4% versus 13.1%; adjusted hazard ratio, 1.57 [95% CI, 1.38-1.79], P <0.001)., Conclusions: Prevalence of PTM in HT recipients nearly tripled over the past 2 decades. Patients with hematologic PTM were at increased risk of early mortality after HT. Patients with PTM were also at higher risk for posttransplant malignancy. Guidelines that reflect contemporary oncological care are needed to inform care of this heterogenous and expanding group of individuals.

Although the burden of end-stage heart failure continues to increase, the number of available organs for heart transplantation (HT) remains inadequate. The HT community has been challenged to find ways to expand the number of donor hearts available. Recent advances include use of hearts from donors infected with hepatitis C virus as well as other previously underutilized donors, including those with left ventricular dysfunction, of older age, and with a history of cocaine use. Concurrently, emerging trends in HT surgery include donation after circulatory death, ex vivo normothermic heart perfusion, and controlled hypothermic preservation, which may enable procurement of organs from farther distances and prevent early allograft dysfunction. Contemporary HT recipients have also evolved in light of the 2018 revision to the U.S. heart allocation policy. This focus seminar discusses recent trends in donor and recipient phenotypes and management strategies for successful HT, as well as evolving areas and future directions., Competing Interests: Funding Support and Author Disclosures Dr Khush is on the scientific advisory board and Speakers Bureau for CareDx. Dr Kilic is a speaker/consultant for Abiomed and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The 2018 U.S. heart allocation system offers an accelerated pathway for heart transplantation to the most urgent patients., Objectives: This study sought to determine whether the new allocation system resulted in lower likelihood of candidate recovery., Methods: Adult patients waitlisted for heart transplantation with temporary mechanical circulatory support at the time of initial listing between 2010 and 2020 in the United Network for Organ Sharing registry were included. Competing events of heart transplantation, waitlist death or delisting for deteriorating condition, and delisting for improved condition (candidate recovery) were analyzed in the new vs old heart allocation system., Results: A total of 688 patients were waitlisted with venoarterial extracorporeal membrane oxygenation or a surgical nondischargeable biventricular assist device (status 1 or old 1A). Overall, 2,237 patients were waitlisted with an intra-aortic balloon pump, a percutaneous left ventricular assist device (LVAD), or a surgical nondischargeable LVAD (status 2 or old 1A). Patients waitlisted with venoarterial extracorporeal membrane oxygenation or a nondischargeable biventricular assist device had significantly shorter median waitlist times (5 vs 31 days), higher incidence for cardiac transplantation (81.5% vs 43.0%), and lower incidence of candidate recovery (1.5% vs 7.9%) in the new vs old heart allocation system (all P < 0.05). Patients waitlisted with an intra-aortic balloon pump or percutaneous or a nondischargeable LVAD also had significantly shorter median waitlist times (8 vs 35 days), higher incidence of transplantation (88.9% vs 64.9%), and lower incidence of candidate recovery (0.2% vs 1.6%) in the new vs old heart allocation system (all P < 0.05)., Conclusions: Current practice of the new allocation system may not offer select temporary mechanical circulatory support patients the opportunity and adequate time to recover to the point of waitlist removal. Further research will determine which patients would benefit from urgent transplantation vs recovery strategy., Competing Interests: Funding Support and Author Disclosures Dr Topkara has been supported by NIH K08 HL146964. Dr Sayer has received consulting fees from Abbott Laboratories. Dr Clerkin has been supported by NIH K23 HL148528. Dr Wever-Pinzon has been supported by NIH K23 HL150322. Dr Burkhoff has received institutional educational grant support from Abiomed; and has received consulting fees from CardioDyme Inc and from Abbott Laboratories unrelated to mechanical circulatory assist. Dr Uriel has received consulting fees from Leviticus and LiveMetric. Dr Drakos is supported by the American Heart Association Heart Failure Strategically Focused Research Network (16SFRN29020000), NIH R01 HL135121, NIH R01 HL132067, Merit Review Award I01 CX0002291 (U.S. Department of Veterans Affairs), and Nora Eccles Treadwell Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition., Methods: All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0-100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires., Results: Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid)., Conclusions: More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Intra-aortic balloon pump (IABP) support may improve the hemodynamic profiles of patients in cardiogenic shock and bridge patients to heart transplant. In 2018, the United Network for Organ Sharing (UNOS) introduced new heart allocation criteria that increased the waitlist status of patients with IABPs to Status 2. This study assesses the impact of this change on IABP use and outcomes of patients with IABPs., Methods: We queried the UNOS database for first adult heart transplant candidates with IABPs listed or transplanted before and after the UNOS policy changes (October 18, 2016-October 17, 2018, or October 18, 2018-September 4, 2020). We compared post-transplant survival and waitlist outcomes using Kaplan-Meier and Fine-Gray analyses., Results: Two thousand three hundred fifty-eight patients met inclusion criteria. Utilization of IABPs for hemodynamic support increased by 338% in the two years after the policy change. Patients with IABPs listed after the policy change were more likely to receive a transplant and were transplanted more quickly (p < .001). Posttransplant survival was comparable before and after the policy change (p = .056), but non-transplanted patients were more likely to be delisted post-policy change (p < .001)., Conclusion: The UNOS allocation criteria have benefited patients bridged with an IABP, given the higher transplant rate and shorter time to transplant., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study. Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels and Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. Electronic medical records were reviewed to examine posttransplant outcomes. Thirty-eight HM3 and 34 HMII patients with complete data were followed for 1.5 ± 1.1 years on device support. HM3 and HMII groups had similar age at implant, female gender, ischemic heart failure etiology, bridge strategy at implant, as well as intraoperative and postoperative transfusion requirements. 39.5% of HM3 and 47.1% of HMII patients developed detectable HLA antibodies by Luminex testing (p = 0.516). Development of high-level (mean fluorescence intensity >10,000) antibodies was significantly lower in HM3 than HMII patients (5.3 vs. 20.6%, p = 0.049). CDC PRA testing showed fewer HM3 patients with a positive result (PRA > 0%) than HMII patients (39.4 vs. 70.0%, p = 0.015). Among transplanted patients, those who had developed de novo sensitization on LVAD support showed a trend toward incidence of moderate to severe grade rejection compared with unsensitized patients (23.8 vs. 4.8%, p = 0.078). HM3 is associated with lower risk of de novo HLA sensitization compared with HMII., (Copyright © ASAIO 2021.)

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., Competing Interests: Funding Support and Author Disclosures Dr Clerkin is supported by National Heart, Lung and Blood Institute grant K23 HL148528. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy; as such, novel systemic therapies are important for the treatment of locally advanced or metastatic disease. Histone deacetylase (HDAC) inhibitors have been increasingly studied in recent years as epigenome-targeted therapy for cSCC. HDACs inhibitors reduce tumorigenesis by blocking HDAC activity and creating a more relaxed chromatin structure, thus inducing gene expression by inhibiting deacetylation of transcription factors. In vitro experiments and in vivo mice studies have shown that HDAC inhibition halts cSCC pathogenesis. Ginsenoside 20(R)-Rg3 has been successfully employed to inhibit HDAC3 and thereby inhibit cSCC epithelial mesenchymal transition. Similarly, vorinostat has been found to blunt growth of human xenograft epidermoid cSCCs in highly immunosuppressed mice. Additionally, trichostatin A induces irreversible growth arrest in SCC cells, and MS-275 significantly reduces cSCC tumor burden in mice. These recent studies indicate that HDAC inhibitors represent a promising emerging therapy for cSCC.

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., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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, 2004, through October 18, 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 1-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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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) and >10 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 P < 0.001). The high CRP group had higher WBC counts and BNP levels (all P < 0.001). After adjustment, higher CRP (>10 mg/L) was associated with greater risk of mortality, RV failure, and stroke postimplant (P < 0.001). In addition, elevated postimplant CRP level at 3 months was associated with increased mortality and stroke on LVAD support (P < 0.001). 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., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

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., (© 2021 Wiley Periodicals LLC.)

The coronavirus disease 2019 (COVID-19) pandemic has fundamentally transformed the landscape of providing dermatologic care. In an age of lockdowns and social distancing, teledermatology (TD) has emerged as a powerful tool to deliver remote care. Here, we review literature on TD use during the pandemic to evaluate the positives and negatives of TD implementation. We especially consider the reception of TD in underserved communities and the developing world as well as the ethico-legal challenges wrought by the burgeoning utilization of this new paradigm of care. The potential of TD to occupy a more prominent role in dermatologic care in a post-COVID-19 world is also discussed.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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 <0.001), without increased risk of death or delisting for worsening clinical status (hazard ratio, 0.83 [0.65-1.05], 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.

Objectives: 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., Background: 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., Methods: 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., Results: 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)., Conclusions: There was no difference in mortality on pump support compared with posttransplant mortality among those bridged from ECMO to LVAD or HT., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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 and 18 F-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.

The new heart transplantation (HT) allocation policy was introduced on 10/18/2018. Using the UNOS registry, we examined early outcomes following HT for restrictive cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis, or cardiac amyloidosis compared to the old system. Those listed who had an event (transplant, death, or waitlist removal) prior to 10/17/2018 were in Era 1, and those listed on or after 10/18/2018 were in Era 2. The primary endpoint was death on the waitlist or delisting due to clinical deterioration. A total of 1232 HT candidates were included, 855 (69.4%) in Era 1 and 377 (30.6%) in Era 2. In Era 2, there was a significant increase in the use of temporary mechanical circulatory support and a reduction in the primary endpoint, (20.9 events per 100 PY (Era 1) vs. 18.6 events per 100 PY (Era 2), OR 1.98, p = .005). Median waitlist time decreased (91 vs. 58 days, p < .001), and transplantation rate increased (119.0 to 204.7 transplants/100 PY for Era 1 vs Era 2). Under the new policy, there has been a decrease in waitlist time and waitlist mortality/delisting due to clinical deterioration, and an increase in transplantation rates for patients with infiltrative, hypertrophic, and restrictive cardiomyopathies without any effect on post-transplant 6-month survival., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Extracorporeal membrane oxygenation (ECMO) is becoming a key tool for bridge to heart, lung, or heart-lung transplantation, and ambulatory ECMO support offers many advantages to prepare the patients. We here present a case of successful en bloc heart and lung transplantation after long-term ambulatory support with a minimally invasive central venoarterial ECMO approach as bridge to transplant.

Background: Late graft failure (LGF) is an unresolved issue after orthotopic heart transplant (OHT). In this study, we report characteristics and outcomes of severe LGF requiring mechanical circulatory support (MCS)., Methods: All patients undergoing OHT from 2000 to 2018 at our center were reviewed. Patients re-admitted to the hospital for late graft failure (>3 months after initial discharge) and developing cardiogenic shock requiring MCS were identified. Outcomes and mortality were evaluated., Results: Twenty-six patients were identified. Median age was 37.3 years (interquartile range: 28.2-47.6) and 69% were male. Median time from initial transplant to MCS was 2.9 years. Etiology of graft failure was rejection in 19 patients (73%), transplant coronary artery disease (tCAD) in 3 (12%), with mixed tCAD or rejection in 4 (15%)., (© 2020 Wiley Periodicals LLC.)

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., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Importance: Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression., Objective: To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19., Design, Setting, and Participants: This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020. All recipients of HT followed up by this center who were infected with COVID-19 were included., Interventions: Heart transplant and a confirmed diagnosis of COVID-19., Main Outcomes and Measures: The primary measure was vital status at end of study follow-up. Secondary measures included patient characteristics, laboratory analyses, changes to immunosuppression, and treatment administered for COVID-19., Results: Twenty-eight patients with HT received a confirmed diagnosis of COVID-19. The median age was 64.0 (interquartile range [IQR], 53.5-70.5) years, 22 (79%) were men, and the median time from HT was 8.6 (IQR, 4.2-14.5) years. Comorbid conditions included hypertension in 20 patients (71%), diabetes in 17 patients (61%), and cardiac allograft vasculopathy in 16 patients (57%). Twenty-two participants (79%) were admitted for treatment, and 7 (25%) required mechanical ventilation. Most (13 of 17 [76%]) had evidence of myocardial injury (median high-sensitivity troponin T, 0.055 [IQR, 0.0205-0.1345] ng/mL) and elevated inflammatory biomarkers (median peak high-sensitivity C-reactive protein, 11.83 [IQR, 7.44-19.26] mg/dL; median peak interleukin 6, 105 [IQR, 38-296] pg/mL). Among patients managed at the study institution, mycophenolate mofetil was discontinued in 16 patients (70%), and 6 (26%) had a reduction in the dose of their calcineurin inhibitor. Treatment of COVID-19 included hydroxychloroquine (18 patients [78%]), high-dose corticosteroids (8 patients [47%]), and interleukin 6 receptor antagonists (6 patients [26%]). Overall, 7 patients (25%) died. Among 22 patients (79%) who were admitted, 11 (50%) were discharged home, 4 (18%) remain hospitalized at the end of the study, and 7 (32%) died during hospitalization., Conclusions and Relevance: In this single-center case series, COVID-19 infection was associated with a case fatality rate of 25% in recipients of HT. Immunosuppression was reduced in most of this group of patients. Further study is required to evaluate the optimal approach to management of COVID-19 infection in the HT population.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 <0.001 for all. Patients with psychosocial risk were significantly more likely to receive an LVAD as destination therapy, P <0.001. In adjusted models, patients with psychosocial risk were at increased hazards for device-related infection, gastrointestinal bleeding, pump thrombosis, and readmission and reduced hazards for cardiac transplantation ( P <0.05 for all). There was no statistically significant difference in survival on pump support or stroke., 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.

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., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: 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., Methods: 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., Results: Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p < 0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p < 0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I-III) as well as in patients with LVAD and HT (p < 0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I-III, p < 0.05) but not in patients with HT., Conclusions: 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., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Importance: Solid organ transplants have declined significantly during the coronavirus disease (COVID-19) pandemic in the US. Limited data exist regarding changes in heart transplant (HT)., Objective: To describe national and regional trends in waitlist inactivations, waitlist additions, donor recovery, and HT volume during COVID-19., Design, Setting, and Participants: This descriptive cross-sectional study used publicly available data from the United Network for Organ Sharing and US Centers for Disease Control and Prevention, using 8 prespecified United Network for Organ Sharing regions. Adult (18 years or older) HT candidates listed and deceased donors recovered between January 19 to May 9, 2020., Exposures: COVID-19 pandemic., Main Outcomes and Measures: Changes in waitlist inactivations, waitlist additions, deceased donor recovery, and transplant volumes from the pre-COVID-19 (January 19-March 15, 2020) to the COVID-19 era (March 15-May 9, 2020). Density mapping and linear regression with interrupted time series analysis were used to characterize changes over time and changes by region., Results: During the COVID-19 era, there were 600 waitlist inactivations compared with 343 during the pre-COVID era (75% increase). Waitlist additions decreased from 637 to 395 (37% reduction). These changes were most profound in the Northeast and Great Lakes regions with high rates of COVID-19. Deceased donor recovery decreased by 26% from 1878 to 1395; the most significant decrease occurred in the North Midwest despite low COVID-19 prevalence. Heart transplant volumes were significantly reduced across all regions except the Northwest. The largest decrease was seen in the Northeast where COVID-19 case rates were highest. From the pre-COVID-19 era to the COVID-19 era, there was significant regional variation in waitlist additions (eg, 69% decrease in the Northeast vs 8.5% increase in the South Midwest; P < .001) and deceased donor recovery (eg, 41% decrease in North Midwest vs 16% decrease in South Midwest; P = .02)., Conclusions and Relevance: Heart transplant volumes have been significantly reduced in recent months, even in regions with a lower prevalence of COVID-19 cases. This has been accompanied by increased waitlist inactivations, decreased waitlist additions, and decreased donor recovery. Future studies are needed to determine if the COVID-19 pandemic is associated with changes in waitlist mortality.