<div><h4>Aortic Root Thrombosis in Patients with HeartMate 3 Left Ventricular Assist Device Support.</h4><i>Carey MR, Marshall D, Clerkin K, Laracuente R, ... Topkara VK, Fried JA</i><br /><b>Background</b><br />Aortic root thrombus (ART) formation is a complication of continuous flow left ventricular assist device (LVAD) therapy. However, the incidence and related complications of ART in HeartMate 3 (HM3) patients remains unknown.<br /><b>Methods</b><br />Patients who underwent HM3 implantation from November 2014 through August 2020 at a quaternary academic medical center were included. Demographics and outcomes were abstracted from the medical record. Echocardiograms and contrast-enhanced CT studies were reviewed to identify patients who developed ART and/or moderate or greater aortic insufficiency (AI) on HM3 support.<br /><b>Results</b><br />The study cohort included 197 HM3 patients with a median post-implant follow-up of 17.5 months. Nineteen patients (9.6%) developed ART during HM3 support, and 15 patients (7.6%) developed moderate or greater AI. Baseline age, gender, race, implantation strategy, and INTERMACS classification were similar between the ART and no-ART groups. ART was associated with an increased risk of death, stroke, or AV intervention (subhazard ratio [SHR] 3.60 [95% CI 1.71-7.56]; p=0.001) and moderate or greater AI (SHR 11.1 [CI 3.60-34.1]; p<0.001) but was not associated with a statistically significantly increased risk of death or stroke on HM3 support (2.12 [0.86-5.22]; p=0.10). Of the 19 patients with ART, 6 (31.6%) developed moderate or greater AI, necessitating more frequent AV interventions (ART: 5 AV interventions [3 surgical repairs, 1 surgical replacement, 1 transcatheter replacement; 26.3%]; no-ART: 0).<br /><b>Conclusion</b><br />Nearly 10% of HM3 patients developed ART during device support. ART was associated with increased risk of a composite endpoint of death, stroke, or AV intervention as well as moderate or greater AI.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 20 Sep 2023; epub ahead of print</small></div>

<div><h4>Perioperative Extracorporeal Membrane Oxygenation Support for Pulmonary Endarterectomy: A 17-year Experience from the UK National Cohort.</h4><i>Chia AXF, Valchanov K, Ng C, Tsui S, ... Fowles JA, Jenkins DP</i><br /><b>Background</b><br />Pulmonary endarterectomy(PEA) is the guideline recommended treatment for patients with chronic thromboembolic pulmonary hypertension(CTEPH). However, some patients develop severe cardiopulmonary compromise either prior to surgery, intraoperatively or early postoperatively. This may result from advanced CTEPH, reperfusion pulmonary oedema, massive endobronchial bleeding or right ventricular(RV) failure secondary to residual pulmonary hypertension. Conventional cardiorespiratory support is ineffective when these complications are severe. Since 2005 we used extracorporeal membrane oxygenation(ECMO) as a rescue therapy for this group. We review our experience with ECMO support in these patients.<br /><b>Methods</b><br />Retrospective analysis of patients who received perioperative ECMO for PEA from a single national centre from August 2005 to July 2022. Data was prospectively collected.<br /><b>Results</b><br />One hundred and ten patients (4.7%) had extreme cardiorespiratory compromise requiring perioperative ECMO. Nine were established on ECMO before PEA. Of those who received ECMO postoperatively, thirty-nine were for refractory reperfusion lung injury, twenty for RV failure, thirty-one for endobronchial bleeding and the remaining eleven were for \'other\' reasons such as cardiopulmonary resuscitation following late tamponade and aspiration pneumonitis. 62 (56.4%) were successfully weaned from ECMO. 57 patients left the hospital alive giving a salvage rate of 51.8%. High BMI was identified as an independent risk factor for worse outcome for patients needing ECMO for reperfusion lung injury(p<0.001). Distal disease(Jamieson Type III) and significant residual pulmonary hypertension were also predictors of mortality on ECMO support. Overall 5 and 10-year survival in patients who were discharged alive following ECMO support was 73.9% (SE: 6.1%) and 58.2% (SE: 9.5%), respectively.<br /><b>Conclusion</b><br />Perioperative ECMO support has an appropriate role as rescue therapy for this group. Over 50% survived to hospital discharge. These patients had satisfactory longer-term survival.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Relationship Between Blood and Tissue-Based Rejection-Related Transcripts in Heart Transplantation.</h4><i>Lee DH, Usmani A, Ravichandran V, Wicks T, ... Oliveira GH, Mackie B</i><br /><b>Purpose</b><br />The purpose of the study is to investigate the relationship between blood and tissue-derived rejection-related transcripts from blood gene expression profiling (GEP) and molecular microscope in the setting of allograft rejection in heart transplant.<br /><b>Methods</b><br />All heart transplant patients from August 2021 to May 2022 with both circulating blood GEP (AlloMap; CareDx) and endomyocardial biopsy with molecular microscope diagnostic system (MMDx, One Lambda) within 4 weeks were included (N=173 samples). We obtained individual blood GEP-based mRNA transcript expression levels of the 11 target genes from CareDx. Student\'s t-test was performed to compare blood GEP transcript expression levels between no rejection and rejection as assessed by MMDx. A Scatter plot with Spearman correlation analysis was performed to compare the relationship between transcript expression levels from AlloMap and MMDx, with and without allograft rejection.<br /><b>Results</b><br />There were 52 samples (30.1%) with antibody-mediated rejection (ABMR) and 15 samples (8.7%) with T-cell-mediated rejection (TCMR), as assessed by MMDx. Expression of one of the blood ITGA4 (Integrin alpha 4) expression level was elevated in ABMR, compared to no ABMR (4607.5 vs 4217.5; p=0.019). Most tissue RAT expression levels were elevated in ABMR, and tissue ROBO4 expression correlated with the blood ITGA4 expression with moderate or greater effect size in all samples (Spearman\'s R 0.31; p<0.001). There was also a positive correlation between blood ITGA4 and tissue ROBO4 expression in samples without ABMR (Spearman\'s R 0.33; p<0.001), but no correlation between blood ITGA4 and tissue ROBO4 expression in samples with ABMR (Spearman\'s R=0.009; p=0.513).<br /><b>Discussion</b><br />Circulating blood ITGA4 expression is elevated in AMR and correlate with myocardial expression of ROBO4. The knowledge of individual transcript expression levels in blood and in tissue may provide insights into various disease processes in heart transplant patients. Taken together, the results of our study reveal an overlap between two objective post-heart transplant rejection surveillance methods, identify potential novel markers for ABMR, and reveal the need for a deeper understanding of molecular mechanisms underlying allograft rejection.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Acute Rejection In Donation After Circulatory Death (DCD) Heart Transplants.</h4><i>Li SS, Funamoto M, Osho AA, Rabi SA, ... Lewis GD, D\'Alessandro DA</i><br /><b>Background</b><br />Donation after circulatory death (DCD) heart transplantation has promising early survival, but effects on rejection remain unclear.<br /><b>Methods</b><br />The United Network for Organ Sharing (UNOS) database was queried for adult heart transplants from 12/01/2019 to 12/31/2021. Multiorgan transplants and loss to follow-up were excluded. Primary outcome was acute rejection, comparing DCD and donation after brain death (DBD) transplants.<br /><b>Results</b><br />A total of 292 DCD and 5582 DBD transplants met study criteria. Most DCD transplants were transplanted at status 3-4 (61.0%) compared to 58.6% of DBD recipients at status 1-2. DCD recipients were less likely to be hospitalized at transplant (26.7% vs 58.3%, p<0.001) and to require IABP (9.6% vs 28.9%, p<0.001), ECMO (0.3% vs 5.9%, p<0.001) or temporary LVAD (1.0% vs 2.7%, p<0.001). DCD recipients were more likely to have acute rejection prior to discharge (23.3% vs 18.4%, p=0.044) and to be hospitalized for rejection (23.4% vs 11.4%, p=0.003) at a median follow-up of 15 months; the latter remained significant after propensity-matching. On multivariable logistic regression, DCD donation was an independent predictor of acute rejection (OR 1.47, 95% CI 1.00-2.15, p=0.048) and hospitalization for rejection (OR 2.03, 95% CI 1.06-3.70, p=0.026). On center-specific subgroup analysis, DCD recipients continued to have higher rates of hospitalization for rejection (23.4% vs 13.8%, p=0.043).<br /><b>Conclusion</b><br />DCD recipients are more likely to experience acute rejection. Early survival is similar between DCD and DBD recipients but long term implications of increased early rejection in DCD recipients requires further investigation.<br /><br />Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 15 Sep 2023; epub ahead of print</small></div>

<div><h4>COVID-19 outcomes in heart transplant recipients: a large Australian cohort.</h4><i>Cherrett C, Cao J, Adams C, Macdonald PS</i><br /><AbstractText>Heart transplant recipients have been reported to be at a significantly elevated risk of poor outcomes from COVID-19 infection owing to their underlying comorbidities and immunosuppression. We conducted a single-centre retrospective cohort of all heart transplant recipients who were known to have contracted COVID-19 between January 2020 to September 2022. Electronic medical records were used to collect baseline demographics, vaccination status, COVID-19 treatment received, hospitalisation data and mortality. Our primary endpoint was mortality and our secondary endpoint was hospitalisation. Between January 2020 and September 2022, 132 heart transplant recipients at our single centre contracted COVID-19 infection. Our population had high rates of vaccination with 124 patients (94%) having received at least 2 vaccines. We found significantly lower rates of mortality and hospitalisation than had been previously reported earlier in the pandemic, with a mortality rate of 8/132 (6%) and hospitalisation rate of 21/132 (16%).</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 14 Sep 2023; epub ahead of print</small></div>

<div><h4>The central role of ubiquitin-specific protease 8 in leptin signaling pathway in pulmonary arterial hypertension.</h4><i>Jutant EM, Chelgham MK, Ottaviani M, Thuillet R, ... Ly TU, Huertas A</i><br /><b>Aims</b><br />Leptin receptor (ObR-b) is overexpressed in pulmonary artery smooth muscle cells (PA-SMCs) from pulmonary arterial hypertension (PAH) patients and is implicated in both mechanisms that contribute to pulmonary vascular remodeling: hyperproliferation and inflammation. Our aim was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in ObR-b overexpression in PAH.<br /><b>Methods and results</b><br />We performed in situ and in vitro experiments in human lung specimens and isolated PA-SMCs combined with two different in vivo models in rodents and we generated a mouse with an inducible USP8 deletion specifically in smooth muscles. Our results showed an upregulation of USP8 in the smooth muscle layer of distal pulmonary arteries from patients with PAH, and upregulation of USP8 expression in PAH PA-SMCs, compared to controls. USP8 inhibition in PAH PA-SMCs significantly blocked both ObR-b protein expression level at the cell surface as well as ObR-b-dependant intracellular signaling pathway as shown by a significant decrease in pSTAT3 expression. USP8 was required for ObR-b activation in PA-SMCs and its inhibition prevented Ob-mediated cell proliferation through STAT3 pathway. USP8 inhibition by the chemical inhibitor DUBs-IN-2 protected against the development of experimental PH in the two established experimental models of PH. Targeting USP8 specifically in smooth muscle cells in a transgenic mouse model also protected against the development of experimental PH.<br /><b>Conclusions</b><br />Our findings highlight the role of USP8 in ObR-b overexpression and pulmonary vascular remodeling in PAH.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Cardiac Allograft Vasculopathy and Survival in Pediatric Heart Transplant Recipients Transitioned to Adult Care.</h4><i>Rodenas-Alesina E, Aleksova N, Stubbs M, Foroutan F, ... Ross H, Dipchand A</i><br /><b>Background</b><br />Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in pediatric recipients transitioned to adult care.<br /><b>Methods</b><br />We conducted a retrospective review of consecutive pediatric HT patients from 1989-2017 at the Hospital for Sick Children who transitioned to adult care at ≥18 years at Toronto General Hospital. We evaluated the incidence of ISHLT CAV grade ≥1 using competing risk models. We assessed the association between all-cause mortality and CAV using Cox proportional hazards and used Kaplan Meier methods to evaluate all-cause mortality stratified by CAV and transplant era (1989-2001, 2002-2017).<br /><b>Results</b><br />96 patients were transitioned to adult care by 01/2022, of which 53 underwent repeat coronary angiography as adults. CAV was newly diagnosed in 49% patients after transition to adult care. The overall incidence of CAV was 3.9 cases per 100 person-years. There was no difference in the adjusted incidence of CAV according to transplant era (SHR = 1.17, 95% CI 0.54-2.66). CAV was associated with a higher risk of death in the early era (HR 10.29, 95% CI 2.16-49.96), but not in the recent era (HR 1.61, 95% 0.35-7.47).<br /><b>Conclusions</b><br />There is a role for continued CAV surveillance after the transition to adult care. The implications of diagnosing CAV after the transition to adult care requires further study, particularly because the risk of death in pediatric HT recipients diagnosed with CAV in the more recent era may be attenuated compared to the earlier HT era.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Living-Donor Lobar Lung Transplantation.</h4><i>Date H</i><br /><AbstractText>Living-donor lobar lung transplantation (LDLLT) is indicated for critically ill patients who would not survive the waiting period in the case of severe brain-dead donor shortage. It is essential to confirm that potential donors are willing to donate without applying psychological pressure from others. In standard LDLLT, the right and left lower lobes donated by two healthy donors are implanted into the recipient under cardiopulmonary support. LDLLT can be applied to various lung diseases including restrictive, obstructive, infectious and vascular lung diseases in both adult and pediatric patients if size matching is acceptable. Functional size matching by measuring donor pulmonary function and anatomical size matching by three-dimensional computed tomography (3D-CT) volumetry are very useful. When two donors with ideal size matching are not available, various transplant procedures, such as single lobe, segmental, recipient lobe-sparing and inverted lobar transplants are valuable options. There seems to be immunological advantages in LDLLT as compared to cadaveric lung transplantation (CLT). Unilateral chronic allograft dysfunction is a unique manifestation after bilateral LDLLT, which may contribute to better prognosis. The growth of adult lung graft implanted into growing pediatric recipients is suggested by radiologic evaluation. Although only two lobes are implanted, postoperative pulmonary function is equivalent between LDLLT and CLT. The long-term outcome after LDLLT is similar to or better than that after CLT. The author has performed 164 LDLLTs resulting in 71.6% survival rate at 10 years. All living-donors returned to their previous life styles. Because of possible serious morbidity in donors, LDLLT should be applied only for critically ill patients.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 11 Sep 2023; epub ahead of print</small></div>

<div><h4>Treatment of Staphylococcus aureus infection with sphingosine in ex vivo perfused and ventilated lungs.</h4><i>Liu Y, Wu Y, Leukers L, Schimank K, ... Gulbins E, Kamler M</i><br /><b>Background</b><br />Ex vivo lung perfusion (EVLP) has expanded the donor pool for lung transplantation. Pulmonary Staphylococcus aureus infection, especially that caused by multidrug resistant strains, is a severe threat to post-transplantation outcomes. Sphingosine is a lipid compound that exhibits broad-spectrum antibacterial activity. Therefore, we aimed to evaluate the effects of S. aureus infection on EVLP and whether sphingosine administration during EVLP prevents infection with S. aureus.<br /><b>Methods</b><br />Eighteen pigs were randomly assigned to three groups: uninfected, infected with S. aureus with NaCl treatment, or infected with sphingosine treatment. Bacterial numbers were determined before and after treatment. Sphingosine concentrations in the lung tissues were determined using biochemical assays. Lung histology, lung physiological parameters, perfusate content, lung weight, and cell death were measured to analyze the effects of infection and sphingosine administration on EVLP.<br /><b>Results</b><br />Sphingosine administration significantly reduced the bacterial load. The concentration of sphingosine in the bronchial epithelium was elevated after sphingosine administration. S. aureus infection increased pulmonary artery pressure and pulmonary vascular resistance. Lung edema, histology scores, lactate and lactate dehydrogenase levels in the perfusate, ΔPO<sub>2</sub> in the perfusate, static lung compliance, and lung peak airway pressure did not differ among the groups.<br /><b>Conclusion</b><br />Infection of S. aureus did not affect the lung function during ex vivo lung perfusion but induced higher pulmonary artery pressure and pulmonary vascular resistance. Administration of sphingosine effectively eliminated S. aureus without side effects in isolated, perfused, and ventilated pig lungs.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 04 Sep 2023; epub ahead of print</small></div>

<div><h4>Extracorporeal driveline vibrations to detect left ventricular assist device thrombosis - a porcine model study.</h4><i>Lilja D, Schalit I, Espinoza A, Hoel TN, ... Pettersen FJ, Halvorsen PS</i><br /><b>Background</b><br />Pump thrombosis (PT) and related adverse complications contributed to the HVAD™ market withdrawal. Many patients still receive lifelong support, with deficient PT surveillance based on pump power trends. Analysis of pump vibrations is better for detecting PT. Here, we investigated the feasibility of an extracorporeal accelerometer to detect PT from pump vibrations propagated out on the driveline.<br /><b>Method</b><br />In a porcine HVAD™ model (n=6), an accelerometer was attached to the pump as a reference and another to the driveline for comparisons of signals. In total, 59 thrombi were injected into the heart to induce PT, followed by intermittent thrombus washout maneuvers. Signals were compared visually in spectrograms and quantitatively in third harmonic saliences (S<sub>3H</sub>) by correlation analysis. ROC curves expressed the method\'s outcome in sensitivity versus specificity, with the overall diagnostic performance in the area under the curve (AUC) score.<br /><b>Results</b><br />Five experiments had good driveline signal strength, with clear spectrographic relationships between the two accelerometers. Third harmonic driveline vibrations were visible 20 versus 30 times in the reference. The comparison in S<sub>3H</sub> showed a strong correlation and yielded an AUC of 0.85. Notably, S<sub>3H</sub> proved robust regarding noise and false PT detections.<br /><b>Conclusion</b><br />An extracorporeal accelerometer on the driveline can be a readily available method for accurate HVAD™ PT detection before an accelerometer integration with LVAD is feasible.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 04 Sep 2023; epub ahead of print</small></div>

<div><h4>Short Airway Telomeres are Associated with Primary Graft Dysfunction and Chronic Lung Allograft Dysfunction.</h4><i>Greenland JR, Guo R, Lee S, Tran L, ... Singer JP, Wolters PJ</i><br /><AbstractText>Primary graft dysfunction (PGD) is a major risk factor for chronic lung allograft dysfunction (CLAD) following lung transplantation, but the mechanisms linking these pathologies are poorly understood. We hypothesized that the replicative stress induced by PGD would lead to erosion of telomeres, and that this telomere dysfunction could potentiate CLAD. In a longitudinal cohort of 72 lung transplant recipients with >6 years median follow-up time, we assessed tissue telomere length, PGD grade, and freedom from CLAD. Epithelial telomere length and fibrosis-associated gene expression were assessed on endobronchial biopsies taken at 2 - 4 weeks post-transplant by TeloFISH assay and nanoString digital RNA counting. Negative-binomial mixed-effects and Cox-proportional hazards models accounted for TeloFISH staining batch effects and subject characteristics including donor age. Increasing grade of PGD severity was associated with shorter airway epithelial telomere lengths (P = 0.01). Transcriptomic analysis of fibrosis-associated genes showed alteration in fibrotic pathways in airway tissue recovering from PGD, while telomere dysfunction was associated with inflammation and impaired remodeling. Shorter tissue telomere length was in turn associated with increased CLAD risk, with a hazard ratio of 1.89 (95% CI 1.16 - 3.06) per standard deviation decrease in airway telomere length, after adjusting for subject characteristics. PGD may accelerate telomere dysfunction, potentiating immune responses and dysregulated repair. Epithelial cell telomere dysfunction may represent one of several mechanisms linking PGD to CLAD.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 28 Aug 2023; epub ahead of print</small></div>

<div><h4>Characteristics and Outcomes of Lung Transplants Performed with Ex-situ Lung Perfusion.</h4><i>Xia Y, Kim ST, Dacey M, Sayah D, Biniwale R, Ardehali A</i><br /><b>Background</b><br />Ex-situ lung perfusion (ESLP) can be used to assess and rehabilitate donor lungs, potentially expanding the donor pool. We examined the characteristics and outcomes of lung transplants performed with ESLP in the United States.<br /><b>Methods</b><br />Retrospective review of the United Network for Organ Sharing (UNOS) registry of primary adult lung transplant recipients from February 28, 2018 to June 30, 2021 was performed, comparing baseline characteristics, in-hospital outcomes, and one-year survival of ESLP versus no ESLP lung transplants.<br /><b>Results</b><br />Of 8,204 lung transplants, 426(5.2%) were performed with ESLP. ESLP donors were older, more donation after circulatory death (DCD), and had lower P:F ratios. Recipients had lower lung allocation scores. ESLP lungs traveled further, had longer preservation times, and were more likely double lung transplants. Reintubation rates, ECMO at 72 hours, and hospital length of stay were greater in the ESLP group. On multivariable analysis, ESLP was not an independent predictor of one-year survival. However, further analysis showed that DCD lungs managed on ESLP had worse 1-year survival compared to DCD lungs preserved with standard cold storage or with donation after brain death donor lungs.<br /><b>Conclusions</b><br />ESLP is used in a small percentage of lung transplants in the US and is not independently associated with one-year survival. ESLP combined with DCD lungs, however, is associated with worse one-year survival and warrants further investigation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Increased disparities in waitlist and post-heart transplantation outcomes according to socioeconomic status with the new heart transplant allocation system.</h4><i>Kelty CE, Dickinson M, Leacche M, Jani M, ... McNeely E, Loyaga-Rendon R</i><br /><b>Background</b><br />The study objective was to assess disparities in outcomes in the waitlist and post-heart transplantation (HT) according to socioeconomic status (SES) in the old and new U.S. HT allocation systems.<br /><b>Methods</b><br />Adult HT candidates in the UNOS database from 2014 through 2021 were included. Old or new system classification was according to listing before or after October 18, 2018. SES was stratified by patient ZIP code and median household income via U.S. Census Bureau and classified into terciles. Competing waitlist outcomes and post-transplantation survival were compared between systems.<br /><b>Results</b><br />In total, 26,450 patients were included. Waitlisted candidates with low SES were more frequently younger, female, African American, and with higher BMI. Reduced cumulative incidence (CI) of HT in the old system occurred in low SES (53.5%) compared to middle (55.7%, p=0.046), and high (57.9%, p<0.001). In the new system, the CI of HT was 65.3% in the low SES versus middle (67.6%, p=0.002) and high (70.2%, p<0.001), and SES remained significant in the adjusted analysis. In the old system, CI of death/delisting was similar across SES. In the new system, low SES had increased CI of death/delisting (7.4%) versus middle (6%, p=0.012) and high (5.4%, p=0.002). The old system showed similar one-year survival across SES. In the new system, recipients with low SES had decreased one-year survival (p=0.041).<br /><b>Conclusion</b><br />SES affects waitlist and post-transplant outcomes. In the new system, all SES had increased access to HT, however low SES had increased death/delisting due to worsening clinical status and decreased post-transplant survival.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Host CD34 Cells Are Replacing Donor Endothelium of Transplanted Heart.</h4><i>Chen T, Sun X, Gong H, Chen M, ... Xu Q, Li W</i><br /><b>Background</b><br />Endothelium dysfunction is a central problem for early rejection due to the host alloimmune response and the late status of arteriosclerosis in heart transplantation. However, reliable pieces of evidence are still limited concerning the source of the regenerated endothelium within the transplanted heart.<br /><b>Methods</b><br />We analyzed single-cell RNA sequencing data and constructed an inducible lineage tracing mouse, combined heart transplantation with bone marrow transplantation and a parabiosis model, cellular components, and endothelial cell populations in cardiac graft lesions.<br /><b>Results</b><br />Our single-cell RNA sequencing analysis of a transplanted heart allowed for the establishment of an endothelial cell atlas with a heterogeneous population, including arterial, venous, capillary, and lymphatic endothelial cells. Along with genetic cell lineage tracing, we demonstrated that the donor cells were mostly replaced by recipient cells in the cardiac allograft, up to 83.29% two weeks after transplantation. Furthermore, recipient non-bone marrow CD34<sup>+</sup> endothelial progenitors contributed significantly to extracellular matrix organization and immune regulation, with higher apoptotic ability in the transplanted hearts. Mechanistically, peripheral blood-derived human endothelial progenitor cells differentiate into endocardial cells via VEGF receptor-mediated pathways. Host circulating CD34<sup>+</sup> endothelial progenitors could repair the damaged donor endothelium presumably through CCL3-CCR5 chemotaxis. Partial depletion of host CD34<sup>+</sup> cells resulted in delayed endothelial regeneration.<br /><b>Conclusions</b><br />We created an annotated fate map of endothelial cells in cardiac allografts, indicating how recipient CD34<sup>+</sup> cells could replace the donor endothelium via chemokine CCL3-CCR5 interactions. The mechanisms we discovered could have a potential therapeutic effect on the long-term outcomes of heart transplantation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 25 Aug 2023; epub ahead of print</small></div>

<div><h4>Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: a propensity-weighted analysis.</h4><i>Yamada Y, Sato T, Oda H, Harada N, ... Ohsumi A, Date H</i><br /><b>Background</b><br />We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx.<br /><b>Methods</b><br />We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6 months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6 months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry.<br /><b>Results</b><br />Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% CI 0.14-0.82, p = 0.017) for OS and 0.47 (95% CI 0.22-1.01, p = 0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors.<br /><b>Conclusion</b><br />Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 25 Aug 2023; epub ahead of print</small></div>

<div><h4>Surgery for fibrosing mediastinitis with severe pulmonary hypertension due to pulmonary venous stenosis.</h4><i>Ye JR, Hu SY, Lin YH, Huang CH, Hsu HH, Huang SC</i><br /><AbstractText>A 21-year-old woman with severe pulmonary hypertension and circulatory collapse was referred to our hospital for possible lung transplantation with extracorporeal membrane oxygenation support. Computed tomography revealed severe stenosis of all four pulmonary veins, and fibrosing mediastinitis was suspected. Surgical reconstruction of the pulmonary veins was performed, and extracorporeal membrane oxygenation support was weaned off. After surgery, pulmonary vascular resistance normalized. This successful case demonstrates that surgical pulmonary venous reconstruction is an important treatment for fibrosing mediastinitis induced by pulmonary venous stenosis and pulmonary hypertension.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 25 Aug 2023; epub ahead of print</small></div>

<div><h4>CT-derived Lung Vessel Morphology Correlates with Prognostic Markers in Pre-capillary Pulmonary Hypertension.</h4><i>Pienn M, Gertz RJ, Gerhardt F, Kröger JR, ... Olschewski H, Bunck AC</i><br /><b>Background</b><br />While computed tomography pulmonary angiography (CTPA) is an integral part of the work-up in patients with suspected pulmonary hypertension (PH), there is no established CTPA-derived prognostic marker. We aimed to assess whether quantitative readouts of lung vessel morphology correlate with established prognostic indicators in PH.<br /><b>Methods</b><br />We applied a fully-automatic in-house developed algorithm for segmentation of arteries and veins to determine lung vessel morphology in patients with pre-capillary PH who underwent right heart catheterization and CTPA between May 2016 and May 2019. Primary endpoint of this retrospective study was the calculation of receiver operating characteristics for identifying low and high mortality risk according to the three-strata risk assessment model presented in the current guidelines.<br /><b>Results</b><br />We analysed 73 patients, median age 65 years (IQR: 54-76), female/male ratio 35/38, median mean pulmonary arterial pressure 37 mmHg (IQR: 30-46), and found significant correlations with important prognostic factors in PAH. N-terminal pro-brain natriuretic peptide, cardiac index, mixed venous oxygen saturation and six-minute walking distance were correlated with the ratio of the number of arteries over veins with vessel diameters of 6-10 mm (Spearman correlation coefficients ρ=0.64, p<0.001; ρ=-0.60, p<0.001; ρ=-0.47, p=0.005; ρ=-0.45, p=0.001, respectively). This ratio predicted a low- and high-risk score with an area under the curve of 0.73 (95% CI: 0.56-0.90) and 0.86 (95% CI: 0.74-0.97), respectively.<br /><b>Conclusion</b><br />The ratio of the number of arteries over veins with diameters between 6 and 10 mm is significantly correlated with prognostic markers in pulmonary hypertension and predicts low and high mortality risk.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 22 Aug 2023; epub ahead of print</small></div>

<div><h4>The Reality of DCD Donor Use in Pediatric Thoracic Transplantation in The United States.</h4><i>Ahmed HF, Guzman-Gomez A, Kulshrestha K, Kantemneni EC, ... Zafar F, Morales DLS</i><br /><AbstractText>In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18yo) who underwent HTx or LTx using DCD donors from June 2004-June 2022 were identified in the UNOS registry. A total of 14 DCD recipients were identified: 7(50%) HTx & 7(50%) LTx. Donor and recipient demographics are described in Table 1. One and five-yr post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 22 Aug 2023; epub ahead of print</small></div>

<div><h4>Clinical Outcomes Following Cessation of Parenteral Immunoglobulin Therapy Following Lung Transplantation.</h4><i>Levin K, Westall G, Ennis S, Snell G</i><br /><AbstractText>Broad use of parenteral immunoglobulin (IgG) therapy in lung transplant (LTx) patients occurs without robust clinical evidence or guidelines. Main indications include secondary hypogammaglobulinemia, antibody mediated rejection (AMR) and treatment or prevention of graft rejection where the use of conventional immunosuppressive therapies is contraindicated. As part of routine auditing of IgG use in our LTx service, we assessed for adverse clinical outcomes related to IgG therapy cessation between November 2017 and February 2022. Of 220 LTx recipients receiving IgG therapy at our centre during this period (approximately 20% of our total LTx cohort), 48 patients ceased therapy. 83.3% experienced no adverse outcomes. 10.4% recommenced therapy for the same indication within 6 months with no longer term sequelae. One AMR patient developed progressive CLAD and died with 12 months, where therapy cessation was patient-initiated and associated with general non-compliance. These data provide reassurance that physician-directed cessation of IgG therapy is safe when based on sound clinical information and part of a robust clinical auditing process.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 21 Aug 2023; epub ahead of print</small></div>

<div><h4>Pleiotropic effects of extracellular vesicles from induced pluripotent stem cell-derived cardiomyocytes on ischemic cardiomyopathy: A pre-clinical study.</h4><i>Tominaga Y, Kawamura T, Ito E, Takeda M, ... Sawa Y, Miyagawa S</i><br /><b>Background</b><br />Stem cell-secreted extracellular vesicles (EVs) play essential roles in intercellular communication and restore cardiac function in animal models of ischemic heart disease. However, few studies have used EVs derived from clinical-grade stem cells and their derivatives with stable quality. Moreover, there is little information on the mechanism and time course of the multifactorial effect of EV therapy from the acute to the chronic phase, the affected cells, and whether the effects are direct or indirect.<br /><b>Methods</b><br />Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) were produced using a clinical-grade differentiation induction system. EVs were isolated from the conditioned medium by ultracentrifugation and characterized in silico, in vitro, and in vivo. A rat model of myocardial infarction was established by left anterior descending artery ligation and treated with iPSCM-derived EVs.<br /><b>Results</b><br />iPSCM-derived EVs contained miRNAs and proteins associated with angiogenesis, antifibrosis, promotion of M2 macrophage polarization, cell proliferation, and anti-apoptosis. iPSCM-derived EV treatment improved left ventricular function and reduced mortality in the rat model by improving vascularization and suppressing fibrosis and chronic inflammation in the heart. EVs were uptaken by cardiomyocytes, endothelial cells, fibroblasts, and macrophages in the cardiac tissues. The pleiotropic effects occurred due to the direct effects of microRNAs and proteins encapsulated in extracellular vesicles and indirect paracrine effects on M2 macrophages.<br /><b>Conclusions</b><br />Clinical-grade iPSCM-derived EVs improve cardiac function by regulating various genes and pathways in various cell types and may have clinical potential for treating ischemic heart disease.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 21 Aug 2023; epub ahead of print</small></div>

<div><h4>Impact of Size Matching on Survival Post Heart Transplant in Infants: Estimated Total Cardiac Volume Ratio Outperforms Donor-Recipient Weight Ratio.</h4><i>Dani A, Ahmed HF, Guzman-Gomez A, Raees MA, ... Morales DL, Zafar F</i><br /><b>Purpose</b><br />Cardiac volume-based estimation offers an alternative to donor-recipient weight ratio (DRWR) in pediatric heart transplantation (HT), but has not been correlated to post-transplant outcomes We sought to determine whether estimated Total Cardiac Volume (eTCV) ratio is associated with HT survival in infants.<br /><b>Methods</b><br />The UNOS database was used to identify infants (age:<1year) who received HT in 1987-2020. Donor and recipient eTCV were calculated from weight using previously published data. Patient cohort was divided according to the significant range of eTCV ratio; characteristics and survival were compared.<br /><b>Results</b><br />2845 infants were identified. Hazard ratio with cubic spline showed prognostic relationship of eTCV ratio and DRWR with the overall survival. The cut-point method determined an optimal eTCV ratio range predictive of infant survival was 1.05-1.85 whereas no range for DRWR was predictive. 75.6% patients had an optimal TCV ratio, while 18.1% were in the lower (LR) and 6.3% in the higher (HR) group. Kaplan-Meier analysis showed better survival for patients within the optimal vs LR (p=0.0017), and a similar significantly better survival when compared to HR (p=0.0053). The optimal eTCV ratio group (n=2151) had DRWR ranging from 1.09-5; 34.3% had DRWR 2-3, and 5.0% DRWR>3.<br /><b>Conclusion</b><br />Currently, an upper DRWR limit has not been established in infants. Therefore, determining the optimal eTCV range is important to identifying an upper limit that significantly predicts survival benefit. This finding suggests a potential increase in donor pool for infant recipients since over 40% of donors in the optimal eTCV range includes DRWR values>2 that are traditionally not considered for candidate listing.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 17 Aug 2023; epub ahead of print</small></div>

<div><h4>Novel Measures to Assess Ventricular Assist Device Patient-reported Outcomes: Findings from the MCS A-QOL Study.</h4><i>Grady KL, Kallen MA, Beiser DG, Lindenfeld J, ... Cella D, Hahn EA</i><br /><b>Background</b><br />Generic and heart failure-specific measures do not capture unique aspects of living with a VAD. Using state-of-the-science psychometric measurement methods, we developed a measurement system to assess post-ventricular assist device (VAD) adjustment and HRQOL.<br /><b>Methods</b><br />Patients were recruited from 10/26/16-2/29/20 from 12 U.S. VAD programs. We created a dataset of participants (n=620) enrolled before left (L)VAD implantation, with data at 3- or 6- months post-implantation (Group1 [n=154]), and participants enrolled after LVAD implantation, with data at one timepoint (Group 2 [n=466]). We constructed five item banks: three modified from existing measures and two new measures. Analyses included item response theory (IRT) modeling, differential item functioning tests for systematic measurement bias, and indicators of reliability and validity.<br /><b>Results</b><br />Of 620 participants, 56% (n=345) were implanted as destination therapy, 51% (n=316) were <12 months post-implantation, mean age=57.3 years, 78% (n=485) male, 70% (n=433) White, 58% (n=353) married/partnered, and 58% (n=357) with >high school education. We developed five new VAD item banks/measures: 6-item VAD Team Communication; 12-item Self-efficacy Regarding VAD Self-care; 11-item Being Bothered by VAD Self-care and Limitations; 7-item Satisfaction with Treatment; and 11-item Stigma. Cronbach\'s alpha reliability ranged from good (≥0.80) to excellent (≥0.90) for item banks/measures. All measures, except VAD Team Communication, demonstrated at least moderate correlations (≥0.30) with construct validity indicators.<br /><b>Conclusions</b><br />These measures meet IRT modeling assumptions and requirements; scores demonstrate reliability and validity. Use of these measures may assist VAD clinicians to inform patients about VADs as a treatment option and guide post-VAD interventions.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>The Widening Care Gap in VAD Therapy.</h4><i>Conway J, Amdani S, Morales D, Lorts A, ... Kirklin JK, Auerbach SR</i><br /><b>Introduction</b><br />The removal of the HeartWare Ventricular Assist Device (HVAD) due to pump malfunctions and inferior outcomes compared to HeartMate 3 (HM3) in adults has created a care gap for younger patients. It is unclear if the reported HVAD survival differs by age and if the initial experience with HM3 can bridge the gap.<br /><b>Methods</b><br />Using the STS Intermacs and Pedimacs registries, durable VAD implants between 09/12-12/21 where identified. Young adults (YA) were defined as <40yrs old in Intermacs. Pts were excluded if they had an isolated right VAD (RVAD) or were implanted as destination therapy (DT). Survival analysis by Kaplan Meier (KM) and Competing Outcomes Curves (COC) was performed, and 1-year survival is reported.<br /><b>Results</b><br />The Intermacs cohort consisted of YA (n=1226; HVAD 818; HM3 408) with a median age of YA was 32.07 (26.66-36.27) (yrs) and weight (wt) 83.2 (68-104.2) Kg. Most had cardiomyopathy (CM) (92.2%). The Pedimacs cohort was 668 pt [median age 9.47 (1.82-14.23) yrs, wt 27.2 (10-57.05) Kg, and most also had CM (70.5%). Device breakdown included: HVAD (n=326), Berlin EXCOR® (n=277) and HM3 (n=65). HVAD survival differed by age in adults, with YA fairing better than adults >40 yrs old (88.8% vs. 79.4% at 1 yr, p<0.0001). YA survival was also better compared to Pedimacs pt (88.9% vs. 83.7%, p=0.0002) but when competing events were analyzed, mortality was similar to YA (9.2% vs. 9.6%, p=0.1) with a higher proportion of pt undergoing transplant at 1 year in Pedimacs (74% vs. 31.3 %, p<0.0001). Survival by device differed between HVAD and HM3 in YA (88.8% vs. 94.4%, p=0.0025). This difference in device survival was not seen in all children (83.7% vs. 87.3%, p=0.21), including those ≥25Kg. Adverse event profiles also differed across the groups with adults seeing less adverse events with the HM3 but the same was not found (including stroke) in the pediatric cohort. Survival outcomes for patients between 10-25Kg were similar with the HVAD compared to the Berlin Heart EXCOR® (p=0.4290), with similarities in stroke risk.<br /><b>Conclusion</b><br />The removal of the HVAD device may result in a care gap in younger pt whose survival outcomes do not mirror that of older adults. The HM3 can fill a portion of this gap with good survival but there remains a subset of pediatric pt that based on initial HM3 use will no longer have access to intracorporeal support and therefore, despite reasonable outcomes with the Berlin Heart EXCOR® will not be able to be discharged home. Lastly, it is essential that future changes to the availability of devices take into account the various patient populations that utilize the device to avoid unintended consequences of access inequality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>Heart Transplantation in Patients from Socioeconomically Distressed Communities.</h4><i>Chen Q, Malas J, Emerson D, Megna D, ... Kobashigawa JA, Bowdish ME</i><br /><b>Background</b><br />Studies examining heart transplantation disparities have focused on individual factors such as race or insurance status. We characterized the impact of a composite community socioeconomic disadvantage index on heart transplantation outcomes.<br /><b>Methods</b><br />From the Scientific Registry of Transplant Recipients, we identified 49,340 primary, isolated adult heart transplant candidates and 32,494 recipients (2005-2020). Zip code-level socioeconomic disadvantage was characterized using Distressed Community Index (DCI: 0-most prosperous, 100-most distressed) based on education, poverty, unemployment, housing vacancies, median income, and business growth. Patients from distressed communities (DCI ≥80) were compared to all others.<br /><b>Results</b><br />Patients from distressed communities were more often non-White, less educated, and had public insurance (all p<0.01). Distressed patients were more likely to require ventricular assist devices at listing (29.4 vs. 27.1%) and before transplant (44.8 vs. 42.0%, both p<0.001), and they underwent transplants at lower-volume centers (23 vs. 26 cases/year, p<0.01). Distressed patients had higher 1-year waitlist mortality or deterioration (12.3% [95% CI 11.6-13.0] vs. 10.9% [95% CI 10.5-11.3]) and inferior 5-year survival (75.3% [95% CI 74.0-76.5] vs. 79.5% [95% CI 79.0-80.0]) (both p<0.001). After adjustment, living in a distressed community was independently associated with an increased risk of waitlist mortality or deterioration (HR 1.10, 95% CI 1.02-1.18) and post-transplant mortality (HR 1.13, 95% CI 1.06-1.20).<br /><b>Conclusions</b><br />Patients from socioeconomically distressed communities have worse waitlist and post-transplant mortality. These findings should not be used to limit access to heart transplantation, but rather highlight the need for further studies to elucidate mechanisms underlying the impact of community-level socioeconomic disparity.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>Decreased Survival of Simultaneous Heart-Kidney Transplant Recipients in the New Heart Allocation Era.</h4><i>Shin M, Iyengar A, Helmers MR, Weingarten N, ... Kelly JJ, Cevasco M</i><br /><b>Objectives</b><br />In 2018, the United Network for Organ Sharing (UNOS) modified their heart allocation policy to reduce waitlist mortality. Rates of simultaneous heart-kidney transplant (SHKT) have dramatically increased in recent years, despite increased rates of post-transplant renal failure in the new policy era. This study sought to investigate the impact of the new allocation system on waitlist and post-transplant outcomes of simultaneous heart-kidney transplantation.<br /><b>Methods</b><br />Adult patients listed for SHKT between 2012 and 2021 were included. Patients were cross-validated across both Thoracic and Kidney UNOS databases to confirm accurate listing and transplant data. Patients were stratified according to listing era. The Fine and Gray model was used to assess waitlist outcomes and post-transplant renal graft function. Kaplan Meier analysis and Cox regression were used to compare post-transplant survival.<br /><b>Results</b><br />A total of 2,588 patients were included, of whom 1,406 (54.1%) were listed between 2012 - 2018 (Era 1) and 1,182 (45.9%) between 2019 - 2021(Era 2). Era 2 was associated with increased likelihood of transplant (aSHR: 1.52; p<0.01) and decreased waitlist mortality (aSHR: 0.63; p<0.01). Post-transplant survival at 2 years was decreased in Era 2 (78.8% vs. 86.9%; p<0.01). Undersized hearts (HR: 2.02; p<0.01), use of extracorporeal membrane oxygenation (HR: 2.67; p<0.1), and transplants performed following the policy change (HR: 1.45; p=0.03) were associated with increased mortality. Actuarial survival (combined waitlist and post-transplant) was significantly lower in the modern era (71.6% vs. 62.2%; p=0.02).<br /><b>Conclusion</b><br />The allocation policy change has improved waitlist outcomes in patients listed for SHKT, but potentially at the cost of worsened post-transplant outcomes.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 12 Aug 2023; epub ahead of print</small></div>

<div><h4>Mechanical Thrombectomy for Acute Pulmonary Embolism in Lung Transplant Recipients.</h4><i>Glavan A, Gadre SK, Haddadin I, Budev MM, Tefera L, Chaudhury P</i><br /><AbstractText>Rates of pulmonary embolism (PE) are high amongst lung transplant (LT) recipients. Management is challenging because of elevated bleeding risks and inadequacy of conventional PE risk stratification tools. New percutaneous large bore mechanical thrombectomy catheters are being increasingly used effectively de-bulk thrombus and restore flow immediately. We describe the use mechanical thrombectomy (MT) in 8 LT recipients. All patients were diagnosed with intermediate/high-risk proximal PE involving the allograft and underwent successful MT within 30 hours of diagnosis. Estimated blood loss was between 200-450cc, with three patients requiring blood transfusions. Improvement in heart rate and oxygenation was seen in all eight patients after the procedure. In the 30 days after MT, 7/8 patients survived. One patient death from major bleeding occurred 16 days after MT and 5 days after venoarterial extracorporeal membrane oxygenator decannulation. Mechanical thrombectomy may provide a feasible management strategy in select lung transplant recipients with pulmonary embolism.</AbstractText><br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 09 Aug 2023; epub ahead of print</small></div>

<div><h4>Impact of age and telomere length on circulating T cells and rejection risk after lung transplantation for idiopathic pulmonary fibrosis.</h4><i>Snyder ME, Anderson MR, Benvenuto LJ, Sutton RM, ... Alder JK, McDyer JF</i><br /><b>Purpose</b><br />Most idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere length (ST). Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs.<br /><b>Methods</b><br />We identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres, 49 with long telomers) as well as a subset from both cohorts who had cryopreserved PBMC at least one timepoint, 6 months post-transplantation. Circulating T cells from before transplantation and at 6 and 12 months-post transplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) acute cellular rejection.<br /><b>Results</b><br />IPF-LTRs with ST were found to have premature \'aging\' of their circulating T cell compartment, with age-agnostic elevations in post-transplant terminal differentiation of CD8<sup>+</sup> T cells, increased granzyme B positivity of both CD8<sup>+</sup> and CD4<sup>+</sup> T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort.<br /><b>Conclusion</b><br />IPF-LTRs with ST have premature \'aging\' of their circulating T cell compartment post transplantation, and a clear age-related decline in ACR burden.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 04 Aug 2023; epub ahead of print</small></div>

<div><h4>Is It Time to Stop Living in a HeartMate II World?</h4><i>Yuzefpolskaya M, Fielder AG, Katz JN, Houston BA</i><br /><AbstractText>Despite improving outcomes with modern pump technology, LVAD utilization for patients with end-stage heart failure has declined significantly in the preceding half decade. Here, we examine this trend, noting an inherent contradiction in declining utilization of an improving therapeutic option. We propose a series of provocative questions as a \"call to action\" for the field of advanced heart failure to consider both scientifically and clinically, focusing on our evaluation parameters for LVAD candidacy, our approach to dichotomous LVAD versus transplant decisions, and our current management paradigms. We conclude that modernization in these areas to match the advantages of modern pump technology is required to best serve patients with advanced heart failure.</AbstractText><br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 01 Aug 2023; epub ahead of print</small></div>

<div><h4>Management and Outcomes of Heart Transplant Candidates with Bloodstream Infection on Temporary Mechanical Circulatory Support.</h4><i>Eichenberger EM, Satola S, Gupta D, Daneshmand M, Pouch S</i><br /><AbstractText>The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between 1/1/2013-4/30/2023, N=136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (IQR 28.3). All TMCS-I were re-activated for transplant within 48-72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (P=0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment.</AbstractText><br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Jul 2023; epub ahead of print</small></div>

<div><h4>The Effect of Warm Ischemia and Donor Ejection Fraction on 30-Day Mortality after Donation after Circulatory Death Heart Transplantation: A National Database Analysis.</h4><i>Paneitz DC, Basha AM, Van Kampen A, Giao D, ... Alessandro DA, Osho AA</i><br /><AbstractText>Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion (DPP) method experience variable durations of warm ischemia at the time of procurement (WIP). We used the OPTN database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation demonstrating an optimal WIP cut-point of <36 minutes. Multivariable logistic regression modelling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve (AUC) for predicting 30-day mortality based on WIP ≥36 minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36 minutes, particularly in donors with LVEF <60%.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 26 Jul 2023; epub ahead of print</small></div>

<div><h4>New System, Old Problem: Increased Wait Time for High Priority Transplant Candidates.</h4><i>Harris E, Sewanan L, Topkara VK, Fried JA, ... Sayer G, Clerkin KJ</i><br /><AbstractText>The 2018 heart allocation policy sought to improve risk stratification and reduce waitlist mortality for the sickest patients. This study sought to evaluate changes in wait times for the highest priority patients since policy implementation. All adult single-organ transplant recipients were identified in the United Network for Organ Sharing registry from 10/18/18-7/8/22 and separated into 4 time periods. Outcomes were compared by blood type and UNOS region. Over the study period 897/9,143 patients were listed as Status 1 with no significant change in median wait time by blood type or region. More patients were listed as Status 2 (4,523/9,143), and each subsequent period post-policy change was associated with a 4.2 day increase in mean Status 2 waitlist time (95% CI 3.0-5.5, p<0.0001). Wait times were longest for candidates with Blood Type O and shortest for AB & A. Regional variations continued, however, wait time increased in every region over time.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 26 Jul 2023; epub ahead of print</small></div>

<div><h4>INTERMACS QUARTERLY REPORT ANALYSIS TO MONITOR LONGITUDINAL OUTCOMES IN A CENTRIFUGAL FLOW ASSIST DEVICE.</h4><i>Li S, Slaughter MS, Hall S, Davis E, ... Pagani FD, Mahr C</i><br /><AbstractText>In June 2021, HVAD™ System distribution ceased due to observational data demonstrating increased mortality and neurological events compared to another commercial device, and a device malfunction with delay or failure to restart, especially in certain subpopulations. To assess ongoing risk for patients on support following subsequent device recalls, the manufacturer\'s Intermacs HVAD System 2022 Quarterly Reports were queried to identify mortality and adverse events trends in a contemporary cohort of 3110 primary HVAD implantations since October 2017, stratified by year-of-implant. Mean duration of support was 21±16 months, with 33% alive on original device, 25% transplanted, 6% undergoing device exchange, 4% recovered, and 32% expired. Kaplan-Meier and event-per-patient-year estimates for survival, freedom from device explant, stroke, and pump thrombus were similar across year-of-implant. Following market withdrawal and recent device recalls, there appears to be no increase in mortality, stroke, pump thrombus, or explant for HVAD-supported patients. Quarterly report monitoring is ongoing.</AbstractText><br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 25 Jul 2023; epub ahead of print</small></div>

<div><h4>MTHFD2 Ablation in T Cells Protects against Heart Transplant Rejection by Perturbing IRF4/PD-1 Pathway through the Metabolic-epigenetic Nexus.</h4><i>Li Y, Chen Z, Cui J, Yu J, ... Wu J, Xia J</i><br /><b>Background</b><br />One-carbon metabolism supports the activation, proliferation, and function of multiple immune cells. However, researchers have not clearly determined whether and how one-carbon metabolic enzymes contribute to heart transplant rejection.<br /><b>Methods</b><br />We investigated the dynamic metabolic adaptation in grafts during heart transplant rejection by conducting transcriptomics, metabolomics and single-cell RNA sequencing studies of cardiac tissue from human and mouse heart transplant recipients. We also assessed the expression of the one-carbon metabolic enzyme MTHFD2 in cardiac grafts by immunofluorescence and flow cytometry assays. Then we constructed a murine heart transplant model with T cell-specific Mthfd2 knockout mice, analyzed T cells function by flow cytometry assays and enzyme-linked immunospot assays, and studied the mechanism by Cleavage Under Targets and Tagmentation assays. Finally, we studied the effect of a pharmacological inhibitor of MTHFD2 in humanized skin transplant model.<br /><b>Results</b><br />We revealed that the one-carbon metabolism enzyme MTHFD2 was a hallmark of alloreactive T cells and was linked to T cell proliferation and function after exposure to alloantigen. And, Mthfd2 ablation prevented murine heart transplant rejection. Mechanistically, we found Mthfd2 ablation affected the IRF4/PD-1 pathway through a metabolic-epigenetic mechanism involving H3K4me3. Furthermore, we found that inhibiting MTHFD2 attenuated human allograft rejection in a humanized skin transplant model.<br /><b>Conclusions</b><br />These data show that the one-carbon metabolic enzyme MTHFD2 serves as a metabolic checkpoint of alloreactive T cells and suggest that it may be a potential therapeutic target for heart transplant rejection.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 24 Jul 2023; epub ahead of print</small></div>

<div><h4>Validation of the clinical utility of microRNA as non-invasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study.</h4><i>Coutance G, Racapé M, Baudry G, Lécuyer L, ... Van Huyen JD, Loupy A</i><br /><AbstractText>While studies have shown an association between microRNAs and cardiac rejection, the clinical relevance of a pre-identified miRNA signature as a non-invasive biomarker has never been assessed in prospective multicentric unselected cohorts. To address this unmet need, we designed a prospective study (NCT02672683) including recipients from 11 centers between 08/2016 to 03/2018. The objective was to validate the association between three previously identified circulating microRNA (10a, 92a, 155) and the histopathological diagnosis of rejection. Both relative and absolute (sensitivity analysis) quantifications of microRNAs were performed. Overall, 461 patients were included (831 biopsies, 79 rejections). A per-protocol interim analysis (258 biopsies, 49 rejections) did not find any association between microRNA and rejection (microRNA10-a: OR=1.05, 95%CI=0.87-1.27, p=0.61; 92-a: OR=0.98, 95%CI=0.87-1.10, p=0.68; 155: OR=0.91, 95%CI=0.76-1.10, p=0.33). These results were confirmed in the sensitivity analysis. The analysis of the remaining sera was stopped for futility. This study shows no clinical utility of circulating microRNAs 10a, 92a and 155 monitoring in heart allograft recipients.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 22 Jul 2023; epub ahead of print</small></div>

<div><h4>Lung Transplantation Outcomes in Patients from Socioeconomically Distressed Communities.</h4><i>Malas J, Chen Q, Megna D, Zaffiri L, ... Chikwe J, Bowdish ME</i><br /><b>Background</b><br />Previous studies have demonstrated racial and gender disparities in lung allocation, but contemporary data regarding socioeconomic disparities in post-transplant outcomes are lacking. We evaluated the impact of a composite socioeconomic disadvantage index on post-transplant outcomes.<br /><b>Methods</b><br />The Scientific Registry of Transplant Recipients identified 27,763 adult patients undergoing isolated primary lung transplantation between 2005 and 2020. Zip code-level socioeconomic distress was characterized using the Distressed Communities Index (DCI: 0-no distress, 100-severe distress) based on education level, poverty, unemployment, housing vacancies, median income, and business growth, and patients were stratified into high (DCI > 60) or low (DCI < 60) distressed groups.<br /><b>Results</b><br />Recipients from high-distress communities (n=8006, 28.8%) were younger (59 years (IQR 50-64) vs. 61 years (IQR 52-66), less often white (73 vs. 85%), less likely to have a college degree (45 vs. 59%), and more likely to have public insurance (57 vs. 49%, all p<0.001) compared to those from low-distress communities. Additionally, high-distress recipients were more likely to have Group A diagnoses (32 vs. 27%) and undergo bilateral lung transplants (72.4 vs. 69.3%, all p<0.001). Post-transplant survival at 5 years was 55.7% (95% CI: 54.4-56.9) in high-distress recipients and 58.2% (95% CI: 57.4-58.9) in low-distress recipients (p=0.003). After adjustment, high distress level was independently associated with an increased risk of 5-year mortality (HR:1.09, 95% CI:1.04-1.15).<br /><b>Conclusion</b><br />Recipients from distressed communities are at increased mortality risk following lung transplantation. Efforts should be focused on increased resource allocation and further study to better understand factors which may mitigate this disparity.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 20 Jul 2023; epub ahead of print</small></div>

<div><h4>ATYPICAL INFILTRATES ON ENDOMYOCARDIAL BIOPSY ARE ASSOCIATED WITH ADVERSE OUTCOMES IN PEDIATRIC HEART TRANSPLANTATION.</h4><i>Hope KD, Morris SA, Kearney DL, Puri K, ... Nicholas SK, Denfield SW</i><br /><b>Background</b><br />The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes.<br /><b>Methods</b><br />We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013-2017. Multi-organ transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare versus predominant) on EMB was recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (re-listing or re-transplant), or death. Presence of atypical infiltrates was evaluated 1) overall using Cox regression with time-dependent covariates and 2) if present by 1 year post-HTx using Kaplan-Meier analysis.<br /><b>Results</b><br />Atypical infiltrates were present in 24/95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (HR 6.22, 95%CI 2.60-14.89, p<0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 non-consecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p=0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p<0.0001). Patients with atypical infiltrates by 1-yr post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p=0.002).<br /><b>Conclusions</b><br />The presence of atypical infiltrates on EMB are associated with significantly worse outcomes in children following HTx. These patients require closer follow up to assess for developing graft dysfunction.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 18 Jul 2023; epub ahead of print</small></div>

<div><h4>Early Optical Coherence Tomography Evaluation of Donor-Transmitted Atherosclerosis and Cardiac Allograft Vasculopathy: Insights from a Prospective, Single-Center Study.</h4><i>Takahashi T, Kobayashi Y, Saeed O, Vukelic S, ... Shin JJ, Patel SR</i><br /><b>Background</b><br />The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor coronary artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality.<br /><b>Methods</b><br />HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by ISHLT criteria up to 4 years of follow-up.<br /><b>Results</b><br />A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3±0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV<sub>1</sub>, 3 CAV<sub>2</sub>, and 1 CAV<sub>3</sub>. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank P=0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, P=0.008) while maximal intimal thickness ≥0.5 mm was not.<br /><b>Conclusions</b><br />Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 14 Jul 2023; epub ahead of print</small></div>

<div><h4>Clinical and functional relevance of right ventricular contraction patterns in pulmonary hypertension.</h4><i>Rako ZA, Yogeswaran A, Lakatos BK, Fábián A, ... Kovács A, Tello K</i><br /><b>Background</b><br />The right ventricle has a complex contraction pattern of uncertain clinical relevance. We aimed to assess the relationship between right ventricular (RV) contraction pattern and RV-pulmonary arterial (PA) coupling defined by the gold-standard pressure-volume loop-derived ratio of end-systolic/arterial elastance (Ees/Ea).<br /><b>Methods</b><br />Prospectively enrolled patients with suspected or confirmed pulmonary hypertension underwent three-dimensional echocardiography, standard right heart catheterization, and RV conductance catheterization. RV-PA uncoupling was categorized as severe (Ees/Ea < 0.8), moderate (Ees/Ea 0.8-1.29), and none/mild (Ees/Ea ≥ 1.3). Clinical severity was determined from hemodynamics using a truncated version of the 2022 European Society of Cardiology/European Respiratory Society risk stratification scheme.<br /><b>Results</b><br />Fifty-three patients were included, 23 with no/mild, 24 with moderate, and 6 with severe uncoupling. Longitudinal shortening was decreased in patients with moderate versus no/mild uncoupling (P < 0.001) and intermediate versus low hemodynamic risk (P < 0.001), discriminating low risk from intermediate/high risk with an optimal threshold of 18% (sensitivity 80%, specificity 87%). Anteroposterior shortening was impaired in patients with severe versus moderate uncoupling (P = 0.033), low versus intermediate risk (P = 0.018), and high versus intermediate risk (P = 0.010), discriminating high risk from intermediate/low risk with an optimal threshold of 15% (sensitivity 100%, specificity 83%). Left ventricular (LV) end-diastolic volume was decreased in patients with severe uncoupling (P = 0.035 versus no/mild uncoupling).<br /><b>Conclusions</b><br />Early RV-PA uncoupling is associated with reduced longitudinal function, whereas advanced RV-PA uncoupling is associated with reduced anteroposterior movement and LV preload, all in a risk-related fashion.<br /><b>Clinicaltrials</b><br />GOV: NCT04663217.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 12 Jul 2023; epub ahead of print</small></div>

<div><h4>Poor Functional Status at the Time of Waitlist for Pediatric Lung Transplant is Associated with Worse Pre-Transplant Outcomes.</h4><i>Himebauch AS, Yehya N, Schaubel DE, Josephson MB, ... Kawut SM, Christie JD</i><br /><b>Background</b><br />Whether functional status is associated with survival to pediatric lung transplant is unknown. We hypothesized that completely dependent functional status at waitlist registration, defined using Lansky Play Performance Scale (LPPS), would be associated with worse outcomes.<br /><b>Methods</b><br />Retrospective cohort study of pediatric lung transplant registrants utilizing UNOS STAR files (2005-2020). Primary exposure was completely dependent functional status, defined as LPPS score of 10-40. Primary outcome was waitlist removal for death/deterioration with cause-specific Cox (CSHR) regression. Subdistribution hazard regression (Fine and Gray, SHR) was used for the secondary outcome of waitlist removal due to transplant/improvement with a competing risk of death/deterioration. Confounders included: sex, age, race, diagnosis, ventilator dependence, ECMO, year, and listing center volume.<br /><b>Results</b><br />964 patients were included (63.5% ≥ 12 years, 50.2% cystic fibrosis [CF]). Median waitlist days was 95; 20.1% were removed for death/deterioration and 68.2% for transplant/improvement. Completely dependent functional status was associated with removal due to death/deterioration (adjusted CSHR 5.30 [95% CI 2.86-9.80]). This association was modified by age (interaction p=0.0102), with a larger effect for age ≥ 12 years, and particularly strong for CF. In the Fine and Gray model, completely dependent functional status did not affect the risk of removal due to transplant/improvement with a competing risk of death/deterioration (adjusted SHR 1.08 [95% CI 0.77-1.49]).<br /><b>Conclusions</b><br />Pediatric lung transplant registrants with the worst functional status had worse pre-transplant outcomes, especially for adolescents and CF patients. Functional status at waitlist registration may be a modifiable risk factor to improve survival to lung transplant.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 10 Jul 2023; epub ahead of print</small></div>

<div><h4>How do mechanical circulatory support patients die? Autopsy findings for left-ventricular assist device/total artificial heart non-survivors.</h4><i>Bart NK, Robson D, Muthiah K, Jansz PC, Hayward CS</i><br /><b>Introduction</b><br />Although life saving for end-stage heart failure (HF) patients, permanent mechanical circulatory support (MCS) is often the proximate cause of death in those that do not survive to transplant. Autopsy remains the gold standard for diagnosing causes of death and a vital tool for better understanding underlying pathology of non-survivors. The aim of this study was to determine the frequency and outcomes of autopsy investigations and compare these with pre-mortem clinical assessment.<br /><b>Methods</b><br />The autopsy findings and medical records of all patients who underwent left ventricular assist device (LVAD) or total artificial heart (TAH) insertion between June 1994 and April 2022 as a bridge to transplant, but subsequently died pre heart transplantation were reviewed.<br /><b>Results</b><br />A total of 203 patients had a LVAD or TAH implanted during the study period. Seventy-eight patients (M=59, F=19) died prior to transplantation (age 55 [14] years, INTERMACS=2). Autopsies were conducted in 26 of 78 patients (33%). Three were limited studies. The leading contributor to cause of death was respiratory (14/26), either nosocomial infection or associated with multi-organ failure. Intracranial haemorrhage was the second most common cause of death (8/26). There was a major discrepancy rate of 17% and a minor discrepancy rate of 43%. Autopsy study added a total of 14 additional contributors of death beyond clinical assessment alone (Graphical Abstract).<br /><b>Conclusion</b><br />Over an observational period of 26 years, the frequency of autopsy was low. To improve LVAD/TAH patient survival to transplant, better understanding as to cause of death is required. Patients with MCS have complex physiology and are at high risk of infection and bleeding complications.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 06 Jul 2023; epub ahead of print</small></div>

<div><h4>Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.</h4><i>Chan JCY, Man HSJ, Asghar UM, McRae K, ... Granton J, de Perrot M</i><br /><b>Background</b><br />The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy.<br /><b>Methods</b><br />Retrospective study of 401 consecutive patients undergoing PEA at our institution between 08/2005 and 03/2020 was performed. Primary outcome was need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement.<br /><b>Results</b><br />Females (n=203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final TPR after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p<0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p=0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs. 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04).<br /><b>Conclusions</b><br />Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients is important. Further investigations into possible mechanisms to explain the differences is warranted.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Jul 2023; epub ahead of print</small></div>

<div><h4>Expanding Use of the HeartMate 3 Ventricular Assist Device in Pediatric and Adult Patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).</h4><i>O\'Connor MJ, Shezad M, Ahmed H, Amdani S, ... Zinn MD, Lorts A</i><br /><b>Background</b><br />We report current outcomes in patients supported with the HeartMate 3 ventricular assist device in a multicenter learning network.<br /><b>Methods</b><br />The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HeartMate 3 implants between 12/2017 - 5/2022. Clinical characteristics, post-implant course, and adverse events were collected. Patients were stratified according to body surface area (<1.4 m<sup>2</sup>, 1.4-1.8 m<sup>2</sup>, and >1.8 m<sup>2</sup>) at device implantation.<br /><b>Results</b><br />During the study period, 170 patients were implanted with the HeartMate 3 at participating network centers, with median age 15.3 years; 27.1% were female. Median body surface area was 1.68 m<sup>2</sup>; the smallest patient was 0.73 m<sup>2</sup> (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5 days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with body surface area <1.4 m<sup>2</sup> had a higher incidence of infection, renal dysfunction, and ischemic stroke.<br /><b>Conclusions</b><br />In this updated cohort of predominantly pediatric patients supported with the HeartMate 3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 05 Jul 2023; epub ahead of print</small></div>

<div><h4>Time to extubation for lung transplant recipients represents a pragmatic endpoint to guide the development of prognostic tests.</h4><i>Sage AT, Peel J, Valero J, Yeung JC, ... Sander B, Keshavjee S</i><br /><AbstractText>The field of transplantation would benefit from the integration of advanced precision medicine techniques. Although predictive tests for lung transplantation require a well-defined clinical endpoint, there exists no consensus regarding which outcomes are optimal endpoints for these purposes. While many possible candidate endpoints exist, we propose that time-to-extubation is an optimal endpoint for prognostic tests because of its: clinical relevance; objectiveness; stability over time; and association with healthcare expenditure. Herein, we describe the rationale for this selection and present the limitations of alternative outcomes for this purpose. Using a 72-hour cut-off, time to extubation correlated well with Primary Graft Dysfunction Grade 3, ICU and hospital length of stay, and a greater than two-fold increase in healthcare cost ratios. Given that time-to-extubation is an objective measure that is readily measured by all lung transplant centers, this metric represents a preferred primary endpoint for prognostic tests developed for lung transplantation.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 03 Jul 2023; epub ahead of print</small></div>

<div><h4>New UNOS allocation system associated with no added benefit in waitlist outcomes and worse post-transplant survival in heart-kidney patients.</h4><i>Francke M, Wolfson AM, Fong MW, Nattiv J, ... Lee R, Vaidya AS</i><br /><b>Background</b><br />The 2018 United Network for Organ Sharing (UNOS) heart transplant policy change (PC) sought to improve waitlist risk stratification to decrease waitlist morality and promote geographically broader sharing for high-acuity patients awaiting heart transplantation. Our analysis sought to determine the effect of the UNOS PC on outcomes in patients waiting for, or who have received, a heart-kidney transplantation.<br /><b>Methods</b><br />We analyzed adult (≥18 years old), first-time, heart-only and heart-kidney transplant candidates and recipients from the UNOS Registry. Patients were divided into pre-PC (PRE: 10/18/2016-5/30/2018) and post-PC (POST: 10/18/2018-5/30/2020) groups for comparison. Competing risks analysis (sub-distribution and cause-specific hazards analyses) was performed to assess for differences in waitlist death/deterioration or heart transplantation. One-year post-transplant survival was assessed with Kaplan-Meier and Cox analyses. We included an interaction term (POLICY ERA X HEART±KIDNEY) in our analyses to evaluate the effect of PC on outcomes in heart-kidney patients.<br /><b>Results</b><br />One-year post-transplant survival was similar (p=0.83) for PRE heart-kidney and heart-only recipients, but worse (p<0.001) for POST heart-kidney versus heart-only recipients. There was a policy-era interaction between heart-kidney and heart-only recipients (HR 1.92[1.04,3.55], p=0.038) indicating a detrimental effect of policy on 1-year survival in POST versus PRE heart-kidney recipients. No added beneficial effect of PC on waitlist outcomes in heart-kidney versus heart-only candidates was observed.<br /><b>Conclusions</b><br />There was no added policy-era benefit on waitlist outcomes for heart-kidney candidates when compared to heart-only candidates. POST heart-kidney recipients experienced worse 1-year survival compared to PRE heart-kidney recipients with no policy effect on heart-only recipients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 30 Jun 2023; epub ahead of print</small></div>

<div><h4>Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation: Practice Patterns and Patient Outcomes.</h4><i>Rando HJ, Fanning JP, Cho SM, Kim BS, ... Bush EL, Keller SP</i><br /><b>Background</b><br />Extracorporeal membrane oxygenation (ECMO) is increasingly relied on to bridge patients with respiratory failure to lung transplantation despite limited evidence for its use in this setting. This study evaluated longitudinal trends in practice patterns, patient characteristics, and outcomes in patients bridged with ECMO to lung transplant.<br /><b>Methods</b><br />A retrospective review of all adult isolated lung transplant patients in the UNOS database between 2000 and 2019 was performed. Patients were classified as \"ECMO\" if supported with ECMO at the time of listing or transplantation and \"non-ECMO\" otherwise. Linear regression was used to evaluate trends in patient demographics during the study period. Trends in mortality were evaluated using Cox proportional hazards modeling, with time period as the primary covariate (2000-2004, 2005-2009, 2010-2014, or 2015-2019) and age, time on the waitlist, and underlying diagnosis as covariates.<br /><b>Results</b><br />40,866 patients were included, of whom 1,387 (3.4%) were classified as ECMO and 39,479 (96.6%) as no ECMO. Average age and initial LAS increased significantly during the study period in both cohorts, but occurred at a slower rate in the ECMO population. The hazard of death was significantly lower in more recent years (2015-2019) for both the ECMO and non-ECMO cohorts (aHR 0.59, 95% CI 0.37-0.96 and aHR 0.74, 95% CI 0.70-0.79) when compared to the early years (2000-2004) of the study period.<br /><b>Conclusions</b><br />Post-transplantation survival for patients bridged to transplantation with ECMO demonstrates ongoing improvement despite cannulation of progressively older and sicker patients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 30 Jun 2023; epub ahead of print</small></div>

<div><h4>The impact of obesity and LVAD-bridging on heart transplant candidate outcomes: A linked STS INTERMACS - OPTN/UNOS data analysis.</h4><i>Alba AC, Kirklin JK, Cantor RS, Deng L, ... Hanff TC, Stehlik J</i><br /><b>Background</b><br />Limited data integrating waitlist and post-heart transplant (HT) mortality have evaluated outcomes of LVAD-bridged strategy vs no LVAD according to patient characteristics. We evaluated waitlist and post-HT mortality in LVAD-bridged vs. non-bridged patients based on body mass index (BMI).<br /><b>Methods</b><br />We included linked adults listed for HT in OPTN/UNOS and patients receiving durable LVAD as bridge to HT or candidacy in STS/INTERMACS databases (2010-2019). Using BMI at listing or LVAD implant, we categorized patients as underweight (<18.5kg/m<sup>2</sup>), normal weight (18.5-24.99kg/m<sup>2</sup>), overweight (25-29.99kg/m<sup>2</sup>) and obese (≥30kg/m<sup>2</sup>). Kaplan-Meier analysis and multivariable Cox proportional hazards models informed the effect of LVAD-bridged and non-bridged strategy by BMI on waitlist, post-HT and overall mortality (including waitlist and post-HT mortality).<br /><b>Results</b><br />Among 11,216 LVAD-bridged and 17,122 non-bridged candidates, bridged candidates were more frequently obese (37.3% vs 28.6%)(p<0.001). Multivariable analysis indicated increased waitlist mortality in LVAD-bridged vs non-bridged with overweight (HR1.18, 95%CI 1.02-1.36) or obesity (HR1.35, 95% CI 1.17-1.56) in comparison to normal weight candidates (HR1.02, 95%CI 0.88-1.19) (p-interaction<0.001). Post-transplant mortality was not statistically different in LVAD-bridged versus non-bridged patients across BMI categories (p-interaction=0.26). There was a non-significant graded increase in overall mortality in LVAD-bridged with overweight (HR1.53, 95%CI 1.39-1.68) or obesity (HR1.61, 95%CI 1.46-1.78) compared to non-bridged patients (p-interaction=0.13).<br /><b>Conclusions</b><br />LVAD-bridged candidates with obesity had higher waitlist mortality compared to non-bridged candidates with obesity. Post-transplant mortality was similar in LVAD-bridged and non-bridged patients, but obesity remained associated with increased mortality in both groups. This study may aid clinicians and advanced heart failure patients with obesity in decision-making.<br /><br />Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Jun 2023; epub ahead of print</small></div>

<div><h4>Adverse events after left ventricular assist device implantation linked to psychosocial risk in women and men.</h4><i>Maukel LM, Weidner G, Jan B, Spaderna H</i><br /><b>Background</b><br />Reasons for women\'s increased probability to experience adverse events (AEs) after left ventricular assist device (LVAD) implantation compared with men\'s remain uncertain. We explored the role of psychosocial risk in the experience of AEs in women and men.<br /><b>Methods</b><br />INTERMACS patients receiving a primary continuous-flow LVAD between 7/2006 and 12/2017, median follow-up 13.6 months, were included (n=20123, 21.3% women). Time-to-event was calculated with cumulative incidence functions for 10 types of AEs separately (e.g., infection, device malfunction), each time accounting for the competing outcomes death, heart transplant and device explant due to recovery. Event-specific Cox proportional hazard models were run with a binary psychosocial risk variable (including: substance abuse, psychiatric diagnoses, limited social support, limited cognition, repeated noncompliance), controlled for covariates.<br /><b>Results</b><br />Psychosocial risk was more prevalent in men than in women (21.4% vs. 17.5%, p <.001). Seven out of ten AEs were more likely in women than in men (e.g., infection 44.5% vs. 39.2%, p <.001). The association of psychosocial risk with each AE was either stronger in women than in men (e.g., device malfunction HR<sub>adj</sub> 1.29, 95% CI [1.06-1.56] vs. HR<sub>adj</sub> 1.10, 95% CI [0.97-1.25]; rehospitalization HR<sub>adj</sub> 1.15, 95% CI [1.02-1.29] vs. HR<sub>adj</sub> 1.03, 95% CI [0.97-1.10]) or similar between sexes.<br /><b>Conclusions</b><br />Independent of clinical parameters, the presence of psychosocial risk is associated with increases in AEs. This suggests that early modification of psychosocial risk factors may have the potential to lower the risk for AEs in this patient population.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 26 Jun 2023; epub ahead of print</small></div>