The Journal of Heart and Lung Transplantation最新文献

{"title":"Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.","authors":"Ruben J Crespo-Diaz,Adrian J daSilva-deAbreu,Andrew N Rosenbaum,Stacy A Bernard,Manish J Gandhi,Shaji Kumar,Taxiarchis Kourelis,Atta Behfar,Alfredo L Clavell,Shannon M Dunlay,Robert P Frantz,Sudhir S Kushwaha,Naveen L Pereira,Yee Weng Wong,Richard C Daly,Philip J Spencer,Mauricio A Villavicencio Theoduloz,Barry A Boilson","doi":"10.1016/j.healun.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.healun.2025.01.021","url":null,"abstract":"BACKGROUNDHuman leukocyte antigen (HLA) sensitization is a significant barrier to transplantation for many patients. Daratumumab has proven safety and tolerability in multiple myeloma. We hypothesized that daratumumab monotherapy could be an effective and safe desensitization strategy in highly sensitized patients awaiting cardiac transplantation.OBJECTIVESThe primary end-point of this trial was the scope of daratumumab in lowering HLA antibodies. Secondary end-points included presence of donor-specific antibody, incidence of cellular and antibody-mediated rejection (AMR) and cardiac allograft function.METHODSSix consecutive highly sensitized patients were enrolled who had a calculated panel reactive antibody >50% using a mean fluorescence intensity (MFI) threshold >4,000 through a single antigen bead assay. Three completed the full 8 weeks of daratumumab therapy. HLA antibodies with MFI >10,000 were considered unacceptable for donor offers. All patients received weekly doses of 1,800 mg daratumumab and 30,000 units hyaluronidase subcutaneously for a planned total of 8 weeks.RESULTSThere was a significant reduction in HLA class I and class II antibodies by the time of heart transplantation. Daratumumab was well tolerated and without any serious adverse events. By the time of this publication, 5 of the total of 6 patients enrolled have been successfully transplanted. None of the patients enrolled experienced AMR and maintain normal cardiac allograft function.CONCLUSIONSDaratumumab monotherapy may be a safe and effective desensitization strategy in highly sensitized patients who are otherwise eligible for heart transplantation and considered too ill for other desensitization strategies.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Pre-Transplant Duration with HeartMate III Left Ventricular Assist Device: A Contemporary Analysis.","authors":"Ahmet Bilgili,Iverson E Williams,Omar M Sharaf,Fabian Jimenez,Yuriy Stukov,Giles J Peek,Mark S Bleiweis,Jeffrey P Jacobs,Thomas M Beaver,Eric I Jeng","doi":"10.1016/j.healun.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.025","url":null,"abstract":"BACKGROUNDThis study evaluates the impact of pretransplant HeartMate III (HM3) left ventricular assist device (LVAD) support duration on post-transplant survival in a contemporary cohort.METHODSA retrospective review of the United Network for Organ Sharing database was conducted for adult heart transplant recipients from January 2019 to December 2023 who were bridged with an HM3 LVAD. We utilized a restricted cubic spline fitted to a Cox proportional hazards model to stratify patients into duration groups based on risk inflection points (<1 year, 1-2 years, and >2 years), and outcomes were compared between and across groups.RESULTSAmong 1,996 patients, 35.2%(n=702), 32.2%(n=642), and 32.7%(n=652) had support durations of <1 year, 1-2 years, and >2 years, respectively. Median support duration was 518 days [IQR: 289-864]. Postoperative rates of stroke and acute rejection did not vary across groups (p>0.05), however rates of postoperative dialysis significantly increased with increasing support time (p>0.001). One-year survival was significantly higher for patients bridged <1 year (90.7% [95%CI: 88.5-93.0]) compared to those bridged >2 years (84.3% [95% CI: 81.4-87.4], p<0.001) but not for those bridged 1-2 years (89.0% [95% CI: 86.6-91.6], p=0.300). In multivariable analysis, patients supported 1-2 years (HR: 1.34 [1.01-1.79], p=0.045) and >2 years (HR: 1.77 [1.32-2.38], p<0.001) had a higher hazard of post-transplant mortality than those bridged <1 year.CONCLUSIONSWhile the HM3 enables extended bridging to transplant, durations longer than 2 years of support are linked to worse post-transplant survival.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ''Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry)'' [J Heart Lung Transplant 43 (2024) 272-283].","authors":"Vallerie McLaughlin,Harrison W Farber,Kristin B Highland,Anna R Hemnes,Murali M Chakinala,Kelly M Chin,Michelle Han,Michelle Cho,Tobore Tobore,Mohammad Rahman,Nick H Kim","doi":"10.1016/j.healun.2025.04.016","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.016","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between Donor-Derived Cell-free DNA and Tissue Gene Expression in Heart Transplant Patients Undergoing for-cause Endomyocardial Biopsies.","authors":"Andrea Fernandez Valledor,Cathrine M Moeller,Daniel Oren,Julia Baranowska,Salwa Rahman,Adi Hertz,Afsana Rahman,Carolyn Hennecken,Gal Rubinstein,Boaz Elad,Ilan Richter,Dor Lotan,Matthew Regan,Brian LaBarre,Adil Yunis,Justin Fried,Ersilia M DeFilippis,Paolo C Colombo,Melana Yuzefpolskaya,Jayant Raihkelkar,Farhana Latif,Kevin D Clerkin,David T Majure,Gabriel T Sayer,Nir Uriel","doi":"10.1016/j.healun.2025.04.019","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.019","url":null,"abstract":"INTRODUCTIONThe introduction of donor-derived cell-free DNA (dd-cfDNA) and the Molecular Microscope (MMDx) is changing how we diagnose rejection following heart transplantation (HT). This study aims to assess the accuracy of dd-cfDNA in detecting rejection as identified by MMDx and histology, with a focus on determining an optimal dd-cfDNA threshold to improve diagnostic performance.METHODSSingle-center prospective study of HT recipients undergoing for-cause biopsies with paired MMDx results and dd-cfDNA levels. We employed a Receiver Operator Curve (ROC) to evaluate the performance of dd-cfDNA levels to detect rejection assessed by both histology and MMDx. We also assessed the correlation between dd-cfDNA levels and MMDx rejection scores. A mixed-effects model was applied to account for repeated dependent samples when appropriate.RESULTS247 for-cause biopsies were identified with a median of 21 months from HT and a median of 11 days between dd-cfDNA and biopsy. 56.7% of the samples had dd-cfDNA levels ≥0.20%. MMDx identified rejection in 27.1% of biopsies, compared to 7.7% identified by histology. Elevated dd-cfDNA levels were associated with a fourfold increase in rejection rates by MMDx, mainly driven by a fivefold increase in ABMR detection when compared to histology. Dd-cfDNA demonstrated superior performance in predicting rejection by MMDx (AUC of 0.77; optimal cut-off dd-cfDNA value 0.30%). When incorporating a mixed-effects model, the predictive performance improved further, (AUC of 0.89; optimal cut-off value 0.26%). In contrast, prediction based on histology resulted in a lower AUC of 0.64. The correlation between dd-cfDNA levels and MMDx rejection scores was moderate (r=0.51; p<0.001).CONCLUSIONSIn a for-cause biopsy population, elevated dd-cfDNA levels were more predictive of rejection on MMDx than on histology, suggesting that molecular techniques may detect rejection at earlier stages than traditional histological methods. A dd-cfDNA cutoff of 0.26% provided the highest predictive accuracy for rejection by MMDx when applied within a mixed-effects model for repeated measures.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absolute Quantification of Donor-Derived Cell-Free DNA Following Pediatric and Adult Heart Transplantation.","authors":"Jens Böhmer,Håkan Wåhlander,Karin Tran-Lundmark,Michal Odermarsky,Maria Sjöborg Alpman,Julia Asp,Staffan Nilsson,Kristjan Karason,Sunnegårdh Jan,Anne Ricksten,Göran Dellgren","doi":"10.1016/j.healun.2025.04.024","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.024","url":null,"abstract":"OBJECTIVETraditional rejection surveillance after heart transplantation (HTx) is based on endomyocardial biopsies (EMB), which are invasive, expensive and associated with complications. Monitoring using cell-free DNA (cfDNA) is promising, but most studies report only on the donor fraction (DF) as the percentage of donor derived-cfDNA (dd-cfDNA) relative to total-cfDNA. We evaluated the performance of absolute as well as relative levels of dd-cfDNA to detect rejection.METHODSHTx patients were prospectively enrolled in a multicenter study, and blood samples collected concurrently with EMB. Dd-cfDNA was quantified using droplet digital PCR (ddPCR). Rejection was defined by EMB-results and compared to non-rejection EMB. Patients with symptomatic rejection were studied as a subgroup and test performance was determined using ROC-analysis.RESULTSWe included 94 patients (70 adults and 24 children) undergoing rejection surveillance during the first year after HTx, which resulted in 1007 EMB and blood samples. In 19 patients, there were 32 rejection episodes > 14 days past HTx, with 15 of them being symptomatic. In ROC analysis, dd-cfDNA and DF could discriminate quiescence from rejection with an AUC of 0.68 and 0.65, respectively. Dd-cDNA at a threshold of 25 copies/ml showed an AUC of 0.87 to detect symptomatic rejection, significantly better than DF (AUC of 0.75).CONCLUSIONSdd-cfDNA found good discrimination between cardiac recipients with and without rejection. Absolute quantification of dd-cfDNA with ddPCR is a fast and effective method to monitor graft health. Analyzing absolute dd-cfDNA levels helps identify other factors, besides rejection, that may influence cfDNA levels, potentially reducing the need for EMB.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belatacept as an Alternative Immunosuppressive Agent for Bone Marrow-Sparing in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres.","authors":"Stefanie J Hannan,Carlo J Iasella,Michel Sciullo,Cody Moore,Ryan Rivosecci,Lauren Sacha,Rachel M Sutton,Ritchie Koshy,Norihisa Shigemura,Pablo G Sanchez,Rafic Farah,Chadi A Hage,Jonathan K Alder,John F McDyer","doi":"10.1016/j.healun.2025.04.022","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.022","url":null,"abstract":"As we have previously shown, Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) with short-telomere length (STL) are prone to develop significant cytopenias and poor tolerance to cell cycle inhibitors, specifically Mycophenolate mofetil (MMF), post-transplant. We investigated the use of Belatacept as an alternative immunosuppressive agent in a prospective, open-label cohort of 9 ST-IPF-LTRs at our institution. These patients were either challenged with MMF (majority) or immediately started on Belatacept post-transplant with the goal to bridge to Everolimus, an mTOR inhibitor that is commonly used post-transplant. We describe outcomes in the first-year post-transplant including the incidence of Acute Cellular Rejection (ACR), Epstein-Barr Virus (EBV) viremia, and one case of Post-Transplant Lymphoproliferative Disorder (PTLD) at 13 months. The use of Belatacept post-lung transplant may be an acceptable short-term alternative therapy to cell cycle inhibitors in ST-IPF-LTRs with cytopenias but may lead to higher risk of EBV viremia and PTLD when Belatacept is used long-term in these patients.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Experience of Donation After Circulatory Death for Lung Transplantation. A Special Report from the International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation.","authors":"Michael Perch,Don Hayes,Wida S Cherikh,Alexandra Lewis,Lucinda Ewing,Eileen Hsich,Tajinder P Singh,Göran Dellgren,Rebecca Cogswell,","doi":"10.1016/j.healun.2025.04.013","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.013","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 2025 Annual Report of Heart and Lung Transplantation.","authors":"Tajinder P Singh,Eileen Hsich,Wida S Cherikh,Michael Perch,Don Hayes,Alexandra Lewis,Göran Dellgren,Rebecca Cogswell,","doi":"10.1016/j.healun.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.014","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Experience of Donation After Circulatory Death for Heart Transplantation: A Special Report from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry.","authors":"Eileen Hsich,Tajinder P Singh,Wida S Cherikh,Alexandra Lewis,Michael Perch,Don Hayes,Göran Dellgren,Rebecca Cogswell,","doi":"10.1016/j.healun.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.009","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of PANoptosis and Ferroptosis during Ex Vivo Lung Perfusion in Human Lungs.","authors":"Yajin Zhao,Lubiao Liang,Abby McCaig,Tanroop Aujla,Shaf Keshavjee,Mingyao Liu","doi":"10.1016/j.healun.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.003","url":null,"abstract":"A recent study demonstrated upregulation of PANoptosis related genes during reperfusion in human lung transplants. However, the impact of ex vivo lung perfusion (EVLP) on different cell death pathways and their relationship with inflammatory genes and clinical characteristics remains unknown. We conducted transcriptomic analyses on pre- and post-EVLP biopsies from 49 donation after brain death (DBD) and 39 donation after circulatory death (DCD) lungs. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to assess the enrichment of cell death and inflammatory pathways. We further explored the relationships between these pathways, donor characteristics, and clinical outcomes. DBD lungs showed significant enrichment of apoptosis and ferroptosis gene sets compared to DCD lungs. During EVLP, pyroptosis, apoptosis, necroptosis, and ferroptosis gene sets were significantly upregulated and strongly correlated with inflammatory pathways in both DBD and DCD donor lungs. Donor age, sex and smoking history were associated with specific cell death pathways. In DCD lungs, the expression of ferroptosis-related genes was associated with recipient early outcomes. In conclusion, the expression of cell death gene sets is donor-type specific. The identification of multiple cell death and inflammatory pathways during EVLP provides potential therapeutic targets to improve donor lung quality and enhance clinical outcomes.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}