The Journal of Heart and Lung Transplantation最新文献

{"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}

{"title":"Rescue Kidney Post Lung Transplant, is the Safety Net Saving the Day?","authors":"Chadi A Hage,Norihisa Shigemura","doi":"10.1016/j.healun.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.006","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885469","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":"Low dose apixaban in HeartMate 3 LVAD patients, interim analysis of the ApixiVAD trial, a randomized controlled study.","authors":"Bruno Schnegg,Ricardo Deveza,Sumita Barua,Sanjay Chavali,Phillip Lo,Lukas Capek,Jolie Bruno,Maryam Pavlicek-Bahlo,Eleni Xourgia,Alexandra Neagoe,Kathrin Zürcher,Kavitha Muthiah,Kaitlyn Lam,David Reineke,Matthias Siepe,Lukas Hunziker,Michele Martinelli,Peter Macdonald,Christopher Hayward","doi":"10.1016/j.healun.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.012","url":null,"abstract":"BACKGROUNDLeft ventricular assist devices (LVADs) improve outcomes in advanced heart failure but require anticoagulation. Vitamin K antagonists (VKAs) have significant limitations, with labile INRs and suboptimal Time in Therapeutic Range (TTR), associated with increased morbidity and mortality. Direct oral anticoagulant therapy (DOAC) has been contraindicated in LVAD patients.METHODThe ApixiVAD study, a 1:1 randomized, open-label pilot trial, compared the reduced-dose apixaban (2.5 mg twice daily) with standard VKAs in stable HeartMate 3 (HM3) patients with TTR > 60%. Aspirin was not mandated. Primary outcomes included thromboembolic events, bleeding and death.RESULTSForty-four patients were randomised, 21 to apixaban and 23 to VKA. Median age was 55 years (50-64), and 6 were women (14%). The median time from LVAD implantation to randomization was 6 months (range 5-8). Patients were followed for a median of 6 months (2 - 8). Twenty-five (57%) were transplanted, 12 (27%) were still on treatment and 5 (11%) had undergone a primary outcome. Event-free survival was similar between groups (HR 1.46, 95% CI 0.64-3.35, P = 0.4, Cox model) as well as Blood product use at transplantation.CONCLUSIONSThese interim results were obtained after the end of recruitment but before all patients reached the full follow-up duration. The rates of bleeding observed in the apixaban group were below those reported in large international studies without any increase in thrombosis, suggesting that apixaban 2.5 mg twice daily may offer an effective balance between bleeding risk and anticoagulation efficacy. These findings should be interpreted as preliminary and hypothesis-generating.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893343","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":"Custodiol-N Versus Custodiol®: Results from A Prospective Noninferiority Randomised Single Blind, Multicenter Phase 3 Trial In Patients Undergoing Heart Transplantation.","authors":"A Aliabadi-Zuckermann,E Osorio-Jaramillo,C Knosalla,J Gummert,G Szabo,F Wittmann,R Yeter,R Schramm,J Goekler,F Hennig,M Morshuis,A Zuckermann","doi":"10.1016/j.healun.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.healun.2025.03.021","url":null,"abstract":"BACKGROUNDCustodiol® is a well-established preservation solution for organ transplantation and was the basis for the development of Custodiol-N to improve graft preservation. Previous results in coronary artery bypass graft surgery have shown effective cardiac protection without safety concerns. This study aimed to evaluate the safety and ability of Custodiol-N to preserve cardiac grafts for heart transplantation.METHODSThis prospective, randomized, single-blind, multicenter, non-inferiority study was conducted at three centers in Austria and Germany. The primary endpoint was creatine kinase (CK-MB) peak value from 4-168 hours after opening of the aortic cross-clamp, with a 30% non-inferiority margin. Key secondary efficacy endpoints include patient and graft survival, incidence of primary graft failure, or length of stay in the intensive care unit. The primary and secondary endpoints were analyzed in both the treated and per protocol populations.RESULTSA total of 105 randomized patients received Custodiol® (n=52) or Custodiol-N (n=53) preserved hearts. Average donor age and ischemic times were comparable. Average CK-MB peak values were 176.94±189.61 U/L for the Custodiol® vs. 130.51±69.60 U/L for the Custodiol-N group (p-value for non-inferiority of Custodiol-N by 30% <.0001). Patient survival was comparable 1-year post-transplantation (90.4% for Custodiol® vs 88.7% for Custodiol-N). The incidence of primary graft failure and median length of intensive care unit stay were higher for Custodiol® group. Safety assessment showed evenly distributed adverse events.CONCLUSIONSThis study shows that Custodiol-N is safe, non-inferior, and provides similar cardiac graft protection as the established Custodiol® solution.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885070","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":"Vented and Vetted: A New Take on Donor Lung Ventilation.","authors":"Laura L Donahoe,Shaf Keshavjee","doi":"10.1016/j.healun.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.008","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885000","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":"CD26/DPP-IV Inhibitors and Associations with Chronic Lung Allograft Dysfunction in a Multicenter Cohort.","authors":"Alexander R Graham,Maria V Grau-Sepulveda,Erika J Bush Buckley,Daniel F Dilling,Albert Faro,Steven R Hays,Jerry L Kirchner,Carli J Lehr,Isabelle Moneke,Samuel Passarelli,Erin Tallarico,Abigail Thaxton Ccrp,Grant A Turner,Bo Young H Yen,Megan L Neely,Laurie D Snyder","doi":"10.1016/j.healun.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.010","url":null,"abstract":"BACKGROUNDCD26/DPP-IV inhibitors (gliptins) target pro-inflammatory pathways that contribute to the development of chronic lung allograft dysfunction (CLAD). We analyzed longitudinal clinical data from 6 North American lung transplant centers to elucidate the effect of gliptin exposure on CLAD development after lung transplantation.METHODSThis cohort included 6 North American lung transplant centers, four sites from the Clinical Trials in Organ Transplantation-20 study and 2 additional sites. First lung transplant recipients between December 2015 and August 2018 were eligible with follow up through June 2021. Gliptin exposures prior to CLAD onset in addition to CLAD risk factors were included in the models. The primary endpoint was a composite of probable CLAD, CLAD related deaths, and CLAD related re-transplant. Cox regression models were used to assess the association between gliptin use and the CLAD composite endpoint.RESULTS779 patients met inclusion criteria, with 126 (16.2%) having any gliptin exposure. 233 (29.9%) patients experienced probable CLAD composite outcome. Across all centers, gliptin exposure at any point was not associated with probable CLAD or definite CLAD across the study period. In a post-hoc analysis of centers with median gliptin exposures > 6 months, exposure within the first 90 days post-transplant was associated with a decreased risk of definite CLAD composite across the study period (HR 0.25; 95% CI, 0.07, 0.83; p<0.05).CONCLUSIONSThe association of gliptins and CLAD is complex, but early gliptin use may help protect against CLAD if started within 90 days post-transplant and used for a prolonged period.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893406","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":"Single-cell RNA Sequencing of Pig Lung Transplantation Reveals Macrophage Ferroptosis in Lung IschemiaReperfusion Injury.","authors":"Fenghui Zhuang,Ye Ning,Chongwu Li,Yunzhe Luo,Peigen Gao,Tao Wang,Chenyang Dai,Huikang Xie,Wenxin He,Junqi Wu,Chang Chen","doi":"10.1016/j.healun.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.011","url":null,"abstract":"Primary graft dysfunction (PGD), which is caused primarily by ischemia-reperfusion injury (IRI), is a major obstacle in lung transplantation. Here, we developed an orthotopic, single-lung transplant pig model to simulate prolonged cold IRI. After 24 hours of cold ischemia and 8 hours of warm reperfusion, the transplanted lung exhibited severe allograft injury. Subsequent single-cell RNA sequencing (scRNA-seq) revealed significant changes in alveolar macrophages after IRI, with prominently enriched ferroptosis pathways. Transmission electron microscopy (TEM) confirmed characteristic ferroptosis changes in lung macrophages, and decreased GPX4 expression in macrophages indicated increased susceptibility to ferroptosis. Overall, our pig orthotopic left lung transplant model effectively simulates IRI after transplantation, which offers a valuable platform for more detailed investigations of early reperfusion injury to pulmonary grafts. Moreover, we preliminarily demonstrated the importance of macrophage ferroptosis in IRI, suggesting that inhibiting macrophage ferroptosis may be a promising therapeutic strategy for lung IRI.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866379","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 white rabbit of heart transplantation: Alice's in Wonderlands solution to heart preservation.","authors":"Alexander M Bernhardt,Hermann Reichenspurner","doi":"10.1016/j.healun.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.005","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853084","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":"Persistent and progressive acute lung allograft dysfunction is linked to cell compositional and transcriptional changes in small airways.","authors":"Elsa Brunet-Ratnasingham,Shivaram Yellamilli,Ruyin Guo,Rashmi Prava Mohanty,Allen Duong,Nicholas A Kolaitis,Steven R Hays,Rupal J Shah,Aida Venado,Julia A Maheshwari,Mary Ellen Kleinhenz,Lorriana E Leard,John McDyer,Tereza Martinu,Alexis J Combes,Daniel R Calabrese,Jonathan P Singer,John R Greenland","doi":"10.1016/j.healun.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.healun.2025.03.010","url":null,"abstract":"BACKGROUNDAcute lung allograft dysfunction (ALAD) is a clinical syndrome of forced expiratory volume in 1-second (FEV1) decline concerning for chronic lung allograft dysfunction (CLAD) onset. Novel diagnostic tools are needed to identify those with ALAD who will progress to CLAD and to target appropriate therapies. We hypothesized that progressive ALAD would be associated with changes in small airway cell composition and cell-specific transcription.METHODSWe prospectively identified recipients with undifferentiated ALAD and controls with stable allograft function for small airway brushing and single-cell RNA sequencing analysis. ALAD outcome group was categorized as (1) control (n = 8), or ALAD with (2) recovered (n = 4), (3) persistent (n = 5), or (4) progressive (n = 3) FEV1 decline. Cell compositional changes, pseudobulk Reactome pathways, and the AI2 score, previously linked to CLAD in airway brush transcriptomes, were assessed as a function of ALAD outcome group.RESULTSAcross 68,140 cells, the distribution of cell composition was linked to ALAD outcome group (PERMANOVA, p = 0.004). Worse ALAD outcomes correlated with loss of basal cells, changes in club and ciliated subsets, a loss of macrophages, and expansion of cytotoxic T cells. The AI2 gene score was positively associated with ALAD outcome group, particularly in epithelial cell subsets (p < 0.001). Pathway analysis showed increased interferon signaling and inhibition of cell proliferation in epithelial cells.CONCLUSIONSIn this pilot study, persistent and progressive ALAD was associated with changes in bronchiolar cell composition and transcriptional programs. Molecular phenotyping may help identify and characterize individuals with ALAD at increased risk for progression.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"179 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889224","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":"Evaluating the Influence of Atrial Fibrillation in Chronic Thromboembolic Pulmonary Hypertension.","authors":"S A Reddy,J Pepke-Zaba","doi":"10.1016/j.healun.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.healun.2025.04.002","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831564","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}