Journal of Heart and Lung Transplantation最新文献

{"title":"Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor.","authors":"Shinichi Kawana, Mikio Okazaki, Tomohisa Sakaue, Kohei Hashimoto, Kentaro Nakata, Haruki Choshi, Shin Tanaka, Kentaroh Miyoshi, Shinji Ohtani, Toshiaki Ohara, Seiichiro Sugimoto, Akihiro Matsukawa, Shinichi Toyooka","doi":"10.1016/j.healun.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.028","url":null,"abstract":"<p><strong>Background: </strong>Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD.</p><p><strong>Methods: </strong>Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1^-/-) mice.</p><p><strong>Results: </strong>NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1^-/- donors significantly improved pulmonary graft function compared to wild-type donors (P < 0.001). Histological analysis showed decreased microvascular endothelial cell death (P = 0.007), neutrophil infiltration (P < 0.001), and albumin leakage (P < 0.001). Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1^-/- donors, correlating with diminished pulmonary edema (P < 0.001). However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1^-/- recipient.</p><p><strong>Conclusions: </strong>Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new day has come: Sotatercept for the treatment of pulmonary arterial hypertension.","authors":"Thomas M Cascino, Sandeep Sahay, Victor M Moles, Vallerie V McLaughlin","doi":"10.1016/j.healun.2024.09.021","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.021","url":null,"abstract":"<p><p>Despite increasing therapeutic options and evolving treatment strategies, including targeting three therapeutic pathways, in the management of pulmonary arterial hypertension (PAH), morbidity and mortality have remained unacceptably high. Sotatercept is a first-in-class, novel activin signaling inhibitor approved for treating PAH based on evolving efficacy and safety evidence. This state-of-the-art review summarizes the current understanding of the mechanism of action, the impact on outcomes that improve how patients feel, function, and survive, and the safety and adverse event profile to inform readers of this breakthrough novel therapy.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Outcome of Restrictive Cardiac Allograft Physiology in Severe Coronary Allograft Vasculopathy.","authors":"Masaki Tsuji, Jignesh K Patel, Michelle M Kittleson, David H Chang, Evan P Kransdorf, Andriana P Nikolova, Lily K Stern, Nayana Bhatnagar, Jon A Kobashigawa","doi":"10.1016/j.healun.2024.09.029","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.029","url":null,"abstract":"<p><strong>Background: </strong>Microvascular dysfunction after heart transplantation leads to restrictive cardiac allograft physiology (RCP), which is classified as severe coronary allograft vasculopathy (CAV); however, the prognosis of RCP remains unclear. Therefore, in this study, we aimed to elucidate the prognosis of RCP in comparison with that of severe angiographic CAV.</p><p><strong>Methods: </strong>We assessed 116 patients with severe CAV who underwent heart transplantation between 2004 and 2023. RCP was defined as symptomatic heart failure with restrictive hemodynamic values (mean right atrial pressure >12 mmHg, pulmonary capillary wedge pressure >25 mmHg, and cardiac index <2.0 L/min/m²). The primary outcome was death or re-transplantation.</p><p><strong>Results: </strong>Of the 116 patients with severe CAV, 42 had RCP (RCP-CAV group) and 74 had severe angiographic CAV without RCP (Angio-CAV group). A significantly shorter time from heart transplantation to diagnosis and lower subsequent percutaneous catheter intervention after diagnosis were seen in the RCP-CAV group than in the Angio-CAV group (both p<0.001). Freedom from death or re-transplantation at 5 years was significantly worse in the RCP-CAV group compared to the Angio-CAV group (18.4% vs 35.4%, p=0.001). In the Cox proportional hazard model, RCP was independently associated with an increased risk of death or re-transplantation (hazard ratio 2.08, 95% confidence intervals 1.26-3.44, p=0.004).</p><p><strong>Conclusions: </strong>The prognosis of patients with RCP was significantly worse than that of patients with severe angiographic CAV. The early detection of microvascular dysfunction and re-transplantation listing may improve the prognosis of patients with RCP.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Perspective on the Added Value of Red Blood Cells during Cardiac Hypothermic Oxygenated Perfusion.","authors":"Mats T Vervoorn, Elisa M Ballan, Selma E Kaffka Genaamd Dengler, Veronique M F Meijborg, Saskia C A de Jager, Richard Van Wijk, Niels P van der Kaaij","doi":"10.1016/j.healun.2024.09.025","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.025","url":null,"abstract":"<p><p>Hypothermic oxygenated perfusion (HOPE) is an emerging technique for donor heart preservation that is currently being studied in multiple clinical trials with promising results. When compared to HOPE for other organs, cardiac protocols involve red blood cell (RBC) supplementation, despite absence of comparative evidence for its benefits. In this perspective paper, we discuss the pros and cons of the addition of RBC's during cardiac HOPE. Although the current clinical results with RBC supplementation during HOPE seem promising, potential downsides of RBC supplementation cannot be ruled out. The impact of supplemented RBC's during cardiac HOPE requires further investigation to improve HOPE protocols, in order to optimize heart preservation using this promising technology.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed cellular and spatial characterization of chronic lung allograft dysfunction using imaging mass cytometry.","authors":"Benjamin Renaud-Picard, Sajad Moshkelgosha, Gregory Berra, May Cheung, David Hwang, David Hedley, Stephen Juvet, Tereza Martinu","doi":"10.1016/j.healun.2024.09.023","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.023","url":null,"abstract":"<p><p>Long-term survival after lung transplantation remains limited by chronic lung allograft dysfunction (CLAD), with two main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). We aimed to assess CLAD lung allografts using imaging mass cytometry (IMC), a high dimensional tissue imaging system allowing a multiparametric in situ exploration at a single cell level. 4 BOS, 4 RAS, and 4 control lung samples were stained with 35 heavy metal-tagged antibodies selected to assess structural and immune proteins of interest. We identified 50 immune and non-immune cell clusters. CLAD lungs had significantly reduced club cells. A Ki67-high basal cell population was mostly present in RAS and in proximity to memory T cells. Memory CD8⁺ T cells were more frequent in CLAD lungs, regulatory T cells more prominent in RAS. IMC is a powerful technology for detailed cellular analysis within intact organ structures that may shed further light on CLAD mechanisms.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining direct and indirect right ventricular unloading.","authors":"Jamel Ortoleva, Dominic V Pisano","doi":"10.1016/j.healun.2024.08.025","DOIUrl":"https://doi.org/10.1016/j.healun.2024.08.025","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous heart and kidney transplantation for high-risk candidates on extracorporeal life support: don't judge a book by its cover.","authors":"Mickaël Lescroart, Guillaume Coutance","doi":"10.1016/j.healun.2024.09.024","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.024","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context Matters: Neighborhood Health Affects Heart Transplant Outcomes Even at High Volume Centers.","authors":"Jaya Batra, Ersilia M DeFilippis","doi":"10.1016/j.healun.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.013","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of post-mortem sevoflurane ventilation and in situ topical cooling provides improved 6h lung preservation in an uncontrolled DCD porcine model.","authors":"Edson Ricardo Brambate Junior, Aizhou Wang, Rafaela Vanin Pinto Ribeiro, Erika L Beroncal, Khaled Ramadan, Vinicius Schenk Michaelsen, Manyin Chen, Aadil Ali, Yu Zhang, Prodipto Pal, Etienne Abdelnour, Gabriel Ricardo Siebiger, Bruno Maineri Pinto, Tom Waddell, Ana C Andreazza, Shaf Keshavjee, Marcelo Cypel","doi":"10.1016/j.healun.2024.09.019","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.019","url":null,"abstract":"<p><strong>Background: </strong>Recent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model.</p><p><strong>Methods: </strong>After uDCD induction, donor pigs were allocated to one of the following groups: Control - static lung inflation only (SLI); TC - SLI + continuous intrapleural topical cooling (TC); or TC+Sevo - SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation.</p><p><strong>Results: </strong>Animals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion.</p><p><strong>Conclusion: </strong>Preservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OUTCOMES OF CONTROLLED DCDD LUNG TRANSPLANTATION AFTER THORACO-ABDOMINAL VS ABDOMINAL NORMOTHERMIC REGIONAL PERFUSION: THE SPANISH EXPERIENCE.","authors":"Anna Minasyan, Mercedes de la Torre, Joel Rosado Rodriguez, Alberto Jauregui Abularach, Alejandra Romero Román, Nuria Novoa Valentin, Ivan Martinez Serna, Pablo Gámez García, Alilis Fontana, Gabriel Sales Badia, Francisco Javier González García, Angel Salvatierra Velazquez, Loreto Berjon, Roberto Mons Lera, Pedro Rodriguez Suarez, Elisabeth Coll, Eduardo Miñambres, Beatriz Domínguez-Gil, Jose Luis Campo-Cañaveral de la Cruz","doi":"10.1016/j.healun.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.018","url":null,"abstract":"<p><strong>Objective: </strong>Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs.</p><p><strong>Methods: </strong>This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in two groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart versus abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, ICU and hospital length of stay, early survival rates, and mid-term outcomes.</p><p><strong>Results: </strong>283 cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs. 7.6%; p=0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3%% vs. 41.5%; p=0.005). We found no significant differences between the groups regarding other post-transplant outcome variables.</p><p><strong>Conclusions: </strong>TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}