Journal of Heart and Lung Transplantation最新文献

{"title":"Early pulmonary isolation of non-tuberculous mycobacterial organisms is associated with increased risk of death and chronic lung allograft dysfunction: A Lung Transplant Outcomes Group Cohort Study.","authors":"Gabrielle Mezochow, Stephen Griffiths, Douglas E Schaubel, Michelle Oyster, Laurel Kalman, Alyssa Mezochow, Emily Blumberg, Gina Hong, Denis Hadjiliadis, Krishna Pandya, Tamara Claridge, Stephanie Witek, Luke Benvenuto, Dennis Lyu, Michael P Combs, Pali Shah, Christian Merlo, Aida Venado Estrada, Jonathan P Singer, Scott Palmer, Jason D Christie, Michaela R Anderson","doi":"10.1016/j.healun.2026.08.017","DOIUrl":"10.1016/j.healun.2026.08.017","url":null,"abstract":"<p><strong>Background: </strong>How pulmonary non-tuberculous mycobacteria (NTM) impact lung transplant outcomes is unknown. We evaluated the effect of pulmonary isolation of NTM on death or re-transplantation and chronic lung allograft dysfunction (CLAD).</p><p><strong>Methods: </strong>We performed a multicenter cohort study of adult lung transplant recipients at five US centers from 2007 to 2022. Our exposure was growth of NTM from pulmonary samples in the first year post-transplant (\"early\") in primary analyses, and growth at any time post-transplant in secondary analyses. We evaluated time from transplantation to death or re-transplantation and CLAD using separate covariate-adjusted proportional hazards models, each with a time-dependent exposure indicator for early first pulmonary NTM isolation.</p><p><strong>Results: </strong>Of 1,766 lung transplant recipients, 223 (13%) had early pulmonary NTM isolation. NTM was first isolated at a median [interquartile range] of 61 [17-158] days after transplantation. Early NTM growth was associated with increased risk of death or re-transplantation (HR 1.30, 95% CI 1.05-1.60), driven by rapid growing NTM (HR 2.17, 95% CI 1.42-3.31). Early growth of NTM was associated with increased risk of CLAD (HR 1.29, 95% CI 1.03-1.62); this association was driven by slow growing NTM (HR 1.33, 95% CI 1.04-1.69). Association appeared modified by acute cellular rejection (p = 0.10) and pre-operative diagnosis (p = 0.04), with a stronger association in recipients with ILD (HR 1.67, 95% CI 1.26-2.20). Similar associations were present for NTM growth at any time post-transplant.</p><p><strong>Conclusions: </strong>Pulmonary growth of NTM in the first post-transplant year occurred frequently and was associated with increased risk of death or re-transplantation and CLAD.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865441","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":"Re-evaluating the role of oxygen delivery and radiographs in the definition of primary graft dysfunction after lung transplantation: A Lung Transplant Outcomes Group cohort study.","authors":"Michaela R Anderson, Robert Gallop, A Russell Localio, Michelle Oyster, Laurel Kalman, Stephen Griffiths, Matthew Hartwig, Laurie D Snyder, Michael Shashaty, Vivek Ahya, Maria Crespo, Mauer Biscotti, Gabrielle Mezochow, Krishna Pandya, Julia Gasior, Daniel Calabrese, John R Greenland, Luke Benvenuto, Gundeep Dhillon, Michael P Combs, John McDyer, Chadi Hage, David Roe, Pali Shah, Christian Merlo, Jonathan P Singer, Scott M Palmer, Jason D Christie","doi":"10.1016/j.healun.2026.08.016","DOIUrl":"10.1016/j.healun.2026.08.016","url":null,"abstract":"<p><strong>Background: </strong>Primary graft dysfunction (PGD) is severe lung injury following lung transplantation. Variable radiograph interpretation and changes in mechanical ventilation and extracorporeal membrane oxygenation (ECMO) support for hypoxemia may limit the current PGD definition's validity.</p><p><strong>Methods: </strong>We assessed whether changes in the PGD definition accounting for oxygen delivery method (intubated, non-intubated, ECMO) were associated with differential graft survival. Severe PGD was grade 3 at 48 or 72 hours after transplant. We estimated crude and standardized time from transplantation to death or retransplantation with each alternate defining criterion. We secondarily evaluated whether excluding chest radiography led to severe PGD re-classification.</p><p><strong>Results: </strong>Among 3,170 recipients, 749 (24%) had severe PGD by current definition. By revised oxygen delivery definition, 182 non-intubated recipients and 372 intubated recipients had severe PGD, and 177 recipients had severe PGD requiring ECMO. Recipients with severe PGD requiring ECMO had the highest 1-year mortality (cumulative incidence of death 0.20, 95%CI 0.17-0.24), followed by intubated severe PGD (0.15, 95%CI 0.13-0.17). Non-intubated recipients had similar mortality with and without severe PGD (non-intubated with PGD: 1-year cumulative incidence of death 0.11, 95%CI 0.09-0.13; non-intubated without severe PGD: 0.10, 95%CI 0.09-0.11). Exclusion of radiographs reclassified 814 recipients, including 89 (11%) reclassified as severe PGD. On review of radiographs from recipients reclassified as severe PGD, the most frequent findings were effusions, atelectasis, and pneumonia.</p><p><strong>Conclusion: </strong>A revised PGD definition stratified by mode of oxygen delivery identifies groups with differential mortality. Chest radiography is critical to excluding alternative causes of lung injury in recipients with severe hypoxemia.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865367","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":"Beyond Donor-Specific Antibodies: Molecular Characterization of Antibody-Mediated Rejection Using Tissue-Based Transcriptomics in Heart Transplantation.","authors":"Andrea Fernandez Valledor, Julia Baranowska, Adi Hertz, Cathrine M Moeller, Salwa Rahman, Daniel Oren, David Bae, Marta Farrero, Ana Garcia Alvarez, Dor Lotan, Justin Fried, Jayant Raihkelhar, Ersilia M DeFilippis, Koji Takeda, Farhana Latif, David T Majure, Kevin J Clerkin, Gabriel T Sayer, Nir Uriel","doi":"10.1016/j.healun.2026.08.015","DOIUrl":"10.1016/j.healun.2026.08.015","url":null,"abstract":"<p><strong>Background: </strong>Antibody-mediated rejection (AMR) contributes to graft dysfunction after heart transplantation, yet histopathology and circulating donor-specific antibodies (DSA) may incompletely capture intragraft biology. We characterized molecular ABMR by human leukocyte antigen (HLA)-DSA status and, within DSA-negative cases, non-HLA antibody status.</p><p><strong>Methods: </strong>We analyzed 579 for-cause endomyocardial biopsies with paired Molecular Microscope Diagnostic System (MMDx) and histopathology. Molecular scores, transcripts, donor-derived cell-free DNA (dd-cfDNA), and gene-expression profiling (GEP) were compared using patient-clustered models with false-discovery-rate correction. Multivariable Cox models evaluated a 2-year composite of death, retransplantation, graft dysfunction (LVEF < 50%), or subsequent histologic rejection (acute cellular rejection [ACR] ≥ 1B/2R or pAMR ≥ 1).</p><p><strong>Results: </strong>MMDx-defined ABMR was present in 83 biopsies (14.3%); 30 (36.1%) were DSA-negative. DSA-negative and DSA-positive ABMR had similar ABMR probabilities (0.66 vs 0.66), global rejection scores, dd-cfDNA (0.83% vs 0.63%), GEP (35 vs 33), and transcriptomic profiles. Within DSA-negative ABMR, non-HLA antibodies were detected in 20/30 (66.7%) and associated with higher ABMR probability (0.69 vs 0.63; p = 0.041), dd-cfDNA (0.91% vs 0.62%; p = 0.048), GEP (35 vs 33; p = 0.019), and greater endothelial, ABMR/NK-cell, interferon-γ, and injury-related transcript activation. Histologic-molecular agreement was limited (κ = 0.14); 70/83 molecular ABMR biopsies lacked histologic pAMR. In joint models, molecular ABMR, but not pAMR, was associated with higher dd-cfDNA (b = 0.38%, p = 0.039). Conversely, histologic pAMR independently predicted the composite outcome (adjusted HR 2.68, 95% CI 1.34-5.35; p = 0.005), whereas molecular ABMR did not (adjusted HR 0.93, 95% CI 0.56-1.56; p = 0.795).</p><p><strong>Conclusions: </strong>Molecular ABMR exhibited similar profiles regardless of HLA-DSA status. Non-HLA antibodies identified greater activation and dd-cfDNA levels within DSA-negative ABMR. Molecular assessment may complement conventional evaluation by refining ABMR phenotyping.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865388","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":"Dapagliflozin in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: The DAPAH randomized controlled trial.","authors":"Mads Kristian Ersbøll, Jesper Kjærgaard, Karin Waidtløw, Lars Køber, Finn Gustafsson, David G Kiely, David Montani, Jørn Carlsen, Kasper Rossing","doi":"10.1016/j.healun.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.healun.2026.07.008","url":null,"abstract":"<p><strong>Background: </strong>SGLT2 inhibitors (SGLT2i) reduce mortality in left heart failure. In pulmonary arterial hypertension (PAH), preclinical data suggest SGLT2i improve right ventricular function through metabolic modulation and inhibition of vascular remodeling via smooth muscle cell pathways. The DAPAH trial evaluated whether the potential benefits of SGLT2 inhibition translate into clinical efficacy for symptomatic patients on background vasodilator therapy with either PAH or chronic thromboembolic pulmonary hypertension.</p><p><strong>Methods: </strong>In this single-center, double-blind trial, 52 patients were randomized (1:1) to dapagliflozin 10 mg daily or placebo for 12 weeks. The primary endpoint was change in Peak VO₂. Secondary endpoints included invasive hemodynamics, NT-proBNP, 6-minute walk distance (6MWD) and REVEAL Lite 2 scores.</p><p><strong>Results: </strong>Baseline characteristics were balanced (n=52; mean age 66.5 years; 63% female; n=40 PAH, n=12 CTEPH). Fifty-one patients had complete data on Peak VO₂. At 12 weeks, there was no significant difference in Peak VO₂ (Adjusted Mean Difference: -0.67 mL/kg/min; 95% CI [-1.67, 0.33]; p=0.187). No significant treatment effects were observed for pulmonary vascular resistance (p=0.255), 6MWD (p=0.22), or NT-proBNP trajectory (interaction p=0.681). REVEAL Lite 2 scores showed a small reduction with dapagliflozin (-0.66; 95% CI [-1.25, -0.06]; p=0.031). Metabolic target engagement was evident from a significant reduction in serum urate (P-interaction < 0.001). Dapagliflozin was safe and well-tolerated.</p><p><strong>Conclusion: </strong>This randomized study of SGLT2i in pre-capillary PH showed that 12 weeks of dapagliflozin did not significantly improve exercise capacity, hemodynamics, or functional status compared to placebo.</p><p><strong>Clinicaltrials: </strong>gov (NCT05179356).</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865410","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":"Measles and varicella protection - surge in cases, but now a surge in hope!","authors":"Robert J Rolfe, Cameron R Wolfe","doi":"10.1016/j.healun.2026.08.013","DOIUrl":"10.1016/j.healun.2026.08.013","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818656","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":"Daratumumab to treat antibody mediated rejection in the absence of donor specific antibodies: Do we need an update in our vocabulary or mental model?","authors":"Jonathan J Edwards, Joseph W Rossano","doi":"10.1016/j.healun.2026.08.012","DOIUrl":"10.1016/j.healun.2026.08.012","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818623","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":"Procurement without borders: Quality, access, and financial fairness in the era of heart organ procurement services.","authors":"Igor Gosev, Matthew Montgomery","doi":"10.1016/j.healun.2026.08.009","DOIUrl":"10.1016/j.healun.2026.08.009","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794119","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":"Beyond the Achilles Heel: Driveline infection as the cancer of durable LVAD therapy.","authors":"Paolo C Colombo, Melana Yuzefpolskaya","doi":"10.1016/j.healun.2026.08.014","DOIUrl":"10.1016/j.healun.2026.08.014","url":null,"abstract":"<p><p>Durable left ventricular assist devices (LVADs) have transformed survival in advanced heart failure, yet driveline infection (DLI) affects 40% of patients by 5 years. The term \"Achilles' heel\" identifies the driveline as the system's critical vulnerability but does not capture the course of DLI. Achilles died acutely from a heel wound; DLI is chronic, recurrent, treatment-resistant, and progressive. It begins at the exit site, persists through biofilm formation, recurs after apparent remission, progresses along the driveline, and may eventually involve the pump and outflow graft, repeatedly exposing patients to hospitalizations for intravenous antibiotics and surgery, and ultimately causing death. We therefore propose that DLI be viewed as the \"cancer\" of LVAD therapy. The analogy is clinical, not biological, and informs treatment: as with cancer, management should be guided by anatomic extent and disease aggressiveness, suppression should not be mistaken for cure, and definitive intervention should precede advanced spread, when source control becomes more difficult. Serial staging and multidisciplinary review are recommended, with hardware removal considered when infection progresses despite suppressive therapy. Potentially curative options for deep DLI include LVAD explantation in patients with sufficient myocardial recovery, transplantation for eligible candidates, and device exchange when transplantation is not feasible. Given the major challenges of treating DLI, every LVAD program must prioritize protocolized prevention from implantation throughout support. Ultimately, eliminating the cancer of LVAD therapy will require a fully implantable system with no driveline to infect.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794105","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":"Elevated Radiographic Assessment of Lung Edema (RALE) score on day 3 after lung transplantation is associated with poor clinical outcomes.","authors":"Ciara M Shaver, Tatsuki Koyama, Aaron Lee, Michelle Oyster, Laurel Kalman, Jonathan Orens, Pali Shah, Luke Benvenuto, Selim M Arcasoy, Joshua Diamond, Jason D Christie, Lorraine B Ware","doi":"10.1016/j.healun.2026.08.008","DOIUrl":"10.1016/j.healun.2026.08.008","url":null,"abstract":"<p><strong>Background: </strong>Primary graft dysfunction (PGD) is associated with lung transplant recipient mortality. However, PGD severity based on hypoxemia may overestimate alveolar edema. We tested whether quantification of pulmonary edema using the Radiographic Assessment of Lung Edema score (RALE) is associated with PGD, hospital length of stay (LOS), or death in a retrospective cohort study.</p><p><strong>Methods: </strong>The cohort included double lung transplant recipients from two Lung Transplant Outcomes Group centers (LTOG, n=253) and Vanderbilt University Medical Center (VUMC, n=252). RALE score (extent and density of opacities) was determined from chest radiographs from post-operative day 3.</p><p><strong>Results: </strong>Median day 3 RALE was 19 (quartiles 13-26) in LTOG and 16 (12-21) at VUMC. Patients with PGD2 or PGD3 had significantly higher RALE than patients with PGD 0/1. There was no association between PaO₂/FiO₂ and LOS or mortality. In LTOG, a 5-point increase in RALE associated with a 3.3-day increase in LOS (95%CI 1.7-4.7, p<0.001) and a 41% increase in 1-year mortality (HR 1.4, 95%CI 1.2-1.8) (p<0.001), each independent of hypoxemia. At VUMC, a 5-point increase in RALE associated with a 4.5-day increase in LOS (95%CI: 2.6-6.4, p<0.001), independent of hypoxemia, but was not associated with mortality (p=0.54).</p><p><strong>Conclusions: </strong>In lung transplant recipients, RALE is associated with PGD grade and is a strong predictor of hospital LOS. These associations are independent of hypoxemia, suggesting that radiographic assessment provides prognostic information beyond severity of hypoxemia. Quantification of pulmonary edema using RALE may be useful for identifying lung transplant recipients at high risk of poor clinical outcomes.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794047","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":"Breathing new life into A-NRP: A commentary on \"Pulmonary-Abdominal Normothermic Regional Perfusion Enables In Situ Lung Evaluation in DCD: A Comparative Study with conventional A-NRP\".","authors":"Lauryn E Spinetta, Suresh Keshavamurthy","doi":"10.1016/j.healun.2026.08.011","DOIUrl":"10.1016/j.healun.2026.08.011","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794112","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}