Journal of Heart and Lung Transplantation最新文献

{"title":"Heart Transplantation in Adult Fontan Patients: New Insights from Fontan-Associated Liver Disease Beyond Traditional Predictors.","authors":"Justyna Rybicka, Louise Coats, David Crossland, Preya Patel, John Scott, Kirsty Anderson, Antony Hermuzi, Kaitav Adhvaryu, Jayant Kakarla, Emre Erturk, Neil Seller, Steven White, Oscar Gonzalez-Fernandez, Guy MacGowan, Mohamed S Nassar, Louise Kenny, Katrijn Jansen","doi":"10.1016/j.healun.2026.10.010","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.010","url":null,"abstract":"<p><strong>Background: </strong>Fontan patients are considered high risk for heart transplantation (HT) owing to their complex anatomy, multiple prior chest entries, and universal Fontan-associated liver disease (FALD). The impact of FALD and other preoperative factors remains, however, uncertain.</p><p><strong>Objectives: </strong>We sought to identify factors associated with 90-day mortality after isolated HT in adults with Fontan circulation, with particular focus on the relationship between liver-related parameters and post-transplant outcomes.</p><p><strong>Methods: </strong>A retrospective cohort study of all adult Fontan patients undergoing isolated HT was conducted. Factors associated with 90-day mortality were assessed using appropriate univariate analyses and penalized multivariable logistic regression. ROC analysis was used to derive liver size cut-offs and compare the discriminative performance of selected variables. A descriptive analysis of adult Fontan patients undergoing combined heart-liver transplantation (CHLT) was also performed for contextual comparison.</p><p><strong>Results: </strong>Thirty-seven patients (mean age 30 years) underwent isolated HT; 19% (n=8) died within 90 days. Factors associated with increased 90-day mortality were >4 previous chest entries, major perioperative bleeding, and small liver size [total liver volume (TLV) ≤1366 mL, total liver volume indexed to body surface area (TLVi) <786 mL/m² and liver transverse dimension (LTD) <21 cm]. Multiple chest veno-venous collaterals, >4 previous chest entries, and small liver were strongly associated with bleeding and subsequent fatal complications including sepsis, graft dysfunction, and bowel ischaemia. Within the study period, five other patients had undergone CHLT. All had biopsy confirmed advanced liver disease with features of clinically significant portal hypertension or hepatocellular carcinoma. One patient died within 90 days following prolonged cardiopulmonary bypass, major bleeding, graft dysfunction and sepsis, culminating in multiorgan failure.</p><p><strong>Conclusions: </strong>In Fontan patients undergoing isolated HT, >4 previous chest entries, major bleeding, and small liver volume were associated with increased 90-day mortality. Objective liver metrics (TLV ≤1366 mL, TLVi <786 mL/m², TLD <21 cm) may provide adjunctive risk stratification for Fontan patients considered for isolated HT; however, these measures and proposed thresholds remain exploratory and require external validation. CHLT is a viable option, although non-liver related transplant risk factors may similarly influence outcomes. Detailed liver assessment and management at experienced, high-volume congenital transplant centres are important to optimizing outcomes in this complex population.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224263","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 HOPE for Hypoplastic Left Heart Syndrome: Technique for Primary En-Bloc Heart and Aorta Transplant with Hypothermic Oxygenated Recovery of a DCD Heart.","authors":"Maja Brøgger Thomassen, Niels Moeslund, Alan McCheyne, Chris Bivona, Henrik Henriksson, James Warburton, Klaes Vincent Lenbroch, Lukas Helming, Matthew Walker, Marx Runge, Paul Henderson, Louise Amelia Kenny","doi":"10.1016/j.healun.2026.10.007","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.007","url":null,"abstract":"<p><strong>Background: </strong>Primary heart transplantation for hypoplastic left heart syndrome (HLHS) has been limited by the scarcity of neonatal donors. Although hypothermic oxygenated machine perfusion (HOPE) enables donation after circulatory death (DCD) heart transplantation, previous cannulation techniques sacrificed the donor aortic arch, precluding the reconstruction required for HLHS.</p><p><strong>Methods: </strong>A neonatal-sized porcine DCD heart was recovered with the entire thoracic aorta preserved en-bloc using a novel split-cannulation strategy compatible with HOPE. Following 304 minutes of ex situ preservation, the heart-aorta graft was transplanted into a recipient after reconstruction designed to replicate HLHS anatomy. Graft function, haemodynamics, myocardial oedema, and systemic outflow were assessed.</p><p><strong>Results: </strong>The split-cannulation strategy enabled stable HOPE preservation of the intact heart-thoracic aorta graft throughout ex situ perfusion. Myocardial oedema was minimal (8% weight increase during preservation, 2% above baseline after transplantation). Successful implantation was demonstrated by spontaneous recovery of electrical activity, restoration of sinus rhythm, progressive improvement in cardiac output, and satisfactory ventricular contraction on epicardial echocardiography. No significant pressure gradient was detected across the reconstructed aortic arch.</p><p><strong>Conclusions: </strong>This study demonstrates the technical feasibility of recovering, preserving, and transplanting an intact neonatal-sized DCD heart-thoracic aorta graft using a novel split-cannulation HOPE strategy. By preserving the donor thoracic aorta for arch reconstruction, this technique overcomes a key anatomical barrier to primary DCD heart transplantation for HLHS and provides the technical foundation for clinical translation.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206999","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 Heart Transplant Alimony- Prior scars causing future strain.","authors":"Rachael M Essig, John M Trahanas","doi":"10.1016/j.healun.2026.10.008","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.008","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207021","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 HeartWise right ventricular assist device: A concept for dedicated, durable right ventricular support.","authors":"Kadir Caliskan, Canberk Yildirim, Tansu Golcez, Kagan Ucak, Osama Soliman","doi":"10.1016/j.healun.2026.09.008","DOIUrl":"https://doi.org/10.1016/j.healun.2026.09.008","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182398","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":"CLAD: translating basic science to clinical practice.","authors":"Ankita Burman, Peter T Bell, Daniel Chambers, Tereza Martinu","doi":"10.1016/j.healun.2026.10.005","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.005","url":null,"abstract":"<p><p>Chronic lung allograft dysfunction (CLAD), a fibrotic manifestation of chronic rejection, remains the major barrier to long-term survival after lung transplantation. CLAD is increasingly recognised as the final common pathway of diverse alloimmune injuries, augmented by non-alloimmune insults, that culminate in irreversible airway and parenchymal remodelling. Recent advances in molecular profiling, single-cell technologies, and biomarker discovery, with corroboration by novel animal and in vitro models, are redefining CLAD pathogenesis. Emerging data implicate distinct pathways involving cytotoxic and senescent T cells, humoral alloimmunity, innate immune activation, epithelial dysfunction, aspiration, and microbial dysbiosis. These observations support a shift from clinical phenotypes such as bronchiolitis obliterans and restrictive allograft syndromes toward biologically defined endotypes that may better predict disease progression and therapeutic responsiveness. Furthermore, the recent recognition of acute lung allograft dysfunction (ALAD) as a heterogeneous syndrome highlights an opportunity to identify and characterise graft injury before irreversible fibrosis develops. Biomarkers such as donor-derived cell-free DNA, airway transcriptomic signatures, autoantibodies, epithelial injury markers and microbiome-derived signals may facilitate risk stratification, patient enrichment and endotype-guided clinical trials. This review highlights recent mechanistic and translational advances in CLAD and discusses how molecular endotyping may enable earlier diagnosis, targeted intervention and more efficient therapeutic development. We hope that these highlights will generate enthusiasm for even greater collaboration between basic and translational researchers, and optimism regarding strategies for earlier detection and treatment of CLAD.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147829","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":"Ex vivo machine perfusion enables robust and widespread lipophilic-conjugated siRNA delivery to the porcine lung.","authors":"Julianna E Buchwald, Claire E Tocheny, Hussein Kharroubi, Bassel Tfayli, Amir Sanatkar, Sara De Taeye, Vella M Ross, William Michaud, Hassan H Fakih, Asishana Osho, Richard N Pierson, Anastasia Khvorova, S Alireza Rabi","doi":"10.1016/j.healun.2026.10.003","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.003","url":null,"abstract":"<p><strong>Background: </strong>Normothermic ex vivo lung perfusion (EVLP) provides a controlled opportunity for direct molecular intervention in donor lungs before transplantation. Small interfering RNAs (siRNAs) enable sequence-specific gene silencing and, when chemically stabilized and conjugated, can be engineered to optimize tissue delivery and intracellular activity following transient exposure. We evaluated whether fully chemically modified docosanoic acid (DCA)-conjugated siRNA could be delivered to donor lungs during EVLP.</p><p><strong>Methods: </strong>Porcine paired lungs underwent normothermic EVLP for 6-to-8-hours with administration of fully chemically modified, DCA-conjugated siRNA targeting Janus kinase 1 (JAK1). Pulmonary siRNA distribution, tissue accumulation, and cellular uptake were assessed using molecular and imaging approaches. Complementary in vivo mouse experiments using the same JAK1-targeting siRNA provided a benchmark for pulmonary accumulation following systemic administration.</p><p><strong>Results: </strong>EVLP resulted in widespread pulmonary distribution of DCA-conjugated siRNA, with detectable uptake within 2 hours and sustained tissue accumulation throughout perfusion. Cellular uptake was demonstrated in multiple pulmonary cell populations, with prominent localization to alveolar epithelial cells and macrophages. Tissue accumulation levels following EVLP was comparable to that observed following systemic administration in mice. Despite efficient tissue accumulation and cellular uptake, functional gene silencing was not detected during the 6-to-8-hour EVLP period.</p><p><strong>Conclusion: </strong>Normothermic EVLP enables widespread delivery and cellular uptake of fully chemically modified, DCA-conjugated siRNA in donor lungs during clinically relevant perfusion times. These findings establish proof-of-concept for EVLP as a controlled platform for ex vivo delivery of programmable oligonucleotide therapeutics. Further studies are needed to determine whether EVLP-delivered siRNA produces sustained post-perfusion gene silencing and improves graft injury and post-transplant outcomes.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147912","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":"Association of donor single-cell cytokine secretion & circulating cytokine levels with the development & trajectory of severe primary graft dysfunction in lung transplantation.","authors":"Divyam Goel, Chih-Hao Shen, Yingmiao Liu, Lauren E Howard, Khalid Tejan-Sie, John C Brady, Kateryna Krynychka, Benjamin Hughes, Matthew Hartwig, Laurie D Snyder, Andrew B Nixon","doi":"10.1016/j.healun.2026.10.004","DOIUrl":"https://doi.org/10.1016/j.healun.2026.10.004","url":null,"abstract":"<p><p>Whether donor immune biology at procurement is associated with primary graft dysfunction (PGD) trajectory is unknown. Pre-transplant donor T-cell function and circulating plasma proteins were profiled to address this gap. Twenty-one recipients were classified as no PGD (NOGD, n=7), recovery after initial PGD3 (RECV, n=5), or sustained PGD3 (SGD, n=9). The polyfunctionality of T-cells isolated from donor peripheral blood mononuclear cell (PBMC) after stimulation and plasma levels of 92 proteins were assessed. CD8+ polyfunctionality strength index (PSI) was lowest in RECV (p=0.019), driven by effector and chemoattractive clusters. CD4+ did not differ. SGD showed higher secretion of several proinflammatory mediators, while NOGD had higher TGF-β1 secretion and circulating CD27, and lower IFN-γ. SGD had the lowest circulating HGF and PDGF-B, while RECV had higher PDCD1, IL-33, HGF, and LAMP3. Donor T-cell polyfunctionality and circulating biomarkers correlated with PGD3 trajectory, with RECV associated with an exhausted and anti-inflammatory donor phenotype.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148152","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":"Bridging the Developmental Gap: Pediatric Considerations for the ISHLT Consensus Statement on Frailty in Lung Transplantation.","authors":"Gregory Burg, Maya L Dewan, Daniel Loeb, Alexis L Benscoter, Nathan K Evanson, Don Hayes","doi":"10.1016/j.healun.2026.09.028","DOIUrl":"https://doi.org/10.1016/j.healun.2026.09.028","url":null,"abstract":"<p><p>The recent International Society for Heart and Lung Transplantation consensus statement on frailty provides a crucial framework for operationalizing objective frailty metrics and prehabilitation in adult lung transplant candidates. However, translating adult frailty constructs to pediatric candidates with end-stage lung disease presents unique physiological and developmental challenges, as measures of physical performance must account for ongoing linear growth, somatic maturation, and neurodevelopmental trajectories. These complexities are heightened in critically ill pediatric patients, particularly those bridged to transplantation via mechanical ventilation or extracorporeal membrane oxygenation (ECMO), where distinguishing acute illness-attributable neuromuscular deconditioning from systemic, irreversible frailty remains an obstacle. The creation and incorporation of developmentally appropriate frailty measures into pediatric transplant evaluation will be essential to refine candidate selection, optimize pre-transplant functional capacity, and improve post-transplant outcomes. Accomplishing this task will require multidisciplinary collaboration involving critical care, lung transplant, nutritional support, rehabilitation, and behavioral health team members. Key priorities include validating pediatric-specific functional tools, establishing longitudinal tracking of sarcopenia and growth, implementing age-appropriate, play-based prehabilitation paired with nutritional support, and standardizing assessment across the transplant trajectory, including for patients bridged to transplant with inpatient mechanical support such as ECMO or lung assist devices, as well as those managed in the outpatient setting with chronic mechanical respiratory support.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136978","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":"Concurrent Mechanical Circulatory Support During VA-ECMO Better Support, Better Outcomes, or Better Selection.","authors":"Andrew Civitello","doi":"10.1016/j.healun.2026.09.020","DOIUrl":"10.1016/j.healun.2026.09.020","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080445","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":"Long-term Exposure to PM_2.5 and Risk of Adverse Pregnancy Events in Women with Pulmonary Hypertension: A Nationwide Multicenter Study.","authors":"Qianqian Wang, Fengchao Liang, Shanshan Du, Qian Li, Li Wen, Hailong Dai, Yanyan Jing, Wenpeng Dong, Zaixin Yu, Kai Huang, Xindan Zhang, Fenling Fan, Ruilian She, Tongbin Li, Shuang Sui, Yunshan Cao, Yingzhang Cheng, Xiaoli Liu, Peng Lu, Jiangtao Cheng, Wei Deng, Qiushang Ji, Jiang Li, Shiyong Yu, Ruifeng Zhang, Ping Zhang, Lin Cai, Haifeng Qi, Xiufeng Yu, Xiaohua Liang, Wei Huang","doi":"10.1016/j.healun.2026.09.021","DOIUrl":"https://doi.org/10.1016/j.healun.2026.09.021","url":null,"abstract":"<p><strong>Background: </strong>Fine particulate matter (PM_2.5) has been linked with adverse pregnancy events. However, the effects of PM_2.5 on pregnant women with pulmonary hypertension (PH) remain poorly understood.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter study of pregnant women with PH hospitalized at 24 tertiary hospitals in China between January 2016 and August 2022. Monthly PM_2.5 exposure was estimated and the average PM_2.5 concentrations during the 3-year exposure proceeding the end of pregnancy was used as the primary exposure metric. Generalized linear models with binomial distributions were applied to assess associations between PM_2.5 exposure and adverse maternal events (maternal death and/or heart failure) and adverse fetal/neonatal events (non-live birth, neonatal death, preterm birth and low birth weight). Pregnancy-specific exposure windows and two-pollutant models were also examined.</p><p><strong>Results: </strong>Among the 751 participants, 198 (26.4%) experienced adverse maternal events, and 449 (59.8%) had adverse fetal/neonatal events. Three-year median PM_2.5 concentration before the end of pregnancy was 32.8 (26.2-44.0) μg/m³. In the fully adjusted model, each 10 μg/m³ increase in PM_2.5, the odds ratio (OR) was 1.169 (95% CI: 1.014-1.349) for the adverse maternal events and 1.169 (95% CI: 1.018-1.348) for adverse fetal/neonatal events. These associations remained robust in two-pollutant models. Furthermore, when exposure assessment was shifted from long-term levels to pregnancy-specific windows, the strongest trimester-specific association was observed during late pregnancy.</p><p><strong>Conclusions: </strong>Long-term PM_2.5 exposure was associated with increased risk of adverse pregnancy events among pregnant women with PH, emphasizing the importance of reducing air pollution exposure in this high-risk population.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080438","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}