Journal of Heart and Lung Transplantation最新文献

{"title":"Tacrolimus, cyclosporine, and lung transplantation in the \"real world\".","authors":"Kieran Halloran","doi":"10.1016/j.healun.2024.11.023","DOIUrl":"10.1016/j.healun.2024.11.023","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716333","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":"Single-cell RNA-sequencing identifies unique cell-specific gene expression profiles in high-grade cardiac allograft vasculopathy.","authors":"Kaushik Amancherla, Kelly H Schlendorf, Nelson Chow, Quanhu Sheng, Jane E Freedman, Jeffrey C Rathmell","doi":"10.1016/j.healun.2024.11.017","DOIUrl":"10.1016/j.healun.2024.11.017","url":null,"abstract":"<p><strong>Background: </strong>Cardiac allograft vasculopathy (CAV) is the leading cause of late graft failure and mortality after heart transplantation (HT). Current strategies for early diagnosis and effective treatment of CAV are lacking. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to investigate cell-specific gene expression profiles and T cell receptor repertoires in CAV that may inform novel biomarkers and pathways to interrupt CAV pathogenesis.</p><p><strong>Methods: </strong>Whole blood was collected from 22 HT recipients with angiographically-confirmed CAV and 18 HT recipients without CAV. PBMCs were isolated and subjected to single-cell RNA-sequencing using a 10X Genomics microfluidic platform. Downstream analyses focused on differential expression of genes, cell compositional changes, and T cell receptor repertoire analyses.</p><p><strong>Results: </strong>Across 40 PBMC samples, we isolated 134,984 cells spanning 31 cell types. Compositional analyses showed subtle, but significant increases in CD4+ T central memory cells, and CD14+ and CD16+ monocytes in high-grade CAV (CAV-2 and CAV-3). 745 genes were differentially expressed in a cell-specific manner in high-grade CAV, enriched for putative pathways involved in inflammation and angiogenesis. Intersection with the druggable genome prioritized 68 targets, including targets with approved drugs in cardiovascular disease (e.g., canakinumab). There were no significant differences in T cell clonality or diversity with increasing CAV severity.</p><p><strong>Conclusions: </strong>Unbiased whole transcriptomic analyses at single-cell resolution identify unique, cell-specific gene expression patterns in CAV, suggesting the potential utility of peripheral gene expression biomarkers in diagnosing CAV. Furthermore, precision targeting of these pathways may offer opportunities to mitigate CAV pathogenesis.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695710","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":"Extended duration of ex-vivo perfusion is associated with worse survival in donation after circulatory death heart recipients: A national database analysis.","authors":"Ruby Singh, George Olverson, Kristian Punu, Adham Makarem, Chijioke C Chukwudi, Sarah A Brownlee, Antonia Kreso, Seyed Alireza Rabi, Eriberto Michel, Gregory D Lewis, David A D'Alessandro, Asishana A Osho","doi":"10.1016/j.healun.2024.11.018","DOIUrl":"10.1016/j.healun.2024.11.018","url":null,"abstract":"<p><strong>Background: </strong>The impact of duration of ex-vivo heart perfusion (EVHP) on patient outcomes following donation after circulatory death (DCD) heart transplantation has not been established.</p><p><strong>Methods: </strong>Adult first-time DCD heart transplants using EVHP were identified in the Organ Procurement & Transplant Network database (12/2019-09/2023). Total out of body time (OBT) was dichotomized based on perfusion duration exceeding the 90th percentile of EVHP hearts in the study. The primary outcome of 6-month mortality was assessed using Kaplan Meier curves and multivariable Cox regression. 30-day, 1-year, and 3-year mortality were also assessed. Secondary postoperative outcomes of index hospitalization length of stay, acute rejection, dialysis, and stroke were assessed using univariable linear or logistic regression.</p><p><strong>Results: </strong>Among 575 recipients of DCD transplantations using EVHP, 58 hearts had extended perfusion times based on an OBT cutoff of 8.3 hours which identified OBT greater than the 90th percentile. Extended perfusion heart recipients had worse overall mortality at 6 months compared to standard perfusion hearts after adjusting for critical donor and recipient factors [aHR = 2.48(1.25,4.93),p = 0.009]. Early 30-day mortality was comparable between the groups (p = 0.592). However, 1-year and 3-year outcomes showed worse mortality in recipients of extended perfusion hearts (both p < 0.05). Post-transplant dialysis requirement and increased length of stay was more likely in the extended perfusion group (both p < 0.05). There was no difference in acute rejection (p = 0.163), and stroke (p = 0.170).</p><p><strong>Conclusions: </strong>There is a potential detrimental effect of extended EVHP duration on DCD heart recipient survival. Future work will explore the identified opportunity to improve organ preservation during EVHP.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693049","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":"Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR).","authors":"Marta Jiménez-Blanco, Maria Generosa Crespo-Leiro, Maria Dolores García-Cosío Carmena, Manuel Gómez Bueno, Raquel López-Vilella, Carlos Ortiz-Bautista, Marta Farrero-Torres, Isabel Zegrí-Reiriz, Beatriz Díaz-Molina, Elena García-Romero, Diego Rangel-Sousa, Nahikari Salterain, Iris Garrido Bravo, Javier Segovia-Cubero","doi":"10.1016/j.healun.2024.11.009","DOIUrl":"10.1016/j.healun.2024.11.009","url":null,"abstract":"<p><strong>Background: </strong>There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB).</p><p><strong>Methods: </strong>Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext assay, Eurofins Genome). The primary end-point was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB.</p><p><strong>Results: </strong>The study included 206 patients from 12 centers, with 1,090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n = 49) were associated with dd-cfDNA levels significantly higher than those without, median 0.189% (interquartilic range 0.05-0.70) vs 0.095% (0.04-0.23), p = 0.013. A dd-cfDNA threshold of 0.10% showed a negative predictive value for ACR of 97%. A statistically significant association between N-terminal prohormone of brain (NTProBNP) and dd-cfDNA was also found, with an increase of 0.007% dd-cfDNA (95% confidence interval 0.003-0.011) for every 500 units of NTproBNP, p 0.001. The combination of both biomarkers for diagnosis of ACR showed an area under the receiver operating characteristic (ROC) curve of 0.681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0.603), p = 0.016. Using a cut-off point of 0.10% for dd-cfDNA and 1,000 UI/ml for NTproBNP, negative predictive value increased to 98.1%.</p><p><strong>Conclusions: </strong>dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone.</p><p><strong>Clinical trial notation: </strong>Donor-derived Cell-Free DNA as a New Biomarker in Cardiac Acute Rejection, NCT04973943.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693047","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 Tale of Two Indications for EVLP.","authors":"Kenneth R McCurry, Toshihiro Okamoto","doi":"10.1016/j.healun.2024.11.022","DOIUrl":"https://doi.org/10.1016/j.healun.2024.11.022","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687276","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 agonal phase duration with heart utilization and post-transplant outcomes in donation after circulatory death heart transplantation.","authors":"Yeahwa Hong, Nicholas R Hess, Ander Dorken-Gallastegi, Nidhi Iyanna, Gavin W Hickey, Michael A Mathier, Dennis M McNamara, Mary E Keebler, Edward T Horn, David J Kaczorowski","doi":"10.1016/j.healun.2024.11.011","DOIUrl":"10.1016/j.healun.2024.11.011","url":null,"abstract":"<p><strong>Background: </strong>This study evaluates the impact of the agonal phase and related hemodynamic measures on post-transplant outcomes and heart utilization in donation after circulatory death (DCD) heart transplantation.</p><p><strong>Methods: </strong>United Network for Organ Sharing registry was queried to analyze adult recipients who underwent isolated DCD heart transplantation between January 1, 2019 and September 30, 2023. The recipients were stratified into 2 groups based on donor agonal period: <30 and ≥30 minutes. The primary outcome was 90-day post-transplant survival. Propensity score-matching was performed. Sub-analysis was performed to evaluate the association of agonal period with donor heart utilization. Additionally, the associations between different hemodynamic thresholds used to indicate onset of warm ischemia during the agonal phase with 90-day mortality were compared.</p><p><strong>Results: </strong>Eight hundred and eighty nine recipients were included, with 179 (20.1%) receiving hearts from donors with an agonal period of ≥30 minutes. Ninety-day survival (88.1% vs. 95.6%, p < 0.001) was significantly lower among the recipients of donors with an agonal period of ≥30 minutes. The lower 90-day survival persisted in a propensity score-matched comparison. Furthermore, longer agonal periods were associated with reduced donor heart utilization. Lastly, a time interval from a systolic blood pressure of 80 ± 5mmHg to death exhibited significantly higher association with 90-day mortality than a time interval from a systemic oxygen saturation 80 ± 5% to death.</p><p><strong>Conclusions: </strong>Utilizing DCD donor hearts with agonal periods ≥30 minutes is associated with reduced post-transplant survival and decreased donor heart utilization. When assessing the onset of warm ischemia during the agonal phase, hypotension may serve as a more accurate indicator of myocardial ischemia and provide improved post-transplant prognostic insight than hypoxia.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687277","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":"Promise of a new day - will EVLP fulfill its therapeutic potential?","authors":"Srineil Vuthaluru, Aleem Siddique","doi":"10.1016/j.healun.2024.11.019","DOIUrl":"10.1016/j.healun.2024.11.019","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686504","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":"Donor sequence number is not associated with worse lung transplant outcomes regardless of transplant center case volume.","authors":"Alfred J Casillan, Emily L Larson, Alice L Zhou, Jessica M Ruck, Armaan F Akbar, Allan B Massie, Dorry L Segev, Christian A Merlo, Errol L Bush","doi":"10.1016/j.healun.2024.11.012","DOIUrl":"10.1016/j.healun.2024.11.012","url":null,"abstract":"<p><strong>Background: </strong>Potential lung transplantation (LTx) recipients are assigned a donor sequence number (DSN) based on their position on the match list. Since a higher DSN offer has already been declined for other recipients, some providers may assume that a high DSN connotates poorer allograft quality. This study evaluated the association between DSN and outcomes, the correlation between transplant program case volume and the utilization of higher DSN lungs, and whether LTx outcomes differ between lower- and higher-volume programs.</p><p><strong>Methods: </strong>Using the Scientific Registry of Transplant Recipients database, LTx cases from 2015-2021 were retrospectively reviewed. Recipients were categorized into low (<20), medium (21-50), high (51-100), and very high (>100) DSN groups. The primary outcome was LTx survival. For cases involving high or very high DSN donors, a subgroup analysis compared survival among programs with annual transplant volumes in the bottom, middle 2, and top quartiles.</p><p><strong>Results: </strong>Median survival was similar among the low (6.9 years), medium (6.1), high (5.9), and very high DSN (6.5) groups (log-rank p = 0.09). Higher DSN donors were more commonly accepted by higher-volume LTx centers. However, the annual case volume of the transplanting institution did not impact survival when high (log-rank p = 0.16) or very high DSN (log-rank p = 0.36) donors were used.</p><p><strong>Conclusions: </strong>Higher DSN should not be considered an independent marker of low allograft quality. Additionally, lower-volume centers achieved similar post-transplant outcomes as higher-volume centers for recipients receiving higher DSN lungs. These findings underscore that surgeons must judge each donor offer independent of other programs' assessments.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687299","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":"Predictors of donation after circulatory death lung utilization and allograft survival.","authors":"Isaac S Alderete, Arya Pontula, Cathlyn K Medina, Samantha E Halpern, Jacob A Klapper, Megan L Neely, Laurie Snyder, Matthew G Hartwig","doi":"10.1016/j.healun.2024.11.013","DOIUrl":"10.1016/j.healun.2024.11.013","url":null,"abstract":"<p><strong>Background: </strong>Understanding donor factors associated with successful lung transplantation (LTx) following donation after circulatory death (DCD) is important in optimizing donor management. In this study, we examined critical care and ventilatory factors associated with DCD LTx and allograft survival using a unique detailed donor management database.</p><p><strong>Methods: </strong>The Donor Management Goals national registry was queried for DCD donors between January 2016 and July 2023. The primary outcomes were DCD lung utilization and allograft survival. Multivariable modeling was used to assess factors associated with DCD LTx and allograft survival.</p><p><strong>Results: </strong>A total of 3,394 donors met inclusion criteria and were included. Transplantation occurred in 202 (6.0%) cases with 85.6% 1-year survival. DCD LTx was more likely to occur following cerebrovascular accidents compared to anoxia and from donors who achieved a targeted PaO₂/FiO₂ (P/F) ratio at the time of organ allocation. Donor factors associated with decreased likelihood of LTx included increasing age, increasing INR, height greater than 168 cm, increasing hematocrit, and higher positive end-expiratory pressure (PEEP) at the time of organ allocation. Donor treatment with steroids and controlled mandatory ventilation, were associated with increased likelihood of graft failure at one year.</p><p><strong>Conclusions: </strong>Successful DCD LTx associates with potentially modifiable donor parameters, including targeted P/F ratio, PEEP, INR, and hematocrit. Additionally, careful consideration of steroid use and ventilator settings may be important for improving long-term graft function. These modifiable factors may inform strategies to increase DCD LTx and improve survival.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687300","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":"Bronchoalveolar lavage cytokine-based risk stratification of clinically-stable lung transplant recipients with undefined rejection: Further insights from a follow-up investigation.","authors":"Liran Levy, Sajad Moshkelgosha, Ella Huszti, Stella Wang, Sarah Hunter, Chen Yang Kevin Zhang, Rasheed Ghany, Shaf Keshavjee, Lianne G Singer, Jussi Tikkanen, Stephen Juvet, Tereza Martinu","doi":"10.1016/j.healun.2024.11.020","DOIUrl":"10.1016/j.healun.2024.11.020","url":null,"abstract":"<p><strong>Background: </strong>Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are primarily used to detect acute cellular rejection (ACR) or infection in lung transplant (LTx) recipients. We previously identified a BAL protein signature associated with chronic lung allograft dysfunction (CLAD) or death/retransplant in patients with stable minimal (grade A1) ACR. This present study aimed to determine whether similar BAL biomarkers predict outcomes in stable patients when ACR grade is undetermined.</p><p><strong>Methods: </strong>The cohort included all adult, first bilateral LTx performed 2010-2017. Clinical status was categorized as unstable or stable based on the presence or absence of a ≥ 10% drop in FEV1. Clinically-stable patients with grade AX TBB (inadequate biopsies) during the first year post-transplant, not preceded by ACR (grade A≥1 or B≥1), were included. IL6, S100A8, IL10, TNF-receptor-1, IL1α, pentraxin3, and CXCL10 were measured in the BAL using a multiplex bead assay. Associations with subsequent CLAD or death/retransplant were assessed using multivariable Cox proportional hazards models, adjusted for relevant clinical covariates.</p><p><strong>Results: </strong>Among 107 patients with stable AX biopsies at a median of 188 days post-transplant, the median times from biopsy to CLAD and death/retransplant were 972 and 1410 days, respectively. CXCL10 was significantly associated with CLAD, while IL6, S100A8, pentraxin3, TNF-receptor-1, and IL10 were associated with death/retransplant (p < 0.05 for all).</p><p><strong>Conclusion: </strong>A focused BAL protein signature in stable patients with ungradable TBB early post-transplant may predict worse outcomes. Such select BAL biomarkers may identify patients who require more aggressive management strategies or closer monitoring.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687298","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}