Jamie L Todd,Jeremy M Weber,Francine L Kelly,Andrew Nagler,Patrick McArthur,Lerin Eason,Jeeyon G Rim,Courtney W Frankel,John A Belperio,Marie Budev,Tereza Martinu,Kunal Patel,John M Reynolds,Pali D Shah,Lianne G Singer,Laurie D Snyder,Wayne Tsuang,S Sam Weigt,Megan L Neely,Scott M Palmer
{"title":"Identification and Validation of a Threshold for Early Posttransplant Bronchoalveolar Fluid Hyaluronan that Distinguishes Lung Recipients at Risk for CLAD.","authors":"Jamie L Todd,Jeremy M Weber,Francine L Kelly,Andrew Nagler,Patrick McArthur,Lerin Eason,Jeeyon G Rim,Courtney W Frankel,John A Belperio,Marie Budev,Tereza Martinu,Kunal Patel,John M Reynolds,Pali D Shah,Lianne G Singer,Laurie D Snyder,Wayne Tsuang,S Sam Weigt,Megan L Neely,Scott M Palmer","doi":"10.1016/j.healun.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.014","url":null,"abstract":"BACKGROUNDFew tools exist for early identification of patients at risk for chronic lung allograft dysfunction (CLAD). We previously showed hyaluronan (HA), a matrix molecule that regulates lung inflammation and fibrosis, accumulates in bronchoalveolar lavage fluid (BALF) and blood in CLAD. We aimed to determine if early posttransplant HA elevations inform CLAD risk.METHODSHA was quantified in 3080 BALF and 1323 blood samples collected over the first posttransplant year in 743 adult lung recipients at 5 centers. The relationship between BALF or blood HA and CLAD was assessed using Cox models with a time-dependent binary covariate for \"elevated\" HA. Potential thresholds for elevated HA were examined using a grid search between the 50th and 85th percentile. The optimal threshold was identified using fit statistics, and the association between the selected threshold and CLAD was internally validated through iterative resampling. A multivariable Cox model using the selected threshold was performed to evaluate the association of elevated HA with CLAD considering other factors that may influence CLAD risk.RESULTSBALF HA levels >19.1ng/mL (65th percentile), had the largest hazard ratio for CLAD (HR 1.70, 95% CI 1.25-1.31; p<0.001), optimized fit statistics, and demonstrated robust reproducibility. In a multivariable model, the occurrence of BALF HA >19.1 ng/mL in the first posttransplant year conferred a 66% increase in the hazards for CLAD (adjusted HR 1.66, 95% CI 1.19-2.32; p=0.003). Blood HA was not significantly associated with CLAD.CONCLUSIONSWe identified and validated a precise threshold for BALF HA in the first posttransplant year that distinguishes patients at increased CLAD risk.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490364","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}
Ye In Christopher Kwon,Elizabeth Bashian,Arman Kilic,Zubair A Hashmi
{"title":"Impact of Procurement Methods on Organ Rejection in Donation After Circulatory Death Heart Transplantation.","authors":"Ye In Christopher Kwon,Elizabeth Bashian,Arman Kilic,Zubair A Hashmi","doi":"10.1016/j.healun.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.015","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488286","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}
Michael P Combs,Krysta Walter,Haley Hixson,Elizabeth A Belloli,Matthew S Najor,Kevin M Chan,Andrew C Chang,Dennis M Lyu
{"title":"Impact of Tacrolimus vs. Cyclosporine on CLAD Incidence and Allograft Survival in the ISHLT Registry.","authors":"Michael P Combs,Krysta Walter,Haley Hixson,Elizabeth A Belloli,Matthew S Najor,Kevin M Chan,Andrew C Chang,Dennis M Lyu","doi":"10.1016/j.healun.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.013","url":null,"abstract":"PURPOSEThe ScanCLAD study reported a lower incidence of CLAD with the use of once-daily tacrolimus vs. twice-daily cyclosporine. Using the ISHLT Thoracic Organ Transplant (TTX) Registry data, we evaluated the hypothesis that tacrolimus is superior to cyclosporine in real world clinical practice.METHODSThis study is a retrospective cohort study of adult lung transplant recipients in the ISHLT Registry from January 1, 2000 through June 30, 2018 with known CLAD status. The primary exposure variable was patients' maintenance calcineurin inhibitor (CNI) regimen captured at post-transplant discharge. The primary outcome variables were time to CLAD development (with death/retransplantation analyzed as a competing risk) and allograft survival (i.e., time to death/retransplant).RESULTSOf the 57,403 adult lung transplant recipients in the registry, 22,222 had both CNI and CLAD data available. Of these, 19,698 (88.6%) received tacrolimus immediate release (IR), 2,477 (11.2%) received cyclosporine, and 47 (0.2%) received tacrolimus extended release (XR) for maintenance CNI. Receiving cyclosporine for maintenance immunosuppression (vs. tacrolimus IR) was associated with an increased risk of developing CLAD (HR 1.16, 95% CI 1.08-1.23, p<0.001) and with an increased overall risk for death/retransplant (HR 1.16, 95% CI 1.09-1.23, p<0.001). Receiving tacrolimus XR vs. tacrolimus IR was not associated with differences in long-term post-transplant outcomes, although these analyses were limited by a small sample size.CONCLUSIONSPatients receiving cyclosporine vs. tacrolimus IR for maintenance calcineurin inhibition had an increased risk of CLAD and decreased overall allograft survival in the ISHLT TTX registry.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488285","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}
Oliver J F Weiner,Moloy Das,Richard H Clayton,Janet M McComb,Alan Murray,Gareth Parry,Stephen W Lord
{"title":"Sympathetic reinnervation in cardiac transplant recipients: Prevalence, time course and association with long-term survival.","authors":"Oliver J F Weiner,Moloy Das,Richard H Clayton,Janet M McComb,Alan Murray,Gareth Parry,Stephen W Lord","doi":"10.1016/j.healun.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.009","url":null,"abstract":"BACKGROUNDPartial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart.METHODSCardiac transplant recipients (n=232) were recruited from outpatient clinic at a single transplant centre in the United Kingdom. Participants were each tested once for the presence of sympathetic reinnervation of the sinus node using the low frequency component of power spectral analysis of heart rate variability, with a cut-off defined as 2 standard deviations above the mean for denervated participants (those tested <56 days post-transplant). Time-course was calculated based on the timing of testing post-transplant. Patients were then followed-up over a period of up to 27 years after transplant for survival analysis.RESULTSThe overall prevalence of cardiac sympathetic reinnervation in the 225 patients tested >56 days post-transplant was 64.9%. Sympathetic reinnervation primarily occurred in the first 18 months after transplant, with a plateau thereafter. The prevalence in participants tested >18 months post-transplant was 69.6%. In Kaplan-Meier survival analysis, sympathetic reinnervation was associated with significantly improved survival (Log-rank P=0.019), with a median survival time for reinnervated patients of 19.9 years compared to 14.4 years for the denervated group.CONCLUSIONSSympathetic reinnervation of the sinus node occurs mostly within 18 months of transplant, is found in 70% of cardiac transplant recipients tested >18 months post-transplant, and is associated with significantly improved long-term survival.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486349","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":"Bridging Gaps in Lung Allocation: A Data-Driven Approach to Overcome Biological Disparities.","authors":"Ankit Bharat","doi":"10.1016/j.healun.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.008","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486342","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":"Severe primary graft dysfunction after heart transplantation - Defining the Subtypes.","authors":"Sanjay Dutta,Peter S Macdonald","doi":"10.1016/j.healun.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.010","url":null,"abstract":"","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486279","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}
Aditya Mehta,Jason Goldberg,Pramita Bagchi,Charles Marboe,Keyur B Shah,Samer S Najjar,Steven Hsu,Maria E Rodrigo,Moon Kyoo Jang,Adam Cochrane,Inna F Tchoukina,Hyesik Kong,Brendan J Lohmar,Erick Mcnair,Hannah A Valantine,Sean Agbor-Enoh,Gerald J Berry,Palak Shah,
{"title":"Pathologist Interrater Reliability and Clinical Implications of Elevated Donor-Derived Cell-Free DNA beyond Heart Transplant Rejection.","authors":"Aditya Mehta,Jason Goldberg,Pramita Bagchi,Charles Marboe,Keyur B Shah,Samer S Najjar,Steven Hsu,Maria E Rodrigo,Moon Kyoo Jang,Adam Cochrane,Inna F Tchoukina,Hyesik Kong,Brendan J Lohmar,Erick Mcnair,Hannah A Valantine,Sean Agbor-Enoh,Gerald J Berry,Palak Shah,","doi":"10.1016/j.healun.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.healun.2024.10.006","url":null,"abstract":"BACKGROUNDThere is significant variability amongst pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR) and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) as compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR).METHODSThe Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020. The center pathologist read was compared to two blinded core cardiac pathologists. ACR and AMR were graded based on the International Society for Heart and Lung Transplantation (ISHLT) criteria. Weighted Cohen's kappa (κ) was used to evaluate interrater reliability between the center and core reads. To assess long-term outcomes, we evaluated a composite of AR, allograft dysfunction, and mortality within 1 year.RESULTSThe study included 94 patients (median age 55 years [IQR 45, 62]), 30% female, 41% Black race) with a total of 429 EMBs and paired dd-cfDNA measures. The concordance rate between center and core pathologists was 77% for ACR (95%CI: 66% - 89%) and 63% for AMR (95%CI: 53% - 74%). 46 patients had an elevation in dd-cfDNA without AR by EMB. The median dd-cfDNA was 0.49% (IQR: 0.35, 1.01) and subsequent AR, allograft dysfunction, or mortality occurred in 59% of these patients at 1 year. In patients with AR by EMB and negative dd-cfDNA (n=5) the composite outcome occurred in 20% of patients at 1 year. At baseline, the positive likelihood ratio (LR+) of dd-cfDNA to detect AR by the center pathologist was 3.74 (95% CI 3.01 - 4.64) and core pathologist was 2.59 (95%CI: 1.95 - 3.45). If the composite outcome was included as a true positive, the LR+ of dd-cfDNA improved to 9.82 (95%CI: 7.04, 13.69) and7.63 (95% CI: 5.61, 10.38) at 1-year, respectively.CONCLUSIONSPathologists interrater reliability is limited in both ACR and AMR. The positive LR of dd-cfDNA when compared to traditional histopathology is limited, but when longitudinal clinical outcomes are included to assess diagnostic performance, the LR+ improves significantly. The value of dd-cfDNA extends beyond the diagnosis of AR to include other clinically meaningful outcomes for patients after heart transplant.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451415","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}
Archer Kilbourne Martin,Olaf Mercier,Ashley Virginia Fritz,Theresa A Gelzinis,Konrad Hoetzenecker,Sandra Lindstedt,Nandor Marczin,Barbara J Wilkey,Marc Schecter,Haifa Lyster,Melissa Sanchez,James Walsh,Orla Morrissey,Bronwyn Levvey,Caroline Landry,Siavosh Saatee,Sakhee Kotecha,Juergen Behr,Jasleen Kukreja,Göran Dellgren,Julien Fessler,Brandi Bottiger,Keith Wille,Kavita Dave,Basil S Nasir,David Gomez-De-Antonio,Marcelo Cypel,Anna K Reed
{"title":"ISHLT consensus statement on the perioperative use of ECLS in lung transplantation: Part II: Intraoperative considerations.","authors":"Archer Kilbourne Martin,Olaf Mercier,Ashley Virginia Fritz,Theresa A Gelzinis,Konrad Hoetzenecker,Sandra Lindstedt,Nandor Marczin,Barbara J Wilkey,Marc Schecter,Haifa Lyster,Melissa Sanchez,James Walsh,Orla Morrissey,Bronwyn Levvey,Caroline Landry,Siavosh Saatee,Sakhee Kotecha,Juergen Behr,Jasleen Kukreja,Göran Dellgren,Julien Fessler,Brandi Bottiger,Keith Wille,Kavita Dave,Basil S Nasir,David Gomez-De-Antonio,Marcelo Cypel,Anna K Reed","doi":"10.1016/j.healun.2024.08.027","DOIUrl":"https://doi.org/10.1016/j.healun.2024.08.027","url":null,"abstract":"The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee. International experts across multiple disciplines, including cardiothoracic surgery, anesthesiology, critical care, pediatric pulmonology, adult pulmonology, pharmacy, psychology, physical therapy, nursing, and perfusion, were selected based on expertise and divided into subgroups examining the preoperative, intraoperative, and postoperative periods. Following a comprehensive literature review, each subgroup developed recommendations to examine via a structured Delphi methodology. Following 2 rounds of Delphi consensus, a total of 39 recommendations regarding intraoperative considerations for ECLS in lung transplantation met consensus criteria. These recommendations focus on the planning, implementation, management, and monitoring of ECLS throughout the entire intraoperative period.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490516","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":"Impact of Routine Extracorporeal Cardiopulmonary Resuscitation Service on the Availability of Donor Organs.","authors":"Jana Smalcova,Petra Krupickova,Eva Pokorna,Ondrej Franek,Michal Huptych,Petra Kavalkova,Martin Balik,Jan Malik,Ondrej Smid,Eva Svobodova,Roman Keleman,Jan Belohlavek","doi":"10.1016/j.healun.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.healun.2024.09.009","url":null,"abstract":"In refractory cardiac arrest, extracorporeal cardiopulmonary resuscitation may increase the survival chance. However, in cases of unsuccessful treatment, extracorporeal cardiopulmonary resuscitation may additionally provide an important source of organ donors. Therefore, we hypothesized that implementing extracorporeal cardiopulmonary resuscitation service into a high-volume cardiac arrest center's routine would increases organ donors' availability.METHODSOur retrospective observational study analyzed out-of-hospital cardiac arrest patients admitted to the General University Hospital in Prague between 2007 and 2020. The following groups were analyzed regarding the recruitment of donors: before and after extracorporeal cardiopulmonary resuscitation implementation. We assessed the number of donors referred, the number of organs harvested, and the organ's survival.RESULTSWe analyzed the results of 1158 patients after out-of-hospital cardiac arrest. In the conventional approach period, 11 donors were referred, of which seven were accepted. During the extracorporeal cardiopulmonary resuscitation period, the number of donors increased to 80, of whom 42 were accepted. The number of donated organs was 18 and 119 in the respective periods, corresponding to 3.6 vs. 13.2 (p = 0.033) harvested organs per year. One-year survival of transplanted organs was 94.4% vs. 99.2%, and five-year survival was 94.4% vs. 95.9% in relevant periods. Conventional and extracorporeal cardiopulmonary resuscitation did not affect donor organ survival.CONCLUSIONEstablishing a high-volume cardiac arrest centre providing an extracorporeal cardiopulmonary resuscitation service may increase not only the number of prolonged cardiac arrest survivors but also the number of organ donors. In addition, the performances of donated organs were high and comparable between both treatment methods.","PeriodicalId":22654,"journal":{"name":"The Journal of Heart and Lung Transplantation","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246786","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}