Pub Date : 2024-07-26DOI: 10.1016/j.healun.2024.07.018
Janne Brouckaert, Katrien Vandendriessche, Karlien Degezelle, Kristof Van de Voorde, Francis De Burghgraeve, Lars Desmet, Dirk Vlasselaers, Catherine Ingels, Dieter Dauwe, Erwin De Troy, Laurens J Ceulemans, Dirk Van Raemdonck, Diethard Monbaliu, Bart Meyns, Raf Van den Eynde, Steffen Rex, Johan Van Cleemput, Filip Rega
{"title":"Successful clinical transplantation of hearts donated after circulatory death using direct procurement followed by hypothermic oxygenated perfusion: A report of the first 3 cases.","authors":"Janne Brouckaert, Katrien Vandendriessche, Karlien Degezelle, Kristof Van de Voorde, Francis De Burghgraeve, Lars Desmet, Dirk Vlasselaers, Catherine Ingels, Dieter Dauwe, Erwin De Troy, Laurens J Ceulemans, Dirk Van Raemdonck, Diethard Monbaliu, Bart Meyns, Raf Van den Eynde, Steffen Rex, Johan Van Cleemput, Filip Rega","doi":"10.1016/j.healun.2024.07.018","DOIUrl":"10.1016/j.healun.2024.07.018","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788329","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}
Pub Date : 2024-07-26DOI: 10.1016/j.healun.2024.06.018
Diyar Saeed, Jonathan Grinstein, Jamila Kremer, Jennifer A Cowger
The development of aortic insufficiency (AI) during HeartMate 3 durable left ventricular assist device (dLVAD) support can lead to ineffective pump output and recurrent heart failure symptoms. Progression of AI often comingles with the occurrence of other hemodynamic-related events encountered during LVAD support, including right heart failure, arrhythmias, and cardiorenal syndrome. While data on AI burdens and clinical impact are still insufficient in patients on HeartMate 3 support, moderate or worse AI occurs in approximately 8% of patients by 1 year and studies suggest AI continues to progress over time and is associated with increased frequency of right heart failure. The first line intervention for AI management is prevention, undertaking surgical intervention on the insufficient valve at the time of dLVAD implant and avoiding excessive device flows and hypertension during long-term support. Device speed augmentation may then be undertaken to try and overcome the insufficient lesion, but the progression of AI should be anticipated over the long term. Surgical or transcatheter aortic valve interventions may be considered in dLVAD patients with significant persistent AI despite medical management, but neither intervention is without risk. It is imperative that future studies of dLVAD support capture AI in clinical end-points using uniform assessment and grading of AI severity by individuals trained in AI assessment during dLVAD support.
在 HeartMate 3 耐用左心室辅助设备(dLVAD)支持过程中出现主动脉瓣关闭不全(AI)会导致泵输出无效和反复出现心衰症状。AI 的发展往往与 LVAD 支持期间遇到的其他血流动力学相关事件同时发生,包括右心衰竭、心律失常和心肾综合征。虽然有关使用 HeartMate 3 支持的患者的 AI 负担和临床影响的数据仍然不足,但约有 8% 的患者在使用 1 年后出现中度或更严重的 AI,而且研究表明 AI 会随着时间的推移继续发展,并与右心衰竭发生频率的增加有关。人工心肌缺血管理的一线干预措施是预防,在植入 dLVAD 时对瓣膜功能不全进行手术干预,并在长期支持期间避免设备流量过大和高血压。然后可以进行设备速度增强,尝试克服瓣膜功能不足的病变,但应预计到人工心肌缺血会长期发展。如果 dLVAD 患者尽管接受了药物治疗,但主动脉瓣仍存在严重的持续性缺血,则可考虑进行手术或经导管主动脉瓣介入治疗,但这两种介入治疗都没有风险。未来的 dLVAD 支持研究必须在 dLVAD 支持过程中,由接受过 AI 评估培训的人员对 AI 严重程度进行统一评估和分级,从而在临床终点中反映 AI 的情况。
{"title":"Aortic insufficiency in the patient on contemporary durable left ventricular assist device support: A state-of-the-art review on preoperative and postoperative assessment and management.","authors":"Diyar Saeed, Jonathan Grinstein, Jamila Kremer, Jennifer A Cowger","doi":"10.1016/j.healun.2024.06.018","DOIUrl":"10.1016/j.healun.2024.06.018","url":null,"abstract":"<p><p>The development of aortic insufficiency (AI) during HeartMate 3 durable left ventricular assist device (dLVAD) support can lead to ineffective pump output and recurrent heart failure symptoms. Progression of AI often comingles with the occurrence of other hemodynamic-related events encountered during LVAD support, including right heart failure, arrhythmias, and cardiorenal syndrome. While data on AI burdens and clinical impact are still insufficient in patients on HeartMate 3 support, moderate or worse AI occurs in approximately 8% of patients by 1 year and studies suggest AI continues to progress over time and is associated with increased frequency of right heart failure. The first line intervention for AI management is prevention, undertaking surgical intervention on the insufficient valve at the time of dLVAD implant and avoiding excessive device flows and hypertension during long-term support. Device speed augmentation may then be undertaken to try and overcome the insufficient lesion, but the progression of AI should be anticipated over the long term. Surgical or transcatheter aortic valve interventions may be considered in dLVAD patients with significant persistent AI despite medical management, but neither intervention is without risk. It is imperative that future studies of dLVAD support capture AI in clinical end-points using uniform assessment and grading of AI severity by individuals trained in AI assessment during dLVAD support.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788326","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}
Pub Date : 2024-07-25DOI: 10.1016/j.healun.2024.07.014
Laura M Kühner, Sarah M Berger, Mila Djinovic, Philippe L Furlano, Lisa M Steininger, Anna-Lena Pirker, Peter Jaksch, Elisabeth Puchhammer-Stöckl, Hannes Vietzen
Plasma-soluble (s)HLA-G and sHLA-E are immunoregulatory proteins that balance the activation of NKG2A+ immune cells. In lung-transplant recipients (LTRs), dysregulated NKG2A+ natural killer cell responses may result in high-level human cytomegalovirus (HCMV) replication as well as chronic lung allograft dysfunction (CLAD), and especially the development of rapidly deteriorating CLAD is associated with high mortality. We thus analyzed the kinetics and function of sHLA-G and sHLA-E in follow-up samples of N = 76 LTRs to evaluate whether these immunoregulatory proteins are associated with the risk for CLAD and high-level HCMV replication. Here, we demonstrate that rapidly deteriorating CLAD LTRs are hallmarked by continually low (<107 ng/ml) sHLA-G levels. In contrast, high sHLA-E levels were associated with the following development of high-level (>1,000 copies/ml) HCMV episodes. Thus, sHLA-G and sHLA-E may serve as novel biomarkers for the development of rapidly deteriorating CLAD and high-level HCMV replication in LTRs.
{"title":"Immunomodulatory soluble HLA-G and HLA-E are associated with rapidly deteriorating CLAD and HCMV viremia after lung transplantation.","authors":"Laura M Kühner, Sarah M Berger, Mila Djinovic, Philippe L Furlano, Lisa M Steininger, Anna-Lena Pirker, Peter Jaksch, Elisabeth Puchhammer-Stöckl, Hannes Vietzen","doi":"10.1016/j.healun.2024.07.014","DOIUrl":"10.1016/j.healun.2024.07.014","url":null,"abstract":"<p><p>Plasma-soluble (s)HLA-G and sHLA-E are immunoregulatory proteins that balance the activation of NKG2A<sup>+</sup> immune cells. In lung-transplant recipients (LTRs), dysregulated NKG2A<sup>+</sup> natural killer cell responses may result in high-level human cytomegalovirus (HCMV) replication as well as chronic lung allograft dysfunction (CLAD), and especially the development of rapidly deteriorating CLAD is associated with high mortality. We thus analyzed the kinetics and function of sHLA-G and sHLA-E in follow-up samples of N = 76 LTRs to evaluate whether these immunoregulatory proteins are associated with the risk for CLAD and high-level HCMV replication. Here, we demonstrate that rapidly deteriorating CLAD LTRs are hallmarked by continually low (<107 ng/ml) sHLA-G levels. In contrast, high sHLA-E levels were associated with the following development of high-level (>1,000 copies/ml) HCMV episodes. Thus, sHLA-G and sHLA-E may serve as novel biomarkers for the development of rapidly deteriorating CLAD and high-level HCMV replication in LTRs.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766236","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}
Pub Date : 2024-07-24DOI: 10.1016/j.healun.2024.07.006
Anthony P Carnicelli, Sean van Diepen, Ann Gage, Alexander M Bernhardt, Jennifer Cowger, Brian A Houston, Matt T Siuba, Rachna Kataria, Craig J Beavers, Kevin J John, Bart Meyns, Navin K Kapur, Ryan J Tedford, Manreet Kanwar
Acute right ventricular failure (RVF) is prevalent in multiple disease states and is associated with poor clinical outcomes. Right-sided temporary mechanical circulatory support (tMCS) devices are used to unload RV congestion and increase cardiac output in cardiogenic shock (CS) with hemodynamically significant RVF. Several RV-tMCS device platforms are available; however consensus is lacking on patient selection, timing of escalation to RV-tMCS, device management, and device weaning. The purposes of this review are to 1) describe the current state of tMCS device therapies for acute RVF with CS, 2) discuss principles of escalation to RV-tMCS device therapy, 3) examine important aspects of clinical management for patients supported by RV-tMCS devices including volume management, anticoagulation, and positive pressure ventilation, and 4) provide a framework for RV-tMCS weaning.
{"title":"Pragmatic approach to temporary mechanical circulatory support in acute right ventricular failure.","authors":"Anthony P Carnicelli, Sean van Diepen, Ann Gage, Alexander M Bernhardt, Jennifer Cowger, Brian A Houston, Matt T Siuba, Rachna Kataria, Craig J Beavers, Kevin J John, Bart Meyns, Navin K Kapur, Ryan J Tedford, Manreet Kanwar","doi":"10.1016/j.healun.2024.07.006","DOIUrl":"10.1016/j.healun.2024.07.006","url":null,"abstract":"<p><p>Acute right ventricular failure (RVF) is prevalent in multiple disease states and is associated with poor clinical outcomes. Right-sided temporary mechanical circulatory support (tMCS) devices are used to unload RV congestion and increase cardiac output in cardiogenic shock (CS) with hemodynamically significant RVF. Several RV-tMCS device platforms are available; however consensus is lacking on patient selection, timing of escalation to RV-tMCS, device management, and device weaning. The purposes of this review are to 1) describe the current state of tMCS device therapies for acute RVF with CS, 2) discuss principles of escalation to RV-tMCS device therapy, 3) examine important aspects of clinical management for patients supported by RV-tMCS devices including volume management, anticoagulation, and positive pressure ventilation, and 4) provide a framework for RV-tMCS weaning.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766237","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}
Pub Date : 2024-07-21DOI: 10.1016/j.healun.2024.07.013
Holger Thiele, Steffen Desch, Anne Freund, Uwe Zeymer
{"title":"Why VA-ECMO should not be used routinely in AMI-cardiogenic shock.","authors":"Holger Thiele, Steffen Desch, Anne Freund, Uwe Zeymer","doi":"10.1016/j.healun.2024.07.013","DOIUrl":"10.1016/j.healun.2024.07.013","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751894","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}
Pub Date : 2024-07-20DOI: 10.1016/j.healun.2024.07.002
Entela Bollano, Arne K Andreassen, Hans Eiskjaer, Finn Gustafsson, Göran Rådegran, Einar Gude, Lars Gullestad, Kaspar Broch, Thea A S Halden, Kristjan Karason, Sven-Erik Bartfay, Niklas Bergh
Background: Early substitution of calcineurin inhibitor (CNI) with mammalian target of rapamycin inhibitors has been shown to improve kidney function and reduce intimal hyperplasia in heart transplant (HTx) recipients but data on long-term outcome of such a regime are still sparse.
Methods: In the SCHEDULE trial, 115 de novo HTx recipients were randomized to (1) everolimus with reduced exposure of CNI followed by CNI withdrawal at week 7-11 post-transplant or (2) standard-exposure with CNI. Both groups received mycophenolate mofetil and corticosteroids. Herein we report on the 10-12-year long-term follow-up of the study.
Results: A total of 78 patients attended the follow-up visit at a median time of 11 years post-transplant. In the everolimus intention to treat (ITT) group 87.5% (35/40 patients) still received everolimus and in the CNI ITT group 86.8% (33/38) still received CNI. Estimated glomerular filtration rate (eGFR) (least square mean (95% CI)) at the 10-12 years visit was 82.7 (74.2-91.1) ml/min/1.73 m2 and 61.0 (52.3-69.7) ml/min/1.73 m2 in the everolimus and CNI group, respectively (p < 0.001). Graft function measured by ejection fraction, ECG, NT-proBNP and drug safety were comparable between groups. During the study period there was a total of 28 deaths, but there was no difference in survival between the everolimus and the CNI group (aHR 0.61 (95% CI 0.29-1.30) p = 0.20). For the composite endpoint of death, re-transplantation, myocardial infarction, PCI, dialysis, kidney transplantation or cancer no between group differences were found (aHR 1.0 (95% CI 0.57-1.77) p = 0.99).
Conclusions: De novo HTx patients randomized to everolimus and low dose CNI followed by CNI free therapy sustained significantly better long-term kidney function than patients randomized to standard therapy. The graft function at 10-12 years was similar in both groups and there was no difference in survival.
{"title":"Long-term follow-up of the randomized, prospective Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance (SCHEDULE) trial.","authors":"Entela Bollano, Arne K Andreassen, Hans Eiskjaer, Finn Gustafsson, Göran Rådegran, Einar Gude, Lars Gullestad, Kaspar Broch, Thea A S Halden, Kristjan Karason, Sven-Erik Bartfay, Niklas Bergh","doi":"10.1016/j.healun.2024.07.002","DOIUrl":"10.1016/j.healun.2024.07.002","url":null,"abstract":"<p><strong>Background: </strong>Early substitution of calcineurin inhibitor (CNI) with mammalian target of rapamycin inhibitors has been shown to improve kidney function and reduce intimal hyperplasia in heart transplant (HTx) recipients but data on long-term outcome of such a regime are still sparse.</p><p><strong>Methods: </strong>In the SCHEDULE trial, 115 de novo HTx recipients were randomized to (1) everolimus with reduced exposure of CNI followed by CNI withdrawal at week 7-11 post-transplant or (2) standard-exposure with CNI. Both groups received mycophenolate mofetil and corticosteroids. Herein we report on the 10-12-year long-term follow-up of the study.</p><p><strong>Results: </strong>A total of 78 patients attended the follow-up visit at a median time of 11 years post-transplant. In the everolimus intention to treat (ITT) group 87.5% (35/40 patients) still received everolimus and in the CNI ITT group 86.8% (33/38) still received CNI. Estimated glomerular filtration rate (eGFR) (least square mean (95% CI)) at the 10-12 years visit was 82.7 (74.2-91.1) ml/min/1.73 m<sup>2</sup> and 61.0 (52.3-69.7) ml/min/1.73 m<sup>2</sup> in the everolimus and CNI group, respectively (p < 0.001). Graft function measured by ejection fraction, ECG, NT-proBNP and drug safety were comparable between groups. During the study period there was a total of 28 deaths, but there was no difference in survival between the everolimus and the CNI group (aHR 0.61 (95% CI 0.29-1.30) p = 0.20). For the composite endpoint of death, re-transplantation, myocardial infarction, PCI, dialysis, kidney transplantation or cancer no between group differences were found (aHR 1.0 (95% CI 0.57-1.77) p = 0.99).</p><p><strong>Conclusions: </strong>De novo HTx patients randomized to everolimus and low dose CNI followed by CNI free therapy sustained significantly better long-term kidney function than patients randomized to standard therapy. The graft function at 10-12 years was similar in both groups and there was no difference in survival.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748394","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}
Pub Date : 2024-07-20DOI: 10.1016/j.healun.2024.07.012
Michal Garaj, Alessandro Francesconi, Miroslav Durila, Jaromir Vajter, Gabriela Holubová, Ingrid Hrachovinová
Background: The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited.
Aims: The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses.
Methods: In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support.
Results: Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05).
Conclusions: Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200.
{"title":"ECMO produces very rapid changes in primary hemostasis detected by PFA-200 during lung transplantation: An observational study.","authors":"Michal Garaj, Alessandro Francesconi, Miroslav Durila, Jaromir Vajter, Gabriela Holubová, Ingrid Hrachovinová","doi":"10.1016/j.healun.2024.07.012","DOIUrl":"10.1016/j.healun.2024.07.012","url":null,"abstract":"<p><strong>Background: </strong>The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited.</p><p><strong>Aims: </strong>The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses.</p><p><strong>Methods: </strong>In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support.</p><p><strong>Results: </strong>Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05).</p><p><strong>Conclusions: </strong>Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748393","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}
Pub Date : 2024-07-20DOI: 10.1016/j.healun.2024.07.007
Margareta Mittendorfer, Leif Pierre, Tibor Huzevka, Jeremy Schofield, Simon T Abrams, Guozheng Wang, Cheng-Hock Toh, Nicholas B Bèchet, Ilma Caprnja, Gunilla Kjellberg, Andrew Aswani, Franziska Olm, Sandra Lindstedt
Background: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).
Methods: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n = 6) or EVLP only (nontreated) (n = 6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs, as well as cytokine levels.
Results: After EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (p = 0.0411). Treated lungs had lower cell-free DNA (p = 0.0260) and lower levels of extracellular histones in EVLP perfusate (p= 0.0260) than nontreated lungs. According to histopathology, treated lungs showed less immune cell infiltration and less edema compared with nontreated lungs, which was reflected in decreased levels of proinflammatory cytokines in EVLP perfusate and bronchoalveolar lavage fluid.
Conclusions: To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.
{"title":"Restoring discarded porcine lungs by ex vivo removal of neutrophil extracellular traps.","authors":"Margareta Mittendorfer, Leif Pierre, Tibor Huzevka, Jeremy Schofield, Simon T Abrams, Guozheng Wang, Cheng-Hock Toh, Nicholas B Bèchet, Ilma Caprnja, Gunilla Kjellberg, Andrew Aswani, Franziska Olm, Sandra Lindstedt","doi":"10.1016/j.healun.2024.07.007","DOIUrl":"10.1016/j.healun.2024.07.007","url":null,"abstract":"<p><strong>Background: </strong>By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).</p><p><strong>Methods: </strong>To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n = 6) or EVLP only (nontreated) (n = 6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs, as well as cytokine levels.</p><p><strong>Results: </strong>After EVLP and NET removal in porcine lungs, PaO<sub>2</sub>/FiO<sub>2</sub> ratios increased significantly compared to those undergoing EVLP alone (p = 0.0411). Treated lungs had lower cell-free DNA (p = 0.0260) and lower levels of extracellular histones in EVLP perfusate (p= 0.0260) than nontreated lungs. According to histopathology, treated lungs showed less immune cell infiltration and less edema compared with nontreated lungs, which was reflected in decreased levels of proinflammatory cytokines in EVLP perfusate and bronchoalveolar lavage fluid.</p><p><strong>Conclusions: </strong>To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748395","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}
Pub Date : 2024-07-17DOI: 10.1016/j.healun.2024.07.011
Joanna M Schaenman, Stephen Samuel Weigt, Mengtong Pan, Joshua J Lee, Xinkai Zhou, David Elashoff, Michael Y Shino, John M Reynolds, Marie Budev, Pali Shah, Lianne G Singer, Jamie L Todd, Laurie D Snyder, Scott Palmer, John Belperio
Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pretransplant sera from the multicenter clinical trials in organ transplantation study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (odds ratio [OR] 0.66 [95% confidence interval {CI} 0.45-0.99], p = 0.043), IL-9 (OR 0.68 [95% CI 0.49-0.94], p = 0.019), IL-13 (OR 0.73 [95% CI 0.55-0.96], p = 0.023), and IL-6 (OR 0.74 [95% CI 0.56-0.98], p = 0.036). Multivariable regression performed for each cytokine, including clinically relevant covariables, confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 [95% CI 0.36-0.89], p = 0.014) and IL-10 (OR 0.55 [95% CI 0.32-0.96], p = 0.035). Higher levels of Th2 immune response before lung transplant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pretransplant cytokine assessments could be utilized for recipient risk stratification.
原发性移植物功能障碍(PGD)是肺移植的一种并发症,会继续导致严重的发病率。Th2 免疫反应已被证明能抵消组织损伤性炎症。我们假设血液中的 Th2 细胞因子/凝血因子与防止 PGD 有关。利用多中心器官移植临床试验(CTOT-20)研究中的移植前血清,我们对 211 名患者的 Th2 细胞因子/造血因子进行了评估。Th2细胞因子浓度升高与免于PGD有关,即IL-4(Odds Ratio (OR) 0.66 (95% CI 0.45-0.99),p=0.043)、IL-9(OR 0.68 (95% CI 0.49-0.94),p=0.019)、IL-13(OR 0.73 (95% CI 0.55-0.96),p=0.023)和IL-6(OR 0.74 (95% CI 0.56-0.98),p=0.036)。对包括临床相关协变量在内的每种细胞因子进行的多变量回归证实了这些相关性,此外还显示与 IL-5(OR 0.57(95% CI 0.36-0.89),p=0.014)和 IL-10(OR 0.55(95% CI 0.32-0.96),p=0.035)相关。肺移植前较高水平的 Th2 免疫反应似乎对 PGD 有保护作用,这与 Th2 在消除炎症和组织损伤中的作用相似。移植前细胞因子评估可用于受者风险分层。
{"title":"Alterations in circulating measures of Th2 immune responses pre-lung transplant associates with reduced primary graft dysfunction.","authors":"Joanna M Schaenman, Stephen Samuel Weigt, Mengtong Pan, Joshua J Lee, Xinkai Zhou, David Elashoff, Michael Y Shino, John M Reynolds, Marie Budev, Pali Shah, Lianne G Singer, Jamie L Todd, Laurie D Snyder, Scott Palmer, John Belperio","doi":"10.1016/j.healun.2024.07.011","DOIUrl":"10.1016/j.healun.2024.07.011","url":null,"abstract":"<p><p>Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pretransplant sera from the multicenter clinical trials in organ transplantation study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (odds ratio [OR] 0.66 [95% confidence interval {CI} 0.45-0.99], p = 0.043), IL-9 (OR 0.68 [95% CI 0.49-0.94], p = 0.019), IL-13 (OR 0.73 [95% CI 0.55-0.96], p = 0.023), and IL-6 (OR 0.74 [95% CI 0.56-0.98], p = 0.036). Multivariable regression performed for each cytokine, including clinically relevant covariables, confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 [95% CI 0.36-0.89], p = 0.014) and IL-10 (OR 0.55 [95% CI 0.32-0.96], p = 0.035). Higher levels of Th2 immune response before lung transplant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pretransplant cytokine assessments could be utilized for recipient risk stratification.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727300","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}
Pub Date : 2024-07-17DOI: 10.1016/j.healun.2024.07.009
Jessica S Clothier, Serge Kobsa, Jonathan Praeger, Markian Bojko, Mark Barr, Sanjeet Patel, Anahat Dhillon, Jonathan Cash, Raymond Lee
Classic Impella exchange interrupts flow when the old device is pulled into the aorta before advancing the new device across the aortic valve, threatening circulatory collapse and loss of left ventricular access. In "double barrel," uninterrupted Impella exchange, the new device is placed into the ventricle alongside the old, where flow is first transitioned completely. Of 31 consecutive patients undergoing this procedure, none experienced intraoperative cardiac arrest, and 96.8% (30/31) had no new aortic insufficiency. One vascular complication ensued following known preoperative iliac injury. One patient suffered nonembolic stroke; another had subarachnoid hemorrhage. Fifty-five percent (17/31) of patients survived, with 22.6% (7/31) recovering, 25.8% (8/31) undergoing transplant, and 6.5% (2/31) transitioning to durable left ventricular assist device. Impella-only survival (83.3%, 10/12) was significantly higher than Impella-extracorporeal membrane oxygenation survival (36.8%, 7/19; (operating room) OR 14.46, 95% ((confidence interval) CI 1.74-119.93, p = 0.01). We conclude the "double barrel" technique is reliable in device-dependent cardiogenic shock patients, offering significant advantages and minimal risk.
{"title":"The double barrel Impella exchange: A reliable method for uninterrupted mechanical circulatory support.","authors":"Jessica S Clothier, Serge Kobsa, Jonathan Praeger, Markian Bojko, Mark Barr, Sanjeet Patel, Anahat Dhillon, Jonathan Cash, Raymond Lee","doi":"10.1016/j.healun.2024.07.009","DOIUrl":"10.1016/j.healun.2024.07.009","url":null,"abstract":"<p><p>Classic Impella exchange interrupts flow when the old device is pulled into the aorta before advancing the new device across the aortic valve, threatening circulatory collapse and loss of left ventricular access. In \"double barrel,\" uninterrupted Impella exchange, the new device is placed into the ventricle alongside the old, where flow is first transitioned completely. Of 31 consecutive patients undergoing this procedure, none experienced intraoperative cardiac arrest, and 96.8% (30/31) had no new aortic insufficiency. One vascular complication ensued following known preoperative iliac injury. One patient suffered nonembolic stroke; another had subarachnoid hemorrhage. Fifty-five percent (17/31) of patients survived, with 22.6% (7/31) recovering, 25.8% (8/31) undergoing transplant, and 6.5% (2/31) transitioning to durable left ventricular assist device. Impella-only survival (83.3%, 10/12) was significantly higher than Impella-extracorporeal membrane oxygenation survival (36.8%, 7/19; (operating room) OR 14.46, 95% ((confidence interval) CI 1.74-119.93, p = 0.01). We conclude the \"double barrel\" technique is reliable in device-dependent cardiogenic shock patients, offering significant advantages and minimal risk.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727301","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}