Pub Date : 2024-07-30DOI: 10.1016/j.healun.2024.07.017
Sambavan Jeyakumar , Helen Nguyen BMedSci(Hons) , Desiree Robson RN , Nick Olsen PhD , Bruno Schnegg MD , Peter Macdonald MD, PhD , Clare L. Fraser MBBS , Gerald Liew MBBS, MMed, PhD , Jacky Jiang , Christopher Hayward MBBS, MD , Kavitha Muthiah MBChB, PhD
Background
Continuous-flow left ventricular assist device (cfLVAD) use is effective in supporting patients with end-stage heart failure (ESHF). Reduced flow pulsatility within the systemic circulation in cfLVAD-supported patients may lead to alterations within the microcirculation. Temporal changes in microvasculature in relation to adverse events in cfLVAD-supported patients have not been studied. We aimed to profile changes within retinal microvasculature and its association with adverse events.
Methods
Retinal photography was performed using Topcon TRC-NW8 nonmydriatic fundus camera in cfLVAD-supported patients and ESHF control patients. Specific retinal measurements were evaluated using a validated semiautomated program. Demographic and adverse event data were documented.
Results
Forty-eight patients were studied (n = 29 cfLVAD, n = 19 ESHF). There were significant trends in retinal arteriolar caliber (B = −0.53 µm, 95% confidence interval [CI]: −0.96 to −0.10, p = 0.016) and retinal fractal dimension parameters (B = 0.014, 95% CI: 0.001-0.002, p = 0.016) in linear mixed model regressions. Among cfLVAD patients, there was a significant association between the incidence of gastrointestinal bleeding and stepwise increases in retinal arteriolar-venular caliber ratio (hazard ratio: 3.03, 95% CI: 2.06-4.45, p = 0.005), a measure of arteriolar narrowing.
Conclusions
We have observed for the first time that alterations in retinal microvasculature in cfLVAD-supported patients may be associated with gastrointestinal bleeding. While understanding these temporal changes may predict future adverse events in cfLVAD-supported patients, further multicenter studies are required to confirm the associations observed.
{"title":"Retinal microvascular remodeling associates with adverse events in continuous-flow left ventricular assist device-supported patients","authors":"Sambavan Jeyakumar , Helen Nguyen BMedSci(Hons) , Desiree Robson RN , Nick Olsen PhD , Bruno Schnegg MD , Peter Macdonald MD, PhD , Clare L. Fraser MBBS , Gerald Liew MBBS, MMed, PhD , Jacky Jiang , Christopher Hayward MBBS, MD , Kavitha Muthiah MBChB, PhD","doi":"10.1016/j.healun.2024.07.017","DOIUrl":"10.1016/j.healun.2024.07.017","url":null,"abstract":"<div><h3>Background</h3><div>Continuous-flow left ventricular assist device (cfLVAD) use is effective in supporting patients with end-stage heart failure (ESHF). Reduced flow pulsatility within the systemic circulation in cfLVAD-supported patients may lead to alterations within the microcirculation. Temporal changes in microvasculature in relation to adverse events in cfLVAD-supported patients have not been studied. We aimed to profile changes within retinal microvasculature and its association with adverse events.</div></div><div><h3>Methods</h3><div>Retinal photography was performed using Topcon TRC-NW8 nonmydriatic fundus camera in cfLVAD-supported patients and ESHF control patients. Specific retinal measurements were evaluated using a validated semiautomated program. Demographic and adverse event data were documented.</div></div><div><h3>Results</h3><div>Forty-eight patients were studied (<em>n</em> = 29 cfLVAD, <em>n</em> = 19 ESHF). There were significant trends in retinal arteriolar caliber (B = −0.53 µm, 95% confidence interval [CI]: −0.96 to −0.10, <em>p</em> = 0.016) and retinal fractal dimension parameters (B = 0.014, 95% CI: 0.001-0.002, <em>p</em> = 0.016) in linear mixed model regressions. Among cfLVAD patients, there was a significant association between the incidence of gastrointestinal bleeding and stepwise increases in retinal arteriolar-venular caliber ratio (hazard ratio: 3.03, 95% CI: 2.06-4.45, <em>p</em> = 0.005), a measure of arteriolar narrowing.</div></div><div><h3>Conclusions</h3><div>We have observed for the first time that alterations in retinal microvasculature in cfLVAD-supported patients may be associated with gastrointestinal bleeding. While understanding these temporal changes may predict future adverse events in cfLVAD-supported patients, further multicenter studies are required to confirm the associations observed.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 12","pages":"Pages 1975-1984"},"PeriodicalIF":6.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875034","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.2024.07.015
Alberto Pinsino MD , Douglas L. Jennings PharmD , Annamaria Ladanyi MD , Phuong Duong MD , Austin O. Sweat MD , Ian Mahoney MD , Bruno Bohn MPH , Ryan T. Demmer MPH, PhD , Koji Takeda MD, PhD , Gabriel T. Sayer MD , Nir Uriel MD, MS , Jay S. Leb MD , Syed A. Husain MD , Sumit Mohan MD, MPH , Paolo C. Colombo MD , Melana Yuzefpolskaya MD
Background
Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in muscle mass. Cystatin C (cysC) is less influenced by muscle mass, but its levels may increase with obesity and steroid use. Herein, we (1) longitudinally compared eGFRcysC and eGFRsCr among HT recipients; (2) investigated the association of body mass index (BMI), steroid use, and muscle mass with discrepancies between eGFRs; and (3) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing.
Methods
cysC and sCr were measured in 294 blood samples obtained from 80 subjects. Intraindividual differences between eGFRs (eGFRdiffcysC-sCr) were calculated with negative values corresponding to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n = 21), pectoralis muscle measures were obtained.
Results
Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr −28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient postoperative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction.
Conclusions
Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.
{"title":"Kidney function assessment using cystatin C and serum creatinine in heart transplantation recipients: Implications for valganciclovir dosing","authors":"Alberto Pinsino MD , Douglas L. Jennings PharmD , Annamaria Ladanyi MD , Phuong Duong MD , Austin O. Sweat MD , Ian Mahoney MD , Bruno Bohn MPH , Ryan T. Demmer MPH, PhD , Koji Takeda MD, PhD , Gabriel T. Sayer MD , Nir Uriel MD, MS , Jay S. Leb MD , Syed A. Husain MD , Sumit Mohan MD, MPH , Paolo C. Colombo MD , Melana Yuzefpolskaya MD","doi":"10.1016/j.healun.2024.07.015","DOIUrl":"10.1016/j.healun.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><div>Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in muscle mass. Cystatin C (cysC) is less influenced by muscle mass, but its levels may increase with obesity and steroid use. Herein, we (1) longitudinally compared eGFRcysC and eGFRsCr among HT recipients; (2) investigated the association of body mass index (BMI), steroid use, and muscle mass with discrepancies between eGFRs; and (3) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing.</div></div><div><h3>Methods</h3><div>cysC and sCr were measured in 294 blood samples obtained from 80 subjects. Intraindividual differences between eGFRs (eGFRdiff<sub>cysC-sCr</sub>) were calculated with negative values corresponding to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (<em>n</em> = 21), pectoralis muscle measures were obtained.</div></div><div><h3>Results</h3><div>Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiff<sub>cysC-sCr</sub> −28 ml/min/1.73 m<sup>2</sup>). eGFRcysC demonstrated stability following a transient postoperative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiff<sub>cysC-sCr</sub> values. Pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiff<sub>cysC-sCr</sub> values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction.</div></div><div><h3>Conclusions</h3><div>Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 12","pages":"Pages 1963-1972"},"PeriodicalIF":6.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788328","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.2024.07.016
Yu Xia MD, MS , Abbas Ardehali MD
{"title":"Comment on: Characteristics and outcomes of lung transplants performed with ex-situ lung perfusion","authors":"Yu Xia MD, MS , Abbas Ardehali MD","doi":"10.1016/j.healun.2024.07.016","DOIUrl":"10.1016/j.healun.2024.07.016","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 11","pages":"Page 1918"},"PeriodicalIF":6.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788327","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.2024.07.018
Janne Brouckaert MD , Katrien Vandendriessche MD , Karlien Degezelle , Kristof Van de Voorde , Francis De Burghgraeve MD , Lars Desmet MD , Dirk Vlasselaers MD, PhD , Catherine Ingels MD, PhD , Dieter Dauwe MD, PhD , Erwin De Troy MD , Laurens J. Ceulemans MD, PhD , Dirk Van Raemdonck MD, PhD , Diethard Monbaliu MD, PhD , Bart Meyns MD, PhD , Raf Van den Eynde MD , Steffen Rex MD, PhD , Johan Van Cleemput MD, PhD , Filip Rega MD, PhD
{"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 MD , Katrien Vandendriessche MD , Karlien Degezelle , Kristof Van de Voorde , Francis De Burghgraeve MD , Lars Desmet MD , Dirk Vlasselaers MD, PhD , Catherine Ingels MD, PhD , Dieter Dauwe MD, PhD , Erwin De Troy MD , Laurens J. Ceulemans MD, PhD , Dirk Van Raemdonck MD, PhD , Diethard Monbaliu MD, PhD , Bart Meyns MD, PhD , Raf Van den Eynde MD , Steffen Rex MD, PhD , Johan Van Cleemput MD, PhD , Filip Rega MD, PhD","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":"43 11","pages":"Pages 1907-1910"},"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 MD, PhD , Jonathan Grinstein MD , Jamila Kremer MD , Jennifer A. Cowger MD, MS
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 MD, PhD , Jonathan Grinstein MD , Jamila Kremer MD , Jennifer A. Cowger MD, MS","doi":"10.1016/j.healun.2024.06.018","DOIUrl":"10.1016/j.healun.2024.06.018","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 11","pages":"Pages 1881-1893"},"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 BSc , Sarah M. Berger BSc , Mila Djinovic MD , Philippe L. Furlano BSc , Lisa M. Steininger BSc , Anna-Lena Pirker MSc , Peter Jaksch MD , Elisabeth Puchhammer-Stöckl MD , Hannes Vietzen PhD
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 BSc , Sarah M. Berger BSc , Mila Djinovic MD , Philippe L. Furlano BSc , Lisa M. Steininger BSc , Anna-Lena Pirker MSc , Peter Jaksch MD , Elisabeth Puchhammer-Stöckl MD , Hannes Vietzen PhD","doi":"10.1016/j.healun.2024.07.014","DOIUrl":"10.1016/j.healun.2024.07.014","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 12","pages":"Pages 2036-2041"},"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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1016/j.healun.2024.07.010
Rashmi Prava Mohanty PhD , Kaveh Moghbeli MD , Jonathan P. Singer MD, MS , Daniel R. Calabrese MD , Steven R. Hays MD , Carlo Iasella PharmD, MPH , Sophia Lieber BS , Lorriana E. Leard MD , Rupal J. Shah MD , Aida Venado MD , Mary E. Kleinhenz MD , Jeffery A. Golden MD , Tereza Martinu MD , Christina Love BA , Ryan Ward BS , Charles R. Langelier MD , John McDyer MD , John R. Greenland MD, PhD
Background
Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure.
Methods
Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function. Candidate genes not associated with CLAD and time to graft failure were excluded, yielding the Airway Inflammation 2 (AI2) gene set. Area under the receiver operating curve (AUC) for CLAD and competing risks of death or graft failure were assessed in an independent validation cohort of 37 CLAD cases and 37 controls.
Results
Thirty-two candidate genes were associated with CLAD and graft failure, comprising the AI2 score, which clustered into 3 subcomponents. The AI2 score identified CLAD before its onset, in early and late post-CLAD brushes, as well as in the validation cohort (AUC 0.69-0.88). The AI2 score association with CLAD was independent of positive microbiology, CLAD stage, or CLAD subtype. However, transcripts most associated with CLAD evolved over time from CLAD onset. The AI2 score predicted time to graft failure and retransplant-free survival in both cohorts (p ≤ 0.03).
Conclusions
This airway inflammation gene score is associated with CLAD development, graft failure, and death. Future studies defining the molecular heterogeneity of airway inflammation could lead to endotype-targeted therapies.
{"title":"Small airway brush gene expression predicts chronic lung allograft dysfunction and mortality","authors":"Rashmi Prava Mohanty PhD , Kaveh Moghbeli MD , Jonathan P. Singer MD, MS , Daniel R. Calabrese MD , Steven R. Hays MD , Carlo Iasella PharmD, MPH , Sophia Lieber BS , Lorriana E. Leard MD , Rupal J. Shah MD , Aida Venado MD , Mary E. Kleinhenz MD , Jeffery A. Golden MD , Tereza Martinu MD , Christina Love BA , Ryan Ward BS , Charles R. Langelier MD , John McDyer MD , John R. Greenland MD, PhD","doi":"10.1016/j.healun.2024.07.010","DOIUrl":"10.1016/j.healun.2024.07.010","url":null,"abstract":"<div><h3>Background</h3><div>Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure.</div></div><div><h3>Methods</h3><div>Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function. Candidate genes not associated with CLAD and time to graft failure were excluded, yielding the Airway Inflammation 2 (AI2) gene set. Area under the receiver operating curve (AUC) for CLAD and competing risks of death or graft failure were assessed in an independent validation cohort of 37 CLAD cases and 37 controls.</div></div><div><h3>Results</h3><div>Thirty-two candidate genes were associated with CLAD and graft failure, comprising the AI2 score, which clustered into 3 subcomponents. The AI2 score identified CLAD before its onset, in early and late post-CLAD brushes, as well as in the validation cohort (AUC 0.69-0.88). The AI2 score association with CLAD was independent of positive microbiology, CLAD stage, or CLAD subtype. However, transcripts most associated with CLAD evolved over time from CLAD onset. The AI2 score predicted time to graft failure and retransplant-free survival in both cohorts (<em>p</em> ≤ 0.03).</div></div><div><h3>Conclusions</h3><div>This airway inflammation gene score is associated with CLAD development, graft failure, and death. Future studies defining the molecular heterogeneity of airway inflammation could lead to endotype-targeted therapies.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 11","pages":"Pages 1820-1832"},"PeriodicalIF":6.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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 MD (Assistant Professor of Medicine/Cardiology) , Sean van Diepen MD , Ann Gage MD , Alexander M. Bernhardt MD , Jennifer Cowger MD , Brian A. Houston MD , Matt T. Siuba DO , Rachna Kataria MD , Craig J. Beavers PharmD , Kevin J. John MD , Bart Meyns MD PhD , Navin K. Kapur MD , Ryan J. Tedford MD , Manreet Kanwar MD
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 MD (Assistant Professor of Medicine/Cardiology) , Sean van Diepen MD , Ann Gage MD , Alexander M. Bernhardt MD , Jennifer Cowger MD , Brian A. Houston MD , Matt T. Siuba DO , Rachna Kataria MD , Craig J. Beavers PharmD , Kevin J. John MD , Bart Meyns MD PhD , Navin K. Kapur MD , Ryan J. Tedford MD , Manreet Kanwar MD","doi":"10.1016/j.healun.2024.07.006","DOIUrl":"10.1016/j.healun.2024.07.006","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 11","pages":"Pages 1894-1904"},"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}
{"title":"Why VA-ECMO should not be used routinely in AMI-cardiogenic shock","authors":"Holger Thiele MD , Steffen Desch MD , Anne Freund MD , Uwe Zeymer MD","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":"43 11","pages":"Pages 1912-1913"},"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 , on behalf of the SCHEDULE (Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance) investigators
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 , on behalf of the SCHEDULE (Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance) investigators","doi":"10.1016/j.healun.2024.07.002","DOIUrl":"10.1016/j.healun.2024.07.002","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>p</em> < 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) <em>p</em> = 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) <em>p</em> = 0.99).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"43 12","pages":"Pages 1948-1959"},"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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}