Pub Date : 2024-08-07DOI: 10.1016/j.healun.2024.07.019
Ei Miyamoto, Daniel Vosoughi, Jinguo Wang, Jamal Al-Refaee, Gregory Berra, Tina Daigneault, Allen Duong, Betty Joe, Sajad Moshkelgosha, Shaf Keshavjee, Kathryn Tinckam, David Hwang, Andrzej Chruscinski, Stephen Juvet, Tereza Martinu
Background: Donor human leukocyte antigen (HLA)-specific antibodies (DSA) and non-HLA antibodies can cause allograft injury, possibly leading to chronic lung allograft dysfunction (CLAD) after lung transplantation. It remains unclear whether these antibodies are produced locally in the graft or derived solely from circulation. We hypothesized that DSA and non-HLA antibodies are produced in CLAD lungs.
Methods: Lung tissue was prospectively collected from 15 CLAD patients undergoing retransplantation or autopsy. 0.3 g of fresh lung tissue was cultured for 4 days without or with lipopolysaccharide or CD40L: lung culture supernatant (LCS) was sampled. Protein eluate was obtained from 0.3 g of frozen lung tissue. The mean fluorescence intensity (MFI) of DSA and non-HLA antibodies was measured by Luminex and antigen microarray, respectively.
Results: LCS from all 4 patients who had serum DSA at lung isolation were positive for DSA, with higher levels measured after CD40L stimulation (CD40L+LCS). Of these, only 2 had detectable DSA in lung eluate. MFI of non-HLA antibodies from CD40L+LCS correlated with those from lung eluate but not with those from sera. Flow cytometry showed higher frequencies of activated lung B cells in patients whose CD40L+LCS was positive for DSA (n = 4) or high non-HLA antibodies (n = 6) compared to those with low local antibodies (n = 5). Immunofluorescence staining showed CLAD lung lymphoid aggregates with local antibodies contained larger numbers of IgG+ plasma cells and greater IL-21 expression.
Conclusions: We show that DSA and non-HLA antibodies can be produced within activated B cell-rich lung allografts.
{"title":"Local intragraft humoral immune responses in chronic lung allograft dysfunction.","authors":"Ei Miyamoto, Daniel Vosoughi, Jinguo Wang, Jamal Al-Refaee, Gregory Berra, Tina Daigneault, Allen Duong, Betty Joe, Sajad Moshkelgosha, Shaf Keshavjee, Kathryn Tinckam, David Hwang, Andrzej Chruscinski, Stephen Juvet, Tereza Martinu","doi":"10.1016/j.healun.2024.07.019","DOIUrl":"10.1016/j.healun.2024.07.019","url":null,"abstract":"<p><strong>Background: </strong>Donor human leukocyte antigen (HLA)-specific antibodies (DSA) and non-HLA antibodies can cause allograft injury, possibly leading to chronic lung allograft dysfunction (CLAD) after lung transplantation. It remains unclear whether these antibodies are produced locally in the graft or derived solely from circulation. We hypothesized that DSA and non-HLA antibodies are produced in CLAD lungs.</p><p><strong>Methods: </strong>Lung tissue was prospectively collected from 15 CLAD patients undergoing retransplantation or autopsy. 0.3 g of fresh lung tissue was cultured for 4 days without or with lipopolysaccharide or CD40L: lung culture supernatant (LCS) was sampled. Protein eluate was obtained from 0.3 g of frozen lung tissue. The mean fluorescence intensity (MFI) of DSA and non-HLA antibodies was measured by Luminex and antigen microarray, respectively.</p><p><strong>Results: </strong>LCS from all 4 patients who had serum DSA at lung isolation were positive for DSA, with higher levels measured after CD40L stimulation (CD40L<sup>+</sup>LCS). Of these, only 2 had detectable DSA in lung eluate. MFI of non-HLA antibodies from CD40L<sup>+</sup>LCS correlated with those from lung eluate but not with those from sera. Flow cytometry showed higher frequencies of activated lung B cells in patients whose CD40L<sup>+</sup>LCS was positive for DSA (n = 4) or high non-HLA antibodies (n = 6) compared to those with low local antibodies (n = 5). Immunofluorescence staining showed CLAD lung lymphoid aggregates with local antibodies contained larger numbers of IgG<sup>+</sup> plasma cells and greater IL-21 expression.</p><p><strong>Conclusions: </strong>We show that DSA and non-HLA antibodies can be produced within activated B cell-rich lung allografts.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889464","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 : 2024-08-07DOI: 10.1016/j.healun.2024.07.022
Ryan Chaban, Ikechukwu Ileka, Gannon McGrath, Kohei Kinoshita, Zahra Habibabady, Madelyn Ma, Victoria Diaz, Akihiro Maenaka, Anthony Calhoun, Megan Dufault, Ivy Rosales, Christiana M Laguerre, Seyed-Amir Sanatkar, Lars Burdorf, David L Ayares, William Eyestone, Prachi Sardana, Kasinath Kuravi, Lori Sorrells, Seth Lederman, Caroline G Lucas, Randall S Prather, Kevin D Wells, Kristin M Whitworth, David K C Cooper, Richard N Pierson
Background: Xenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ''transgenes''. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique.
Methods: Eight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.β4GalNT2KO.hCD55, n = 3), 9-GE (GalKO.β4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47. HO-1, n = 3) or 10-G (9-GE+CMAHKO, n = 2) pigs using Steen's cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid.
Results: All three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events.
Conclusion: Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.
{"title":"Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression.","authors":"Ryan Chaban, Ikechukwu Ileka, Gannon McGrath, Kohei Kinoshita, Zahra Habibabady, Madelyn Ma, Victoria Diaz, Akihiro Maenaka, Anthony Calhoun, Megan Dufault, Ivy Rosales, Christiana M Laguerre, Seyed-Amir Sanatkar, Lars Burdorf, David L Ayares, William Eyestone, Prachi Sardana, Kasinath Kuravi, Lori Sorrells, Seth Lederman, Caroline G Lucas, Randall S Prather, Kevin D Wells, Kristin M Whitworth, David K C Cooper, Richard N Pierson","doi":"10.1016/j.healun.2024.07.022","DOIUrl":"10.1016/j.healun.2024.07.022","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ''transgenes''. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique.</p><p><strong>Methods: </strong>Eight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.β4GalNT2KO.hCD55, n = 3), 9-GE (GalKO.β4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47. HO-1, n = 3) or 10-G (9-GE+CMAHKO, n = 2) pigs using Steen's cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid.</p><p><strong>Results: </strong>All three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events.</p><p><strong>Conclusion: </strong>Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889463","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 : 2024-08-05DOI: 10.1016/j.healun.2024.07.008
{"title":"A remembrance of Daniel R. Goldstein, MD","authors":"","doi":"10.1016/j.healun.2024.07.008","DOIUrl":"10.1016/j.healun.2024.07.008","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901995","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 : 2024-08-05DOI: 10.1016/j.healun.2024.07.023
R Moayedifar, A Zuckermann
{"title":"Recipient outcomes with extended criteria donors using advanced heart preservation: Response letter and insights into the data.","authors":"R Moayedifar, A Zuckermann","doi":"10.1016/j.healun.2024.07.023","DOIUrl":"10.1016/j.healun.2024.07.023","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901994","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 : 2024-08-05DOI: 10.1016/S1053-2498(24)01763-7
{"title":"Information for Readers","authors":"","doi":"10.1016/S1053-2498(24)01763-7","DOIUrl":"10.1016/S1053-2498(24)01763-7","url":null,"abstract":"","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961223","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 : 2024-07-31DOI: 10.1016/j.healun.2024.07.020
Aprotim C Bhowmik, Brian Wayda, Helen Luikart, Yingjie Weng, Shiqi Zhang, R Patrick Wood, Javier Nieto, Tahnee Groat, Nikole Neidlinger, Jonathan Zaroff, Darren Malinoski, Kiran K Khush
The use of 50+ year-old donors for heart transplant (HT) is rare in the United States. We assessed reasons for this-and whether it reflects concern about age itself or associated risk factors-using a survey of US HT centers. The Donor Heart Study enrolled US adult potential heart donors from 2015 to 2020. A total of 6,814 surveys across 2,197 donors cited, on average, 2.4 reasons (per donor) for offer refusal. Age was cited often (by ≥50% of centers surveyed) for 715 donors (33%). In this subgroup, accompanying donor-related reasons for refusal were infrequent, with no cardiac abnormality cited in most cases. Donor age showed associations with (1) age as a reason for refusal and (2) discard. Both abruptly increased at age 50: 55% of 50 to 51-year-old donors were refused often due to age (vs 38% of 48-49-year-olds), and 72% were discarded (vs 55% of 48-49-year-olds), despite no evidence of a threshold effect of age on outcomes.
{"title":"Just a number? Donor age and (lack of) associated reasons for heart offer refusal.","authors":"Aprotim C Bhowmik, Brian Wayda, Helen Luikart, Yingjie Weng, Shiqi Zhang, R Patrick Wood, Javier Nieto, Tahnee Groat, Nikole Neidlinger, Jonathan Zaroff, Darren Malinoski, Kiran K Khush","doi":"10.1016/j.healun.2024.07.020","DOIUrl":"10.1016/j.healun.2024.07.020","url":null,"abstract":"<p><p>The use of 50+ year-old donors for heart transplant (HT) is rare in the United States. We assessed reasons for this-and whether it reflects concern about age itself or associated risk factors-using a survey of US HT centers. The Donor Heart Study enrolled US adult potential heart donors from 2015 to 2020. A total of 6,814 surveys across 2,197 donors cited, on average, 2.4 reasons (per donor) for offer refusal. Age was cited often (by ≥50% of centers surveyed) for 715 donors (33%). In this subgroup, accompanying donor-related reasons for refusal were infrequent, with no cardiac abnormality cited in most cases. Donor age showed associations with (1) age as a reason for refusal and (2) discard. Both abruptly increased at age 50: 55% of 50 to 51-year-old donors were refused often due to age (vs 38% of 48-49-year-olds), and 72% were discarded (vs 55% of 48-49-year-olds), despite no evidence of a threshold effect of age on outcomes.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875033","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 : 2024-07-30DOI: 10.1016/j.healun.2024.07.021
In-Cheol Kim, Randall C Starling, Kiran Khush, Elizabeth Passano, James Mirocha, Peter Bernhardt, Babak Azarbal, Richard Cheng, Fardad Esmailian, Donna Mancini, Jignesh K Patel, Takuma Sato, Shaida Varnous, Jon A Kobashigawa
Background: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated.
Methods: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year.
Results: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002).
Conclusions: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.
背景:尚未对心脏移植(HTx)患者前瞻性队列中早期血管内超声(IVUS)发现的长期临床结果进行评估:本研究纳入了 RAD B253 研究原始队列中来自欧洲、北美和南美 20 个中心的患者。在这些患者中,91人在基线和移植后1年时有成对的IVUS图像,其中依维莫司1.5毫克组25人,依维莫司3.0毫克组33人,硫唑嘌呤组33人。主要结果是10年随访期内心血管死亡、再次移植、心肌梗死(MI)、冠状动脉血运重建和心脏异体移植血管病变(CAV)的综合结果。次要结果是全因死亡、心血管死亡、再次移植、心肌梗死、冠状动脉血运重建和CAV。供体疾病的定义是基线最大内膜厚度(MIT)大于0.66毫米,快速进展的定义是一年后MIT的变化大于0.59毫米:结果:供体疾病(46 例患者)与较高的主要结局发生率相关(HR 4.444,95% CI 1.946-10.146,p 结论:基线 MIT > 0.66 mm 的患者,其主要结局发生率较高:热灌注术后通过IVUS测量的基线MIT增加> 0.66 mm和第一年MIT变化> 0.59 mm与长达10年的不良预后有关。早期IVUS检查结果可作为替代终点,用于评估热灌注治疗临床试验的长期疗效。
{"title":"Ten-year follow-up cohort of the everolimus versus azathioprine multinational prospective study focusing on intravascular ultrasound findings.","authors":"In-Cheol Kim, Randall C Starling, Kiran Khush, Elizabeth Passano, James Mirocha, Peter Bernhardt, Babak Azarbal, Richard Cheng, Fardad Esmailian, Donna Mancini, Jignesh K Patel, Takuma Sato, Shaida Varnous, Jon A Kobashigawa","doi":"10.1016/j.healun.2024.07.021","DOIUrl":"10.1016/j.healun.2024.07.021","url":null,"abstract":"<p><strong>Background: </strong>Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated.</p><p><strong>Methods: </strong>This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year.</p><p><strong>Results: </strong>Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002).</p><p><strong>Conclusions: </strong>An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875035","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 : 2024-07-30DOI: 10.1016/j.healun.2024.07.017
Sambavan Jeyakumar, Helen Nguyen, Desiree Robson, Nick Olsen, Bruno Schnegg, Peter Macdonald, Clare L Fraser, Gerald Liew, Jacky Jiang, Christopher Hayward, Kavitha Muthiah
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, Desiree Robson, Nick Olsen, Bruno Schnegg, Peter Macdonald, Clare L Fraser, Gerald Liew, Jacky Jiang, Christopher Hayward, Kavitha Muthiah","doi":"10.1016/j.healun.2024.07.017","DOIUrl":"10.1016/j.healun.2024.07.017","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":null,"pages":null},"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, Douglas L Jennings, Annamaria Ladanyi, Phuong Duong, Austin O Sweat, Ian Mahoney, Bruno Bohn, Ryan T Demmer, Koji Takeda, Gabriel T Sayer, Nir Uriel, Jay S Leb, Syed A Husain, Sumit Mohan, Paolo C Colombo, Melana Yuzefpolskaya
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, Douglas L Jennings, Annamaria Ladanyi, Phuong Duong, Austin O Sweat, Ian Mahoney, Bruno Bohn, Ryan T Demmer, Koji Takeda, Gabriel T Sayer, Nir Uriel, Jay S Leb, Syed A Husain, Sumit Mohan, Paolo C Colombo, Melana Yuzefpolskaya","doi":"10.1016/j.healun.2024.07.015","DOIUrl":"10.1016/j.healun.2024.07.015","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (n = 21), pectoralis muscle measures were obtained.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</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":"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, Abbas Ardehali
{"title":"Comment on: Characteristics and outcomes of lung transplants performed with ex-situ lung perfusion.","authors":"Yu Xia, Abbas Ardehali","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":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":"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}