Pub Date : 2025-01-01DOI: 10.1016/j.healun.2024.08.016
Selianne Graf PhD , Manuel Egle MD , Maria-Nieves Sanz PhD , Adrian Segiser MSc , Alexia Clavier MSc , Maria Arnold PhD , Didier Gsponer , Maris Bartkevics MD , Alexander Kadner MD , Matthias Siepe MD , Peter Vermathen PhD , Sarah Longnus PhD
Background
Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality.
Methods
Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 minutes. Hearts were explanted and underwent ex-situ perfusion for 3 hours in an unloaded mode, followed by left ventricular loading for 1 hour, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy.
Results
Circulating adrenaline, both in the donor and at 10 minutes ex-situ heart perfusion, negatively correlated with cardiac recovery (p < 0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p < 0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 minutes.
Conclusions
In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.
{"title":"Circulating factors, in both donor and ex-situ heart perfusion, correlate with heart recovery in a pig model of DCD","authors":"Selianne Graf PhD , Manuel Egle MD , Maria-Nieves Sanz PhD , Adrian Segiser MSc , Alexia Clavier MSc , Maria Arnold PhD , Didier Gsponer , Maris Bartkevics MD , Alexander Kadner MD , Matthias Siepe MD , Peter Vermathen PhD , Sarah Longnus PhD","doi":"10.1016/j.healun.2024.08.016","DOIUrl":"10.1016/j.healun.2024.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ<em>,</em> as potential biomarkers for cardiac graft quality.</div></div><div><h3>Methods</h3><div>Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 minutes. Hearts were explanted and underwent ex-situ perfusion for 3 hours in an unloaded mode, followed by left ventricular loading for 1 hour, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy.</div></div><div><h3>Results</h3><div>Circulating adrenaline, both in the donor and at 10 minutes ex-situ heart perfusion, negatively correlated with cardiac recovery (<em>p</em> < 0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (<em>p</em> < 0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 minutes.</div></div><div><h3>Conclusions</h3><div>In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 92-101"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165913","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 : 2025-01-01DOI: 10.1016/j.healun.2024.08.024
Shin Lin MD, PhD, MHS , Ioannis Dimarakis MD, PhD , Elina Minami MD , Ramasamy Bakthavatsalam MBBS , Renuka Bhattacharya MD , April Stempien-Otero MD , Yiing Lin MD, PhD , Aris Karatasakis MD , Maziar Khorsandi MBChB , Elaine Chou-Wu PhD , Idoia Gimferrer MD, PhD , Mariya Y. Golub RN , Daniel Fishbein , Richard K. Cheng MD, MSc , Ryutaro Hirose MD , Mark Sturdevant MD , Jay D. Pal MD, PhD
For patients with end-stage heart disease and borderline hemodynamics, high human leukocyte antigen allosensitization presents a barrier to heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant on a single patient without liver disease. We describe this patient's course to date as well as 4 subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.
{"title":"Highly sensitized patients listed for heart after liver transplantation with or without domino","authors":"Shin Lin MD, PhD, MHS , Ioannis Dimarakis MD, PhD , Elina Minami MD , Ramasamy Bakthavatsalam MBBS , Renuka Bhattacharya MD , April Stempien-Otero MD , Yiing Lin MD, PhD , Aris Karatasakis MD , Maziar Khorsandi MBChB , Elaine Chou-Wu PhD , Idoia Gimferrer MD, PhD , Mariya Y. Golub RN , Daniel Fishbein , Richard K. Cheng MD, MSc , Ryutaro Hirose MD , Mark Sturdevant MD , Jay D. Pal MD, PhD","doi":"10.1016/j.healun.2024.08.024","DOIUrl":"10.1016/j.healun.2024.08.024","url":null,"abstract":"<div><div>For patients with end-stage heart disease and borderline hemodynamics, high human leukocyte antigen allosensitization presents a barrier to heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant on a single patient without liver disease. We describe this patient's course to date as well as 4 subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 125-128"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120010","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 : 2025-01-01DOI: 10.1016/j.healun.2024.09.007
Laneshia K. Tague MD MS , Hephzibah Anthony MBBS , Noha N. Salama PhD , Ramsey R. Hachem MD , Brian F. Gage MD MS , Andrew E. Gelman PhD
Background
Mycophenolic Acid (MPA) is the most used anti-proliferative in lung transplantation, but its pharmacokinetic (PK) variability has precluded therapeutic drug monitoring. Both genetic and clinical factors have been implicated in MPA variability. This study aimed to integrate genetic and clinical factors with PK measurements to quantify MPA exposure.
Methods
We performed 12-hour pharmacokinetic analysis on 60 adult lung transplant recipients maintained on MPA for immunosuppression. We genotyped a SLCO1B3 polymorphisms previously associated MPA metabolism and collected relevant clinical data. We calculated area under the curve (AUC0–12) and performed univariate linear regression analysis to evaluate its association with genetic, clinical, and pharmacokinetic variables. We performed lasso regression analysis to create final AUC estimation tools.
Results
PK-only measurements obtained 2, 3, and 8 hours after MPA administration (C2, C3, and C8) were strongly associated with MPA AUC0–12 (R267%, 67% and 68% respectively). Clinical and genetic factors associated with MPA AUC0–12 included the MPA dose (p = 0.001), transplant diagnosis (p = 0.015), SLCO1B3 genotype (p = 0.049), and body surface area (p = 0.050). The best integrated single-sampling strategy included C2 and achieved an R2 value of 80%. The best integrated limited-sampling strategy included C0, C0.25, and C2 and achieved an R2 value of 90%.
Conclusions
An integrated limited sampling strategy (LSS) for MPA allows increased accuracy in prediction of MPA AUC0–12 compared to PK-only modeling. Validation of this model will allow for clinically feasible MPA therapeutic drug monitoring and help advance precision management of MPA.
{"title":"An integrated sampling strategy for therapeutic mycophenolic acid monitoring in lung transplant recipients","authors":"Laneshia K. Tague MD MS , Hephzibah Anthony MBBS , Noha N. Salama PhD , Ramsey R. Hachem MD , Brian F. Gage MD MS , Andrew E. Gelman PhD","doi":"10.1016/j.healun.2024.09.007","DOIUrl":"10.1016/j.healun.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Mycophenolic Acid (MPA) is the most used anti-proliferative in lung transplantation, but its pharmacokinetic (PK) variability has precluded therapeutic drug monitoring. Both genetic and clinical factors have been implicated in MPA variability. This study aimed to integrate genetic and clinical factors with PK measurements to quantify MPA exposure.</div></div><div><h3>Methods</h3><div>We performed 12-hour pharmacokinetic analysis on 60 adult lung transplant recipients maintained on MPA for immunosuppression. We genotyped a SLCO1B3 polymorphisms previously associated MPA metabolism and collected relevant clinical data. We calculated area under the curve (AUC<sub>0–12</sub>) and performed univariate linear regression analysis to evaluate its association with genetic, clinical, and pharmacokinetic variables. We performed lasso regression analysis to create final AUC estimation tools.</div></div><div><h3>Results</h3><div>PK-only measurements obtained 2, 3, and 8 hours after MPA administration (C<sub>2</sub>, C<sub>3,</sub> and C<sub>8</sub>) were strongly associated with MPA AUC<sub>0–12</sub> (<em>R</em><sup><em>2</em></sup> <em>67%, 67% and 68% respectively</em>). Clinical and genetic factors associated with MPA AUC<sub>0–12</sub> included the MPA dose (<em>p</em> = 0.001), transplant diagnosis (<em>p</em> = 0.015), SLCO1B3 genotype (<em>p</em> = 0.049), and body surface area (<em>p</em> = 0.050). The best integrated single-sampling strategy included C<sub>2</sub> and achieved an R<sup>2</sup> value of 80%. The best integrated limited-sampling strategy included C<sub>0</sub>, C<sub>0.25</sub>, and C<sub>2</sub> and achieved an R<sup>2</sup> value of 90%.</div></div><div><h3>Conclusions</h3><div>An integrated limited sampling strategy (LSS) for MPA allows increased accuracy in prediction of MPA AUC<sub>0–12</sub> compared to PK-only modeling. Validation of this model will allow for clinically feasible MPA therapeutic drug monitoring and help advance precision management of MPA.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 46-56"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246773","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 : 2025-01-01DOI: 10.1016/j.healun.2024.09.029
Masaki Tsuji MD, PhD, Jignesh K. Patel MD, PhD, Michelle M. Kittleson MD, PhD, David H. Chang MD, Evan P. Kransdorf MD, PhD, Andriana P. Nikolova MD, Lily K. Stern MD, Nayana Bhatnagar BS, Jon A. Kobashigawa MD
Background
Microvascular dysfunction after heart transplantation leads to restrictive cardiac allograft physiology (RCP), which is classified as severe coronary allograft vasculopathy (CAV); however, the prognosis of RCP remains unclear. Therefore, in this study, we aimed to elucidate the prognosis of RCP in comparison with that of severe angiographic CAV.
Methods
We assessed 116 patients with severe CAV who underwent heart transplantation between 2004 and 2023. RCP was defined as symptomatic heart failure with restrictive hemodynamic values (mean right atrial pressure >12 mm Hg, pulmonary capillary wedge pressure >25 mm Hg, and cardiac index <2.0 liter/min/m2). The primary outcome was death or retransplantation.
Results
Of the 116 patients with severe CAV, 42 had RCP (RCP-CAV group) and 74 had severe angiographic CAV without RCP (Angio-CAV group). A significantly shorter time from heart transplantation to diagnosis and lower subsequent percutaneous catheter intervention after diagnosis were seen in the RCP-CAV group than in the Angio-CAV group (both p < 0.001). Freedom from death or retransplantation at 5 years was significantly worse in the RCP-CAV group compared to the Angio-CAV group (18.4% vs 35.4%, p = 0.001). In the Cox proportional hazard model, RCP was independently associated with an increased risk of death or retransplantation (hazard ratio 2.08, 95% confidence intervals 1.26-3.44, p = 0.004).
Conclusions
The prognosis of patients with RCP was significantly worse than that of patients with severe angiographic CAV. The early detection of microvascular dysfunction and retransplantation listing may improve the prognosis of patients with RCP.
{"title":"The outcome of restrictive cardiac allograft physiology in severe coronary allograft vasculopathy","authors":"Masaki Tsuji MD, PhD, Jignesh K. Patel MD, PhD, Michelle M. Kittleson MD, PhD, David H. Chang MD, Evan P. Kransdorf MD, PhD, Andriana P. Nikolova MD, Lily K. Stern MD, Nayana Bhatnagar BS, Jon A. Kobashigawa MD","doi":"10.1016/j.healun.2024.09.029","DOIUrl":"10.1016/j.healun.2024.09.029","url":null,"abstract":"<div><h3>Background</h3><div>Microvascular dysfunction after heart transplantation leads to restrictive cardiac allograft physiology (RCP), which is classified as severe coronary allograft vasculopathy (CAV); however, the prognosis of RCP remains unclear. Therefore, in this study, we aimed to elucidate the prognosis of RCP in comparison with that of severe angiographic CAV.</div></div><div><h3>Methods</h3><div>We assessed 116 patients with severe CAV who underwent heart transplantation between 2004 and 2023. RCP was defined as symptomatic heart failure with restrictive hemodynamic values (mean right atrial pressure >12 mm Hg, pulmonary capillary wedge pressure >25 mm Hg, and cardiac index <2.0 liter/min/m<sup>2</sup>). The primary outcome was death or retransplantation.</div></div><div><h3>Results</h3><div>Of the 116 patients with severe CAV, 42 had RCP (RCP-CAV group) and 74 had severe angiographic CAV without RCP (Angio-CAV group). A significantly shorter time from heart transplantation to diagnosis and lower subsequent percutaneous catheter intervention after diagnosis were seen in the RCP-CAV group than in the Angio-CAV group (both <em>p</em> < 0.001). Freedom from death or retransplantation at 5 years was significantly worse in the RCP-CAV group compared to the Angio-CAV group (18.4% vs 35.4%, <em>p</em> = 0.001). In the Cox proportional hazard model, RCP was independently associated with an increased risk of death or retransplantation (hazard ratio 2.08, 95% confidence intervals 1.26-3.44, <em>p</em> = 0.004).</div></div><div><h3>Conclusions</h3><div>The prognosis of patients with RCP was significantly worse than that of patients with severe angiographic CAV. The early detection of microvascular dysfunction and retransplantation listing may improve the prognosis of patients with RCP.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 57-63"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381049","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 : 2025-01-01DOI: 10.1016/j.healun.2024.07.019
Ei Miyamoto MD, PhD , Daniel Vosoughi HBSc , Jinguo Wang PhD , Jamal Al-Refaee MSc , Gregory Berra MD , Tina Daigneault MSc , Allen Duong HBSc , Betty Joe BSc , Sajad Moshkelgosha PhD , Shaf Keshavjee MD, MSc , Kathryn Tinckam MD, MBA, MMSc , David Hwang MD, PhD , Andrzej Chruscinski MD, PhD , Stephen Juvet MD, PhD , Tereza Martinu MD, MHS
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 MD, PhD , Daniel Vosoughi HBSc , Jinguo Wang PhD , Jamal Al-Refaee MSc , Gregory Berra MD , Tina Daigneault MSc , Allen Duong HBSc , Betty Joe BSc , Sajad Moshkelgosha PhD , Shaf Keshavjee MD, MSc , Kathryn Tinckam MD, MBA, MMSc , David Hwang MD, PhD , Andrzej Chruscinski MD, PhD , Stephen Juvet MD, PhD , Tereza Martinu MD, MHS","doi":"10.1016/j.healun.2024.07.019","DOIUrl":"10.1016/j.healun.2024.07.019","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>n</em> = 4) or high non-HLA antibodies (<em>n</em> = 6) compared to those with low local antibodies (<em>n</em> = 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.</div></div><div><h3>Conclusions</h3><div>We show that DSA and non-HLA antibodies can be produced within activated B cell-rich lung allografts.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 105-117"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.healun.2024.07.003
Tatsuki Koyama PhD , Zhiguo Zhao MS , John R. Balmes MD , Carolyn S. Calfee MD, MAS , Michael A. Matthay MD , John P. Reilly MD, MSCE , Mary K. Porteous MD, MSCE , Joshua M. Diamond MD, MSCE , Jason D. Christie MD, MS , Edward Cantu MD, MSCE , Lorraine B. Ware MD , the Lung Transplant Outcomes Group
Background
Primary graft dysfunction (PGD) contributes substantially to both short- and long-term mortality after lung transplantation, but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation and chronic lung allograft dysfunction, but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients.
Methods
Using data from 1428 lung transplant recipients and their donors enrolled in the Lung Transplant Outcomes Group observational cohort study, we evaluated the association between the development of PGD and zip-code-based estimates of long-term exposure to 6 major air pollutants (ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particulate matter 2.5, and particulate matter 10) in both the lung donor and the lung recipient. Exposure estimates used daily EPA air pollutant monitoring data and were based on the geographic centroid of each subject’s residential zip code. Associations were tested in both univariable and multivariable models controlling for known PGD risk factors.
Results
We did not find strong associations between air pollutant exposures in either the donor or the recipient and PGD.
Conclusions
Exposure to ambient air pollutants, at the levels observed in this study, may not be sufficiently harmful to prime the donor lung or the recipient to develop PGD, particularly when considering the robust associations with other established PGD risk factors.
{"title":"Long-term air pollution exposure and the risk of primary graft dysfunction after lung transplantation","authors":"Tatsuki Koyama PhD , Zhiguo Zhao MS , John R. Balmes MD , Carolyn S. Calfee MD, MAS , Michael A. Matthay MD , John P. Reilly MD, MSCE , Mary K. Porteous MD, MSCE , Joshua M. Diamond MD, MSCE , Jason D. Christie MD, MS , Edward Cantu MD, MSCE , Lorraine B. Ware MD , the Lung Transplant Outcomes Group","doi":"10.1016/j.healun.2024.07.003","DOIUrl":"10.1016/j.healun.2024.07.003","url":null,"abstract":"<div><h3>Background</h3><div>Primary graft dysfunction (PGD) contributes substantially to both short- and long-term mortality after lung transplantation, but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation and chronic lung allograft dysfunction, but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients.</div></div><div><h3>Methods</h3><div>Using data from 1428 lung transplant recipients and their donors enrolled in the Lung Transplant Outcomes Group observational cohort study, we evaluated the association between the development of PGD and zip-code-based estimates of long-term exposure to 6 major air pollutants (ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particulate matter 2.5, and particulate matter 10) in both the lung donor and the lung recipient. Exposure estimates used daily EPA air pollutant monitoring data and were based on the geographic centroid of each subject’s residential zip code. Associations were tested in both univariable and multivariable models controlling for known PGD risk factors.</div></div><div><h3>Results</h3><div>We did not find strong associations between air pollutant exposures in either the donor or the recipient and PGD.</div></div><div><h3>Conclusions</h3><div>Exposure to ambient air pollutants, at the levels observed in this study, may not be sufficiently harmful to prime the donor lung or the recipient to develop PGD, particularly when considering the robust associations with other established PGD risk factors.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 64-74"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633728","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}
While structural socioeconomic inequity has been linked with inferior health outcomes, some have postulated reduced access to high-quality care to be the mediator. We assessed whether treatment at high-volume centers (HVC) would mitigate the adverse impact of area deprivation on heart transplantation (HT) outcomes.
Methods
All HT recipients ≥18 years were identified in the 2005-2022 Organ Procurement and Transplantation Network. Neighborhood socioeconomic deprivation was assessed using the previously validated Area Deprivation Index. Recipients with scores in the highest quintile were considered Most Deprived (others: Less Deprived). Hospitals in the highest quartile by cumulative center volume (≥21 transplants/year) were classified as HVC. The primary outcome was post-transplant survival.
Results
Of 38,022 HT recipients, 7,579 (20%) were considered Most Deprived. Following risk adjustment, Most Deprived demonstrated inferior survival at 3 (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.06-1.21) and 5 years following transplantation (HR 1.13, CI 1.07-1.20). Similarly, Most Deprived faced greater graft failure at 3 (HR 1.14, CI 1.06-1.22) and 5 years (HR 1.13, CI 1.07-1.20).
Evaluating patients transplanted at HVC, Most Deprived continued to face greater mortality at 3 (HR 1.10, CI 1.01-1.21) and 5 years (HR 1.10, CI 1.01-1.19). The interaction between Most Deprived status and care at HVC was not significant, such that transplantation at HVC did not ameliorate the survival disparity between Most and Less Deprived.
Conclusions
Area socioeconomic disadvantage is independently associated with inferior survival. Transplantation at HVC did not eliminate this inequity. Future efforts are needed to increase engagement with longitudinal follow-up care and address systemic root causes to improve outcomes.
{"title":"Hospital volume does not mitigate the impact of area socioeconomic deprivation on heart transplantation outcomes","authors":"Sara Sakowitz MS, MPH , Syed Shahyan Bakhtiyar MD, MBE , Saad Mallick MD , Amulya Vadlakonda BS , Nikhil Chervu MD , Richard Shemin MD , Peyman Benharash MD, MS","doi":"10.1016/j.healun.2024.08.012","DOIUrl":"10.1016/j.healun.2024.08.012","url":null,"abstract":"<div><h3>Background</h3><div>While structural socioeconomic inequity has been linked with inferior health outcomes, some have postulated reduced access to high-quality care to be the mediator. We assessed whether treatment at high-volume centers (HVC) would mitigate the adverse impact of area deprivation on heart transplantation (HT) outcomes.</div></div><div><h3>Methods</h3><div>All HT recipients ≥18 years were identified in the 2005-2022 Organ Procurement and Transplantation Network. Neighborhood socioeconomic deprivation was assessed using the previously validated Area Deprivation Index. Recipients with scores in the highest quintile were considered <em>Most Deprived</em> (others: <em>Less Deprived</em>). Hospitals in the highest quartile by cumulative center volume (≥21 transplants/year) were classified as HVC. The primary outcome was post-transplant survival.</div></div><div><h3>Results</h3><div>Of 38,022 HT recipients, 7,579 (20%) were considered <em>Most Deprived</em>. Following risk adjustment, <em>Most Deprived</em> demonstrated inferior survival at 3 (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.06-1.21) and 5 years following transplantation (HR 1.13, CI 1.07-1.20). Similarly, <em>Most Deprived</em> faced greater graft failure at 3 (HR 1.14, CI 1.06-1.22) and 5 years (HR 1.13, CI 1.07-1.20).</div><div>Evaluating patients transplanted at HVC, <em>Most Deprived</em> continued to face greater mortality at 3 (HR 1.10, CI 1.01-1.21) and 5 years (HR 1.10, CI 1.01-1.19). The interaction between <em>Most Deprived</em> status and care at HVC was not significant, such that transplantation at HVC did not ameliorate the survival disparity between <em>Most</em> and <em>Less Deprived</em>.</div></div><div><h3>Conclusions</h3><div>Area socioeconomic disadvantage is independently associated with inferior survival. Transplantation at HVC did not eliminate this inequity. Future efforts are needed to increase engagement with longitudinal follow-up care and address systemic root causes to improve outcomes.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 33-43"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348136","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 : 2025-01-01DOI: 10.1016/j.healun.2024.08.001
Erik J. Henricksen PharmD , Brian Wayda MD , Jeffrey J. Teuteberg MD , Helen Luikart , Joyce Njoroge MD , Brandon A. Guenthart MD , Kiran K. Khush MD, MAS
Background
Patients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies.
Methods
This was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant.
Results
Recipients ≥70 had a 1-year survival of 87.5%, compared to 91.1% for <60%, and 88.4% for 60–69 years (p < 0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at 5 years for <60 years (80.6%), compared to 60–69 years (78.2%) and ≥70 years (77.1%). When comparing 60–69 years to ≥70 years by this same metric, there was significant difference (p = 0.12). One year survival for those ≥70 years has improved from 2000–2009 (80.7%) to 88.5% since October 2018 (p < 0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (p < 0.001).
Conclusion
Overall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.
{"title":"Trends in heart transplant outcomes for patients over the age of 70 years in the United States: An analysis of the scientific registry of transplant recipients database","authors":"Erik J. Henricksen PharmD , Brian Wayda MD , Jeffrey J. Teuteberg MD , Helen Luikart , Joyce Njoroge MD , Brandon A. Guenthart MD , Kiran K. Khush MD, MAS","doi":"10.1016/j.healun.2024.08.001","DOIUrl":"10.1016/j.healun.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Patients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies.</div></div><div><h3>Methods</h3><div>This was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant.</div></div><div><h3>Results</h3><div>Recipients ≥70 had a 1-year survival of 87.5%, compared to 91.1% for <60%, and 88.4% for 60–69 years (<em>p</em> < 0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at 5 years for <60 years (80.6%), compared to 60–69 years (78.2%) and ≥70 years (77.1%). When comparing 60–69 years to ≥70 years by this same metric, there was significant difference (<em>p</em> = 0.12). One year survival for those ≥70 years has improved from 2000–2009 (80.7%) to 88.5% since October 2018 (<em>p</em> < 0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (<em>p</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>Overall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.</div></div>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":"44 1","pages":"Pages 75-81"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912959","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 : 2024-12-30DOI: 10.1016/j.healun.2024.12.019
Sascha Ott, Lorenzo Germinario, Lukas M Müller-Wirtz, Gaik Nersesian, Felix Hennig, Matthias Hommel, Kurt Ruetzler, Christian Stoppe, Christoph Vandenbriele, Felix Schoenrath, Christoph T Starck, Benjamin O'Brien, Volkmar Falk, Evgenij Potapov, Pia Lanmüller
Background: Temporary mechanical circulatory support (tMCS) has become a standard treatment in cardiogenic shock but is associated with high complication rates. This study analyzes common complications associated with modern tMCS devices and their impact on mortality depending on the tMCS approach.
Methods: We conducted a retrospective single-center analysis of patients with all-cause cardiogenic shock treated with veno-arterial extracorporeal life support, microaxial flow pump, and a combination of both (ECMELLA). The primary outcome was the impact of cumulative complications on mortality, evaluated separately for nonsurgical (non-PCCS) and cardiac surgical (PCCS) patients. Secondary outcomes included the impact of complications on mortality stratified by tMCS type and rates of bleeding, the need for renal replacement therapy (RRT), hemolysis, neurological complications, bloodstream infections, and ischemic limb complications.
Results: We included 493 patients, totaling 4,881 days on tMCS support. Non-PCCS patients with 1 complication had a hazard ratio (HR) of 1.92 (95% confidence interval [CI]: 1.22, 3.00, p = 0.004) for mortality and 3.73 (95% CI: 2.48, 5.60, p < 0.001) for 2 or more complications compared to those without complications. In PCCS patients, 1 complication was associated with an HR of 2.22 (95% CI: 1.29, 3.81, p = 0.004) and 3.44 (95% CI: 2.04, 5.78, p < 0.001) for 2 or more complications. The most common complications in both non-PCCS and PCCS patients were bleeding (33% and 60%), need for RRT (31% and 43%), and severe hemolysis (26% and 35%).
Conclusion: Complications among tMCS-treated patients are common and clearly associated with an elevated mortality risk.
背景：临时机械循环支持装置（tMCS）已成为心源性休克的标准治疗选择，但其并发症发生率较高。本研究分析了与现代tMCS装置相关的常见并发症及其对tMCS入路的死亡率影响。方法：我们对接受静脉-动脉体外生命支持、微轴流泵及两者联合（ECMELLA）治疗的全因心源性休克患者进行了回顾性单中心分析。主要结局是并发症累积数量对死亡率的影响，分别对非手术（非PCCS）和心脏手术（PCCS）患者进行评估。次要结局包括并发症对死亡率的影响，按tMCS类型和出血率分层，需要肾脏替代治疗，溶血，神经系统并发症，血流感染和缺血性肢体并发症。结果：我们纳入了493例患者，总共4881天的tMCS支持。与无并发症的患者相比，有一种并发症的非pccs患者的死亡率风险比（HR）为1.92 (95%CI: 1.22, 3.00, p = 0.004)，两种或两种以上并发症的死亡率风险比（HR）为3.73 （95%CI: 2.48, 5.60, p < 0.001）。在pccs患者中，一种并发症与两种或两种以上并发症相关的HR为2.22 （95%CI: 1.29, 3.81, p = 0.004）和3.44 (95%CI: 2.04, 5.78), p < 0.001)。非pccs和pccs患者最常见的并发症是出血（33%和60%），需要肾脏替代治疗（31%和43%），以及严重溶血（26%和35%）。结论：tmcs治疗患者的并发症很常见，且明显与死亡风险升高相关。
{"title":"Impact of complications on survival outcomes in different temporary mechanical circulatory support techniques: A large retrospective cohort study of cardiac surgical and nonsurgical patients.","authors":"Sascha Ott, Lorenzo Germinario, Lukas M Müller-Wirtz, Gaik Nersesian, Felix Hennig, Matthias Hommel, Kurt Ruetzler, Christian Stoppe, Christoph Vandenbriele, Felix Schoenrath, Christoph T Starck, Benjamin O'Brien, Volkmar Falk, Evgenij Potapov, Pia Lanmüller","doi":"10.1016/j.healun.2024.12.019","DOIUrl":"10.1016/j.healun.2024.12.019","url":null,"abstract":"<p><strong>Background: </strong>Temporary mechanical circulatory support (tMCS) has become a standard treatment in cardiogenic shock but is associated with high complication rates. This study analyzes common complications associated with modern tMCS devices and their impact on mortality depending on the tMCS approach.</p><p><strong>Methods: </strong>We conducted a retrospective single-center analysis of patients with all-cause cardiogenic shock treated with veno-arterial extracorporeal life support, microaxial flow pump, and a combination of both (ECMELLA). The primary outcome was the impact of cumulative complications on mortality, evaluated separately for nonsurgical (non-PCCS) and cardiac surgical (PCCS) patients. Secondary outcomes included the impact of complications on mortality stratified by tMCS type and rates of bleeding, the need for renal replacement therapy (RRT), hemolysis, neurological complications, bloodstream infections, and ischemic limb complications.</p><p><strong>Results: </strong>We included 493 patients, totaling 4,881 days on tMCS support. Non-PCCS patients with 1 complication had a hazard ratio (HR) of 1.92 (95% confidence interval [CI]: 1.22, 3.00, p = 0.004) for mortality and 3.73 (95% CI: 2.48, 5.60, p < 0.001) for 2 or more complications compared to those without complications. In PCCS patients, 1 complication was associated with an HR of 2.22 (95% CI: 1.29, 3.81, p = 0.004) and 3.44 (95% CI: 2.04, 5.78, p < 0.001) for 2 or more complications. The most common complications in both non-PCCS and PCCS patients were bleeding (33% and 60%), need for RRT (31% and 43%), and severe hemolysis (26% and 35%).</p><p><strong>Conclusion: </strong>Complications among tMCS-treated patients are common and clearly associated with an elevated mortality risk.</p>","PeriodicalId":15900,"journal":{"name":"Journal of Heart and Lung Transplantation","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914437","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号