Journal: J Heart Lung Transplant

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<div><h4>Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.</h4><i>Kraus MJ, Smits JM, Meyer AL, Strelniece A, ... Frey N, Kreusser MM</i><br /><b>Background</b><br />When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival.<br /><b>Methods</b><br />Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable.<br /><b>Results</b><br />Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model.<br /><b>Conclusions</b><br />HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 12 Jan 2023; epub ahead of print</small></div>
Kraus MJ, Smits JM, Meyer AL, Strelniece A, ... Frey N, Kreusser MM
J Heart Lung Transplant: 12 Jan 2023; epub ahead of print | PMID: 36710093
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<div><h4>Mitochondrial transplant after ischemia reperfusion promotes cellular salvage and improves lung function during ex-vivo lung perfusion.</h4><i>Cloer CM, Givens CS, Buie LK, Rochelle LK, ... Hogan SS, Petersen TH</i><br /><b>Background</b><br />In lung transplantation, ischemia-reperfusion injury associated with mitochondrial damage can lead to graft rejection. Intact, exogenous mitochondria provide a unique treatment option to salvage damaged cells within lung tissue.<br /><b>Methods</b><br />We developed a novel method to freeze and store allogeneic mitochondria isolated from porcine heart tissue. Stored mitochondria were injected into a model of induced ischemia-reperfusion injury using porcine ex-vivo lung perfusion. Treatment benefits to immune modulation, antioxidant defense, and cellular salvage were evaluated. These findings were corroborated in human lungs undergoing ex-vivo lung perfusion. Lung tissue homogenate and primary lung endothelial cells were then used to address underlying mechanisms.<br /><b>Results</b><br />Following cold ischemia, mitochondrial transplant reduced lung pulmonary vascular resistance and tissue pro-inflammatory signaling and cytokine secretion. Further, exogenous mitochondria reduced reactive oxygen species by-products and promoted glutathione synthesis, thereby salvaging cell viability. These results were confirmed in a human model of ex-vivo lung perfusion wherein transplanted mitochondria decreased tissue oxidative and inflammatory signaling, improving lung function. We demonstrate that transplanted mitochondria induce autophagy and suggest that bolstered autophagy may act upstream of the anti-inflammatory and antioxidant benefits. Importantly, chemical inhibitors of the MEK autophagy pathway blunted the favorable effects of mitochondrial transplant.<br /><b>Conclusions</b><br />These data provide direct evidence that mitochondrial transplant improves cellular health and lung function when administered during ex-vivo lung perfusion and suggest the mechanism of action may be through promotion of cellular autophagy. Data herein contribute new insights into the therapeutic potential of mitochondrial transplant to abate ischemia-reperfusion injury during lung transplant, and thus reduce graft rejection.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 11 Jan 2023; epub ahead of print</small></div>
Cloer CM, Givens CS, Buie LK, Rochelle LK, ... Hogan SS, Petersen TH
J Heart Lung Transplant: 11 Jan 2023; epub ahead of print | PMID: 36707296
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<div><h4>Airway oscillometry parameters in baseline lung allograft dysfunction: Associations from a multicenter study.</h4><i>Darley DR, Nilsen K, Vazirani J, Borg BM, ... Plit ML, Tonga KO</i><br /><b>Background</b><br />Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD.<br /><b>Objectives</b><br />This study aims to describe and measure the association between airway oscillometry parameters [Reactance (X<sub>rs5</sub>, Ax), Resistance (R<sub>rs5</sub>, R<sub>rs5-19</sub>)] (1) stable LTx recipients, comparing those with normal spirometry and those with BLAD; and (2) in recipients with chronic lung allograft dysfunction (CLAD), comparing those with normal baseline spirometry and those with BLAD.<br /><b>Methods</b><br />A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD.<br /><b>Results</b><br />A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower X<sub>rs5</sub> Z-Score (aOR 0.50 95% CI 0.37-0.76, p = 0.001) was independently associated with BLAD. CLAD was present in 104 (35.0%) recipients. Among recipients with CLAD, lower X<sub>rs5</sub> Z-Score (aOR 0.73 95% CI 0.56-0.95, p = 0.02) was associated with BLAD.<br /><b>Conclusions</b><br />Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between X<sub>rs5</sub> and BLAD, in both stable recipients and those with CLAD suggests that respiratory mechanics, in particular abnormal elastance, is an important physiologic feature. Further longitudinal studies are needed to understand the trajectory of oscillometry parameters in relation to allograft outcomes.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Jan 2023; epub ahead of print</small></div>
Darley DR, Nilsen K, Vazirani J, Borg BM, ... Plit ML, Tonga KO
J Heart Lung Transplant: 06 Jan 2023; epub ahead of print | PMID: 36681528
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<div><h4>Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfunction.</h4><i>Kransdorf EP, Rushakoff JA, Han J, Benck L, ... Khush KK, Patel JK</i><br /><b>Background</b><br />Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT.<br /><b>Methods</b><br />A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation.<br /><b>Results</b><br />Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO<sub>2</sub>), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO<sub>2</sub> ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort.<br /><b>Conclusions</b><br />Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Jan 2023; epub ahead of print</small></div>
Kransdorf EP, Rushakoff JA, Han J, Benck L, ... Khush KK, Patel JK
J Heart Lung Transplant: 06 Jan 2023; epub ahead of print | PMID: 36682894
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<div><h4>Triaging donor lungs based on a microaspiration signature that predicts adverse recipient outcome.</h4><i>Ramendra R, Sage AT, Yeung J, Fernandez-Castillo JC, ... Keshavjee S, Martinu T</i><br /><b>Background</b><br />Aspiration is a relative contraindication to accepting donor lungs for transplant and is currently assessed by visual inspection of the airways via bronchoscopy. However, this method is limited as it does not assess for microaspiration. Bile acids measured in large airway bronchial wash (LABW) samples have been shown to be a marker of aspiration in lung transplant recipients. Herein, we investigate the utility of measuring total bile acids (TBA) in donor LABW to predict performance of donor lungs and recipient outcomes.<br /><b>Methods</b><br />TBA was measured in 605 consecutive lung donors at the Toronto Lung Transplant Program. TBA levels were compared in donor lungs deemed unsuitable for transplant, requiring further assessment on ex vivo lung perfusion (EVLP), and those suitable for direct transplantation using Mann-Whitney-U tests. Relationships between LABW TBA concentrations and recipient outcomes were evaluated using multivariable Cox-PH models and log-rank analysis.<br /><b>Results</b><br />Donor TBA was highest in lungs deemed unsuitable for transplant and correlated with clinical assessment of aspiration. LABW TBA concentration correlated with calcium, decreased pH, and increased pro-inflammatory mediators in EVLP perfusate. TBA cut-off of 1245 nM was able to differentiate donor lungs directly declined from those suitable for direct transplantation with a 91% specificity (AUROC: 73%). High donor TBA status was associated with the increased rate of primary graft dysfunction, longer time to extubation, and shorter time to chronic lung allograft dysfunction.<br /><b>Conclusions</b><br />In a large retrospective cohort, we observed that donor LABW TBA was associated with suitability of donor lungs for transplant, performance of the organ on EVLP, and adverse recipient outcomes.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Jan 2023; epub ahead of print</small></div>
Ramendra R, Sage AT, Yeung J, Fernandez-Castillo JC, ... Keshavjee S, Martinu T
J Heart Lung Transplant: 06 Jan 2023; epub ahead of print | PMID: 36710092
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<div><h4>Long term employment following heart transplantation in the United States.</h4><i>Cramer CL, Marsh K, Krebs ED, Mehaffey JH, ... Teman NR, Yarboro LT</i><br /><b>Background</b><br />Employment is an important metric of post-transplant functional status and the quality of life yet remains poorly described after heart transplant. We sought to characterize the prevalence of employment following heart transplantation and identify patients at risk for post-transplant unemployment.<br /><b>Methods</b><br />Adults undergoing single-organ heart transplantation (2007-2016) were evaluated using the UNOS database. Univariable analysis was performed after stratifying by employment status at 1-year post-transplant. Fine-Gray competing risk regression was used for risk adjustment. Cox regression evaluated employment status at 1 year with mortality.<br /><b>Results</b><br />Of 10,132 heart transplant recipients who survived to 1 year and had follow-up, 22.0% were employed 1-year post-transplant. Employment rate of survivors increased to 32.9% by year 2. Employed individuals were more likely white (70.8% vs 60.4%, p < 0.01), male (79.6% vs 70.7% p < 0.01), held a job at listing/transplant (37.6% vs 7.6%, p < 0.01), and had private insurance (79.1% vs 49.5%, p < 0.01). Several characteristics were independently associated with employment including age, employment status at time of listing or transplant, race and ethnicity, gender, insurance status, education, and postoperative complications. Of 1,657 (14.0%) patients employed pretransplant, 58% were working at 1-year. Employment at 1year was independently associated with mortality with employed individuals having a 26% decreased risk of mortality.<br /><b>Conclusion</b><br />Over 20% of heart transplant patients were employed at 1 year and over 30% at 2 years, while 58% of those working pretransplant had returned to work by 1-year. While the major predictor of post-transplant employment is preoperative employment status, our study highlights the impact of social determinants of health.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Jan 2023; epub ahead of print</small></div>
Cramer CL, Marsh K, Krebs ED, Mehaffey JH, ... Teman NR, Yarboro LT
J Heart Lung Transplant: 06 Jan 2023; epub ahead of print | PMID: 36669942
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<div><h4>Real-time transcription polymerase chain reaction cycle threshold values as criteria for utilization of incidental COVID-19 positive lung donors.</h4><i>Hwang J, Yuen A, Rhoades J, Barnes D, ... Zaffiri L, Rampolla R</i><br /><AbstractText>Shortage of organ donors is an ongoing limiting factor in lung transplantation (LT). Despite increasing prevalence of asymptomatic COVID-19 infection, positive COVID-19 testing from a potential donor remains a contraindication at many LT centers. In this report, we present the outcomes of LT utilizing an algorithm based on donor clinical presentation, and COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) with cycle threshold (Ct) values evaluation. The Ct value threshold for organ acceptance was >35. A total of 8 COVID-positive donors were included. No donor-to-recipient transmissions of COVID-19 were observed. Short-term outcomes were comparable to those reported in pre-COVID literature. Survival-to-date is 100% with median POD of 161 days. Our findings support the safety and efficacy of utilizing our algorithm including Ct value threshold for selection of donors with incidental COVID-19 positive testing.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 28 Dec 2022; epub ahead of print</small></div>
Hwang J, Yuen A, Rhoades J, Barnes D, ... Zaffiri L, Rampolla R
J Heart Lung Transplant: 28 Dec 2022; epub ahead of print | PMID: 36624019
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<div><h4>Racial disparity exists in the utilization and post-transplant survival benefit of ventricular assist device support in children.</h4><i>Greenberg JW, Bryant R, Villa C, Fields K, ... Zafar F, Morales DLS</i><br /><b>Purpose</b><br />Children of minority race and ethnicity experience inferior outcomes postheart transplantation (HTx). Studies have associated ventricular assist device (VAD) bridge-to-transplant (BTT) with similar-to-superior post-transplant-survival (PTS) compared to no mechanical circulatory support. It is unclear whether racial and ethnic discrepancies exist in VAD utilization and outcomes.<br /><b>Methods</b><br />The United Network for Organ Sharing (UNOS) database was used to identify 6,121 children (<18 years) listed for HTx between 2006 and 2021: black (B-22% of cohort), Hispanic (H-21%), and white (W-57%). VAD utilization, outcomes, and PTS were compared between race/ethnicity groups. Multivariable Cox proportional analyses were used to study the association of race and ethnicity on PTS with VAD BTT, using backward selection for covariates.<br /><b>Results</b><br />Black children were most ill at listing, with greater proportions of UNOS status 1A/1 (p < 0.001 vs H & W), severe functional limitation (p < 0.001 vs H & W), and greater inotrope requirements (p < 0.05 vs H). Non-white children had higher proportions of public insurance. VAD utilization at listing was: B-11%, H-8%, W-8% (p = 0.001 for B vs H & W). VAD at transplant was: B-24%, H-21%, W-19% (p = 0.001 for B vs H). At transplant, all VAD patients had comparable clinical status (functional limitation, renal/hepatic dysfunction, inotropes, mechanical ventilation; all p > 0.05 between groups). Following VAD, hospital outcomes and one-year PTS were equivalent but long-term PTS was significantly worse among non-whites-(p < 0.01 for W vs B & H). On multivariable analysis, black race independently predicted mortality (hazard ratio 1.67 [95% confidence interval 1.22-2.28]) while white race was protective (0.54 [0.40-0.74]).<br /><b>Conclusions</b><br />Pediatric VAD use is, seemingly, equitable; the most ill patients receive the most VADs. Despite similar pretransplant and early post-transplant benefits, non-white children experience inferior overall PTS after VAD BTT.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 28 Dec 2022; epub ahead of print</small></div>
Greenberg JW, Bryant R, Villa C, Fields K, ... Zafar F, Morales DLS
J Heart Lung Transplant: 28 Dec 2022; epub ahead of print | PMID: 36710094
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<div><h4>Detection and management of HLA sensitization in candidates for adult heart transplantation.</h4><i>DeFilippis EM, Kransdorf EP, Jaiswal A, Zhang X, ... Baran DA, Kittleson MM</i><br /><AbstractText>Heart transplantation (HT) remains the preferred therapy for patients with advanced heart failure. However, for sensitized HT candidates who have antibodies to human leukocyte antigens , finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting HT has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. This State-of-the-Art review discusses the assessment of human leukocyte antigens antibodies, potential desensitization strategies including mechanisms of action and specific protocols, the approach to a potential donor including the use of complement-dependent cytotoxicity, flow cytometry, and virtual crossmatches, and peritransplant induction management.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Dec 2022; epub ahead of print</small></div>
DeFilippis EM, Kransdorf EP, Jaiswal A, Zhang X, ... Baran DA, Kittleson MM
J Heart Lung Transplant: 27 Dec 2022; epub ahead of print | PMID: 36631340
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<div><h4>Primary graft dysfunction grade 3 following pediatric lung transplantation is associated with chronic lung allograft dysfunction.</h4><i>Wong W, Cheng PC, Josephson MB, Maeda K, ... Yehya N, Himebauch AS</i><br /><b>Background</b><br />Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), in adults. However, PGD associations with long-term outcomes following pediatric lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48- or 72-hours would be associated with shorter CLAD-free survival following pediatric lung transplantation.<br /><b>Methods</b><br />This was a single center retrospective cohort study of patients ≤ 21 years of age who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of follow-up. PGD and CLAD were defined by published criteria. We evaluated the association of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses.<br /><b>Results</b><br />Fifty-one patients were included (median age 12.7 years; 51% female). The most common transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%). Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis, PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI 1.01-4.37, p=0.047). This association remained when adjusting individually for multiple potential confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20).<br /><b>Conclusions</b><br />PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with shorter CLAD-free survival. Sex may be a modifier of this association.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Dec 2022; epub ahead of print</small></div>
Wong W, Cheng PC, Josephson MB, Maeda K, ... Yehya N, Himebauch AS
J Heart Lung Transplant: 27 Dec 2022; epub ahead of print | PMID: 36639317
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<div><h4>It\'s not only the pump: Assessment of human factors of wearable components and user experience of patients with left ventricular assist devices.</h4><i>Schlöglhofer T, Grausenburger AS, Widhalm G, Haberl L, ... Zimpfer D, Schima H</i><br /><b>Background</b><br />Despite design improvements in left ventricular assist devices (LVADs) over the past decade, limitations of external, wearable VAD components affect patient quality of life and safety. The aim of this study was to describe both user experience and human factor issues of 2 contemporary LVADs.<br /><b>Methods</b><br />This single-center, cross-sectional study included LVAD outpatients who were at least 3 months after implantation. Before developing the 16-item survey, a systematic literature review and 2-round Delphi method involving 9 VAD clinicians were used to select items in 6 domains: power supply, emergency situations, wearability, mobility, and freedom to travel, user modifications, lifestyle, and home adaptations.<br /><b>Results</b><br />Fifty-eight patients (61.6 ± 11.6 years, 13.8% female, HeartMate 3 (HM3)/HVAD: n = 39/19) completed the one-time survey after median of 853 days on device: 10.3% reported problems changing power supply, 12.7% unintentional driveline disconnection (HM3: 5.6% vs HVAD: 26.3%, p = 0.041). Against the recommendation 74.1% sleep with battery-support (HM3: 88.9% vs HVAD: 44.4%, p = 0.001). About 65.3% criticized the carry bag weight/size (HM3: 71.4% vs HVAD: 50.0%, p = 0.035), thus 24.1% wear an own carrying-system, 42.1% modified their wearables, 38.9% their clothing, and 65.3% their home to cope with life on LVAD support. Mobility is reduced due to limited wearability: 18.9% went abroad (only 3.7% by plane) and 40.0% use less public transport than before implantation (the older the less: r = -0.37, p = 0.013).<br /><b>Conclusions</b><br />HVAD and HM3 wearables still show a variety of human factors issues and potential for improved user experience. User-centered design and incorporation of patient feedback may increase user satisfaction, and patient safety.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Dec 2022; epub ahead of print</small></div>
Schlöglhofer T, Grausenburger AS, Widhalm G, Haberl L, ... Zimpfer D, Schima H
J Heart Lung Transplant: 27 Dec 2022; epub ahead of print | PMID: 36682893
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<div><h4>Complications related to the access site after transaxillary implantation of a microaxial left ventricular assist device.</h4><i>Lewin D, Nersesian G, Lanmüller P, Schoenrath F, ... Potapov EV, Ott S</i><br /><b>Background</b><br />Impella 5.0 and 5.5 (summarized as Impella 5+) are microaxial, catheter-based left ventricular assist devices (LVAD) that are implanted via a vascular graft sutured to the axillary artery and provide blood flow of up to 5.5 liter/min. This study aims to investigate the incidence of long-term complications following circulatory support with Impella 5+.<br /><b>Methods</b><br />A single-center retrospective analysis of 203 consecutive adult patients treated between January 2017 and September 2021 with a surgically implanted Impella 5.0 or 5.5 via a vascular graft sutured to the axillary artery.<br /><b>Results</b><br />The median Impella support duration was 8 days. Of 203 patients, 78 (38.4%) died while on temporary mechanical circulatory support. Fifty-five (27.1%) were successfully weaned from Impella 5+ and 70 (34.5%) were bridged to a durable LVAD with a median follow-up time of 232 (IQR 68.5, 597) days after Impella 5+ explantation. In 119 of these patients, the Impella was explanted and the vascular graft was shortened, ligated, and pushed under the pectoralis muscle; in 6 patients early graft infection prompted complete graft removal during explantation. In addition, 13 patients (10.9%) developed a late-onset graft infection after a median of 86 days, requiring complete (n = 10) or partial (n = 2) explantation of the retained graft. In 1 patient, the graft infection was successfully treated by conservative therapy. Our analysis identified no specific risk factors for graft infections. Of the 203 patients, 5 (2.5%) developed a brachial plexus injury resulting in neurological dysfunction.<br /><b>Conclusions</b><br />In 10.9% of patients, retaining the vascular graft was complicated by a late graft infection. Complete explantation of the graft prosthesis may decrease the infection rate, but may in turn increase the risk of brachial plexus injury. On the other hand, this method offers the possibility of bedside explantation.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 27 Dec 2022; epub ahead of print</small></div>
Lewin D, Nersesian G, Lanmüller P, Schoenrath F, ... Potapov EV, Ott S
J Heart Lung Transplant: 27 Dec 2022; epub ahead of print | PMID: 36653272
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<div><h4>Resolution of post-lung transplant ischemia-reperfusion injury is modulated via Resolvin D1-FPR2 and Maresin 1-LGR6 signaling.</h4><i>Leroy V, Cai J, Tu Z, McQuiston A, ... Upchurch GR, Sharma AK</i><br /><b>Background</b><br />Dysregulation of inflammation-resolution pathways leads to postlung transplant (LTx) ischemia-reperfusion (IR) injury and allograft dysfunction. Our hypothesis is that combined treatment with specialized pro-resolving lipid mediators, that is, Resolvin D1 (RvD1) and Maresin-1 (MaR1), enhances inflammation-resolution of lung IR injury.<br /><b>Methods</b><br />Expression of RvD1 and MaR1 was analyzed in bronchoalveolar lavage (BAL) fluid of patients on days 0, 1, and 7 post-LTx. Lung IR injury was evaluated in C57BL/6 (WT), FPR2<sup>-/-</sup>, and LGR6 siRNA treated mice using a hilar-ligation model with or without administration with RvD1 and/or MaR1. A donation after circulatory death and murine orthotopic lung transplantation model was used to evaluate the protection by RvD1 and MaR1 against lung IR injury. In vitro studies analyzed alveolar macrophages and type II epithelial cell activation after treatment with RvD1 or MaR1.<br /><b>Results</b><br />RvD1 and MaR1 expressions in BAL from post-LTx patients was significantly increased on day 7 compared to days 0 and 1. Concomitant RvD1 and MaR1 treatment significantly mitigated early pulmonary inflammation and lung IR injury in WT mice, which was regulated via FPR2 and LGR6 receptors. In the murine orthotopic donation after cardiac death LTx model, RvD1 and MaR1 treatments significantly attenuated lung IR injury and increased PaO<sub>2</sub> levels compared to saline-treated controls. Mechanistically, RvD1/FPR2 signaling on alveolar macrophages attenuated HMGB1 and TNF-α secretion and upregulated uptake of macrophage-dependent apoptotic neutrophils (efferocytosis), whereas MaR1/LGR6 signaling mitigated CXCL1 secretion by epithelial cells.<br /><b>Conclusions</b><br />Bioactive proresolving lipid mediator-dependent signaling that is, RvD1/FPR2 and MaR1/LGR6- offers a novel therapeutic strategy in post-LTx injury.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 21 Dec 2022; epub ahead of print</small></div>
Leroy V, Cai J, Tu Z, McQuiston A, ... Upchurch GR, Sharma AK
J Heart Lung Transplant: 21 Dec 2022; epub ahead of print | PMID: 36628837
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<div><h4>Vascular pathobiology of pulmonary hypertension.</h4><i>Gallardo-Vara E, Ntokou A, Dave JM, Jovin DG, Saddouk FZ, Greif DM</i><br /><AbstractText>Pulmonary hypertension (PH), increased blood pressure in the pulmonary arteries, is a morbid and lethal disease. PH is classified into several groups based on etiology, but pathological remodeling of the pulmonary vasculature is a common feature. Endothelial cell dysfunction and excess smooth muscle cell proliferation and migration are central to the vascular pathogenesis. In addition, other cell types, including fibroblasts, pericytes, inflammatory cells and platelets contribute as well. Herein, we briefly note most of the main cell types active in PH and for each cell type, highlight select signaling pathway(s) highly implicated in that cell type in this disease. Among others, the role of hypoxia-inducible factors, growth factors (e.g., vascular endothelial growth factor, platelet-derived growth factor, transforming growth factor-β and bone morphogenetic protein), vasoactive molecules, NOTCH3, Kruppel-like factor 4 and forkhead box proteins are discussed. Additionally, deregulated processes of endothelial-to-mesenchymal transition, extracellular matrix remodeling and intercellular crosstalk are noted. This brief review touches upon select critical facets of PH pathobiology and aims to incite further investigation that will result in discoveries with much-needed clinical impact for this devastating disease.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 21 Dec 2022; epub ahead of print</small></div>
Gallardo-Vara E, Ntokou A, Dave JM, Jovin DG, Saddouk FZ, Greif DM
J Heart Lung Transplant: 21 Dec 2022; epub ahead of print | PMID: 36604291
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<div><h4>Assessment and management of allosensitization following heart transplant in adults.</h4><i>Jaiswal A, Bell J, DeFilippis EM, Kransdorf EP, ... Kittleson MM, Baran DA</i><br /><AbstractText>Immunological injury to the allograft, specifically by antibodies to de novo donor specific human leukocyte antigen (dnDSA) and antibody mediated injury and rejection are the major limitations to graft survival after heart transplantation (HT). As such, our approach to allosensitization remains limited by the inability of contemporaneous immunoassays to unravel pathogenic potential of dnDSA. Additionally, the role of dnDSA is continuously evaluated with emerging methods to detect rejection. Moreover, the timing and frequency of dnDSA monitoring for early detection and risk mitigation as well as management of dnDSA remain challenging. A strategic approach to dnDSA employs diagnostic assays to determine relevant antibodies in conjunction with clinical presentation and injury/rejection of allograft to tailor therapeutics. In this review, we aim to outline contemporary knowledge involving detection, monitoring and management of dnDSA after HT. Subsequently, we propose a diagnostic and therapeutic approach that may mitigate morbidity and mortality while balancing adverse reactions from pharmacotherapy.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 20 Dec 2022; epub ahead of print</small></div>
Jaiswal A, Bell J, DeFilippis EM, Kransdorf EP, ... Kittleson MM, Baran DA
J Heart Lung Transplant: 20 Dec 2022; epub ahead of print | PMID: 36702686
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<div><h4>Oral and gut microbiome alterations in heart failure: Epidemiology, pathogenesis and response to advanced heart failure therapies.</h4><i>Yuzefpolskaya M, Bohn B, Ladanyi A, Khoruts A, Colombo PC, Demmer RT</i><br /><AbstractText>Despite significant advances in therapies, heart failure (HF) remains a progressive disease that, once advanced, is associated with significant death and disability. Cardiac replacement therapies with left ventricular assist device (LVAD) and heart transplantation (HT) are the only treatment options for advanced HF, while lifesaving they can also be lifespan limiting due to the associated complications. Systemic inflammation is mechanistically important in HF pathophysiology and progression. However, directly targeting inflammation in HF has not been beneficial thus far. These failed attempts at therapeutics might be related to our limited understanding of the factors that cause inflammation in HF, and, therefore, to our inability to investigate these triggers in interventional studies. Observational studies have consistently demonstrated associations between alterations in the digestive (gut and oral) microbiome, inflammation and HF risk and progression. Additionally, recent data indicate that these microbial perturbations persist following LVAD and HT, along with residual inflammation and oxidative stress. Furthermore, there is rising recognition of the critical contribution of the microbiome to the metabolism of immunosuppressive drugs after HT. Cumulatively, these findings might posit a mechanistic link between microbiome alterations, systemic inflammation, and adverse outcomes in HF patients before and after cardiac replacement therapies. This review (1) provides an update on available data linking changes in digestive tract microbiota, inflammation, and oxidative stress, to HF pathogenesis and progression; (2) describes evolution of these relationships following LVAD and HT; and (3) outlines present and future intervention strategies that can manipulate the microbiome and possibly modify HF disease trajectory.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 15 Dec 2022; epub ahead of print</small></div>
Yuzefpolskaya M, Bohn B, Ladanyi A, Khoruts A, Colombo PC, Demmer RT
J Heart Lung Transplant: 15 Dec 2022; epub ahead of print | PMID: 36586790
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<div><h4>Outcome and growth of lobar graft after pediatric living-donor lobar lung transplantation.</h4><i>Tanaka S, Nakajima D, Sakamoto R, Oguma T, ... Ikeda T, Date H</i><br /><b>Background</b><br />Living-donor lobar lung transplantation (LDLLT) remains a life-saving option for pediatric patients with respiratory failure. However, the long-term survival and post-transplant quality of adult lobar grafts transplanted into children are unknown. Therefore, this study aimed to evaluate the outcomes of pediatric LDLLT and post-transplant graft growth.<br /><b>Methods</b><br />We retrospectively reviewed the prospectively collected clinical data of 25 living-donor lung transplantations performed in 24 pediatric recipients aged ≤17 years. The annual pulmonary function test data and computed tomography scans of 12 recipients, followed up for >5 years without significant complications, were used to evaluate growth in height, graft function, and radiological changes. The Kaplan-Meier method and simple linear regression were performed for analysis.<br /><b>Results</b><br />Bilateral lower lobe transplantation was performed in 12 patients, unilateral lower lobe transplantation in 12, and bilateral middle lobe transplantation in 1. The median volumetric size matching at transplantation was 142% (range, 54%-457%). The 5- and 10-year overall survival rates were 87.7% and 75.1༅, respectively. Chronic lung allograft dysfunction occurred in 2 patients. During a median follow-up of 6 years, the median increases in height and vital capacity were 14.4% (range, 0.80%-43.5%) and 58.5% (range, 6.7%-322%), respectively. Graft weight was positively correlated with graft volume (r<sup>2</sup>=0.622, p<0.001) after the graft volume exceeded the original lobar volume in the donor.<br /><b>Conclusions</b><br />This study shows that pediatric LDLLT offers satisfactory long-term survival, with the growth of mature adult lobes transplanted into growing children.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 15 Dec 2022; epub ahead of print</small></div>
Tanaka S, Nakajima D, Sakamoto R, Oguma T, ... Ikeda T, Date H
J Heart Lung Transplant: 15 Dec 2022; epub ahead of print | PMID: 36585287
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<div><h4>Ventricular assist device support for failing Glenn circulation: Impact of concomitant Fontan completion in select patients.</h4><i>Moon J, Tunuguntla H, Tume S, Bocchini C, ... Teruya J, Adachi I</i><br /><b>Background</b><br />Ventricular assist device (VAD) support for failing Glenn circulation represents a unique challenge.<br /><b>Methods</b><br />We conducted a retrospective review of clinical outcomes in patients with VAD support for failing Glenn circulation between 2010 and 2020 at a tertiary pediatric institution.<br /><b>Results</b><br />Ten patients were included: INTERMACS profiles were 1 in 3 patients and 2 in 7 patients. The median age, weight, and body surface area were 3.2 years, 13.0 kg, and 0.5 m<sup>2</sup>, respectively. Seven patients (70%) were implanted with continuous-flow devices and 3 with para-corporeal devices. Nine patients (90%) received heart transplant, with a median support duration of 77 days. Four (67%) out of 6 patients supported with discharge-capable devices were managed as outpatients. Post-transplant survival was 100%, with a median (range) follow up duration of 3.5 (1.8-11.9) years. There were 3 neurologic complications in 3 patients (0.9 events per patient-year); 2 intraoperative events (fatal hypoxia and symptomatic embolic stroke) and 1 postoperative (asymptomatic subarachnoid hemorrhage). Pump thrombosis occurred in one patient (0.3 events per patient-year), requiring pump exchange at day 65. Five patients (50%) received concomitant Fontan completion (fenestrated in 1). The Fontan-upgraded patients (vs Glenn) tended to be larger (median (range): 15.9 (12.6-22.9) vs 9.1 (7.7-22.8) kg), older (4.7 (3.1-6.5) vs 1.1 (0.9-10.1) years) and had a higher PaO<sub>2</sub>/FiO<sub>2</sub> ratio (192 (52-336) vs 76 (59-78) mm Hg) on postoperative day 1.<br /><b>Conclusion</b><br />Our experience suggests the feasibility of durable VAD support for failing Glenn circulation. Concomitant Fontan completion may be considered in select patients to improve oxygen delivery.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 13 Dec 2022; epub ahead of print</small></div>
Moon J, Tunuguntla H, Tume S, Bocchini C, ... Teruya J, Adachi I
J Heart Lung Transplant: 13 Dec 2022; epub ahead of print | PMID: 36610928
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<div><h4>Effects of Intra-Aortic Balloon Pump delayed deflation timing on carotid blood flow and cardiac mechanics: An ultrasound and haemodynamic study.</h4><i>Boccellino A, Sacchi S, Pazzanese V, Calvo F, ... Cappelletti A, Baldetti L</i><br /><AbstractText>Intra-Aortic Balloon Pump (IABP) efficacy is critically affected by the inflation/deflation timing. Balloon deflation may cause a sucking effect, and a steal phenomenon on carotid flow. Delaying IABP deflation reduces the degree of this flow reversal, but at the same time exposes patients to the risk of increased proto-systolic afterload with detrimental effects on the LV. The purpose of this study was to investigate the effects of a delayed IABP deflation timing on cerebral blood flow and LV hemodynamics, by means of simultaneous carotid artery ultrasonography, trans-thoracic echocardiography and central aortic pressure analysis. Delaying IABP deflation trigger to the beginning of QRS effectively increased the cerebral blood flow by 20%, mostly by reducing the reverse component flow caused by the diastolic balloon deflation. Extending the deflation to the early systole was safe and favourably impacted on cardiac mechanics, increasing CO by 15% without prolonging LV isovolumetric contraction and ejection phases.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 12 Dec 2022; epub ahead of print</small></div>
Boccellino A, Sacchi S, Pazzanese V, Calvo F, ... Cappelletti A, Baldetti L
J Heart Lung Transplant: 12 Dec 2022; epub ahead of print | PMID: 36682892
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<div><h4>Delayed versus primary sternal closure for left ventricular assist device implantation: Impact on mechanical circulatory support infections.</h4><i>Akay MH, Jezovnik MK, Salas De Armas IA, Ilic M, ... Kar B, Gregoric ID</i><br /><b>Background</b><br />Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk.<br /><b>Methods</b><br />We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021. Patients were divided into delayed sternal closure (DSC) and primary sternal closure (PSC) groups. We used chi-squared or Fisher Exact tests, as appropriate, to compare the incidence of postoperative LVAD-related infections (mediastinal/sternal wound) and LVAD-specific infections (driveline and pump pocket) after definitive chest closure between these two groups.<br /><b>Results</b><br />A total of 327 patients met eligibility criteria, including 127 (39%) patients that underwent DSC and 200 (61%) patients that had a PSC. Demographic and clinical characteristics were similar except for an overrepresentation of men (87% vs. 75%, p = .016), Interagency Registry of Mechanically Assisted Circulatory Support class I-II patients (89% vs 66%, p < .001), patients with a previous sternotomy (43% vs 13%, p < .001), and patients with chronic kidney disease (55% vs 43%, p = .030) in the DSC group. The median DSC time was 24 (IQR: 24-48) hours. The incidence of LVAD-related mediastinal/sternal wound infection was similar between the DSC and PSC groups (4.7% vs 3.0%, p = .419). There was no difference between DSC and PSC groups in the incidence of driveline infection (6.3% vs 9%, p = .411) and pump pocket infection (1.6% vs 1.5%, p =.901), respectively.<br /><b>Conclusions</b><br />DSC does not seem to increase the incidence of LVAD-related or LVAD-specific infection rates in heart failure patients undergoing device implantation surgery.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 11 Dec 2022; epub ahead of print</small></div>
Akay MH, Jezovnik MK, Salas De Armas IA, Ilic M, ... Kar B, Gregoric ID
J Heart Lung Transplant: 11 Dec 2022; epub ahead of print | PMID: 36641296
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<div><h4>Utilization of COVID-19 positive donors for Heart transplantation and associated short-term outcomes.</h4><i>DeFilippis EM, Wayda B, Lala A, Givertz MM, Khush KK</i><br /><b>Background</b><br />The safety and efficacy of using COVID-19 positive donors in heart transplantation (HT) are increasingly relevant, but not well established. The present study evaluated the characteristics and utilization of such donors and associated post-HT outcomes.<br /><b>Methods</b><br />All adult (≥18 years old) potential donors and HT recipients in the United States from April 21, 2020 to March 31, 2022 were included. Donor COVID-19 status was defined by the presence (or absence) of any positive test within 21 days of organ recovery. Donor and recipient characteristics and post-HT outcomes, including a primary composite of death, graft failure, and re-transplantation, were compared by donor COVID-19 status.<br /><b>Results</b><br />Of 967 COVID-19(+) potential donors, 19.3% (n = 187) were used for HT compared to 26.7% (n = 6277) of COVID-19(-) donors (p < 0.001). Transplanted COVID-19(+) vs COVID-19(-) donors were younger, but otherwise were similar. Recipients of hearts from COVID-19+ vs COVID-19(-) donors less frequently received pre-HT inotropes (24.1% vs 31.7%, p = 0.023) and ventricular assist device therapy (29.7% vs 36.8%, p = 0.040). There were no significant differences in any post-HT outcome by donor COVID-19 status, including the primary composite outcome at 90 days (5.4% vs 5.6%, p = 0.91). Among COVID-19(+) donors, the presence of a subsequent negative test prior to transplant was not associated with posttransplant outcomes.<br /><b>Conclusions</b><br />Our results suggest that carefully selected COVID-19 positive donors may be used for HT with no difference in short-term post-transplant outcomes. Additional data regarding donor and recipient treatments and impact of vaccination should be collected to better inform our use of organs from COVID(+) donors.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 11 Dec 2022; epub ahead of print</small></div>
DeFilippis EM, Wayda B, Lala A, Givertz MM, Khush KK
J Heart Lung Transplant: 11 Dec 2022; epub ahead of print | PMID: 36609092
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<div><h4>Imaging the right atrium in pulmonary hypertension: A systematic review and meta-analysis.</h4><i>Richter MJ, Fortuni F, Alenezi F, D\'Alto M, ... Ghofrani HA, Tello K</i><br /><b>Background</b><br />Right atrial (RA) imaging has emerged as a promising tool for the evaluation of patients with pulmonary hypertension (PH), albeit without systematic validation.<br /><b>Methods</b><br />PubMed, Web of Science and the Cochrane library were searched for studies investigating the prognostic value of RA imaging assessment in patients with PH from 2000 to June 2021 (PROSPERO Identifier: CRD42020212850). An inverse variance-weighted meta-analysis of univariable hazard ratios (HRs) was performed using a random effects model.<br /><b>Results</b><br />Thirty-five studies were included (3,476 patients with PH; 74% female, 86% pulmonary arterial hypertension). Risk of bias was low/moderate (Quality of Prognosis Studies checklist). RA area (HR 1.06; 95% confidence interval [CI] 1.04-1.08), RA indexed area (HR 1.09; 95% CI 1.04-1.14), RA peak longitudinal strain (PLS; HR 0.94; 95% CI 0.91-0.97) and RA total emptying fraction (HR 0.96; 95% CI 0.94-0.98) were significantly associated with combined end-points including death, clinical worsening and/or lung transplantation; RA volume and volume index showed marginal significant associations. RA area (HR 1.06; 95% CI 1.04-1.07), RA indexed area (HR 1.12; 95% CI 1.07-1.17) and RA PLS (HR 0.98; 95% CI 0.97-0.99) showed significant associations with mortality; RA total emptying fraction showed a marginal association.<br /><b>Conclusions</b><br />Imaging-based RA assessment qualifies as a relevant prognostic marker in PH. RA area reliably predicts composite end-points and mortality, which underscores its clinical utility. RA PLS emerged as a promising imaging measure, but is currently limited by the number of studies and different acquisition methods.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 09 Dec 2022; epub ahead of print</small></div>
Richter MJ, Fortuni F, Alenezi F, D'Alto M, ... Ghofrani HA, Tello K
J Heart Lung Transplant: 09 Dec 2022; epub ahead of print | PMID: 36610927
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<div><h4>Impact of race and health coverage on listing and waitlist mortality in pediatric cardiac transplantation.</h4><i>Bansal N, Lal AK, Koehl D, Cantor RS, ... Amdani S, Urschel S</i><br /><b>Background</b><br />Social factors like race and insurance affect transplant outcomes. However, little is known in pediatric heart transplantation. We hypothesized that race and insurance coverage impact listing and waitlist outcomes across eras.<br /><b>Methods</b><br />Data from the Pediatric Heart Transplant Society multi-center registry prospectively collected between January 1, 2000-December 31, 2019 were analyzed. Patients were divided by race as Black, White and other and by insurance coverage at listing (US governmental, US private and non-US single payer systems (UK, Canada). Clinical condition at listing and waitlist outcomes were compared across races and insurance coverages. Categorical variables were compared using a chi-square test and continuous variables using the Wilcoxon rank sum test. Risk factors for waitlist mortality were examined using multiphase parametric hazard modeling. A sensitivity analysis using parametric hazard explored the interaction between race and insurance.<br /><b>Results</b><br />At listing, compared to Whites (n = 5391) and others (n = 1167), Black patients (n = 1428) were older, more likely on US governmental insurance and had cardiomyopathy as the predominant diagnosis (p < 0.0001). Black patients were more likely to be higher status at listing, in hospital, on inotropes or a ventricular assist device (p < 0.0001). Black patients had significantly shorter time on the waitlist compared to other races (p < 0.0001) but had higher waitlist mortality (p = 0.0091), driven by the earlier era (2000-2009) (p = 0.0005), most prominently within the US private insurance cohort (p = 0.015). Outcomes were not different in other insurance cohorts or in the recent era (2010-2019).<br /><b>Conclusion</b><br />Black children are older and sicker at the time of listing, deteriorate more often and face a higher wait list mortality, despite a shorter waitlist period and favorable clinical factors, with improvement in the recent era associated with the recent US healthcare reforms. The social construct of race appears to disadvantage Black children by limiting referral, consideration or access to pediatric cardiac transplantation.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 08 Dec 2022; epub ahead of print</small></div>
Bansal N, Lal AK, Koehl D, Cantor RS, ... Amdani S, Urschel S
J Heart Lung Transplant: 08 Dec 2022; epub ahead of print | PMID: 36641295
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<div><h4>Evaluating age-based eligibility thresholds for heart re-transplantation - an analysis of the united network for organ sharing database.</h4><i>Chen Q, Malas J, Chan J, Esmailian G, ... Kobashigawa J, Esmailian F</i><br /><b>Background</b><br />Risk-adjusted survival after late heart re-transplantation may be comparable to primary transplant, but the efficacy of re-transplantation in older candidates is not established. We evaluated outcomes after heart re-transplantation in recipients > 60 years.<br /><b>Methods</b><br />We identified 1026 adult patients undergoing isolated heart re-transplantation between 2003 and 2020 from the United Network for Organ Sharing database. Older recipients (> 60 years, n=177) were compared to younger recipients (≤ 60 years, n=849). Five and ten-year post-transplant survival was estimated using the Kalpan-Meier method and adjusted with multivariable Cox models.<br /><b>Results</b><br />Older recipients were more likely to be male and have diabetes or previous malignancies with higher baseline creatinine. They also more frequently required pre-transplant ECMO (11.9% vs. 6.8%, p=0.02) and received re-transplantation due to primary graft failure (13.6% vs. 8.5%, p=0.03). After the transplant, older recipients had a higher incidence of stroke (6.8% vs. 2.6%, p=0.01) and dialysis requirements (20.3% vs. 13.2%) before discharge (both p<0.05), and more frequently died from malignancy-related causes (16.3% vs. 3.9%, p<0.001). After adjustment, recipient age >60 was associated with an increased risk of both 5-year (HR 1.42, 95% CI 1.02-2.01, p=0.04) and 10-year mortality (HR 1.72, 95% CI 1.20-2.45, p=0.003). Restricted cubic spline showed a non-linear relationship between recipient age and 10-year mortality.<br /><b>Conclusions</b><br />Heart re-transplantation in recipients > 60 years has inferior outcomes compared to younger recipients. Strict patient selection and close follow-up are warranted to ensure the appropriate utilization of donor hearts and to improve long-term outcomes.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Dec 2022; epub ahead of print</small></div>
Chen Q, Malas J, Chan J, Esmailian G, ... Kobashigawa J, Esmailian F
J Heart Lung Transplant: 06 Dec 2022; epub ahead of print | PMID: 36535808
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<div><h4>\'My Transplanted Self\': Adolescent recipients\' experience of post-traumatic growth following thoracic transplantation.</h4><i>Anthony SJ, Nicholas DB, Regehr C, West LJ</i><br /><b>Background</b><br />Despite heart and lung transplantation being life-saving therapies for children and adolescents, little research has focused on recipients\' lived experience post-transplant. This study captures the subjective experiences of adolescent thoracic transplant recipients, providing insight into the impact of life changes following transplantation in this population.<br /><b>Methods</b><br />A grounded theory approach guided an iterative process of data collection and data analysis. Adolescent heart and lung transplant recipients were recruited from a large Canadian pediatric teaching hospital to participate in one-on-one semi-structured interviews. Analysis using line-by-line coding and constant comparison methods facilitated reflection and agreement on categories and emergent themes.<br /><b>Results</b><br />A total of 27 heart and 5 lung transplant recipients (66% female) participated at a median age of 15.9 years and a median time post-transplant of 2.7 years. Participant narratives illuminated three themes describing (1) personal growth - an awareness of personal strengths and coping abilities, (2) relationship growth - a greater appreciation for family and friends, and (3) introspective growth - a developing life philosophy. Findings suggest that adolescents experience an emergent \'transplanted self\', positioning thoracic transplantation as a potential catalyst for positive growth and personal change.<br /><b>Conclusions</b><br />The study findings describe pediatric thoracic transplantation as potentially transformative in nature and sheds light on the application of post-traumatic growth theory. Practitioners and researchers are encouraged to acknowledge the possibility of growth, transformation, and positive change that may be possible within the adolescent thoracic transplant experience and leverage such strengths in clinical care.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Dec 2022; epub ahead of print</small></div>
Anthony SJ, Nicholas DB, Regehr C, West LJ
J Heart Lung Transplant: 06 Dec 2022; epub ahead of print | PMID: 36543705
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<div><h4>Results of non-elective withdrawal of continuous-flow left ventricular assist devices in selected patients.</h4><i>Knierim J, Tsyganenko D, Stein J, Mulzer J, ... Falk V, Potapov E</i><br /><b>Background</b><br />Protocols have been developed to identify patients for elective withdrawal of continuous-flow left ventricular device (cfLVAD) support. However, little is known about non-elective explantation or decommissioning of cfLVADs.<br /><b>Methods</b><br />A retrospective analysis of all patients who underwent left ventricular assist device (LVAD) explantation or decommissioning at a single center between 2002 and 2021 was performed.<br /><b>Results</b><br />Sixty-one patients underwent withdrawal of a cfLVAD (HeartMate II [Abbott] n = 17, HeartMate 3 [Abbott] n = 2, HeartWare HVAD [Medtronic] n = 36, INCOR [Berlin Heart] n = 6). The median follow-up after withdrawal was 1,039 days. The survival at 5 years was 76.1% (95% CI: 64.2%-95.2%). Predictors of worse outcomes in univariate regressive analysis were the duration of heart failure and the age at LVAD implantation. Of the 61 patients, 40 underwent elective withdrawal following a specific protocol. The other twenty-one patients underwent non-elective withdrawal of the cfLVAD because of device infection (n = 12), device thrombosis (n = 6), device malfunction (n = 2) or due to acute intracerebral bleeding (n = 1), also with an excellent survival at 5 years of 81.3%. (95% CI: 63.8-1). The withdrawal was performed in these patients even though they did not fulfill established criteria for successful explantation or decommissioning like clinical stability (n = 21), left ventricular end-diastolic diameter ≤ 55 mm (n = 3), performance of right heart catheterization (n = 6), or pulmonary artery wedge pressure ≤ 15 mm Hg (n = 3).<br /><b>Conclusion</b><br />Non-elective withdrawal is possible in selected patients after discussion in a team of experienced cardiac surgeons, cardiologists, technicians, and VAD coordinators. The appropriate preoperative assessment before decommissioning or explantation of a cfLVAD warrants further investigation.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Dec 2022; epub ahead of print</small></div>
Knierim J, Tsyganenko D, Stein J, Mulzer J, ... Falk V, Potapov E
J Heart Lung Transplant: 06 Dec 2022; epub ahead of print | PMID: 36529649
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<div><h4>Laparoscopic fundoplication after lung transplantation does not appear to alter lung function trajectory.</h4><i>Frankel A, Kellar T, Zahir F, Chambers D, Hopkins P, Gotley D</i><br /><b>Background</b><br />The primary aim of this study was to determine if allograft function in lung transplant (LTx) recipients improves or stabilizes after laparoscopic fundoplication (LF). The secondary aim was to examine the differences in forced expiratory volume in 1 second (FEV1) before and after LF for various subgroups to identify patients who obtained a superior respiratory outcome after LF, and potential predictive factors for this outcome.<br /><b>Methods</b><br />Retrospective analysis of consecutive LTx recipients undergoing LF at a single centre in Brisbane, Australia between 2004 and 2018. 149/431 proceeded to LF after clinical review and pH study. Regular pre- and post-fundoplication pulmonary function tests were collected from participants. Data were analyzed with linear mixed models, random intercept models, the Reliable Change Index (RCI), and graphical and visual analysis of the trajectory of FEV1.<br /><b>Results</b><br />There was 100% follow-up. After Bonferroni adjustment for multiple comparison was performed, none of the models demonstrated statistical significance. The Reliable Change Index showed one patient had a significant improvement in lung function across that time period, while nine had a significant reduction. The rate of change before and after LF was similar for the 132/149 patients for whom the first and last pre- and post-LF FEV1 values were available. A subset of patients had a considerable reduction in their FEV1 in the peri-operative period (i.e., a large difference between the first measurement post-LF and the final measurement pre-LF).<br /><b>Conclusion</b><br />In the largest published cohort to date, LF performed in a high-volume center did not appear to alter the reduction in allograft function seen with time.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 05 Dec 2022; epub ahead of print</small></div>
Frankel A, Kellar T, Zahir F, Chambers D, Hopkins P, Gotley D
J Heart Lung Transplant: 05 Dec 2022; epub ahead of print | PMID: 36609090
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<div><h4>COVID-19 in pediatric lung transplant recipients: Clinical course and outcome.</h4><i>Schütz K, Davids J, Petrik B, Scharff AZ, ... Müller C, Schwerk N</i><br /><b>Background</b><br />COVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients.<br /><b>Methods</b><br />Between March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded.<br /><b>Results</b><br />Nineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p = 0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable.<br /><b>Conclusions</b><br />Unlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 05 Dec 2022; epub ahead of print</small></div>
Schütz K, Davids J, Petrik B, Scharff AZ, ... Müller C, Schwerk N
J Heart Lung Transplant: 05 Dec 2022; epub ahead of print | PMID: 36526496
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<div><h4>Long-term safety and durability of novel intra-aortic percutaneous mechanical circulatory support device.</h4><i>Lu C, Krisher J, Benavides O, Palmer A, ... Durst C, Heuring J</i><br /><AbstractText>An unmet need exists for minimally invasive percutaneous mechanical circulatory support (pMCS) devices to provide partial support and promote cardiac rest and recovery in non-end-stage heart failure patients. This indication requires safe, long-term, ambulatory use with standard anticoagulation. The Aortix pump (Procyrion, Houston, Texas, USA) is a percutaneously deployed intra-aortic pump currently being clinically evaluated for subacute use and has the potential to provide extended therapy for non-end-stage heart failure patients. The device has demonstrated hemocompatibility and hemodynamic impact and has features well suited for home use. To evaluate the Aortix pump for long-term, ambulatory use, pumps were implanted in 4 untethered sheep. Pumps operated for 90 to 142 days and were stopped electively. Pump bearing components were found to have only superficial wear. No clinically significant hemolysis was observed and aorta and kidney histopathology showed no device-related findings or adhesions, suggesting Aortix is suitable for long-term (>6 months) ambulatory use.</AbstractText><br /><br />Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 01 Dec 2022; 41:1712-1715</small></div>
Lu C, Krisher J, Benavides O, Palmer A, ... Durst C, Heuring J
J Heart Lung Transplant: 01 Dec 2022; 41:1712-1715 | PMID: 36435579
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<div><h4>The mitigating effect of exogenous carbon monoxide on chronic allograft rejection and fibrosis post-lung transplantation.</h4><i>Aoki Y, Walker NM, Misumi K, Mimura T, ... Pinsky DJ, Lama VN</i><br /><b>Background</b><br />Small airway inflammation and fibrosis or bronchiolitis obliterans (BO) is the predominant presentation of chronic lung allograft dysfunction (CLAD) post-lung transplantation. Carbon monoxide (CO) is a critical endogenous signaling transducer with known anti-inflammatory and anti-fibrotic effects but its therapeutic potential in CLAD remains to be fully elucidated.<br /><b>Methods</b><br />Here we investigate the effect of inhaled CO in modulating chronic lung allograft rejection pathology in a murine orthotopic lung transplant model of BO (B6D2F1/J→DBA/2J). Additionally, the effects of CO on the activated phenotype of mesenchymal cells isolated from human lung transplant recipients with CLAD were studied.<br /><b>Results</b><br />Murine lung allografts treated with CO (250 ppm × 30 minutes twice daily from days 7 to 40 post-transplantation) demonstrated decreased immune cell infiltration, fibrosis, and airway obliteration by flow cytometry, trichrome staining, and morphometric analysis, respectively. Decreased total collagen, with levels comparable to isografts, was noted in CO-treated allografts by quantitative hydroxyproline assay. In vitro, CO (250 ppm × 16h) was effective in reversing the fibrotic phenotype of human CLAD mesenchymal cells with decreased collagen I and β-catenin expression as well as an inhibitory effect on ERK1/2 MAPK, and mTORC1/2 signaling. Sildenafil, a phosphodiesterase 5 inhibitor, partially mimicked the effects of CO on CLAD mesenchymal cells and was partially effective in decreasing collagen deposition in murine allografts, suggesting the contribution of cGMP-dependent and -independent mechanisms in mediating the effect of CO.<br /><b>Conclusion</b><br />These results suggest a potential role for CO in alleviating allograft fibrosis and mitigating chronic rejection pathology post-lung transplant.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 26 Nov 2022; epub ahead of print</small></div>
Aoki Y, Walker NM, Misumi K, Mimura T, ... Pinsky DJ, Lama VN
J Heart Lung Transplant: 26 Nov 2022; epub ahead of print | PMID: 36522238
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<div><h4>Cardiac output assessment methods in left ventricular assist device patients: A problem of heteroscedasticity.</h4><i>Azih NI, Read JM, Jackson GR, Inampudi C, ... Tedford RJ, Houston BA</i><br /><AbstractText>Equipoise remains about how best to measure cardiac output (CO) in patients with left ventricular assist devices (LVAD). In this study, direct Fick CO was compared with thermodilution (TD) and indirect Fick (iFick) CO in 61 LVAD patients. TD and LaFarge iFick showed moderate correlation with direct Fick (R<sup>2</sup> = 0.49 and R<sup>2</sup> = 0.38, p < 0.001 for both), while Dehmer and Bergstra iFick showed poor correlation with direct Fick (R<sup>2</sup> = 0.29 and R<sup>2</sup> = 0.31, p < 0.001 for both). Absolute bias between all CO estimation techniques and direct Fick CO was lowest for TD compared to iFick methods but significant for all methods. All methods tended to overestimate CO compared to direct Fick, with greatest overestimation present in those with the lowest measured direct Fick CO. Bias and frequency of significant discrepancy were least using TD and Lafarge iFick CO estimation methods in this study, with TD CO demonstrating modestly better correlation and less heteroscedasticity compared to Lafarge.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 18 Nov 2022; epub ahead of print</small></div>
Azih NI, Read JM, Jackson GR, Inampudi C, ... Tedford RJ, Houston BA
J Heart Lung Transplant: 18 Nov 2022; epub ahead of print | PMID: 36481112
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<div><h4>Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.</h4><i>Spielberg DR, Melicoff E, Heinle JS, Hosek K, Mallory GB</i><br /><b>Background</b><br />Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates.<br /><b>Methodology</b><br />We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management.<br /><b>Results</b><br />We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor.<br /><b>Conclusions</b><br />In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 17 Nov 2022; epub ahead of print</small></div>
Spielberg DR, Melicoff E, Heinle JS, Hosek K, Mallory GB
J Heart Lung Transplant: 17 Nov 2022; epub ahead of print | PMID: 36564335
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<div><h4>Technique for xenogeneic cross-circulation to support human donor lungs ex vivo.</h4><i>Kelly Wu W, Guenthart BA, O\'Neill JD, Hozain AE, ... Vunjak-Novakovic G, Bacchetta M</i><br /><b>Background</b><br />Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and recover injured human donor lungs ex vivo.<br /><b>Methods</b><br />Human donor lungs (n = 9) declined for transplantation were procured, cannulated, and subjected to 24 hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus) and complement-depleting cobra venom factor. Standard lung-protective perfusion and ventilation strategies, including periodic lung recruitment maneuvers, were used throughout xenogeneic XC. Every 6 hours, ex vivo donor lung function (gas exchange, compliance, airway pressures, pulmonary vascular dynamics, lung weight) was evaluated. At the experimental endpoint, comprehensive assessments of the lungs were performed by bronchoscopy, histology, and electron microscopy. Student\'s t-test and 1-way analysis of variance with Dunnett\'s post-hoc test was performed, and p < 0.05 was considered significant.<br /><b>Results</b><br />After 24 hours of xenogeneic XC, gas exchange (PaO2/FiO2) increased by 158% (endpoint: 364 ± 142 mm Hg; p = 0.06), and dynamic compliance increased by 127% (endpoint: 46 ± 20 ml/cmH<sub>2</sub>O; p = 0.04). Airway pressures, pulmonary vascular pressures, and lung weight remained stable (p > 0.05) and within normal ranges. Over 24 hours of xenogeneic XC, gross and microscopic lung architecture were preserved: airway bronchoscopy and parenchymal histomorphology appeared normal, with intact blood-gas barrier.<br /><b>Conclusions</b><br />Xenogeneic cross-circulation is a robust method for ex vivo support, evaluation, and improvement of injured human donor lungs declined for transplantation.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 14 Nov 2022; epub ahead of print</small></div>
Kelly Wu W, Guenthart BA, O'Neill JD, Hozain AE, ... Vunjak-Novakovic G, Bacchetta M
J Heart Lung Transplant: 14 Nov 2022; epub ahead of print | PMID: 36456408
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<div><h4>Determining the impact of ex-vivo lung perfusion on hospital costs for lung transplantation: A retrospective cohort study.</h4><i>Peel JK, Keshavjee S, Naimark D, Liu M, ... Pullenayegum EM, Sander B</i><br /><b>Introduction</b><br />Ex-vivo lung perfusion (EVLP) has improved organ utilization for lung transplantation, but it is not yet known whether the benefits of this technology offset its additional costs. We compared the institutional costs of lung transplantation before vs after EVLP was available to identify predictors of costs and determine the health-economic impact of EVLP.<br /><b>Methods</b><br />We performed a retrospective, before-after, propensity-score weighted cohort study of patients wait-listed for lung transplant at University Health Network (UHN) in Ontario, Canada, between January 2005 and December 2019 using institutional administrative data. We compared costs, in 2019 Canadian Dollars ($), between patients referred for transplant before EVLP was available (Pre-EVLP) to after (Modern EVLP). Cumulative costs were estimated using a novel application of multistate survival models. Predictors of costs were identified using weighted log-gamma generalized linear regression.<br /><b>Results</b><br />A total of 1,199 patients met inclusion criteria (352 Pre-EVLP; 847 Modern EVLP). Mean total costs for the transplant hospitalization were $111,878 ($94,123-$130,767) in the Pre-EVLP era and $110,969 ($87,714-$136,000) in the Modern EVLP era. Cumulative five-year costs since referral were $278,777 ($82,575-$298,135) in the Pre-EVLP era and $293,680 ($252,832-$317,599) in the Modern EVLP era. We observed faster progression to transplantation when EVLP was available. EVLP availability was not a predictor of waitlist (cost ratio [CR] 1.04 [0.81-1.37]; p = 0.354) or transplant costs (CR 1.02 [0.80-1.29]; p = 0.425) but was associated with lower costs during posttransplant years 1&2 (CR 0.75 [0.58-1.06]; p = 0.05) and posttransplant years 3+ (CR 0.43 [0.26-0.74]; p = 0.001).<br /><b>Conclusions</b><br />At our center, EVLP availability was associated with faster progression to transplantation at no significant marginal cost.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 09 Nov 2022; epub ahead of print</small></div>
Peel JK, Keshavjee S, Naimark D, Liu M, ... Pullenayegum EM, Sander B
J Heart Lung Transplant: 09 Nov 2022; epub ahead of print | PMID: 36411188
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<div><h4>Temporal trends in the use and outcomes of temporary mechanical circulatory support as a bridge to cardiac transplantation in Spain. Final report of the ASIS-TC study.</h4><i>Barge-Caballero E, González-Vílchez F, Almenar-Bonet L, Carmena MDG, ... Muñiz J, Crespo-Leiro MG</i><br /><b>Background</b><br />We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain.<br /><b>Methods</b><br />Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020).<br /><b>Results</b><br />Over time, the proportion of candidates listed with intra-aortic balloon pumps decreased (Era 1 = 55.9%, Era 2 = 32%, Era 3 = 0.9%; p < 0.001), while the proportion of candidates listed with surgical continuous-flow temporary VADs (Era 1 = 10.6%, Era 2 = 32%, Era 3 = 49.1%; p < 0.001) and percutaneous VADs (Era 1 = 0.3%, Era 2 = 6.3%; Era 3 = 17.2%; p < 0.001) increased. Rates of HTx increased from Era 1 (79.4%) to Era 2 (87.8%), and Era 3 (87%) (p = 0.004), while rates of death before HTx decreased (Era 1 = 17.7%; Era 2 = 11%, Era 3 = 12.4%; p = 0.037) Median time from listing to HTx increased in patients supported with intra-aortic balloon pumps (Era 1 = 8 days, Era 2 = 15 days; p < 0.001) but remained stable in other candidates (Era 1 = 6 days; Era 2 = 5 days; Era 3 = 6 days; p = 0.134). One-year post-transplant survival was 71.4% in Era 1, 79.3% in Era 2, and 76.5% in Era 3 (p = 0.112). Preoperative bridging with ECMO was associated with increased 1-year post-transplant mortality (adjusted HR=1.71; 95% CI 1.15-2.53; p = 0.008).<br /><b>Conclusions</b><br />During the period 2010 to 2020, successive changes in the Spanish organ allocation protocol were followed by a significant increase of the rate of HTx and a significant reduction of waiting list mortality in candidates supported with temporary MCS. One-year post-transplant survival rates remained acceptable.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 09 Nov 2022; epub ahead of print</small></div>
Barge-Caballero E, González-Vílchez F, Almenar-Bonet L, Carmena MDG, ... Muñiz J, Crespo-Leiro MG
J Heart Lung Transplant: 09 Nov 2022; epub ahead of print | PMID: 36470772
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<div><h4>Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity.</h4><i>Greissman S, Anderson M, Dimango A, Grewal H, ... Arcasoy S, Benvenuto L</i><br /><b>Background</b><br />Blood group O candidates have lower lung transplantation rates despite having the most common blood group. We postulated that waitlist outcomes among these candidates and those with other blood types vary with disease severity and lung allocation score (LAS).<br /><b>Methods</b><br />We performed a retrospective cohort study of 32,772 waitlist candidates using the United Network of Organ Sharing registry from May 2005 to 2020. After identifying an interaction between blood group and LAS, we evaluated the association between blood group and waitlist outcomes within LAS quartiles using unadjusted and adjusted competing risk models.<br /><b>Results</b><br />In the lowest LAS quartile, blood group O had a 20% reduced transplantation rate (SHR: 0.80, 95%CI: 0.75-0.85) and higher waitlist death/removal (1.33, 95%CI: 1.15-1.55) compared with group A. Blood group AB had a 52% higher transplantation rate (SHR: 1.52, 95%CI: 1.34-1.73) in the lowest LAS quartile compared with group A. In the highest LAS quartile, there was no difference in transplantation rates between groups O and A. In contrast, group B had a 19% reduced transplantation rate (SHR, 0.81 95%CI: 0.73-0.89) and AB had a 28% reduced transplantation rate (SHR: 0.72, 95%CI: 0.61-0.86) in the highest LAS quartile. Additionally, groups B and AB had increased risk of waitlist death/removal in the highest LAS quartile compared with A (SHR: 1.27, 95%CI: 1.08-1.48; SHR: 1.31, 95%CI: 1.00-1.72).<br /><b>Conclusions</b><br />Waitlist outcomes among ABO blood groups vary depending on illness severity, which is represented by LAS. Blood group O has lower transplantation rates at low LAS while groups B and AB have lower transplantation rates at high LAS.<br /><br />Published by Elsevier Inc.<br /><br /><small>J Heart Lung Transplant: 07 Nov 2022; epub ahead of print</small></div>
Greissman S, Anderson M, Dimango A, Grewal H, ... Arcasoy S, Benvenuto L
J Heart Lung Transplant: 07 Nov 2022; epub ahead of print | PMID: 36464610
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<div><h4>Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension.</h4><i>Hirsch K, Nolley S, Ralph DD, Zheng Y, ... Leary PJ, Rayner SG</i><br /><b>Background</b><br />Subtypes of pulmonary arterial hypertension (PAH) differ in both fundamental disease features and clinical outcomes. Angiogenesis and inflammation represent disease features that may differ across subtypes and are of special interest in connective tissue disease-associated PAH (CTD-PAH). We compared inflammatory and angiogenic biomarker profiles across different etiologies of PAH and related them to clinical outcomes.<br /><b>Methods</b><br />Participants with idiopathic PAH, CTD-PAH, toxin-associated PAH (tox-PAH), or congenital heart disease-associated PAH (CHD-PAH) were enrolled into a prospective observational cohort. Baseline serum concentrations of 33 biomarkers were related to 3-year mortality, echocardiogram, REVEAL score, and 6-minute walk distance (6MWD). Findings were validated using plasma proteomic data from the UK PAH Cohort Study.<br /><b>Results</b><br />One hundred twelve patients were enrolled: 45 idiopathic, 27 CTD-PAH, 20 tox-PAH, and 20 CHD-PAH. Angiogenic and inflammatory biomarkers were distinctly elevated within the CTD-PAH cohort. Six biomarkers were associated with mortality within the entire PAH cohort: interleukin-6 (IL-6, HR:1.6, 95% CI:1.18-2.18), soluble fms-like tyrosine kinase 1 (sFlt-1, HR:1.35, 95% CI:1.02-1.80), placental growth factor (PlGF, HR:1.55, 95% CI:1.07-2.25), interferon gamma-induced protein 10 (IP-10, HR:1.44, 95% CI:1.04-1.99), tumor necrosis factor-beta (TNF-β, HR:1.81, 95% CI:1.11-2.95), and NT-proBNP (HR:2.19, 95% CI:1.52-3.14). Only IL-6 and NT-proBNP remained significant after controlling for multiple comparisons. IL-6, IP-10, and sFlt-1 significantly associated with mortality in CTD-PAH, but not non-CTD-PAH subgroups. In the UK cohort, IP-10, PlGF, TNF-β, and NT-proBNP significantly associated with 5-year survival.<br /><b>Conclusion</b><br />Levels of angiogenic and inflammatory biomarkers are elevated in CTD-PAH, compared with other etiologies of PAH, and may correlate with clinical outcomes including mortality.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 07 Nov 2022; epub ahead of print</small></div>
Hirsch K, Nolley S, Ralph DD, Zheng Y, ... Leary PJ, Rayner SG
J Heart Lung Transplant: 07 Nov 2022; epub ahead of print | PMID: 36470771
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<div><h4>TTV viral load as a predictor of antibody response to SARS COV-2 vaccination.</h4><i>Focosi D, Baj A, Azzi L, Novazzi F, Maggi F</i><br /><AbstractText>The measure of torquetenovirus (TTV) viremia is widely recognized as an optimal biomarker of an individual immune status. In the context of COVID-19, the predictive role of TTV load with regard to vaccine response has also been demonstrated, suggesting other intriguing applications for this widespread anellovirus.</AbstractText><br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Nov 2022; epub ahead of print</small></div>
Focosi D, Baj A, Azzi L, Novazzi F, Maggi F
J Heart Lung Transplant: 06 Nov 2022; epub ahead of print | PMID: 36424253
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<div><h4>Large animal preclinical investigation into the optimal extracorporeal life support configuration for pulmonary hypertension and right ventricular failure.</h4><i>Ukita R, Stokes JW, Wu WK, Patel YJ, ... Rosenzweig EB, Bacchetta M</i><br /><b>Introduction</b><br />Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH). Mechanical circulatory support holds promise for patients with medically refractory PH, but there are no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and circuit configurations for PH-induced RVF (PH-RVF) are needed.<br /><b>Methods</b><br />Eleven sheep underwent previously published chronic PH model. We then evaluated a low-profile, ventricular assist device (VAD)-quality pump combined with a novel low-resistance membrane oxygenator (Pulmonary Assist Device, PAD) under one of four central cannulation strategies: right atrium-to-left atrium (RA-LA, N = 3), RA-to-pulmonary artery (RA-PA, N=3), pumpless pulmonary artery-to-left atrium (PA-LA, N = 2), and RA-to-ascending aorta (RA-Ao, N = 3). Acute-on-chronic RVF (AoC RVF) was induced, and mechanical support was provided for up to 6 hours at blood flow rates of 1 to 3 liter/min. Circuit parameters, physiologic, hemodynamic, and echocardiography data were collected.<br /><b>Results</b><br />The RA-LA configuration achieved blood flow of 3 liter/min. Meanwhile, RA-PA and RA-Ao faced challenges maintaining 3 liter/min of flow due to higher circuit afterload. Pumpless PA-LA was flow-limited due to anatomical limitations inherent to this animal model. RA-LA and RA-Ao demonstrated serial RV unloading with increasing circuit flow, while RA-PA did not. RA-LA also improved left ventricular (LV) and septal geometry by echocardiographic assessment and had the lowest inotropic dependence.<br /><b>Conclusion</b><br />RA-LA and RA-Ao configurations unload the RV, while RA-LA also lowers pump speed and inotropic requirements, and improves LV mechanics. RA-PA provide inferior support for PH-RVF, while an alternate animal model is needed to evaluate PA-LA.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 06 Nov 2022; epub ahead of print</small></div>
Ukita R, Stokes JW, Wu WK, Patel YJ, ... Rosenzweig EB, Bacchetta M
J Heart Lung Transplant: 06 Nov 2022; epub ahead of print | PMID: 36435685
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<div><h4>Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.</h4><i>Shou BL, Ong CS, Premraj L, Brown P, ... Whitman GJR, Cho SM</i><br /><b>Background</b><br />Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO<sub>2</sub>) and carbon dioxide (PaCO<sub>2</sub>) on ABI occurrence.<br /><b>Methods</b><br />We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO<sub>2</sub> and PaCO<sub>2</sub> with ABI.<br /><b>Results</b><br />Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89).<br /><b>Conclusions</b><br />Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 05 Nov 2022; epub ahead of print</small></div>
Shou BL, Ong CS, Premraj L, Brown P, ... Whitman GJR, Cho SM
J Heart Lung Transplant: 05 Nov 2022; epub ahead of print | PMID: 36435686
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Abstract
<div><h4>L-alanyl-L-glutamine modified perfusate improves human lung cell functions and extend porcine ex vivo lung perfusion.</h4><i>Huang L, Hough O, Vellanki RN, Takahashi M, ... Keshavjee S, Liu M</i><br /><b>Background</b><br />The clinical application of normothermic ex vivo lung perfusion (EVLP) has increased donor lung utilization for transplantation through functional assessment. To develop it as a platform for donor lung repair, reconditioning and regeneration, the perfusate should be modified to support the lung during extended EVLP.<br /><b>Methods</b><br />Human lung epithelial cells and pulmonary microvascular endothelial cells were cultured, and the effects of Steen solution (commonly used EVLP perfusate) on basic cellular function were tested. Steen solution was modified based on screening tests in cell culture, and further tested with an EVLP cell culture model, on apoptosis, GSH, HSP70, and IL-8 expression. Finally, a modified formula was tested on porcine EVLP. Physiological parameters of lung function, histology of lung tissue, and amino acid concentrations in EVLP perfusate were measured.<br /><b>Results</b><br />Steen solution reduced cell confluence, induced apoptosis, and inhibited cell migration, compared to regular cell culture media. Adding L-alanyl-L-glutamine to Steen solution improved cell migration and decreased apoptosis. It also reduced cold preservation and warm perfusion-induced apoptosis, enhanced GSH and HSP70 production, and inhibited IL-8 expression on an EVLP cell culture model. L-alanyl-L-glutamine modified Steen solution supported porcine lungs on EVLP with significantly improved lung function, well-preserved histological structure, and significantly higher levels of multiple amino acids in EVLP perfusate.<br /><b>Conclusions</b><br />Adding L-alanyl-L-glutamine to perfusate may provide additional energy support, antioxidant, and cytoprotective effects to lung tissue. The pipeline developed herein, with cell culture, cell EVLP, and porcine EVLP models, can be used to further optimize perfusates to improve EVLP outcomes.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 03 Nov 2022; epub ahead of print</small></div>
Huang L, Hough O, Vellanki RN, Takahashi M, ... Keshavjee S, Liu M
J Heart Lung Transplant: 03 Nov 2022; epub ahead of print | PMID: 36411189
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Abstract
<div><h4>The dynamic cellular landscape of grafts with acute rejection after heart transplantation.</h4><i>Kong D, Huang S, Miao X, Li J, ... Xi R, Gong W</i><br /><b>Background</b><br />Acute cellular rejection (ACR) is a major barrier to the long-term survival of cardiac allografts. Although immune cells are well known to play critical roles in ACR, the dynamic cellular landscape of allografts with ACR remains obscure.<br /><b>Methods</b><br />Single-cell RNA sequencing (scRNA-seq) was carried out for mouse cardiac allografts with ACR. Bioinformatic analysis was performed, and subsequent transplant experiments were conducted to validate the findings.<br /><b>Results</b><br />Despite an overall large depletion of cardiac fibroblasts (CFBs), highly expanded cytotoxic T lymphocytes and a CXCL10+Gbp2+ subcluster of CFBs were enriched within grafts at the late stage. CXCL10+Gbp2+ CFBs featured strong interferon responsiveness and high expression of chemokines and major histocompatibility complex molecules, implying their involvement in the recruitment and activation of immune cells. Cell‒cell communication analysis revealed that CXCL9/CXCL10-CXCR3 might contribute to regulating CXCL10+Gbp2+ CFB-induced chemotaxis and immune cell recruitment. In vivo transplant studies revealed the therapeutic potential of CXCR3 antagonism in transplant rejection.<br /><b>Conclusions</b><br />The findings of our study unveiled a novel CFB subcluster that might mediate acute cardiac rejection. Targeting CXCR3 could prolong allograft survival.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 02 Nov 2022; epub ahead of print</small></div>
Kong D, Huang S, Miao X, Li J, ... Xi R, Gong W
J Heart Lung Transplant: 02 Nov 2022; epub ahead of print | PMID: 36411190
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Abstract
<div><h4>Heart transplant offers are less likely to be accepted on weekends, holidays, and conferences.</h4><i>Greenberg JW, Fatuzzo SH, Ramineni A, Chin C, ... Zafar F, Morales DLS</i><br /><b>Background</b><br />The existence of a \"weekend effect\" in heart transplantation (HTx) is understudied. The present study sought to determine whether the odds of (HTx) offer acceptance differed for adult and pediatric candidates depending upon the day on which the offer occurred.<br /><b>Methods</b><br />United Network for Organ Sharing data were used to identify all HTx offers to adult (listing age ≥18) and pediatric candidates from 2000-2019. Odds of offer acceptance were studied, comparing weekends, holidays, and conferences (Society of Thoracic Surgeons [STS], American Association for Thoracic Surgery [AATS], International Society for Heart and Lung Transplantation [ISHLT]) to \"baseline\" (all other days). Multivariable binary logistic regression analyses were performed to determine independent predictors of offer nonacceptance, controlling for the impacts of program transplant volume, region, and candidate characteristics.<br /><b>Results</b><br />A total of 323,953 offers occurred - 298,405 to adults and 25,548 to pediatric candidates. Clinically significant differences did not exist in donor or candidate characteristics between baseline or other events. The number of offers per day was stable throughout the year for both adults (p = 0.191) and pediatrics (p = 0.976). In adults, independently lower odds of acceptance existed on weekends (OR 0.88 [95% CI 0.84-0.92]), conferences in aggregate (0.86 [0.77-0.95]), and holidays in aggregate (0.81 [0.72-0.91]). In children, independently lower odds of acceptance were seen on weekends (0.88 [0.79-0.98]), during STS (0.46 [0.25-0.83], and during Christmas (0.32 [0.14-0.76]).<br /><b>Conclusions</b><br />The day on which a HTx offer occurs significantly impacts its likelihood of acceptance. Further work can determine the impacts of human behavior or resource distribution, but knowledge of this phenomenon can inform efforts to ensure ideal organ allocation throughout the year.<br /><br />Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 02 Nov 2022; epub ahead of print</small></div>
Greenberg JW, Fatuzzo SH, Ramineni A, Chin C, ... Zafar F, Morales DLS
J Heart Lung Transplant: 02 Nov 2022; epub ahead of print | PMID: 36509608
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This program is still in alpha version.