Journal: J Heart Lung Transplant

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Abstract

Methane supplementation improves graft function in experimental heart transplantation.

Benke K, Jász DK, Szilágyi ÁL, Baráth B, ... Hartmann P, Boros M
Background
Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH4) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH4-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX).
Methods
The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH4-saturated CS solution (CS-CH4) (n = 12 each). Standard heterotopic HTX was performed, and 60 minutes later, the left ventricular (LV) pressure-volume relationships LV systolic pressure (LVSP), systolic pressure increment (dP/dtmax), diastolic pressure decrement, and coronary blood flow (CBF) were measured. Tissue samples were taken to detect proinflammatory parameters, structural damage (by light microscopy), endoplasmic reticulum (ER) stress, and apoptosis markers (CCAAT/enhancer binding protein [C/EBP] homologous protein, GRP78, glycogen synthase kinase-3β, very low-density lipoprotein receptor, caspase 3 and 9, B-cell lymphoma 2, and bcl-2-like protein 4), whereas mitochondrial functional changes were analyzed by high-resolution respirometry.
Results
LVSP and dP/dtmax increased significantly at the largest pre-load volumes in CS-CH4 grafts as compared with the CS group (114.5 ± 16.6 mm Hg vs 82.8 ± 4.6 mm Hg and 3,133 ± 430 mm Hg/s vs 1,739 ± 169 mm Hg/s, respectively); the diastolic function and CBF (2.4 ± 0.4 ml/min/g vs 1.3 ± 0.3 ml/min/g) also improved. Mitochondrial oxidative phosphorylation capacity was more preserved (58.5 ± 9.4 pmol/s/ml vs 27.7 ± 6.6 pmol/s/ml), and cytochrome c release was reduced in CS-CH4 storage. Signs of HTX-caused myocardial damage, level of ER stress, and the transcription of proapoptotic proteins were significantly lower in CS-CH4 grafts.
Conclusion
The addition of CH4 during 1 hour of cold storage improved early in vitro graft function and reduced mitochondrial dysfunction and activation of inflammation. Evidence shows that CH4 reduced ER stress-linked proapoptotic signaling.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Feb 2021; 40:183-192
Benke K, Jász DK, Szilágyi ÁL, Baráth B, ... Hartmann P, Boros M
J Heart Lung Transplant: 27 Feb 2021; 40:183-192 | PMID: 33277170
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Abstract

The impact of gastrointestinal dysmotility on the aerodigestive microbiome of pediatric lung transplant recipients.

Lötstedt B, Boyer D, Visner G, Freiberger D, ... Alm E, Rosen R
Background
Delayed gastric emptying has been associated with increased graft rejection, although the mechanism of this association is not known. This study aims to investigate the interrelationship between delays in gastrointestinal motility and the diversity and composition of gastric, oropharyngeal, and lung microbiomes in pediatric lung transplant recipients.
Methods
We prospectively recruited 23 pediatric lung transplant recipients and 98 pediatric patients with respiratory symptoms undergoing combined endoscopy and bronchoscopy. Gastric, oropharyngeal, and bronchoalveolar lavage samples were collected for 16S sequencing. Gastric samples were also analyzed for bile composition using liquid chromatography.
Results
Patients who underwent lung transplantation had significantly reduced alpha diversity in gastric and oropharyngeal sites compared with patients with respiratory symptoms. This reduction in alpha diversity was especially evident in gastric samples in patients with delayed gastric emptying defined as abnormal gastric emptying on nuclear scintigraphy or as an elevation in gastric bile concentration (p ≤ 0.05). Whereas monocolonies were seen in the lungs of patients who underwent transplantation, these were not the same microbes seen in the stomach; the microbial overlap between lung and gastric samples within patients was low, and data indicated high individual variation between lung transplant recipients. Other contributors to reduced alpha diversity included antibiotics in combination with proton pump inhibitors, especially in gastric and oropharyngeal samples.
Conclusions
Lung transplant recipients have reduced microbial diversity in gastric fluid (GF) and oropharynx compared with patients who did not undergo lung transplantation. The decreased alpha diversity in GF may be associated with dysmotility.

Copyright © 2020. Published by Elsevier Inc.

J Heart Lung Transplant: 27 Feb 2021; 40:210-219
Lötstedt B, Boyer D, Visner G, Freiberger D, ... Alm E, Rosen R
J Heart Lung Transplant: 27 Feb 2021; 40:210-219 | PMID: 33349521
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Abstract

Outcomes after heart transplantation and total artificial heart implantation: A multicenter study.

Carrier M, Moriguchi J, Shah KB, Anyanwu AC, ... Cossette M, Noly PE
Background
We sought to assess the outcomes after heart transplantation (HT) of patients supported with a temporary total artificial heart (t-TAH) as a bridge to transplantation in high-volume centers.
Methods
A retrospective analysis of 217 consecutive patients who underwent t-TAH (SynCardia Systems, Tucson, Arizona) implantation between January 2014 and May 2019 in 6 high-volume North American centers was performed. End points included survival and adverse events after t-TAH and HT.
Results
The mean age of patients was 49 ± 12 years, and heart failure etiologies were non-ischemic dilated cardiomyopathy (36%), ischemic (25%), restrictive (12%), and cardiac graft failure (9%). A total of 101 (48%) patients had Interagency Registry for Mechanically Assisted Circulatory Support patient profile 1, and 65 (31%) had Interagency Registry for Mechanically Assisted Circulatory Support patient profile 2. At the end of the study period, 138 of 217 (63.5%) patients had undergone HT, and 75 (34.5%) patients died before HT. The mean time between t-TAH implantation and HT averaged 181 ± 179 days (range: 0-849) and the mean follow-up after HT was 35 ± 25 months. The overall survival in the entire cohort was 75%, 64%, and 58% at 1, 2, and 5 years, respectively. Post-transplant survival was 88%, 84%, 79%, and 74% at 6 months, 1 year, 2 years, and 5 years, respectively. Among the 32 patients (23%) who died after HT, the main causes of death were chronic allograft vasculopathy (25%), multiorgan failure (21.8%), sepsis (15.6%), and stroke (9%).
Conclusion
In this multicenter study, almost two thirds of patients implanted with a t-TAH could be transplanted. The overall and post-transplantation survival after t-TAH was satisfactory in these critically ill patients.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Feb 2021; 40:220-228
Carrier M, Moriguchi J, Shah KB, Anyanwu AC, ... Cossette M, Noly PE
J Heart Lung Transplant: 27 Feb 2021; 40:220-228 | PMID: 33341359
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Abstract

Bridging the survival gap in cystic fibrosis: An investigation of lung transplant outcomes in Canada and the United States.

Stephenson AL, Ramos KJ, Sykes J, Ma X, ... Chaparro C, Goss CH
Background
Previous literature in cystic fibrosis (CF) has shown a 10-year survival gap between Canada and the United States (US). We hypothesized that differential access to and survival after lung transplantation may contribute to the observed gap. The objectives of this study were to compare CF transplant outcomes between Canada and the US and estimate the potential contribution of transplantation to the survival gap.
Methods
Data from the Canadian CF Registry and the US Cystic Fibrosis Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. The probability of surviving after transplantation between 2005 and 2016 was calculated using the Kaplan‒Meier method. Survival by insurance status at the time of transplantation and transplant center volume in the US were compared with those in Canada using Cox proportional hazard models. Simulations were used to estimate the contribution of transplantation to the survival gap.
Results
Between 2005 and 2016, there were 2,653 patients in the US and 470 in Canada who underwent lung transplantation for CF. The 1-, 3-, and 5-year survival rates were 88.3%, 71.8%, and 60.3%, respectively, in the US compared with 90.5%, 79.9%, and 69.7%, respectively, in Canada. Patients in the US were also more likely to die on the waitlist (p < 0.01) than patients in Canada. If the proportion of who underwent transplantation and post-transplant survival in the US were to increase to those observed in Canada, we estimate that the survival gap would decrease from 10.8 years to 7.5 years.
Conclusions
Differences in waitlist mortality and post-transplant survival can explain up to a third of the survival gap observed between the US and Canada.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Feb 2021; 40:201-209
Stephenson AL, Ramos KJ, Sykes J, Ma X, ... Chaparro C, Goss CH
J Heart Lung Transplant: 27 Feb 2021; 40:201-209 | PMID: 33386232
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Abstract

The results of a single-center experience with HeartMate 3 in a biventricular configuration.

McGiffin D, Kure C, McLean J, Marasco S, ... Taylor A, Kaye D
Background
Right ventricular (RV) failure after left ventricular assist device (VAD) implantation is a difficult problem. One solution is the implantation of continuous-flow VADs in a biventricular configuration. Disappointing survival and a concerning incidence of right-sided pump thrombosis have been previously reported.
Methods
From May 2017 to April 2020, a total of 12 patients underwent implantation of HeartMate 3 (HM3) biventricular VADs (BiVADs) as a bridge to cardiac transplantation. The right-sided pump was implanted in the right atrium in all cases. Adverse events and patient outcomes were determined.
Results
Patients were male, and the mean age was 44 years. The etiology was dilated cardiomyopathy (6 patients), sarcoid heart disease (2 patients), ischemic cardiomyopathy (1 patient), anthracycline cardiomyopathy (1 patient), non-compaction cardiomyopathy (1 patient), and arrhythmogenic RV cardiomyopathy with biventricular involvement (1 patient). There was 1 death from multisystem failure. There were 3 episodes of right VAD thrombus (thrombosis or clot ingestion); 1 managed medically, 1 recognized intraoperatively treated with clot retrieval, and 1 requiring pump exchange. There were 3 driveline infections. At 18 months after the procedure, 5 patients (41.7%) had undergone cardiac transplantation, 5 patients (41.7%) were alive and on biventricular support, 1 patient had died (8.3%), and 1 patient had VAD explantation for myocardial recovery (8.3%). Actuarial survival at 18 months was 91.7%.
Conclusions
In this small study, HM3 BiVAD in these critically ill patients was used with low mortality. This suggests that the timely deployment of biventricular support with HM3 can be associated with favorable outcomes.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 27 Feb 2021; 40:193-200
McGiffin D, Kure C, McLean J, Marasco S, ... Taylor A, Kaye D
J Heart Lung Transplant: 27 Feb 2021; 40:193-200 | PMID: 33423854
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Impact:
Abstract

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation.

Fessler J, Fischler M, Sage E, Ouattara J, ... Vallee A, Le Guen M
Background
Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors.
Methods
This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients.
Results
Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028).
Conclusions
OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 04 Feb 2021; epub ahead of print
Fessler J, Fischler M, Sage E, Ouattara J, ... Vallee A, Le Guen M
J Heart Lung Transplant: 04 Feb 2021; epub ahead of print | PMID: 33632637
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Impact:
Abstract

Clinical utility of donor-derived cell-free DNA testing in cardiac transplantation.

Khush KK
Surveillance of allograft health after transplantation has traditionally relied on biopsy procedures that enable pathologic assessment for acute rejection. Noninvasive methods to assess for graft injury have been developed and tested over the past decade, and now offer a convenient way to reduce reliance on invasive testing and improve patient satisfaction. Emerging evidence suggests that detection of allograft injury via donor-derived cell-free DNA (dd-cfDNA) may, in fact, have better sensitivity compared to traditional biopsy-based strategies. This state-of-the-art review describes the development, testing, and current use of dd-cfDNA assays for acute rejection monitoring after heart transplantation, and discusses innovative ways that such assays can be used for personalized patient management.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 03 Feb 2021; epub ahead of print
Khush KK
J Heart Lung Transplant: 03 Feb 2021; epub ahead of print | PMID: 33610430
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Impact:
Abstract

Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices.

Tran T, Muralidhar A, Hunter K, Buchanan C, ... Pal J, Cornwell WK
Background
Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population.
Methods
A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function.
Results
In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6.
Conclusions
Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:128-137
Tran T, Muralidhar A, Hunter K, Buchanan C, ... Pal J, Cornwell WK
J Heart Lung Transplant: 30 Jan 2021; 40:128-137 | PMID: 33281029
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Impact:
Abstract

The impact of frailty on mortality after heart transplantation.

Macdonald PS, Gorrie N, Brennan X, Aili SR, ... Iyer A, Jansz PC
Background
Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx.
Methods
We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF).
Results
Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93-100) and 95% (91-99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76-96) and 74% (60-84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4-10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort.
Conclusions
Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:87-94
Macdonald PS, Gorrie N, Brennan X, Aili SR, ... Iyer A, Jansz PC
J Heart Lung Transplant: 30 Jan 2021; 40:87-94 | PMID: 33279391
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Impact:
Abstract

Right ventricular area strain from 3-dimensional echocardiography: Mechanistic insight of right ventricular dysfunction in pediatric pulmonary hypertension.

Jone PN, Duchateau N, Pan Z, Ivy DD, Moceri P
Background
Right ventricular (RV) function is a major contributor to the outcome of pulmonary arterial hypertension (PAH). Adult studies demonstrated that regional and global changes in RV deformation are prognostic in PAH using 3-dimensional echocardiography (3DE). However, regional and global dynamic changes in RV mechanics have not been described in pediatric PAH. We compared 3DE RV regional and global deformation between pediatric patients who had associated PAH with congenital heart disease (APAH-CHD), pediatric patients who had idiopathic PAH (IPAH), and normal controls, and evaluated the clinical outcomes.
Methods
A total of 48 controls, 47 patients with APAH-CHD, and 45 patients with IPAH were evaluated. 3DE RV sequences were analyzed and post-processed to extract global and regional deformation (circumferential, longitudinal, and area strain). Statistical analyses compared the sub-groups on the basis of global and regional deformation, and outcome analysis was performed.
Results
Patients with PAH had significantl8y different global and regional deformation (p < 0.001) compared with controls. Patients with APAH-CHD and and those with IPAH significantly differed in global circumferential strain (p < 0.010), area strain (inlet septum, p = 0.041), and circumferential strain at the inlet septum (p < 0.019), apex free wall (p < 0.004), and inlet free wall (p < 0.004). Circumferential strain at the inlet free wall and circumferential, longitudinal, and area strain at the apex free wall were predictors of adverse events.
Conclusions
RV regional and global strain differ between controls and pediatric patients with PAH. RV apical free-wall area strain provides insight into the mechanism of RV dysfunction in pediatric patients with PAH, with regional strain emerging as outcome predictors, suggesting that this novel measure may be considered as a future measure of RV function.

Published by Elsevier Inc.

J Heart Lung Transplant: 30 Jan 2021; 40:138-148
Jone PN, Duchateau N, Pan Z, Ivy DD, Moceri P
J Heart Lung Transplant: 30 Jan 2021; 40:138-148 | PMID: 33268039
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Impact:
Abstract

A novel method of donor‒recipient size matching in pediatric heart transplantation: A total cardiac volume‒predictive model.

Szugye NA, Zafar F, Ollberding NJ, Villa C, ... Morales DLS, Moore RA
Background
The pediatric heart transplant community uses weight-based donor-to-recipient size matching almost exclusively, despite no evidence to validate weight as a reliable surrogate of cardiac size. Donor size mismatch is the second most common reason for the refusal of donor hearts in current practice (∼30% of all refusals). Whereas case-by-case segmentation of total cardiac volume (TCV) by computed tomography (CT) for direct virtual transplantation is an attractive option, it remains limited by the unavailability of donor chest CT. We sought to establish a predictive model for donor TCV on the basis of anthropomorphic and chest X-ray (CXR) cardiac measures.
Methods
Banked imaging studies from 141 subjects with normal CT chest angiograms were obtained and segmented using 3-dimensional modeling to derive TCV. CXR data were available for 62 of those subjects. A total of 3 predictive models of TCV were fit through multiple linear regression using the following variables: Model A (weight only); Model B (weight, height, sex, and age); Model C (weight, height, sex, age, and 1-view anteroposterior CXR maximal horizontal cardiac width).
Results
Model C provided the most accurate prediction of TCV (optimism corrected R2 = 0.99, testing set R2 = 0.98, mean absolute percentage error [MAPE] = 8.6%) and outperformed Model A (optimism corrected R2 = 0.94, testing set R2 = 0.94, MAPE = 16.1%) and Model B (optimism corrected R2 = 0.97, testing set R2 = 0.97, MAPE = 11.1%).
Conclusions
TCV can be predicted accurately using readily available anthropometrics and a 1-view CXR from donor candidates. This simple and scalable method of TCV estimation may provide a reliable and consistent method to improve donor size matching.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:158-165
Szugye NA, Zafar F, Ollberding NJ, Villa C, ... Morales DLS, Moore RA
J Heart Lung Transplant: 30 Jan 2021; 40:158-165 | PMID: 33317957
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Impact:
Abstract

Improved survival after heart transplantation in patients bridged with extracorporeal membrane oxygenation in the new allocation system.

Gonzalez MH, Acharya D, Lee S, Leacche M, ... Jovinge S, Loyaga-Rendon RY
Background
Historically, patients bridged on extracorporeal membrane oxygenation (ECMO) to heart transplantation (HT) have very high post-transplant mortality. In the new heart transplant allocation system, ECMO-supported patients have the highest priority for HT. However, data are lacking on the outcomes of these critically ill patients. We compared the waitlist and post-transplant outcomes of ECMO-supported patients in the new and old allocation systems.
Methods
Adult patients supported by ECMO at the time of listing or transplantation who were registered in the United Network for Organ Sharing database between November 1, 2015 and September 30, 2019 were included. Clinical characteristics, outcomes in the waitlist, and post-transplant survival were compared between the old and new systems. Cox Proportional and subdistribution hazard regression models were used to evaluate the variables contributing to the post-transplant and waitlist outcomes
Results:
A total of 296 ECMO-supported patients were listed for HT. Of these, 191 were distributed to the old system, and 105 were distributed to the new system. Patients listed in the new system had a higher cumulative incidence of HT (p < 0.001) and lower incidence of death or removal (p = 0.001) from the transplant list than patients listed in the old system. The 6-month survival after transplantation was 74.6% and 90.6% for the old- and new-era patients, respectively (p = 0.002). Among ECMO-supported patients, being listed or transplanted on the new system was independently associated with improved outcomes in the waitlist and after transplantation.
Conclusions
With the implementation of the new heart transplant allocation system, ECMO-supported patients have a shorter waitlist time, improved frequency of HT, and improved short-term post-transplant survival.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:149-157
Gonzalez MH, Acharya D, Lee S, Leacche M, ... Jovinge S, Loyaga-Rendon RY
J Heart Lung Transplant: 30 Jan 2021; 40:149-157 | PMID: 33277169
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Impact:
Abstract

Bronchiolitis obliterans syndrome is associated with increased senescent lymphocytes in the small airways.

Hodge G, Hodge S, Liu H, Nguyen P, Holmes-Liew CL, Holmes M
Background
Immunosuppression therapy is ineffective at preventing bronchiolitis obliterans syndrome (BOS), primarily a disease of the small airways (SAs). Our previous reports show increased senescent CD28null T and natural killer T (NKT)-like cells in the peripheral blood of patients with BOS and increased cytotoxic, proinflammatory lymphocytes in the SAs. We hypothesized that the cytotoxic, proinflammatory lymphocytes in the SAs would be steroid-resistant senescent CD28null lymphocytes.
Methods
Intracellular cytotoxic mediator granzyme B, interferon (IFN)-γ and tumor necrosis factor (TNF)-α proinflammatory cytokines, and CD28 were measured in the blood, bronchoalveolar lavage, large airway, and SA brushing T and NKT-like cells from 10 patients with BOS, 11 stable lung transplant recipients, and 10 healthy age-matched controls. SA brushings were cultured in the presence of ±1 µmol/liter prednisolone, ±5 mg/liter theophylline, and ±2.5 ng/ml cyclosporine A, and IFN-γ and TNF-α proinflammatory cytokines were assessed using flow cytometry.
Results
Increased SA CD28null T and NKT-like cells were identified in patients with BOS compared with that in the controls and stable transplant recipients. Loss of CD28 was associated with increased T and NKT-like cells expressing granzyme B, IFN-γ, and TNF-α. Loss of CD28 expression by CD8+ T cells was significantly associated with forced expiratory volume in 1 sec (R = 0.655, p = 0.006) and with time after transplantation (R = -0.552, p = 0.041). Treatment with prednisolone + theophylline + cyclosporin A inhibited IFN-γ and TNF-α production by SA CD28null CD8+ T and NKT-like cells additively.
Conclusions
BOS is associated with the loss of CD28 in SA cytotoxic, proinflammatory senescent T and NKT-like lymphocytes. Treatment options that target the proinflammatory nature of these cells in the SAs may improve graft survival.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:108-119
Hodge G, Hodge S, Liu H, Nguyen P, Holmes-Liew CL, Holmes M
J Heart Lung Transplant: 30 Jan 2021; 40:108-119 | PMID: 33317956
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Impact:
Abstract

Ventilation in the prone position improves oxygenation and results in more lungs being transplanted from organ donors with hypoxemia and atelectasis.

Marklin GF, O\'Sullivan C, Dhar R
Background
Hypoxemia is the most common barrier to lungs being transplanted from eligible organ donors who are brain dead (BD). Atelectasis is the principal reversible contributing factor to hypoxemia after brain death. We evaluated prospectively whether ventilation in the prone position in donors who are BD would reverse atelectasis, improve oxygenation, and result in more lungs being transplanted.
Methods
Organ donors managed at the recovery center of 1 organ procurement organization over a 2-year period who exhibited hypoxemia (partial pressure of arterial oxygen [PaO2]/fraction of inspired oxygen of <300 mm Hg) and had evidence of atelectasis were ventilated in the prone position for 12 hours or longer during donor management. A subset underwent computed tomography (CT) imaging to quantify the degree of atelectasis before and after prone positioning. Outcomes were compared with those of a control group with hypoxemia and atelectasis managed similarly but in the supine position in the previous 2 years.
Results
A total of 40 lung-eligible donors who were BD with hypoxemia and atelectasis were managed in a prone position and compared with 79 donors in supine position. Baseline PaO2 was similar between the prone and the supine groups (194 ± 78 vs 177 ± 77 mm Hg, p = 0.26) but increased more in the prone group at 4 hours (by 113 vs 54 mm Hg, p = 0.001) and remained 74-mm Hg higher at 12 hours (340 vs 266 mm Hg, p = 0.0006). CT-graded atelectasis was significantly reduced after ventilation in the prone position but persisted in the supine group (p = 0.001). Final PaO2 was not significantly higher (344 vs 306, p = 0.12), but lungs were more often transplanted in the prone group (45% vs 24%, p = 0.03).
Conclusions
Ventilation in the prone position reverses atelectasis and rapidly and sustainably improves oxygenation in organ donors who are BD with hypoxemia. This effect appears to translate into more lungs being transplanted.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:120-127
Marklin GF, O'Sullivan C, Dhar R
J Heart Lung Transplant: 30 Jan 2021; 40:120-127 | PMID: 33339675
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Impact:
Abstract

Impact of cytomegalovirus infection on gene expression profile in heart transplant recipients.

Kanwar MK, Khush KK, Pinney S, Sherman C, ... Uriel N, Kobashigawa J
Background
Cytomegalovirus (CMV) infection has been implicated in the pathogenesis of allograft rejection in heart transplant (HT) recipients. The effect of a CMV infection on the gene expression profiling (GEP, AlloMap) scores in the absence of acute rejection is not known.
Methods
Data from 14,985 samples collected from 2,288 adult HT recipients enrolled in Outcomes AlloMap Registry were analyzed. Patients with known CMV serology at the time of HT who had at least 1 AlloMap score reported during follow-up were included. AlloMap scores for those patients with CMV (but no ongoing rejection) were compared with those who were never infected. An exploratory analysis on the impact of CMV on available donor-derived cell-free DNA (AlloSure) was also performed.
Results
A total of 218 patients (10%) were reported to have CMV infection after transplantation. AlloMap score in those samples with CMV infection (n = 311) had a GEP score (34; range: 29-36) significantly higher than the GEP score from samples (n = 14,674) obtained in the absence of CMV infection (30; range: 26-34; p < 0.0001). Both asymptomatic viremia and CMV disease demonstrated significantly higher AlloMap scores than no CMV infection samples (median scores: 33, 35, and 30, respectively; p < 0.0001). AlloSure levels, available for 776 samples, were not significantly different (median: 0.23% in 18 samples with CMV infection vs 0.15% in 776 samples without CMV infection; p = 0.66).
Conclusions
CMV infection in HT recipients is associated with an increase in AlloMap score, whereas AlloSure results do not appear to be impacted. This information should be considered when clinically interpreting abnormal/high AlloMap scores in HT recipients.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Jan 2021; 40:101-107
Kanwar MK, Khush KK, Pinney S, Sherman C, ... Uriel N, Kobashigawa J
J Heart Lung Transplant: 30 Jan 2021; 40:101-107 | PMID: 33341360
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Impact:
Abstract

Native lung complications after living-donor lobar lung transplantation.

Mineura K, Chen-Yoshikawa TF, Tanaka S, Yamada Y, ... Menju T, Date H
Background
Living-donor lobar lung transplantation (LDLLT) is viable for critically ill patients in situations of donor shortage. Because it is sometimes difficult to find 2 ideal living donors with suitable graft sizes, we developed native lung-sparing procedures, including single LDLLT and native upper lobe-sparing LDLLT. This study aimed to investigate native lung complications (NLCs) in native lung-sparing LDLLT.
Methods
Between April 2002 and March 2019, 92 LDLLTs and 124 cadaveric lung transplantations (CLTs) were performed at the Kyoto University Hospital. Our prospectively maintained database and clinical records were reviewed to compare NLCs among recipients who underwent native lung-sparing LDLLT (n = 21) with those among recipients who underwent single CLT (n = 61).
Results
Among 21 recipients who underwent native lung-sparing LDLLT, 11 NLCs occurred in 8 recipients. No fatal NLC was noted; however, 2 required surgical intervention. Post-transplant survival was not significantly different between native lung-sparing LDLLT recipients with NLCs and those without NLCs. The incidence of NLCs was comparable between native lung-sparing LDLLT recipients and single CLT recipients (8/21 vs 26/61, p = 0.80); however, NLCs occurred significantly later in LDLLT recipients than in CLT recipients (median: 665 vs 181.5 days after transplantation, p = 0.014).
Conclusions
NLCs after native lung-sparing LDLLT had favorable outcomes. Therefore, native lung-sparing LDLLT is a useful treatment option for severely ill patients who cannot wait for CLT. However, it is important to recognize that NLCs may occur later in LDLLT than in CLT.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 23 Jan 2021; epub ahead of print
Mineura K, Chen-Yoshikawa TF, Tanaka S, Yamada Y, ... Menju T, Date H
J Heart Lung Transplant: 23 Jan 2021; epub ahead of print | PMID: 33602629
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Impact:
Abstract

Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial.

Brautaset Englund KV, Østby CM, Rolid K, Gude E, ... Gullestad L, Broch K
Aims
Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients.
Methods and results
This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39).
Conclusion
Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%.
Trial registration number
http//www.clinicaltrials.gov identifier NCT03662789.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 22 Jan 2021; epub ahead of print
Brautaset Englund KV, Østby CM, Rolid K, Gude E, ... Gullestad L, Broch K
J Heart Lung Transplant: 22 Jan 2021; epub ahead of print | PMID: 33612360
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Impact:
Abstract

Risk of primary graft dysfunction following lung transplantation in selected adults with connective tissue disease-associated interstitial lung disease.

Natalini JG, Diamond JM, Porteous MK, Lederer DJ, ... Kawut SM, Bernstein EJ
Background
Previous studies have reported similarities in long-term outcomes following lung transplantation for connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis (IPF). However, it is unknown whether CTD-ILD patients are at increased risk of primary graft dysfunction (PGD), delays in extubation, or longer index hospitalizations following transplant compared to IPF patients.
Methods
We performed a multicenter retrospective cohort study of CTD-ILD and IPF patients enrolled in the Lung Transplant Outcomes Group registry who underwent lung transplantation between 2012 and 2018. We utilized mixed effects logistic regression and stratified Cox proportional hazards regression to determine whether CTD-ILD was independently associated with increased risk for grade 3 PGD or delays in post-transplant extubation and hospital discharge compared to IPF.
Results
A total of 32.7% (33/101) of patients with CTD-ILD and 28.9% (145/501) of patients with IPF developed grade 3 PGD 48-72 hours after transplant. There were no significant differences in odds of grade 3 PGD among patients with CTD-ILD compared to those with IPF (adjusted OR 1.12, 95% CI 0.64-1.97, p = 0.69), nor was CTD-ILD independently associated with a longer post-transplant time to extubation (adjusted HR for first extubation 0.87, 95% CI 0.66-1.13, p = 0.30). However, CTD-ILD was independently associated with a longer post-transplant hospital length of stay (median 23 days [IQR 14-35 days] vs17 days [IQR 12-28 days], adjusted HR for hospital discharge 0.68, 95% CI 0.51-0.90, p = 0.008).
Conclusion
Patients with CTD-ILD experienced significantly longer postoperative hospitalizations compared to IPF patients without an increased risk of grade 3 PGD.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 22 Jan 2021; epub ahead of print
Natalini JG, Diamond JM, Porteous MK, Lederer DJ, ... Kawut SM, Bernstein EJ
J Heart Lung Transplant: 22 Jan 2021; epub ahead of print | PMID: 33637413
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Impact:
Abstract

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

Alba AC, Foroutan F, Buchan TA, Alvarez J, ... Rao V, Billia F
Background
Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS).
Methods
In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology.
Results
We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA.
Conclusions
Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 Jan 2021; epub ahead of print
Alba AC, Foroutan F, Buchan TA, Alvarez J, ... Rao V, Billia F
J Heart Lung Transplant: 18 Jan 2021; epub ahead of print | PMID: 33551227
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Impact:
Abstract

Safety of reduced anti-thrombotic strategy in patients with HeartMate 3 left ventricular assist device.

Marshall D, Sanchez J, Yuzefpolskaya M, Sayer GT, ... Uriel N, Topkara VK
There are limited safety data on reduced anti-thrombotic therapy (RT) in patients with HeartMate 3 (HM3) left ventricular assist device (LVAD). We conducted a single-center, retrospective study of patients with HM3 managed with RT from November 2014 through January 2020. We analyzed baseline characteristics, RT indications, and bleeding and thrombotic complications. We found that 50 of 161 patients with HM3 (31.1%) received RT starting at a median time of 90.5 days after LVAD implantation. Patients on RT were older and more likely to have ischemic heart failure than patients on standard anti-thrombotic therapy (ST). The most common indication for RT was gastrointestinal bleeding (29 patients [58.0%]). At 1-year follow-up, 5.0% of patients on RT developed a thrombotic event. Switching patients from ST to RT reduced the occurrence of major bleeding from 1.252 to 0.324 events per patient-year (p = 0.006). In our population of patients with HM3 LVAD, RT reduces bleeding without increasing the incidence of thrombosis. Our retrospective study suggests that an upfront RT strategy in patients with HM3 may be beneficial and should be prospectively studied.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 Jan 2021; epub ahead of print
Marshall D, Sanchez J, Yuzefpolskaya M, Sayer GT, ... Uriel N, Topkara VK
J Heart Lung Transplant: 18 Jan 2021; epub ahead of print | PMID: 33551226
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Impact:
Abstract

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

Zafar F, Conway J, Bleiweis MS, Al-Aklabi M, ... Villa C, ACTION Learning Network Investigators
Background
The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration.
Methods
ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014).
Results
Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group.
Conclusions
The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 Jan 2021; epub ahead of print
Zafar F, Conway J, Bleiweis MS, Al-Aklabi M, ... Villa C, ACTION Learning Network Investigators
J Heart Lung Transplant: 18 Jan 2021; epub ahead of print | PMID: 33579597
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Impact:
Abstract

Systemic ventricular assist device support in Fontan patients: A report by ACTION.

Cedars A, Kutty S, Danford D, Schumacher K, ... Zinn M, ACTION Learning Network Investigators:
Background
The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients.
Methods
We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation.
Results
We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals.
Conclusions
VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 18 Jan 2021; epub ahead of print
Cedars A, Kutty S, Danford D, Schumacher K, ... Zinn M, ACTION Learning Network Investigators:
J Heart Lung Transplant: 18 Jan 2021; epub ahead of print | PMID: 33642140
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Impact:
Abstract

Spectrum of findings on ventilation‒perfusion lung scintigraphy after lung transplantation and association with outcomes.

Mohanka M, Pinho DF, Garcia H, Kanade R, ... Zhang S, Banga A
Background
Air trapping (AT) is one of the hallmarks of allograft dysfunction after lung transplantation (LT). Inert gas‒based ventilation‒perfusion (VQ) lung scintigraphy has excellent sensitivity in the detection of AT.
Methods
We reviewed the charts of patients who underwent single or double LT between January 2012 and December 2014 (N = 193). Patients without a VQ scintigraphy at the first annual visit (n = 16) and those who did not survive till 1 year (n = 26) were excluded (final n = 151, mean age = 55.8 [SD =14] years, male = 85, female = 66). VQ scintigraphy was independently reviewed and reconciled for the presence and severity of AT by 2 investigators blinded to the clinical data (D.F.P. and D.M.). A 3-year post-transplant survival was the primary end-point.
Results
AT was common (n = 73, 48.3%). Patients with obstructive lung diseases as the underlying diagnosis (adjusted odds ratio [OR], 4.36, 95% CI: 1.64‒11.6; p = 0.003) and those with lower body mass index (BMI) (BMI < 25 kg/m2 and 25‒30 kg/m2; p < 0.001) had an increased risk of developing AT in the allograft. The presence of AT (adjusted OR, 2.33, 95% CI: 1.01‒5.36; p = 0.04) and peak forced expiratory volume in 1 sec (FEV1) <60% predicted during the first year after LT were independently associated with 3-year mortality. The association of AT with post-transplant mortality was the strongest among patients with BMI <30 kg/m2 and peak FEV1 <60% predicted.
Conclusions
The finding of AT on VQ scintigraphy at the first annual visit after LT is independently associated with worse post-transplant mortality. The sub-group of patients who fail to achieve a peak FEV1 of 60% predicted during the first year after LT appears to be the key driver of this association.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 15 Jan 2021; epub ahead of print
Mohanka M, Pinho DF, Garcia H, Kanade R, ... Zhang S, Banga A
J Heart Lung Transplant: 15 Jan 2021; epub ahead of print | PMID: 33648871
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Impact:
Abstract

Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.

Kraft BD, Mahmood K, Harlan NP, Hartwig MG, ... Suliman HB, Shofer SL
Background
Central airway stenosis (CAS) is a severe airway complication after lung transplantation associated with bronchial ischemia and necrosis. We sought to determine whether hyperbaric oxygen therapy (HBOT), an established treatment for tissue ischemia, attenuates post-transplant bronchial injury.
Methods
We performed a randomized, controlled trial comparing usual care with HBOT (2 atm absolute for 2 hours × 20 sessions) in subjects with extensive airway necrosis 4 weeks after transplantation. Endobronchial biopsies were collected at 4, 7, and 10 weeks after transplantation for a quantitative polymerase chain reaction. Coprimary outcomes were incidence of airway stenting and acute cellular rejection (ACR) at 1 year.
Results
The trial was stopped after enrolling 20 subjects (n = 10 per group) after a pre-planned interim analysis showed no difference between usual care and HBOT groups in stenting (both 40%), ACR (70% and 40%, respectively), or CAS (40% and 60%, respectively). Time to first stent placement (median [interquartile range]) was significantly shorter in the HBOT group (150 [73-150] vs 186 [167-206] days, p < 0.05). HIF gene expression was significantly increased in donor tissues at 4, 7, and 10 weeks after transplantation but was not altered by HBOT. Subjects who developed CAS or required stenting had significantly higher HMOX1 and VEGFA expression at 4 weeks (both p < 0.05). Subjects who developed ACR had significant FLT1, TIE2, and KDR expression at 4 weeks (all p < 0.05).
Conclusions
Incidence of CAS is high after severe, established airway necrosis after transplantation. HBOT does not reduce CAS severity or stenting. Elevated HMOX1 and VEGFA expressions appear to associate with airway complications.

Published by Elsevier Inc.

J Heart Lung Transplant: 14 Jan 2021; epub ahead of print
Kraft BD, Mahmood K, Harlan NP, Hartwig MG, ... Suliman HB, Shofer SL
J Heart Lung Transplant: 14 Jan 2021; epub ahead of print | PMID: 33518452
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Impact:
Abstract

Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE.

Kim NH, Hemnes AR, Chakinala MM, Highland KB, ... Narayan V, Farber HW
Background
Selexipag is a selective oral prostacyclin receptor agonist indicated for pulmonary arterial hypertension (PAH) treatment. SelexiPag: tHe usErs dRug rEgistry (SPHERE) (NCT03278002) is collecting data from selexipag-treated patients in real-world clinical practice to elucidate and describe the clinical characteristics, outcomes, and dosing/titration regimens of patients treated with selexipag in routine clinical practice.
Methods
SPHERE is a United States (US)-based, ongoing, multicenter, prospective observational study (target N = 800). This study enrolls patients who are either newly initiated on selexipag (≤60 days before enrollment) or were previously receiving selexipag with documentation of dose titration at study enrollment. Data collection for the study occurs at routine clinic visits. In this paper, we report on the first 500 patients enrolled.
Results
Median follow-up was 17.8 months; 77.6% of patients completed the planned 18 months follow-up, and 22.4% discontinued early from the study. At diagnosis, 94.8% of patients had PAH (World Health Organization [WHO] Group 1), most commonly idiopathic (49.2%) and connective tissue disease associated (26.4%). Most patients (72.4%) initiated selexipag more than 60 days before enrollment. At initiation, 31.0% of patients had WHO functional class (FC) II disease, and 49.6% had WHO FC II or III disease. In addition, 55.0% of patients were receiving double therapy (most commonly an endothelin receptor antagonist plus phosphodiesterase type 5 inhibitor [42.3%]), whereas 30.6% were receiving monotherapy. Despite most patients already receiving PAH-specific therapy, at selexipag initiation, 67.2% (336 of 500) were at intermediate risk, and 9.6% (48 of 500) were at high risk of 1-year mortality. Risk scores remained stable in ∼55% of patients and improved in ∼20% at the end of the study. In total, 72.2% of patients had at least 1 adverse event (AE), and 37.6% reported a serious AE. The median selexipag maintenance dose was 1,200 µg twice daily (interquartile range: 800-1,600 µg twice daily).
Conclusions
Real-world, US-based patients with PAH initiating selexipag typically have WHO FC II/III disease and are at intermediate risk, despite receiving PAH-specific treatment. Selexipag was prescribed as part of a combination regimen in most patients. The study identified no unexpected adverse effects.

Copyright © 2021. Published by Elsevier Inc.

J Heart Lung Transplant: 14 Jan 2021; epub ahead of print
Kim NH, Hemnes AR, Chakinala MM, Highland KB, ... Narayan V, Farber HW
J Heart Lung Transplant: 14 Jan 2021; epub ahead of print | PMID: 33526303
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Impact:
Abstract

Less invasive surgical implant strategy and right heart failure after LVAD implantation.

Saeed D, Muslem R, Rasheed M, Caliskan K, ... Houston BA, Tedford RJ
Background
Conventional median sternotomy (CMS) is still the standard technique utilized to implant left ventricular assist devices (LVADs). Recent studies suggest that less invasive surgery (LIS) may be beneficial; however, robust data on differences in right heart failure (RHF) are lacking. This study aimed to determine the impact of LIS compared with that of CMS on RHF outcomes after LVAD implantation.
Methods
An international multicenter retrospective cohort study was conducted across 5 centers. Patients were grouped according to their implantation technique (LIS vs CMS). Only centrifugal devices were included. RHF was defined as severe or severe acute RHF according to the 2013 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition. Logistic multivariate regression and propensity score‒matched analyses were performed to account for confounding.
Results
Overall, 427 implantations occurred during the study period, with 305 patients implanted using CMS and 122 using LIS. Pre-operative extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) use was more common in the CMS group; off-pump implantation was more common in the LIS group. Other pre-implant variables, including age, creatinine, hemodynamics, and tricuspid regurgitation, did not differ between the 2 groups. Post-operative RHF was less common in the patients who underwent LIS than in those who underwent CMS as was post-operative right ventricular assist device (RVAD) use. LIS remained associated with less RHF in the multivariate analysis. After propensity score matching conditional for age, sex, INTERMACS profile, ECMO, and IABP use in a ratio of 2:1 (CMS to LIS), RHF (29.9% vs 18.6%, p = 0.001) and the need for post-operative RVAD (18.6% vs 8.2%; p = 0.009) remained more common in the CMS group than in the LIS group. There were no significant differences in survival up to 1 year between the groups.
Conclusions
LIS may be associated with less RHF after LVAD implantation compared with CMS. Despite the possible reduction in RHF, there was no difference in 1-year survival. LIS is an alternative to traditional CMS.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 Jan 2021; epub ahead of print
Saeed D, Muslem R, Rasheed M, Caliskan K, ... Houston BA, Tedford RJ
J Heart Lung Transplant: 11 Jan 2021; epub ahead of print | PMID: 33509653
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Impact:
Abstract

Clinical features and prognosis of surgically proven constrictive pericarditis after orthotopic heart transplantation.

Lloyd JW, Oh JK, Daly RC, Frantz RR, ... Allen LS, Miranda WR
Constrictive pericarditis (CP) results in pericardial non-compliance and diastolic dysfunction. Definitive treatment is pericardiectomy, but data on CP after orthotopic heart transplantation (OHT) are limited. Accordingly, a retrospective review of 8 cases of surgically proven CP after OHT undergoing pericardiectomy was conducted. In this series, all patients were male. The median time to symptomatic CP after OHT was 1.7 years (range: 0.8-18.1 years). The echocardiographic assessment was diagnostic for CP in 3 cases (38%). Cross-sectional imaging was performed in 6 cases, revealing ≥ mild pericardial thickening in all. A total of 6 patients (75%) underwent cardiac catheterization, which revealed CP in 5 (83%). Post-pericardiectomy 30-day mortality was 13% (1 patient). The median survival after pericardiectomy was 2.3 years (range: 18 days-14.6 years) and 5-year survival was 29%. Overall, CP after OHT represents a subset of patients with CP with high morbidity and mortality, and multimodality assessment is essential for its diagnosis. Despite a relatively low surgical mortality, long-term survival is poor.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 11 Jan 2021; epub ahead of print
Lloyd JW, Oh JK, Daly RC, Frantz RR, ... Allen LS, Miranda WR
J Heart Lung Transplant: 11 Jan 2021; epub ahead of print | PMID: 33546972
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Impact:
Abstract

COVID-19 vaccination in our transplant recipients: The time is now.

Aslam S, Goldstein DR, Vos R, Gelman AE, ... Wolfe C, Danziger-Isakov L
We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients.

Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 01 Jan 2021; epub ahead of print
Aslam S, Goldstein DR, Vos R, Gelman AE, ... Wolfe C, Danziger-Isakov L
J Heart Lung Transplant: 01 Jan 2021; epub ahead of print | PMID: 33487534
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Impact:
Abstract

Ventilation parameters and early graft function in double lung transplantation.

Schwarz S, Benazzo A, Dunkler D, Muckenhuber M, ... Klepetko W, Hoetzenecker K
Background
Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU).
Methods
A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (PIP), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest.
Results
In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (PIP, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679.
Conclusions
The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:4-11
Schwarz S, Benazzo A, Dunkler D, Muckenhuber M, ... Klepetko W, Hoetzenecker K
J Heart Lung Transplant: 30 Dec 2020; 40:4-11 | PMID: 33144029
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Impact:
Abstract

Ex situ heart perfusion: The past, the present, and the future.

Wang L, MacGowan GA, Ali S, Dark JH
Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening. Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability. This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:69-86
Wang L, MacGowan GA, Ali S, Dark JH
J Heart Lung Transplant: 30 Dec 2020; 40:69-86 | PMID: 33162304
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Abstract

Risk factors for mortality in lung transplant recipients aged ≥65 years: A retrospective cohort study of 5,815 patients in the scientific registry of transplant recipients.

Mosher CL, Weber JM, Frankel CW, Neely ML, Palmer SM
Background
Lung transplantation is increasingly performed in recipients aged ≥65 years. However, the risk factors for mortality specific to this population have not been well studied. In lung transplant recipients aged ≥65 years, we sought to determine post-transplant survival and clinical factors associated with post-transplant mortality.
Methods
We investigated 5,815 adult lung transplants recipients aged ≥65 years in the Scientific Registry of Transplant Recipients. Mortality was defined as a composite of recipient death or retransplantation. The Kaplan-Meier method was used to estimate the median time to mortality. Univariable and multivariable Cox proportional hazards regression models were used to examine the association between time to mortality and 23 donor, recipient, or center characteristics.
Results
Median survival in lung transplant recipients aged ≥65 years was 4.41 years (95% CI: 4.21-4.60 years) and significantly worsened by increasing age strata. In the multivariable model, increasing recipient age strata, creatinine level, bilirubin level, hospitalization at the time of transplantation, single lung transplant operation, steroid use at the time of transplantation, donor diabetes, and cytomegalovirus mismatch were independently associated with increased mortality.
Conclusions
Among the 8 risk factors we identified, 5 factors are readily available, which can be used to optimize post-transplant survival by informing risk during candidate selection of patients aged ≥65 years. Furthermore, bilateral lung transplantation may confer improved survival in comparison with single lung transplantation. Our results support that after careful consideration of risk factors, lung transplantation can provide life-extending benefits in individuals aged ≥65 years.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:42-55
Mosher CL, Weber JM, Frankel CW, Neely ML, Palmer SM
J Heart Lung Transplant: 30 Dec 2020; 40:42-55 | PMID: 33208278
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Abstract

Donor ventilation parameters as predictors for length of mechanical ventilation after lung transplantation: Results of a prospective multicenter study.

Benazzo A, Schwarz S, Frommlet F, Sinn K, ... Cypel M, Hoetzenecker K
Background
The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval.
Methods
A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV.
Results
In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (Cdyn) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and Cdyn was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293).
Conclusion
In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that Cdyn is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:33-41
Benazzo A, Schwarz S, Frommlet F, Sinn K, ... Cypel M, Hoetzenecker K
J Heart Lung Transplant: 30 Dec 2020; 40:33-41 | PMID: 33246712
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Abstract

Histologic features of thrombosis events with a centrifugal left ventricular assist device.

Jessen SL, Kaulfus CN, Chorpenning K, Ginn-Hedman AM, Tamez D, Weeks BR
Background
Histology of thrombosis events in left ventricular assist devices (LVADs) may point to differences between the etiology of either ingested or de novo thrombus formation within LVADs. Materials ingested by the pump would have features suggestive of lifting and folding, whereas thrombi formed de novo would have uniform, parallel layers. This study tested this hypothesis in a cohort of explanted HeartWare Ventricular assist devices (HVADs) (Medtronic, Miami Lakes, Florida).
Methods
Histology of thrombi from 59 explanted HVAD pumps were classified as presumed ingested, presumed de novo, or undeterminable on the basis of pre-defined criteria. The apparent size and location of the thrombotic materials were noted.
Results
Histologically, all thrombotic materials were either presumed to be ingested (73%; 95 of 130 total histology cassettes examined) or of undeterminable origin (27%; 35 of 130 histology cassettes). Undetermined origin commonly was due to a lack of sufficient material for analysis. The larger materials (>800 mm3) tended to be in the inflow region. The most common finding was smaller thrombotic materials (<150 mm3) within the pump (64%; 38 of 59 HVADs); when these smaller materials were ingested by the pump, they were most often found within the smaller flow pathways within the pump.
Conclusions
Our study suggests that the thrombi within HVAD pumps are commonly ingested materials rather than de novo thrombus formation within the pump. Further research to understand the source of this ingested material and the consideration to mitigate this complication should be considered.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:56-64
Jessen SL, Kaulfus CN, Chorpenning K, Ginn-Hedman AM, Tamez D, Weeks BR
J Heart Lung Transplant: 30 Dec 2020; 40:56-64 | PMID: 33339557
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Abstract

Transplantation for congenital heart disease is associated with an increased risk of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in children.

Offor UT, Bacon CM, Roberts J, Powell J, ... Reinhardt Z, Bomken S
Background
Children undergoing heart transplant are at higher risk of developing post-transplant lymphoproliferative disorder (PTLD) than other solid organ recipients. The factors driving that risk are unclear. This study investigated risk factors for PTLD in children transplanted at 1 of 2 United Kingdom pediatric cardiac transplantation centers.
Methods
All children (<18 years, n = 200) transplanted at our institution over a 16-year period were analyzed. Freedom from PTLD was assessed using the Kaplan-Meier method and Cox proportional regression.
Results
PTLD occurred in 17 of 71 children transplanted for congenital heart disease (CHD) and 18 of 129 transplanted for acquired cardiomyopathy (ACM). The cumulative incidence of all PTLD was 21.1% at 5 years after transplant. Median time from transplant to PTLD was 2.9 years (interquartile range: 0.9-4.6). Negative Epstein-Barr virus (EBV) serostatus pre-transplant (adjusted hazard ratio [HR]: 2.7, 95% CI: 1.3-5.6, p = 0.01) and underlying CHD (adjusted HR: 3.2, 95% CI: 1.4-7.4, p = 0.007) were independently associated with higher risk of PTLD. Age at thymectomy was significantly different between children with CHD and ACM (0.4 vs 5.5 years, p < 0.01). Median CD4+ and CD8+ T lymphocyte counts at 2 years after transplant were significantly lower in children transplanted for CHD vs ACM (CD4+: 391/µl vs 644/µl, p = 0.01; CD8+: 382/µl vs 500/µl, p = 0.01). At 5 years after transplant, those differences persisted among patients who developed PTLD (CD4+, 430/µl vs 963/µl, p < 0.01 and CD8+, 367/µl vs 765/µl, p < 0.01).
Conclusion
Underlying CHD is an independent risk factor for PTLD and is associated with a younger age at thymectomy. A persistent association with altered T lymphocyte subsets may contribute to the impaired response to primary EBV infection and increase the risk of PTLD.

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:24-32
Offor UT, Bacon CM, Roberts J, Powell J, ... Reinhardt Z, Bomken S
J Heart Lung Transplant: 30 Dec 2020; 40:24-32 | PMID: 33339556
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Abstract

The autotaxin-lysophosphatidic acid pathway mediates mesenchymal cell recruitment and fibrotic contraction in lung transplant fibrosis.

Sinclair KA, Yerkovich ST, Hopkins PM, Fieuw AM, ... O\'Sullivan B, Chambers DC
Background
Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality in lung transplant recipients. CLAD is characterized by respiratory failure owing to the accumulation of fibrotic cells in small airways and alveoli, inducing tissue contraction and architectural destruction. However, the source of the fibroblastic cells and the mechanism(s) underlying the accumulation and activation remain unexplained. Mesenchymal stromal cells (MSCs) are multipotent progenitors that are normally located in the lung tissue but can be isolated from the alveolar space in lung transplant recipients, where they have a profibrotic phenotype. Our objective was to identify the mediator(s) inducing migration and contractile differentiation of lung tissue MSCs.
Methods
Bronchoalveolar lavage (BAL) (7 healthy controls and 21 lung transplant recipients), CCL2, HGF, TGFB, EGF, and PDGF-BB and autotaxin were measured by enzyme-linked immunosorbent assay. BAL (7 healthy controls and 31 lung transplant recipients) lysophosphatidic acid (LPA) (16:0, 18:0, 18:1, 22:4) was measured by liquid chromatography with tandem mass spectrometry. The effect of inhibition of candidate mediators on BAL-mediated chemoattraction of MSCs and contraction of MSC-spiked collagen gel assays was assessed. BAL cells from a lung transplant recipient with CLAD were analyzed by single-cell RNA sequencing.
Results
We first demonstrate that BAL fluid from lung transplant recipients and particularly those with CLAD is potently chemoattractive to human lung tissue‒derived MSCs and induces a contractile phenotype. After excluding several candidate mediators, we show that LPA blockade completely abrogated transplant recipient BAL‒mediated chemoattraction of MSCs and contraction of MSC-spiked collagen gels. Furthermore, LPA levels were enriched in transplant recipient BAL, and LPA replicated the observed in vitro profibrotic effects of transplant recipient BAL. Finally, we identify BAL monocyte‒derived macrophages with autotaxin (ENPP2) and fibrotic transcriptional signature.
Conclusions
Autotaxin-expressing alveolar macrophages are present in CLAD BAL. These cells potentially provide a local source of autotaxin/LPA that drives MSC recruitment and tissue contraction in CLAD. These cells are analogous to an aberrant macrophage population recently identified in idiopathic pulmonary fibrosis, suggesting an overlap in pathogenesis between CLAD and other forms of lung fibrosis.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:12-23
Sinclair KA, Yerkovich ST, Hopkins PM, Fieuw AM, ... O'Sullivan B, Chambers DC
J Heart Lung Transplant: 30 Dec 2020; 40:12-23 | PMID: 33339555
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Abstract

Risk assessment in patients with pulmonary arterial hypertension in the era of COVID 19 pandemic and the telehealth revolution: State of the art review.

Wesley Milks M, Sahay S, Benza RL, Farber HW
Patients affected by pulmonary arterial hypertension (PAH) benefit from intensive, continuous clinical monitoring to guide escalation of treatments that carry the potential to improve survival and quality of life. During the coronavirus disease 2019 pandemic, the need for physical distancing has fueled the expeditious expansion of various telehealth modalities, which may apply in a unique manner to individuals with PAH. Performance of objective risk assessments in patients with PAH remotely via telemedical visits and other telehealth mechanisms is unprecedented and not yet rigorously validated. The uniquely high risk for rapid deterioration in patients with PAH demands a high degree of sensitivity to detect changes in functional assessments. In this review, several telehealth modalities for potential utilization in risk assessment and treatment titration in patients with PAH are explored, yet additional study is needed for their validation with the pre-pandemic care paradigm.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 30 Dec 2020; 40:172-182
Wesley Milks M, Sahay S, Benza RL, Farber HW
J Heart Lung Transplant: 30 Dec 2020; 40:172-182 | PMID: 33414063
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Abstract

Venous or arterial thromboses after venoarterial extracorporeal membrane oxygenation support: Frequency and risk factors.

Bidar F, Lancelot A, Lebreton G, Pineton de Chambrun M, ... Bouglé A, Luyt CE
Background
Although venous thrombosis after venovenous-extracorporeal membrane oxygenation (ECMO) is well described, vascular complications occurring after venoarterial ECMO (VA-ECMO) removal have not yet been thoroughly described. Our aim was to evaluate the frequency of vascular (arterial and venous) complications after VA-ECMO removal and try to identify the risk factors associated with them.
Methods
Retrospective analysis of data prospectively collected in 2 intensive care units was performed. Consecutive patients successfully weaned off VA-ECMO during year 1 were screened for cannula-associated deep vein thrombosis (CaDVT) or arterial complications (arterial thrombosis/stenosis) using Doppler ultrasonography.
Results
From November 2018 to November 2019, a total of 107 patients with a median (interquartile range [IQR]) age of 54 (42-63) years and a median (IQR) ECMO support duration of 8 (2-5) days were successfully weaned off VA-ECMO and included. CaDVT occurred in 44 patients (41%), and arterial complications occurred in 15 (14%) (9 acute leg ischemia, 1 arteriovenous femoral fistula, and 5 late femoral stenosis). Multivariable analysis retained longer duration of ECMO support (odds ratio [OR]: 1.12 per day; 95% CI: 1.02-1.22) and infection occurring on ECMO (OR: 3.03; 95% CI: 1.14-8.03) as independent risk factors for CaDVT, whereas older age (OR: 0.97 per year; 95% CI: 0.94-0.99) and previous anti-coagulation use (OR: 0.21; 95% CI: 0.06-0.68) were protective factors for CaDVT. No risk factors for arterial complications were identified.
Conclusions
In patients requiring VA-ECMO support, vascular complications occurred frequently after its removal, especially CaDVT. Arterial complications, either early leg ischemia or late arterial stenosis, were observed less often. Strategies aimed at preventing CaDVT after VA-ECMO remain to be determined.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 29 Dec 2020; epub ahead of print
Bidar F, Lancelot A, Lebreton G, Pineton de Chambrun M, ... Bouglé A, Luyt CE
J Heart Lung Transplant: 29 Dec 2020; epub ahead of print | PMID: 33422407
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Abstract

Comparison of combined heart‒liver vs heart-only transplantation in pediatric and young adult Fontan recipients.

Sganga D, Hollander SA, Vaikunth S, Haeffele C, ... Bernstein D, Chen S
Background
Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT.
Methods
We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT.
Results
A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5-52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) (p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes.
Conclusions
Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

J Heart Lung Transplant: 28 Dec 2020; epub ahead of print
Sganga D, Hollander SA, Vaikunth S, Haeffele C, ... Bernstein D, Chen S
J Heart Lung Transplant: 28 Dec 2020; epub ahead of print | PMID: 33485775
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This program is still in alpha version.