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We have previously shown that human-xenogeneic cross-circulation (HX-XC) can rehabilitate human lungs deemed unsuitable for transplant. We found that porcine antibodies and leukocytes infiltrate the human lung during HX-XC, raising concern that re-exposure to human blood may trigger hyperacute rejection. The purpose of our study is to evaluate the consequences of human blood re-exposure on a lung recovered with HX-XC. Donor lungs deemed unsuitable for transplant and autologous whole blood were procured. Lungs were perfused by an immunosuppressed swine host for 12 hrs. After removal from HX-XC, lungs were placed on EVLP with autologous human blood for 5 hrs. Physiologic data and biopsies were collected during HX-XC and EVLP. Tissue was stained with H&E; IHC was used to assess for apoptosis (TUNEL, caspase-3) and complement activation (C4d, membrane attack complex, MAC). During HX-XC, PaO 2 /FiO 2 and mean airway pressure (MAP) remained stable (mean 254±20 mmHg and 6.8± 0 cmH 2 O, respectively). Dynamic compliance improved from 23 to 52 mL/cmH 2 O. During blood re-exposure with EVLP, dynamic compliance and MAP remained stable. The structural integrity of the lung was maintained after re-exposure to human blood, without evidence of diffuse pulmonary edema. Though apoptosis was detected during HX-XC, these levels did not increase during blood re-exposure. Complement and MAC deposition were focally present after blood re-exposure. A human lung rescued with HX-XC and re-exposed to autologous blood maintained physiologic function, despite exposure to porcine antigen. These preliminary data suggest there may be minimal deleterious effect of re-exposure to human blood after xeno cross-circulation. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Donation after cardiac death (DCD) and ex vivo lung perfusion (EVLP) have increased donor lung availability. Normothermic regional perfusion (NRP) has increased utilization of donor hearts, livers, and kidneys from DCD. However, the impact of NRP on lung utilization after EVLP is unknown. We aimed to compare lung utilization after EVLP between NRP-DCD donors and DCD donors without NRP. Based on our early experience, we hypothesized that NRP may limit lung recovery for transplant. Retrospective comparison of DCD vs NRP-DCD donor lung utilization after EVLP. All DCD (n=27) and NRP-DCD (n=6) lungs that had EVLP at Lung Bioengineering from 10/2020 to 10/2022 were included. The primary outcome was lung utilization rate. Secondary outcomes included parameters of EVLP performance. Comparisons were made with Fisher's exact or Mann Whitney U tests. Details of NRP procedures were not available for analysis. NRP-DCD donors were younger than DCD donors (median 20y vs 32y, p=0.008) and more often male (83% vs 41%, p=0.08). NRP-DCD and DCD donors had similar tobacco use, ABO, causes of death, P/F at referral, and cold ischemic time (p=ns). In DCD donors, the lung utilization rate was 37%, confirming the utility of EVLP in lung recovery. The lung utilization rate after NRP-DCD was 17% (Figure). Although NRP-DCD donors had lower lung recovery, this difference was not statistically significant (p=0.64). When limiting analysis to donors <35y, the lung utilization rate was 43% for DCD and 17% for NRP-DCD (p=0.35). NRP-DCD and DCD lungs on EVLP had similar delta PO2, compliance, peak airway pressure, and perfusate loss at 3h (p=ns). These preliminary data suggest that lung recovery after EVLP from NRP-DCD donors may be similar to that from DCD. However, lack of transparency with NRP protocols prevented analysis of contributors to lower lung recovery after NRP-DCD despite adequate gas exchange. This work highlights the unclear impact of NRP on donor lungs and the need for more efforts to collect data prospectively in this growing field. [ABSTRACT FROM AUTHOR]

In kidney transplant, relative change in % donor-derived cell-free DNA (%dd-cfDNA) is superior to absolute thresholds for detection of injury, though in lung transplantation a cut-off of 1% is used as an arbiter of acute lung allograft dysfunction (ALAD). We previously showed that a normal dd-cfDNA% level in patients >2 years post-lung transplantation without allograft injury is 0.45% (IQR 0.21 - 0.64) with a relative change value of 73%. We now seek to determine test characteristics for the ability of a relative change >73% to distinguish graft injury vs. an absolute value >1%. We performed an observational study of lung recipients >2 years post-transplantation without CLAD, measuring plasma dd-cfDNA every 3-4 months (CareDx). ALAD was adjudicated based on symptoms, decline in FEV 1 >10%, infection, de novo donor specific antibodies, or biopsy-proven acute rejection. Chi-squared and Mann-Whitney U testing were used for statistical comparisons of binary and continuous data, respectively. Seventy patients had >3 baseline dd-cfDNA measurements and were included in this analysis. In this cohort 29 (41%) patients developed ALAD. There were no significant baseline differences in age, sex, race, transplant type, lung diagnosis, or primary graft dysfunction, between subjects that developed ALAD or not. Leading causes of ALAD included respiratory viruses (34%), decline in FEV1 of unclear etiology (21%), and possible antibody-mediated rejection (17%). Relative change of %dd-cfDNA >73% of baseline had a 90% sensitivity, 88% specificity, 84% positive predictive value (PPV), and 92% negative predictive value (NPV) to detect ALAD. An absolute threshold of 1% was associated with a sensitivity of 52%, specificity of 78%, PPV of 63% and NPV of 70%. Relative change in %dd-cfDNA >73% of baseline identifies ALAD better than an absolute threshold of 1% in patients >2 years post- lung transplant. [ABSTRACT FROM AUTHOR]

Background: Utilization of temporary mechanical circulatory support, including veno-arterial extra-corporeal membrane oxygenation as a bridge to heart transplantation (HT) has increased significantly under the revised United Network for Organ Sharing (UNOS) donor heart allocation system. The revised heart allocation system aimed to lower waitlist times and mortality for the most critically ill patients requiring biventricular, nondischargeable, mechanical circulatory support. While previous reports have shown improved 1-year post-HT survival in the current era, 3-year survival and factors associated with mortality among bridge-to-transplant (BTT) extra-corporeal membrane oxygenation (ECMO) patients are not well described., Methods: We queried the UNOS database for all adult (age ≥ 18 years) heart-only transplants performed between 2010 and 2019. Patients were stratified as either pre- (January 2010-September 2018; era 1) or post-allocation change (November 2018-December 2019; era 2) cohort based on their HT date. Baseline recipient characteristics and post-transplant outcomes were compared. A Cox regression analysis was performed to explore risk factors for 3-year mortality among BTT-ECMO patients in era 2. For each era, 3-year mortality was also compared between BTT ECMO patients and those transplanted without ECMO support., Results: During the study period, 116 patients were BTT ECMO during era 1 and 154 patients during era 2. Baseline recipient characteristics were similar in both groups. Median age was 48 (36-58 interquartile range (IQR)) years in era 2, while it was 51 (27-58 IQR) years in era 1. The majority of BTT-ECMO patients were males in both era 2 and era 1 (77.7% vs 71.5%, p = 0.28). Median ECMO run times while listed for HT were significantly shorter (4 days vs 7 days, p < 0.001) in era 2. Waitlist mortality among BTT ECMO patients was also significantly lower in era 2 (6.3% vs 19.3%, p < 0.001). Post-HT survival at 6 months (94.2% vs 75.9%, p < 0.001), 1 year (90.3% vs 74.2%, p < 0.001), and 3 years (87% vs 66.4%, p < 0.001) was significantly improved in era 2 as compared to era 1. Graft failure at 1 year (10.3% vs 25.8%, p = 0.0006) and 3 years (13.6% vs 33.6%, p = 0.0001) was also significantly lower in era 2 compared to era 1. Three-year survival among BTT ECMO patients in era 2 was similar to that of patients transplanted in era 2 without ECMO support (87% vs 85.7%, p = 0.75). In multivariable analysis of BTT-ECMO patients in era 2, every 1 kg/m 2 increase in body mass index was associated with higher mortality at 3 years (hazard ratio (HR) 1.09, 95% CI 1.02-1.15, p = 0.006). Similarly, both post-HT stroke (HR 5.58, 95% CI 2.57-12.14, p < 0.001) and post-HT renal failure requiring hemodialysis (HR 4.36, 95% CI 2.43-7.82, p < 0.001) were also associated with 3-year mortality., Conclusions: Three years post-HT survival in patients bridged with ECMO has significantly improved under the revised donor heart allocation system compared to prior system. BTT ECMO recipients under the revised system have significantly shorter ECMO waitlist run times, lower waitlist mortality and 3-year survival similar to those not bridged with ECMO. Overall, the revised allocation system has allowed more rapid transplantation of the sickest patients without a higher post-HT mortality., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS's axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p > 0.05). This study demonstrates equivalent hemocompatibility of the PAS's AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup., Competing Interests: Disclosure: D.J.S., M.B., and K.E.C. are equity owners of Advanced Respiratory Technologies, Inc. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes., (© 2024 Wiley‐VCH GmbH.)

Competing Interests: Disclosure: M.B. is a coinventor on a patent application (WO2018013849A1) for cross-circulation as a platform for extracorporeal organ recovery, regeneration, and maintenance. W.K.W., R.U., and M.B. are co-inventors on a patent application for an alternate configuration of cross-circulation for the same purpose. The other authors have no conflicts of interest to report.

Background: Anemia is a risk factor for increased morbidity and mortality in multiple medical conditions, yet the impact of pretransplant anemia in patients with advanced lung disease on post-transplant outcomes remains under-explored. We sought to determine whether pretransplant anemia serves as a marker of altered inflammation in the host and associates with short-term outcomes following lung transplantation., Study Design and Methods: We performed a single-center, retrospective analysis of 238 lung transplant recipients. We assessed for risk factors of pretransplant anemia and identified associations with short-term post-transplant outcomes., Results: Pretransplant anemia was associated with increased intraoperative transfusion of packed red blood cells and a trend towards increased index hospital length of stay and 1-year mortality. Conversely, pretransplant anemia was associated with a decreased incidence of acute cellular rejection., Conclusion: These preliminary data suggest that anemia may be a biomarker of altered inflammation in the host recipient and influences post-transplant outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The pulmonary assist system (PAS) is a wearable respiratory support system that is currently under development for patients with chronic lung disease as a bridge to lung transplantation or as destination therapy. This study evaluates the long-term performance and biocompatibility of the PAS in a 5-d awake, ovine model., Methods: The PAS was attached to normal sheep in venovenous configuration. Components of the PAS included a 0.9 m2 surface area oxygenator and a lightweight, battery-powered axial flow pump. The system was also tested using the Abbott PediMag as the control pump. Each sheep was supported on the PAS for 5 d with 2 L/min blood flow and 4 L/min sweep gas. Activated clotting times of 200-240 s were maintained using intravenous heparin. Pump performance, oxygen transfer, oxygenator resistance, and hematologic parameters were measured throughout the support., Results: The PAS, either using the axial flow pump or PediMag (n = 4 each), was well tolerated by the sheep without signs of device-related organ damage or hemolysis. All the studies achieved the full, 5-d study duration. The oxygenator resistance remained consistent without significant clot formation in all experiments with an average resistance of 2.55 ± 0.10 mm Hg/(L/min). The system achieved an average oxygen transfer rate of 116.4 ± 5.5 mL/min, with an average Hb concentration of 9.2 ± 0.6 g/dL. White blood cell, platelet, and hematocrit levels also remained stable and within normal limits throughout the study period., Conclusions: The PAS provided 5 d of uncomplicated ambulatory respiratory support with minimal clot formation, stable gas exchange, blood flow resistance, and hematologic parameters., Competing Interests: This research was supported by the US Army Congressionally Directed Medical Research Programs grant (W81XWH2110591). Y.H. is supported, in part, by the National Heart, Lung, and Blood Institute (T32HL160526) and Thoracic Surgery Foundation Resident Research fellowships. D.J.S., M.B., and K.E.C. are equity owners of Advanced Respiratory Technologies Inc. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Epithelial polarity is fundamental in maintaining barrier integrity and tissue protection. In cystic fibrosis (CF), apicobasal polarity of the airway epithelium is altered, resulting in increased apical fibronectin deposition and enhanced susceptibility to bacterial infections. Here, we evaluated the effect of highly effective modulator treatment (HEMT) on fibronectin apical deposition and investigated the intracellular mechanisms triggering the defect in polarity of the CF airway epithelium. To this end, primary cultures of CF (F508del variant) human airway epithelial cells (HAECs) and a HAEC line, Calu-3, knocked down for CFTR (CF transmembrane conductance regulator) were compared with control counterparts. We show that CFTR mutation in primary HAECs and CFTR knockdown cells promote the overexpression and oversecretion of TGF-β1 and DKK1 when cultured at an air-liquid interface. These dynamic changes result in hyperactivation of the TGF-β pathway and inhibition of the Wnt pathway through degradation of β-catenin leading to imbalanced proliferation and polarization. The abnormal interplay between TGF-β and Wnt signaling pathways is reinforced by aberrant Akt signaling. Pharmacological manipulation of TGF-β, Wnt, and Akt pathways restored polarization of the F508del CF epithelium, a correction that was not achieved by HEMT. Our data shed new insights into the signaling pathways that fine-tune apicobasal polarization in primary airway epithelial cells and may provide an explanation to the mitigated efficacy of HEMT on lung infection in people with CF.

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Venoarterial extracorporeal membrane oxygenation is increasingly used for mechanical circulatory support during lung transplant. Optimal intensity of intraoperative anticoagulation would be expected to mitigate thromboembolism without increasing bleeding and blood product transfusions. Yet, the optimal intensity of intraoperative anticoagulation is unknown. We performed a retrospective cohort study of 163 patients who received a bilateral lung transplant at a single center. We categorized the intensity of anticoagulation into 4 groups (very low to high) based on the bolus dose of unfractionated heparin given during lung transplant and compared the rates of intraoperative blood transfusions and the occurrence of thromboembolism between groups. When compared to the very low-intensity group, each higher intensity group was associated with higher red blood cell, fresh frozen plasma, and platelet transfusions. The occurrence of thromboembolism was similar across groups. These preliminary data suggest that lower intensity anticoagulation may reduce the rate of intraoperative blood transfusions, although further study is needed., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung-mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro., (© 2024 Wiley‐VCH GmbH.)

Objective: Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia., Methods: Swine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation., Results: Recipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours., Conclusions: We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects. Furthermore, we identified disease interaction eQTLs and demonstrated that this class of associations is more likely to be cell-type-specific and linked to cellular dysregulation in pulmonary fibrosis. Finally, we connected lung disease risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression and implicates context-specific eQTLs as key regulators of lung homeostasis and disease., (© 2024. The Author(s).)

Objectives: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients., Design: This was a single-center retrospective cohort study., Setting: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee., Participants: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022., Interventions: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications., Measurements and Main Results: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion., Conclusions: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Defective hydration of airway surface mucosa is associated with lung infection in cystic fibrosis (CF), partly caused by disruption of the epithelial barrier integrity. Although rehydration of the CF airway surface liquid (ASL) alleviates epithelium vulnerability to infection by junctional protein expression, the mechanisms linking ASL to barrier integrity are unknown. We show here the strong degradation of YAP1 and TAZ proteins in well-polarized CF human airway epithelial cells (HAECs), a process that was prevented by ASL rehydration. Conditional silencing of YAP1 in rehydrated CF HAECs indicated that YAP1 expression was necessary for the maintenance of junctional complexes. A higher plasma membrane tension in CF HAECs reduced endocytosis, concurrent with the maintenance of active β 1-integrin ectopically located at the apical membrane. Pharmacological inhibition of β 1-integrin accumulation restored YAP1 expression in CF HAECs. These results indicate that dehydration of the CF ASL affects epithelial plasma membrane tension, resulting in ectopic activation of a β 1-integrin/YAP1 signaling pathway associated with degradation of junctional proteins., (© 2024 Simonin et al.)

Objective: Right heart remodeling and tricuspid regurgitation (TR) are common in patients with chronic thromboembolic pulmonary hypertension. This study aimed to investigate the significance of right heart remodeling and TR after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension., Methods: Patients who underwent PEA with preoperative and postoperative transthoracic echocardiograms at our center between June 2010 and July 2019 were retrospectively reviewed. The composite end point was defined as death or hospitalization due to worsening heart failure, bleeding, or recurrent pulmonary embolism., Results: In total, 158 patients were included for analysis. Right ventricular basal (48 [45-52] vs 43 [39-47] mm, P < .001), midcavitary (46 [42-50] vs 38 [34-42] mm, P < .001), and longitudinal dimensions (87 [83-93] vs 80 [75-84] mm, P < .001), along with the right atrial volume index (37 [25-51] vs 24 [18-34] mL/m 2 , P < .001), significantly decreased, whereas left ventricular and atrial sizes and left ventricular ejection fraction increased after PEA. Overall, 78 patients (49%) showed significant TR on preoperative transthoracic echocardiograms, and 33 (21%) had significant residual TR after PEA. Fourteen patients died, and 24 patients met the composite end point. Residual TR after PEA was independently associated with mortality (P = .005) and the composite end point (P = .003). Patients with residual TR had significantly worse survival (log-rank P < .001) and greater event rates (log-rank P = .003) than those without residual TR., Conclusions: Significant improvements in right heart remodeling were seen following PEA. However, residual TR was a poor prognostic marker., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure., Methods: In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7 days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed., Results: Six subjects underwent the chronic disease model for 56 to 71 days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit., Conclusions: Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: Refractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit., Methods: We performed a retrospective cohort study of all patients with COVID-19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes., Results: Of 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge., Conclusions: In select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)