Journal of Heart and Lung Transplantation最新文献

Purpose: We conducted a randomized trial of open lung protective ventilation (OLPV) compared to conventional ventilation (CV) in deceased donors. The primary outcome was lung utilization for transplantation.

Methods: Eligible donors were ≥13 years with PaO₂/FiO₂ between 150 and 400 mmHg. Donors were randomized to volume control with OLPV [tidal volume (TV) 8 ml/kg, PEEP 10 cmH₂O, protocolized recruitment maneuvers (RM)] or CV [TV 10ml/kg, PEEP 5 cm H₂O, RM only after vent disconnect] for duration of donor management. Lungs were evaluated for transplantation on standardized ventilator settings in both arms [TV 10ml/kg, PEEP 5 cm H₂O, FiO₂ 1.0].

Results: 153 donors were randomized (74 to OLPV, 79 to CV) and included in the final analysis. Median duration of treatment was 50 hours and did not differ by arm. Donor lung utilization was 23% in the OLPV arm and 22% in the CV arm, P = 0.85. Change in PaO₂/FiO₂ from randomization to procurement did not differ by treatment; median increase (quartiles) in OLPV versus CV was 68 mmHg (18, 127) vs 74 (-27 to 170), P = 0.72. There was no difference in need for vasopressors or serious adverse events between arms. Among 28 lung recipients in whom detailed outcomes were available, duration of mechanical ventilation, ICU stay and hospital stay were not different by treatment arm.

Conclusions: An open lung protective ventilator strategy was safe but did not improve donor lung utilization or oxygenation compared to a conventional ventilator strategy in a population of US organ donors. NCT03439995.

Introduction: In 2023, a new UNOS policy established criteria for a kidney allocation safety net for lung transplant recipients (LTRs) with chronic renal dysfunction. We sought to evaluate the demographics and outcomes of past lung transplant recipients who would have been eligible for a rescue kidney under the new criteria.

Methods: Using the UNOS OPTN registry, we identified lung transplant recipients from 2005-2023 who fit the eligibility for rescue kidneys. Rescue kidney eligibility was defined as recipients who had an eGFR≤20mL/min, CrCl≤20mL/min, or were receiving chronic dialysis at any point 60 to 365 days post-transplant. Baseline characteristics and survival out to 1 and 3 years were evaluated for the rescue kidney-eligible cohort compared to all other lung transplant recipients in the study period.

Results: 554 (2.1%) of all recipients would have been eligible for a rescue kidney under the new policy. Comparing to non-eligible group, they were older (median, 62 vs 61 years; P <.001), had higher BMI (27 vs 26; P <.001), and were more often Black (13% vs 9%; P <.001). They also had a significantly higher proportion of renal dysfunction (including CKD stage III, IV and V) at the time of transplant (17% vs 7%; P <.001) and higher likelihood of pre-transplant dialysis (7% vs 0%; P <.001). The rescue-eligible recipients had higher rates of life support (14% vs 11%; P =.031) and greater LAS at transplant (median 40 vs 39; P <.01). Compared to non-eligible recipients, rescue kidney-eligible recipients had lower survival at 1 year (42% vs. 88%, p<.001) and 3 years (28% vs. 71%, p<.001). These differences in mortality risk persisted after adjusting for donor and recipient characteristics (1-year mortality aHR 9.27; 95% CI 8.16-10.55; P <.001; 3-year aHR 5.55; 95% CI 4.97-6.20; P <.001).

Conclusion: While relatively few recipients would have been eligible for a rescue kidney under the new policy, they had significantly worse survival than non-eligible recipients. This underscores the severe illness of these patients and the importance of assessing whether rescue kidneys can reduce these mortality differences.

Objective: Atrial fibrillation (AFib) reduces the quality of life and increases hospitalization frequency in patients with pulmonary hypertension (PH). Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of PH with a specific pathophysiology, treatment methods, and demographics; however, the factors that correlate with AFib in this population have not yet been determined. This study aimed to investigate the variables that influence the AFib development in patients with CTEPH and assess the impact of arrhythmia on the mortality rate in this population.

Design: Data were obtained from the Database of Pulmonary Hypertension in the Polish Population (NCT03959748), a registry containing data on patients with pulmonary arterial hypertension and CTEPH who were diagnosed and treated in all Polish PH Centers.

Participants: This study included 784 adult patients diagnosed with CTEPH.

Exposure: We compared echocardiographic, hemodynamic, and demographic variables between patients with and without AFib during database enrollment (retrospective arm) and with and without AFib diagnosis during follow-up (prospective arm).

Results: A total of 106 patients (13,5%) with CTEPH were already diagnosed with AFib at enrollment to the registry. We observed a higher incidence of arterial hypertension and chronic renal disease in the arrhythmia than in the non-arrhythmia group. According to the logistic regression analysis, the independent risk factors for AFib development were only pulmonary artery wedge pressure (PAWP, odds ratio [OR] 1,27 per mmHg, 95% confidence interval [CI] 1,082-1,497, p=0,004) and Left Atrial Area (LA area, OR 1,279, 95% CI 1,109-1,476, p=0,001). AFib is associated with higher serum N-terminal prohormone of natriuretic peptide (NTproBNP) levels and is not an independent predictor of mortality.

Conclusions: AFib in patients with CTEPH is related to comorbidities similar to those in the general population. The independent predictors of arrhythmia occurrence are PAWP and LA area, suggesting dominant role of left heart disease in AFib development. Atrial fibrillation does not remain an independent predictor of mortality in patients with CTEPH but is associated with increased NTproBNP serum levels.

Trial registration: Not applicable.

Background: There is growing evidence that many patients undergoing lung transplantation report significant distress and low physical activity (PA), which might not improve despite lung transplantation and may be associated with worse clinical outcomes. Few studies have attempted to improve psychological outcomes and functional capacity and PA after transplant.

Methods: INSPIRE-III is a single-site, randomized clinical trial in which 180 post-lung transplant patients, recruited between November 2019 and October 2023, completed a psychometric test battery to assess distress and functional capacity measured by the Six-Minute Walk Test and PA assessed by 7 consecutive days of continuous activity monitoring. Participants were then were randomly assigned to either a 12-week Coping Skills Training and Exercise intervention (CSTEX) or a Standard of Care and Education (SoC-ED) program delivered via telephone. Participants were then retested after completion of the telehealth interventions.

Results: After 12 weeks, both intervention groups achieved small but similar improvements in distress and functional capacity. Although there were no between group differences overall, patients who were considered clinically depressed at baseline and received CSTEX achieved greater improvements in depression compared to depressed patients who received SoC-ED.

Conclusions: Although patients in both CSTEX and SoC-ED showed only modest benefit from their respective interventions, a subgroup of patients in CSTEX who were depressed at study entry had greater reductions in depressive symptoms compared to SoC-ED. Depressive symptoms should be carefully monitored post-transplant and referred for treatment if symptoms persist.

Trial registry: NCT04093869.

Background: Abdominal Normothermic Regional Perfusion (A-NRP) improves outcomes for transplanted abdominal organs from Donation after Circulatory Death (DCD) donors. Concerns have been raised about the effect of A-NRP on lungs procured during multi-organ donation. We present the UK experience of performing direct procurement (DRP) of lungs from DCD donors with A-NRP.

Methods: Retrospective analysis of all 487 UK DCD lung donors between 1 April 2011 and 31 December 2023. Organ transplantation rate and30-day, 90-day and 1-year survival rates were compared between DRP of DCD lungs, DRP of DCD lungs with A-NRP and DBD lungs. PGD rates were compared between DCD lungs with and without A-NRP.

Results: Three hundred ninety-seven DCD donors resulted in a lung transplant (22 retrieved by DRP with A-NRP). There was no difference in lung transplantation rates between DRP and DRP with A-NRP. Of the 390 first adult-only lung transplants performed from DCD donors, there was no significant difference in 30-day, 90-day and 1-year survival between DRP of DCD lungs and DRP with A-NRP. There was a significant difference in survival between standard DCD donors and DBD donors at 30-days and 90-days, but not 1 year. There was no significant difference in grade 3 PGD rates at 72 hours post-implantation for DCD lungs with or without A-NRP.

Conclusion: In the UK experience, use of A-NRP is not detrimental to procurement of DCD lungs. We advocate the use of this technique until further studies can explore the safety and efficacy of thoraco-abdominal NRP for lungs in multi-organ retrieval.

Background: Donation after circulatory death (DCD) donors remains an underutilized source in the U.S due to concerns of ischemia-reperfusion injury (IRI) after prolonged ischemic times. Lung-derived exosomes have shown potential in mitigating pulmonary fibrosis by promoting lung repair. Here, we sought to investigate the potential of lung-derived exosomes to prevent and repair lung IRI.

Methods: We used a porcine DCD model to induce lung injury. Following the determination of optimal warm ischemic time (WIT), donor pigs were allocated into three study groups (n=5, each): control, pre-DCD exosome treatment, and post-DCD exosomes treatment. Lungs were assessed using ex-vivo lung perfusion (EVLP) for functional parameters, histological evaluation, and molecular analysis of inflammatory markers and oxidative stress.

Results: A 1-hour WIT induced consistent lung injury, which was ameliorated with pre-DCD exosome treatment exhibiting significantly improved lung function during EVLP compared to controls. This group presented higher pO2, better lung compliance, lower airway pressures, and reduced pulmonary vascular resistance. Histological analysis indicated reduced edema, vascular congestion, and leukocyte infiltration. Key inflammatory cytokines such as IL-6, IL-1β, TNF-α were significantly downregulated, and reactive oxygen species (ROS) levels were lower than controls. Despite inferior response compared to pre-DCD treatment, post-DCD exosomes treatment also improved lung function and reduced edema formation, with significant decrease in TNF-α expression.

Conclusions: Lung-derived exosome therapy significantly mitigates IRI in a porcine DCD model, improving lung function and reducing inflammation and oxidative stress. These findings support the potential of exosome therapy to increase donor lung utilization, warranting further mechanistic and clinical studies.

Pulmonary arterial hypertension (PAH) guidelines advocate measures of area for right atrial (RA) dimensions, while echocardiographic guidelines recommend RA volume. We compared the prognostic value of RA echocardiographic parameters to predict transplant-free survival in 332 adult patients with PAH. RA area correlated strongly with volume (r = 0.96). After adjusting for age and sex, for every 1-standardized unit increase in RA area index, volume index, and major axis dimension, there were 21%, 18%, and 18% higher hazards of mortality or transplant, respectively. However, no RA parameter was independently associated with transplant-free survival when adjusted for Registry to Evaluate Early and Long-Term PAH Disease Management lite score. RA area index had the highest area under the curve for predicting transplant-free survival.