Journal of Heart and Lung Transplantation最新文献

Temporary mechanical circulatory support (tMCS) using extracorporeal life support (ECLS), has been widely implemented in patients with cardiogenic shock (CS), although evidence regarding its efficacy and safety remains unclear. This lack of clarity has recently raised concerns about the role of tMCS in CS management. Conducting randomized controlled trials (RCTs) in the context of CS poses significant challenges due to ethical considerations and logistical complexities. In response to these challenges, emulated trials (ETs) are emerging as a promising alternative. By incorporating design features from idealized RCTs, they use robust and rigorous methods to assess the efficacy and safety of health interventions in real-life settings, using observational data. In our manuscript, we highlight the complementary nature of RCT and ETs by evaluating tMCS for CS patients. While RCTs follow a rigorous experimental design and provide reliable evidence, ETs can swiftly estimate the risk-benefit ratio without encountering logistical barriers thereby offering clinicians' early reassurance about the potential benefits of routinely used interventions. Furthermore, ETs offer potential value in unethical situations (refractory cardiac arrest or "crash and burn" CS) where interventional therapies, such as tMCS, are used as a last resort.

Background: The Organ Care System and Non-ischemic Heart Preservation methods have emerged as significant advancements in heart transplantation, designed to mitigate ischemic injury and extend preservation times. However, their high costs and logistical complexities necessitate strategic utilization.

Methods: We evaluated data from 83,761 heart transplants registered in the International Society for Heart and Lung Transplantation registry from 1988 to 2018. Utilizing a Cox proportional hazards model, we explored the influence of donor age and ischemic time on transplant survival. A key innovation of our study is the development of a nomogram to predict post-transplant survival, incorporating both traditional and advanced statistical methods.

Results: The median age of recipients was 52 years (22% female) and 33 years (31% female) for donors. Analysis revealed a median ischemic time of 3 hours and median survival of 11.5 years across the cohort. The nomogram showed a decline in survival probabilities with increasing donor age, notably from age 40 and more significantly with ischemic times >4 hours. Ischemic times ≥4 hours versus <2 hours were associated with hazard ratio (HR) of 1.2 (95% CI, 1.1-1.3) for donors aged 40-59, a disparity that escalated for donors aged ≥60 (HR: 2.0; 95% CI, 1.5-2.7).

Conclusions: This study highlights the importance of careful donor selection and indicates that certain groups, particularly older donors with prolonged ischemic times, might benefit from ex-vivo preservation techniques. The developed nomogram offers a practical tool for clinicians, enhancing decision-making by providing detailed insights into the relationship between donor age, ischemic time, and post-transplant mortality.

Pediatric heart transplantation (HTx) faces challenges such as limited donor availability and the need for complex reconstructions, particularly in patients with congenital anomalies. Ex vivo perfusion offers a promising approach to minimize graft ischemic time and potentially expand the donor pool. We report our single-center experience using the TransMedics Organ Care System (OCS) for ex vivo perfusion in pediatric HTx. From 2020-2024, eight pediatric patients received OCS-perfused donor hearts. Median recipient age was 13 years (range 9-18), and median weight was 58.8 kg (33.2-127.8). Indications for HTx included dilated cardiomyopathy (n=4), hypertrophic cardiomyopathy (n=1), graft vasculopathy (n=1), and Fontan failure (n=2). Median OCS time was 273 minutes (195-328), and recipient ischemic time was 85 minutes (64-139). Post-transplant, all patients had normal LV function at discharge. Over a median follow-up of 11.9 months, there were no deaths. These findings suggest that ex vivo perfusion is a valuable technique in pediatric HTx.

Background: In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction. However, the molecular mechanisms of rewarming ischemic injury in this context remain unexplored. We aimed to characterize the rewarming ischemia phase during LuTx by measuring organ temperature and comparing transcriptome and metabolome profiles in tissue obtained at the end versus the start of implantation.

Methods: In a clinical observational study, 34 double-LuTx with ice preservation were analyzed. Lung core and surface temperature (n=65 and 55 lungs) was measured during implantation. Biopsies (n=59 lungs) were wedged from right middle lobe and left lingula at start and end of implantation. Tissue transcriptomic and metabolomic profiling were performed.

Results: Temperature increased rapidly during implantation, reaching core/surface temperatures of 21.5°C/25.4°C within 30min. Transcriptomics showed increased pro-inflammatory signaling and oxidative stress at the end of implantation. Upregulation of NLRP3 and NFKB1 correlated with RIT. Metabolomics indicated elevated levels of amino acids, hypoxanthine, uric acid, cysteineglutathione disulfide alongside decreased levels of glucose and carnitines. Arginine, tyrosine, and 1-carboxyethylleucine showed correlation with incremental RIT.

Conclusions: The final rewarming ischemia phase in LuTx involves rapid organ rewarming, accompanied by transcriptomic and metabolomic changes indicating pro-inflammatory signaling and disturbed cell metabolism. Limiting implantation time and lung cooling represent potential interventions to alleviate rewarming ischemic injury.

Background: Non-intubated extracorporeal membrane oxygenation (ECMO) has become an increasingly common method of support for patients with severe respiratory failure. Since data on its use as a bridge to lung transplant remain limited to single-center studies, we evaluated its use in a national cohort.

Methods: Adult lung-only transplant recipients bridged with ECMO 5/4/2005-3/8/2023 in the United Network for Organ Sharing database were categorized by use of ECMO and mechanical ventilation at transplant (ECMO+MV vs. ECMO-only). We compared post-transplant intubation and ECMO at 72 hours using logistic regression, length of stay using negative binomial regression, and post-transplant survival using Cox regression.

Results: The 1,599 transplants identified included 902 (56.4%) bridged with ECMO+MV and 697 (43.6%) bridged with ECMO-only. ECMO-only recipients had higher median age (52 vs. 49 years, p<0.001), shorter ischemic times (5.7 vs. 6.0 hours, p=0.003), and similar lung allocation scores (89.5 vs. 89.6, p=0.11). ECMO-only recipients had lower likelihood of intubation at 72 hours (56.5% vs. 77.5%; aOR 0.33 [95% CI: 0.25, 0.42], p<0.001) and shorter lengths of stay (28 vs. 35 days; coefficient -0.19 [95% CI: -0.27, -0.11], p<0.001). ECMO-only recipients had higher 90-day survival (92.1% vs. 89.1%; aHR 0.69 [95% CI: 0.48, 0.99], p=0.04) but similar 1-year (83.1% vs. 81.5%; aHR 0.87 [95% CI: 0.67, 1.12], p=0.27) and 5-year (54.6% vs. 54.7%; aHR 0.98 [95% CI: 0.82, 1.17], p=0.83) survival.

Conclusions: Non-intubated ECMO bridge to lung transplant was associated with improved perioperative outcomes and short-term survival and should be considered for candidates requiring ECMO.

Background: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course.

Methods: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed.

Results: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p < 0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48-4.89, p = 0.001) and 4.25 (95% confidence interval, 1.98-9.10, p < 0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer.

Conclusions: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment.

Mucosal or endobronchial biopsies (EBB) are typically used in the diagnosis of directly visualized bronchial lesions, infection, and sarcoidosis, but their utility in the evaluation of lung transplant recipients is controversial. EBB represents an attractive alternative to transbronchial biopsy (TBB): EBB provides straightforward sampling of airway pathology with decreased complication rates due to minimal and visualizable bleeding and the elimination of pneumothorax risk. In lung transplant recipients, EBB may be obtained when TBB is too high-risk, including in the setting of acute lung allograft dysfunction (ALAD) requiring mechanical ventilation or in advanced chronic lung allograft dysfunction (CLAD). Most centers do not include EBB in post-transplant surveillance or for-cause bronchoscopy protocols, possibly due to a lack of a common histologic interpretation system. Previous work has demonstrated that lymphocytic inflammation in lung transplant EBB is associated with acute cellular rejection and future risk for CLAD, but these have not translated into subsequent studies on clinical utility or into clinical practice. Recent multicenter studies suggest that gene expression-based diagnostics leveraging EBB may outperform histologic grading and provide important prognostic utility in predicting graft loss. Herein, we will review what is known about the lung transplant mucosa including recent diagnostic advances and propose how EBB analyses could be incorporated into research studies and clinical workflows. We propose that mucosal sampling could provide safe, consistent, and informative data to improve patient outcomes after lung transplant.

Background: Right ventricular (RV) pressure-volume (PV) loops require postacquisition volume calibration by cardiac MRI (CMR) or hypertonic saline (HS). We defined the impact of these 2 volume calibration methods on rest-to-exercise ventricular contractility (end-systolic elastance: Ees), arterial afterload (Ea), and coupling (Ees/Ea).

Methods: In a prospective study, 82 RV PV-loop datapoints (rest, exercise stages every 25 W, and recovery) and CMR were acquired in 19 participants.

Results: In comparison to CMR, HS-based calibration overestimated RV end-systolic volume at rest, mean (SD) by +38 ml (48) and end-diastolic volume by +46 ml (68), resulting in underestimated right ventricular ejection fraction (RVEF) by -8%. However, Ees and Ea were similar at rest (r² = 0.76 and 0.71, respectively, p < 0.001 for both), and Ees:Ea was identical (r² = 1.00, p < 0.001). Exercise metrics also remained similar: RV reserve (ΔEes) and change in coupling (ΔEes/Ea).

Conclusions: In comparison to CMR (gold-standard), HS-based calibration underestimates RVEF at rest; however, it is a robust approach for measuring coupling and RV reserve.