Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare cause of Pulmonary Hypertension (PH) in children.There is limited data on long-term outcomes following pulmonary endarterectomy (PEA) in this demographic.We conducted a retrospective analysis of the United Kingdom National Registry for Paediatric Pulmonary Hypertension (2001-2024) identifying 5 children with CTEPH diagnosed through standardised criteria including cardiac catheterisation and cross-sectional imaging.Among our cohort (60% female, mean age 12 years, range 4-14 years), 80% had identifiable thromboembolic risk factors, predominantly indwelling lines (60%) and thrombophillic conditions (20%).Follow-up duration ranged from 1-5years, with 2 patients followed up for over 4 years.At diagnosis, patients demonstrated reduced exercise capacity (mean six-minute walking distance 361m, range 299-349m) and had echocardiographic evidence of PH (mean TR Vmax 3.67m/s).All patients underwent Cardiac MRI, demonstrating right ventricular (RV) enlargement (mean RV end diastolic volume 109.6ml/m 2 ) and mild-moderate RV systolic impairment (mean RVEF 39.2%).Invasive haemodynamic assessment confirmed significant pressure elevation with mean mPAP 55.6mmHg (range 29-68mmHg) and mean pulmonary vascular resistance index 12.2 WU.m 2 (range 5-21WU.m2).Following PEA (100%), improvements were observed in six-minute walking distance (+45m, p=0.0276),RV volumes (-30ml/m 2 , p=0.0113), RV systolic function (+14.8%,p=0.0031), and haemodynamics (mPAP -28.6mmHg p=0.010;PVRI -11.4WU.m 2 , p=0.0172).However normalisation of pulmonary haemodynamics to mPAP < 20mmHg was achieved in only 1 patient (20%).In this paediatric CTEPH cohort, thromboembolic risk factors were highly prevalent.While PEA resulted in significant haemodynamic and functional improvement, complete normalization of pulmonary haemodynamics was uncommon.This suggests residual PH following PEA may be more frequent in paediatric CTEPH compared to adult cohorts.Longitudinal follow-up into adulthood is important to determine long term outcomes in this population.

Pulmonary hypertension in COPD patients and identifying accompanying factors in clinical decisions are very important. The current study aimed to determine the relationship between phenotypic and echocardiographic findings with the help of pulmonary artery pressure in patients with COPD. In this study, 100 COPD patients referred to a specialized clinic participated in the study. The prevalence of pulmonary hypertension (PH) and its relationship with phenotypic criteria, spirometry, laboratory findings, and echocardiography in COPD patients were investigated. Among the COPD patients, 76 cases were classified as having chronic bronchitis, nine as having emphysema, and 15 were classified as mixed phenotype by Chest high-resolution computed tomography (HRCT) methods. The prevalence of PH in the study was 36% (moderate 24% and severe 12%). The average pulmonary arterial pressure (PAP) was significantly difference in different phenotypes (p < 0.001). Heart rate and PAP significantly increase in mixed phenotypes p = 0.029 and p = 0.002, respectively. Also, the modified Medical Research Council scale (mMRC) and BODE index were significantly increase in mixed phenotypes of COPD patients (p < 0.05 to p < 0.001). Compared the factors related to PH in different phenotypes of patients with COPD indicated that PH are related with heart rate, PCO2, creatinine, triglycerides, 6MWT and BODE Index.

ABSTRACTSegmental pulmonary hypertension (PH) in congenital heart disease remains poorly understood with data limited to case studies. We performed a retrospective, single center study in children treated with PH medications after unifocalization/pulmonary artery reconstruction for major aortopulmonary collaterals (MAPCA). Drug response was determined by hemodynamic changes across at least two cardiac catheterizations. Mechanical properties of the segmental arteries were quantified by distensibility, stiffness, and augmentation indices. Twenty‐five patients were included (8 surgical shunt, 17 complete repair), with 76% considered responsive to PH medications based on the relative decrease in maximum segmental mean pulmonary artery pressure (mPAP). At a median duration of 14 months (Q1–Q3 9.5–29), mPAP decreased from 33 mmHg (28–38) to 23 mmHg (21–32) (p &lt; 0.001) with no significant change in blood flow distribution by lung perfusion scintigraphy. Subgroup analysis demonstrated a trend towards a larger percent decrease in mPAP of 35% (18–45) on dual therapy compared to 23% (Q1–Q3 3–36) on monotherapy (p = 0.16). In repaired patients, arterial distensibility at initial catheterization correlated with residual elevation in mPAP at follow‐up (R2 0.687, p &lt; 0.001), with distensibility &lt; 1.7%/mmHg associated with treatment failure. Among the lowest distensibility values were patients with JAG1 mutations, and among patients with extended follow‐up, progressive increase in mPAP was identified only in those with hereditary PH‐associated mutations. Children with segmental PH following pulmonary artery reconstruction can be successfully treated with PH medications. Although treatment efficacy may be limited in patients with high vascular stiffness and those with pathologic vascular mutations.

ABSTRACTFibrotic lung diseases are often characterized by chronic inflammation and the progressive destruction of the vasculature, parenchyma, and airways, leading to cellular metabolic changes. As a result, these changes activate several pathological pathways, contributing to the disease's progression and worsening. However, the precise impact of metabolic changes and their contributions to the progression of fibrotic lung diseases need deeper exploration. The current review highlights the interplay between immunometabolites and hypoxia in bringing out cellular and epigenetic changes that progress and further exacerbate pulmonary fibrosis. Notably, the mitochondrial‐linked immunometabolites such as lactate, succinate, 2‐hydroxyglutarate (2‐HG), fumarate, and itaconate have the potential to determine cellular fate in health and disease. For instance, lactate accumulation is one of the vital factors associated with pulmonary fibrosis (PF). The metabolite succinate promotes hypoxia response, inflammatory markers accumulation, fibroblast activation, and PF, whereas L‐2‐HG impairs the TCA cycle, reduces glycolysis, and disrupts the nicotinamide adenine dinucleotide (NADH/NAD+) ratio, ultimately leading to dysfunctional mitochondrial respiration and contributing to lung fibrosis. Due to the progressive and degenerative nature of fibrotic lung diseases, individuals affected by them need ongoing clinical support and monitoring. The currently available pharmacological treatments are limited and come with multiple side effects. Therefore, the search for newer therapeutics in the form of small molecules targeting these metabolites is increasingly being formulated to treat chronic fibrotic pulmonary conditions through their exhaustive mechanistic investigations backed by robust preclinical and clinical trials.

ABSTRACTRecent international guidelines recommend a multidisciplinary evaluation and care model for patients with chronic thromboembolic pulmonary hypertension (CTEPH), but there is a paucity of supporting data. The aim of this study was to describe the outcomes of a multidisciplinary team approach to the comprehensive care of CTEPH patients. This single‐center cohort study enrolled 166 consecutive adult patients undergoing CTEPH treatment evaluation from 2016 to 2022 at a tertiary care, academic regional referral and comprehensive CTEPH center with pulmonary thromboendarterectomy (PTE) and balloon pulmonary angioplasty (BPA) capabilities. Patients underwent PTE, BPA, or medical management after consensus evaluation by a multidisciplinary team including pulmonary hypertension physicians, surgeons, interventional cardiologists, and radiologists. 86% (142/166) of patients underwent interventional therapies; 100 (60%) underwent PTE and 42 (25%) BPA. Of the 24 (14%) medically treated patients, 13 patients were offered but deferred intervention; 11 patients had non‐intervenable disease. 30‐day mortality in both PTE and BPA was 0%. 1‐ and 3‐year survival was 99% and 96% for PTE, 100% and 93% for BPA, 79% and 79% for medical management. Patients who underwent PTE had the best hemodynamic response (∆PVR: PTE −278.8 ± 366.9 dyne/sec/cm5; BPA −15.9 ± 171.8 dyne/sec/cm5; medical −60.2 ± 233.1 dyne/sec/cm5; p = 0.001), largest improvement in Borg Dyspnea Scale; [PTE −1.0 (−2.8 to 0.0), BPA + 0.5 (−0.8 to 5.0), medical +1.0 (0.75 to 3.0), p = 0.01], and most improvement in NYHA functional class [% improving at least 1 functional class: PTE 64% (47/73), BPA 18% (5/28), medical 21% (4/19), p = 0.0004].

ABSTRACTBufei huoxue capsules (BFHX), manufactured products of traditional Chinese medicine, have demonstrated anti‐inflammatory properties and efficacy against chronic pulmonary diseases and COVID‐19. This study was designed to further determine the clinical efficacy of BFHX in diverse patient subgroups during the convalescent phase of COVID‐19, extending upon previously reported findings from a multicenter randomized controlled trial. Patients who had clinically recovered from COVID‐19 were blindly assigned to BFHX or placebo groups. All enrolled patients underwent chest computed tomography (CT) imaging, 6‐min walking distance (6MWD) test, and fatigue assessment inventory (FAI) at monthly follow‐up for 3 months. A post hoc subgroup reanalysis was performed on subgroups of sex, age, severity of acute illness, and positive/negative IgG antibody against S antigen variants. A total of 129 patients were enrolled in BFHX (N = 64) and placebo groups (N = 65). The 6MWD and FAI scores were more significantly improved in females and mild patients than in males and severe patients after BFHX treatment. Lung CT image evaluated by the change in whole lung volume and mean CT value showed that the patients below 60 years gained more therapeutic effects after 3 months of BFHX treatment (p = 0.0008; p = 0.017; p = 0.0313, respectively). The subgroup reanalysis implies that the therapeutic effectiveness of BFHX in managing COVID‐19 convalescence could potentially be influenced by factors including gender, age, and disease severity.Trial registration: This study was registered with the China Clinical Trial Registration Center (registration number: ChiCTR2000032573).

ABSTRACTFibrosing mediastinitis (FM) can block pulmonary vessels and airways, hindering treatment efficacy. Pulmonary artery (PA) stenting might provide a solution in such cases. This study involved 30 patients who had 49 PA stenting procedures for FM. Data on baseline characteristics, CT pulmonary angiography images, stent patency, and hemodynamics were collected. Patients with FM often had a history of chronic obstructive pulmonary disease (15/30), tuberculosis (12/30), and pneumoconiosis (11/30). Patients exhibited typical symptoms such as dyspnea, exercise intolerance, and cough. FM appeared as multiple bilateral shadows with enlarged hilar and mediastinal lymph nodes. Our study found that the PA involvement alone was predominantly in the left and right lower basilar trunk, with the left lower pulmonary arteries (LLPA) involved in 80% of cases and the right lower pulmonary arteries (RLPA) in 100%. Moreover, over 2/3 of patients showed involvement of both PA and pulmonary vein (PV), mainly in the bilateral upper lung lobes, then in the right middle lobe and left lingual lobe. After PA stent implantation, patients showed enhanced tricuspid annular plane systolic excursion (20.6 vs. 18.5, p < 0.001) and reduced right atrial diameter (35.5 vs. 37.3, p = 0.042), along with significant gains in 6‐min walk distance (465.2 vs. 392.7, p = 0.002) and improved World Health Organization functional class (p < 0.001). Hemodynamic parameters improved after PA stent placement with significant reductions in systolic pulmonary artery pressure (PAP) (51.1 vs. 64.2, p < 0.001), mean PAP (28.4 vs. 35.2, p < 0.001), pulmonary vascular resistance (4.7 vs. 5.9, p = 0.004), and stent gradient (11.2 vs. 33.4, p < 0.001), along with increased patency (84.8% vs. 28%, p < 0.001), and fractional flow reserve (0.84 vs. 0.44, p < 0.001). Over a median follow‐up of 331 days (range 45–980), no significant stent stenosis occurred (p = 0.287). Mild adverse events like cough and mild hemoptysis were noted during the procedure. Secondary intervention was needed for 5 of 49 stents. PA stents placement, especially the LLPA and RLPA, improved pulmonary vascular patency, hemodynamics, and symptoms.

ABSTRACTPrognostic markers of Group 3 pulmonary hypertension (PH) remain largely unknown. In this study, we evaluate clinical data to provide a comprehensive profile of patients with Group 3 PH and evaluate the potential use of vasoreactivity testing as a prognostic tool within this population. We hypothesized that patients with a stronger vasoconstrictive component of their pulmonary vascular disease would have a more favorable prognosis. Patients were given inhaled nitric oxide during their right heart catheterization to determine if they met the European Respiratory Society guidelines for having a positive vasoreactivity test as defined for patients with Group 1 pulmonary arterial hypertension (PAH). While vasoreactivity response is proven to predict survival in subgroups of PAH, there was no significant relationship between change in mean pulmonary artery pressure (mPAP) during acute vasodilator challenge and survival within our cohort. On the contrary, patients with larger decreases in pulmonary vascular resistance (PVR) during the acute vasodilator challenge were at a significantly higher risk of mortality. The data suggests that the change in PVR during acute vasodilator challenge may be a better indicator of survival in patients with WHO Group 3 PH than the change in mPAP.

ABSTRACTThis study aimed to investigate the vascular effects of a radiofrequency electromagnetic field (RF‐EMF) applied in the lung ischemia and reperfusion (IR) model on the hypoxia‐inducible factor 1 alpha (Hif‐1α)/endothelial nitric oxide synthase (eNOS) pathway and B cell lymphoma 2 (BCL2)/BCL‐2 associated X protein (BAX) signaling. Forty male Wistar rats were randomly divided into four groups, each consisting of 10 rats: Sham, IR, IR + RF‐EMF, and RF‐EMF. IR was applied to rats by 60 min of clamping hilus of left lungs and 60 min of reperfusion. Rats were kept in the RF‐EMF unit for 60 min with or without activation. After sacrification, lung tissues were excised for histopathological, immunohistochemical, biochemical, and genetic analyses. IR injury led to increased damage‐related emphysematous findings, significant hyperemia, and increased septal tissue thickness, as observed histopathologically, and immunoexpression levels of tumor necrosis factor‐alpha and caspase‐3. In addition, it was noted that the biochemical parameters total oxidant status, oxidative stress index, and genetic parameters Hif 1 α, eNOS, BAX increased, and BCL2 decreased due to IR damage. In the IR‐RF‐EMF group, improvement has been detected in all parameters. RF‐EMF applied in the IR model exerts antioxidant, antiapoptotic, and anti‐inflammatory effects on lung tissue damage through the Hif‐1α/eNOS pathway and BCL‐2/BAX signaling. The use of RF‐EMF in IR damage is promising, as models that examine the long‐term effects of RF‐EMF at different frequencies.

ABSTRACTCombined post‐ and precapillary pulmonary hypertension (CpcPH) comprises the most severe form of postcapillary PH. A severe precapillary component (pulmonary vascular resistance [PVR] > 5 WU) is critical for therapeutic decisions. Current treatment guidelines focus on optimizing underlying cardiac disease, while there are conflicting data regarding the efficacy and safety of pulmonary arterial hypertension (PAH) drugs in selected patients. This study examines the impact of PVR > 5 WU on survival in heart failure with preserved ejection fraction (HFpEF) and CpcPH and evaluates the effect of treatment with phosphodiesterase 5 inhibitors (PDE5is) on clinical and hemodynamic parameters and on prognosis. The Hellenic Pulmonary Hypertension Registry (HOPE) enrolls patients from all PH groups in Greece. This study focuses on Group 2 CpcPH patients with HFpEF. Propensity score matching was performed to reduce the risk of bias in the treatment selection and potential confounders. Kaplan–Meier curve was used to estimate 5‐year survival, and the log‐rank test was used for the comparisons. A total of 98 patients were included, with a median follow‐up of 2.9 years. PVR > 5 WU and age were independently associated with worse survival ([HR 2.15, 95% CI 1.13–4.83, p = 0.04], [HR 1.07, 95% CI 1.03–1.13, p = 0.003], respectively). Propensity‐matched cohort analysis indicated that PDE5i treatment was associated with a significant reduction in PVR at follow‐up (from median [IQR] 4.89 [1.9] WU to 3.1 [2.0] WU, p = 0.04) and a trend towards improved survival. Severe precapillary component is associated with impaired prognosis in CpcPH. While PDE5i treatment shows promise in improving hemodynamic outcomes, its effect on long‐term survival requires further investigation.