Treatment Of Chronic Thromboembolic Pulmonary Hypertension Research Articles

Right ventricular remodelling and long-term survival after pulmonary endarterectomy versus balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension

BackgroundPulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an alternative for inoperable patients. We aimed to compare right...

Identification of Anoikis-related potential biomarkers and therapeutic drugs in chronic thromboembolic pulmonary hypertension via bioinformatics analysis and in vitro experiment

There is growing evidence that programmed cell death plays a significant role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). Anoikis is a newly discovered type of programmed death and has garnered great attention. However, the precise involvement of Anoikis in the progression of CTEPH remains poorly understood. The goal of this study was to identify Anoikis-related genes (ARGs) and explore potential therapeutic drugs for CTEPH. Differentially expressed genes were identified by limma and weighted gene co-expression network analysis (WGCNA) packages, and functional analyses were conducted based on the differentially expressed genes. Subsequently, a combination of protein–protein interaction (PPI), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine Recursive Feature Elimination (SVM-RFE) methodologies was employed to screen hub genes associated with CTEPH, which were further verified by dataset GSE188938, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. CIBERSORT was utilized to evaluate the infiltration of immune cells and the relationship between infiltration-related immune cells and ARGs. Finally, targeted drug analysis and molecular docking were used to predict drugs targeting Anoikis process to treat CTEPH. Thirty-two differentially expressed genes related to Anoikis and CTEPH were screened through WGCNA analysis. Then, the key ARGs FASN, PLAUR, BCL2L1, HMOX1 and RHOB were screened by PPI, Lasso and SVM-RFE machine learning. Validation through dataset GSE188938, qRT-PCR, and Western blot analyses confirmed HMOX1 and PLAUR as powerful and promising biomarkers in CTEPH. In addition, CIBERSORT immunoinfiltration revealed that Mast_cells_activated and Neutrophils were involved in the pathological regulation of CTEPH. Correlation analysis indicated that HMOX1 was positively correlated with Neutrophils, while PLAUR was negatively correlated with Mast_cells_activated. Finally we used targeted drug analysis and molecular docking to identify that STANNSOPORFIN as a potential drug targeting HMOX1 for the treatment of CTEPH. HMOX1 and PLAUR emerge as potential biomarkers for CTEPH and may influence the development of CTEPH by regulating Anoikis. Mast_cells_activated and Neutrophils may be involved in Anoikis resistance in CTEPH patients, presenting novel insights into CTEPH therapeutic targets. STANNSOPORFIN is a potential agents targeting Anoikis process therapy for CTEPH.

Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach. Plasma ET-1 levels were measured in a cohort of 59 CTEPH patients and 41 healthy controls. Additionally, we evaluated the expression of key ET-1 pathway members in pulmonary explants from CTEPH, idiopathic PAH, and control patients. We used an in vitro system to test the hypothesis that the turbulent flow, observed near the vascular obstructions pathognomonic of CTEPH, enhances ET-1 expression. Our findings were further validated in vivo using a CTEPH piglet model that contains distinct regions representing pre- and post-thrombus lung territories. We found a twofold increase in circulating ET-1 levels in CTEPH patients compared to healthy subjects. Pulmonary explants from CTEPH patients exhibited pronounced overexpression of ET-1, endothelin receptor A (ETA), and phosphorylated myosin light chain (p-MLC) in muscularized pulmonary microvessels, suggesting heightened vascular contraction. In vitro experiments showed that turbulent flow facilitates ET-1 secretion compared to laminar flow regions. Additionally, in the CTEPH piglet model, elevated plasma ET-1 levels were observed compared to controls. Immunofluorescence and confocal microscopy analyses confirmed increased ETA and p-MLC in remodeled arteries from both pulmonary territories. However, ET-1 protein elevation was exclusively observed in the obstructed territory. These findings collectively indicate impaired vascular tone in microvessels of CTEPH patients and the CTEPH piglet model. Furthermore, our data implicates the ET-1 pathway in microvasculopathy, with turbulent flow playing a pathological role. These insights underscore the potential utility of ET-1 receptor antagonists as a promising therapeutic approach for CTEPH treatment.

Different treatments in chronic thromboembolic pulmonary hypertension: comparison of strategies in the Italian centre real-world experience

Abstract Rationale Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients declared not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in real-world setting. Methods All CTEPH referred to our Centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups. Results We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival. Conclusions We confirm the superiority of PEA compared to any alternative treatment in CTEPH and we observe that BPA, in patients declared not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.

Endarterectomy in CTEPH: hemodynamic improvement and RV-PA coupling

Abstract Introduction Pulmonary artery endarterectomy (PAE) remains the gold standard in treating chronic thromboembolic pulmonary hypertension (CTEPH). Reducing the thrombotic burden and mechanical obstruction of the pulmonary artery (PA) leads to significant hemodynamic improvement, allowing for favorable right ventricular (RV) remodeling. Methods Single center retrospective study, including 30 pts submitted to PEA over a 7-year period. Hemodynamic assessment was performed by right heart catheterization (RHC) before PEA, immediately after and at 6-month follow-up (FUP). Echocardiographic assessment of RV function was acquired at baseline and 6m FUP. Mean absolute differences were calculated before and after PEA. Differences between groups were assessed with ANOVA analysis and ROC curve analysis allowed us to define a cut-off point in mPAP reduction to predict favorable RV remodeling. Results We included 30 pts with a mean age of 57,9 ± 13 years old and slight predominance of female sex (57%). Regarding risk assessment with the 4 strata tool at baseline, 23% of pts were high risk, 20% intermediate high, 27% intermediate low and 6% at low risk. Pulmonary hemodynamics improved immediately after PEA, as indicated by a mean reduction of 28,3 ±17 mmHg in mPAP; 44,4±27,6mmHg in sPAP; 8±3,4 Wu in PVR and an increase in CO of 0,5±1 l/min. This improvement was sustained at 6-m post PEA assessment, with a mean reduction of 31,5 ±26,7 mmHg in mPAP; 48,3±41,2mmHg in sPAP; 6,3±6,2Wu in PVR and a 0,5±1 l/min increase in CO. Regarding RV remodeling at 6m post PEA, an increase of 0.15±0.2mm/mmHg in TAPSE/PSAP ratio and 3±2,8cm/s in Tricuspid S’ were recorded. RV/PA uncoupling, defined as TAPSE/PSAP <0,31 mm/mmHg, was evident in 73% of pts at baseline, 25% of which recovered at 6m follow-up. There were no significant differences between groups, according to the 4 strata risk assessment at baseline, regarding pulmonary hemodynamics and RV remodeling. Through ROC curve analysis, we were able to define a cut-off point of 37mmHg in immediate mPAP post-op reduction to predict RV-RA coupling normalization at 6-m FUP (sensitivity 70%, specificity 89%). Conclusions PEA remains a cornerstone of CTEPH treatment. It’s impact on improving pulmonary hemodynamics is immediate and maintained at 6-month FUP. This improvement may be expected regardless of risk assessment at baseline. Reducing RV afterload allows favorable remodeling and an immediate post operative reduction of mPAP > 37mmHg may predict normalization of RV-PA coupling.

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

Differential effects of balloon pulmonary angioplasty on chronic thromboembolic pulmonary disease

BackgroundDecreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for...

The Importance of Topographical Recognition of Pulmonary Arteries in Diagnostics and Treatment of CTEPH, Based on an Analysis of a Dissected Case Model-A Pilot Study.

Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three dimensions (3D) is paramount. This study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles. One pair of embalmed human cadaver lungs was dissected by a scalpel and surgical forceps and was measured up to the subsegmental arteries. The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30-45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs. Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations.

Chronic Thromboembolic Pulmonary Hypertension: the therapeutic assessment.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe and complex condition that evolves from unresolved pulmonary embolism, leading to fibrotic obstruction of pulmonary arteries, pulmonary hypertension, and potential right heart failure. The cornerstone of CTEPH management lies in a multifaceted therapeutic approach tailored to individual patient profiles, reflecting the disease's heterogeneity. This review delves into the current therapeutic strategies for CTEPH, including surgical pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and targeted pharmacological treatments such as PDE5 inhibitors, endothelin receptor antagonists, sGC stimulators, and prostanoids. Lifelong anticoagulation is also highlighted as a preventive strategy against recurrent thromboembolism. Special emphasis is placed on the interdisciplinary nature of CTEPH care, necessitating collaboration among PEA surgeons, BPA interventionists, PH specialists, and thoracic radiologists to ensure comprehensive treatment planning and execution. The review underscores the importance of selecting an appropriate treatment modality based on the patient's specific disease characteristics and the evolving landscape of CTEPH treatment, aiming to improve patient outcomes through integrated care strategies.

Guidelines for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (2024 edition)

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 pulmonary hypertension, characterized by pulmonary arterial thrombotic occlusion leading to vascular stenosis or obstruction, progressive elevation of pulmonary vascular resistance and pulmonary arterial pressure, ultimately leading to right heart failure and even death. Recent years have seen rapid progress in the diagnostic and therapeutic in CTEPH field. More and more patients with CTEPH have been accurately diagnosed and assessed in time. Nevertheless, there is still a lot of work to do in the popularization of CTEPH diagnostic and therapeutic technique and the building of CTEPH expert center. To better guide clinical practice in our country, Pulmonary Embolism & Pulmonary Vascular Diseases Group of the Chinese Thoracic Society, Pulmonary Embolism & Pulmonary Vascular Disease Working Group of Chinese Association of Chest Physicians, National Cooperation Group on Prevention & Treatment of Pulmonary Embolism & Pulmonary Vascular Disease, National Expert Panel on the Development of a Standardized Framework for Pulmonary Arterial Hypertension, convened multidisciplinary experts for deliberation and Delphi expert consensus to develop the "Guidelines for the Diagnosis and Treatment of Chronic Thromboembolic Pulmonary Hypertension (2024 edition) ". These guidelines systematically evaluate domestic and international evidence-based medical research on CTEPH and propose recommendations tailored to clinical practice in our country. The key areas covered include definitions, epidemiology, pathogenesis, diagnosis and assessment, treatment, and management, with the aim of further standardizing the clinical diagnosis and treatment of CTEPH in our country.

Atrial Arrhythmias Following Pulmonary Thromboendarterectomy: A Comprehensive Review Of Current Literature.

Chronic thromboembolic pulmonary hypertension (CTEPH) presents as a progressive vascular condition arising from previous episodes of acute pulmonary embolism, contributing to the development of pulmonary hypertension (PH). Pulmonary thromboendarterectomy (PTE) is the gold-standard surgical treatment for CTEPH; however, it may be associated with postoperative sequelae, including atrial arrhythmias (AAs). This comprehensive literature review explores the potential mechanisms for PTE-induced AAs with emphasis on the role of PH-related atrial remodelling and the predisposing factors. The identified preoperative predictors for AAs include advanced age, male gender, elevated resting heart rate, previous AAs, and baseline elevated right atrial pressure. Furthermore, we explore the available data on the association between post-PTE pericardial effusions and the development of AAs. Lastly, we briefly discuss the emerging role of radiomic analysis of epicardial adipose tissue as an imaging biomarker for predicting AAs.

Treatment and management of chronic thromboembolic pulmonary hypertension (CTEPH):A global cross-sectional scientific survey (CLARITY).

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.

Diagnosis andmanagement of chronic thromboembolic pulmonary hypertension (CTEPH) in sickle cell disease: A review.

Pulmonary hypertension in sickle cell disease (SCD) is a complex phenomenon resulting from multiple overlapping etiologies, including pulmonary vasoconstriction in the setting of chronic hemolytic anemia, diastolic dysfunction, and chronic thromboembolic disease. The presence of pulmonary hypertension of any cause in SCD confers a significant increase in mortality risk. Evidence to guide the management of patients with sickle cell disease and chronic thromboembolic pulmonary hypertension(CTEPH) is scant and largely the realm of case reports and small case series. Centered on a discussion of a complex young patient with hemoglobin hemoglobin SC who ultimately underwent treatment with pulmonary thromboendarterectomy, we review the available literature to guide management and discuss and overview of treatment of CTEPH in SCD, considering the unique considerations and challenges facing patients suffering from this multisystem disease.

Nationwide trends of balloon pulmonary angioplasty and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (2012-2019).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of a pulmonary embolus that occurs in approximately 1%-3% of patients. Pulmonary thromboendoarterectomy (PTE) can be a curative procedure, but balloon pulmonary angioplasty (BPA) has emerged as an option for poor surgical candidates. We used the National Inpatient Sample to query patients who underwent PTE or BPA between 2012 and 2019 with CTEPH. The primary outcome was a composite of in-hospital mortality, myocardial infarction, stroke, tracheostomy, and prolonged mechanical ventilation. Outcomes were compared between low- and high-volume centers, defined as 5 and 10 procedures per year for BPA and PTE, respectively. During our study period, 870 BPA and 2395 PTE were performed. There was a 328% relative increase in the number of PTE performed during the study period. Adverse events for BPA were rare. There was an increase in the primary composite outcome for low-volume centers compared to high-volume centers for PTE (24.4% vs. 12.1%, p = 0.003). Patients with hospitalizations for PTE in low-volume centers were more likely to have prolonged mechanical ventilation (20.0%% vs. 7.2%, p < 0.001) and tracheostomy (7.8% vs. 2.6%, p = 0.017). In summary, PTE rates have been rising over the past 10 years, while BPA rates have remained stable. While adverse outcomes are rare for BPA, patients with hospitalizations at low-volume centers for PTE were more likely to have adverse outcomes. For patients undergoing treatment of CTEPH with BPA or PTE, referral to high-volume centers with multidisciplinary teams should be encouraged for optimal outcomes.

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. gov: NCT02637050; registered December 2015.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): Aglobal cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the recognition and diagnosis of CTEPH and the referral and evaluation of these patients. The survey was offered to hospital-based medical specialists through Scientific Societies and other medical organizations, from September 2021 to May 2022. Response data from 353 physicians showed that self-reported awareness of CTEPH increased over the past 10 years among96% of respondents. Clinical practices in acute pulmonary embolism (PE) follow-up and CTEPH diagnosis differed amongrespondents. While 50% of respondents working in a nonexpert center reported to refer patients to an expert pulmonary hypertension/CTEPH center when CTEPH is suspected, 51% of these physicians did not report referral of patients with a confirmed diagnosis for further evaluation. Up to 50% of respondents involved in the evaluation of referred patients have concluded a different operability status than that indicated by the referring center. This study indicates that early diagnosis and timely treatment of CTEPH is challenged by suboptimal acute PE follow-up and patient referral practices. Nonadherence to guideline recommendations may be impacted by various barriers to care, which were shown to vary by geographical region.

The significance of CD16+ monocytes in the occurrence and development of chronic thromboembolic pulmonary hypertension: insights from single-cell RNA sequencing.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH. Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining. The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression. CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

Chronic thromboembolic pulmonary hypertension: clinical case and problem review

In this article there was presented a clinical case of the chronic thromboembolic pulmonary hypertension (CTEPH) in the patient with small arteries damage. The thromb visualization was done by the lung perfusion multispiral computer tomography. The general positions of the definition, the diagnosis and treatment of the CTEPH were elucidated too. It was stated the CTEPH is a potential curable disease in case of the surgery in time. But there are some situations when it is not possible to provide the surgery and, in this case, the CTEPH treatment by specific pulmonary hypertension drugs could be used

Histopathological Evaluation of Pulmonary Thromboendarterectomy Specimens of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. P ulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and s mooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1. In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A. Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

Balloon pulmonary angioplasty in the current era of CTEPH treatment: How did we get here?

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved pulmonary embolism. The treatment of choice is pulmonary thromboendarterectomy (PTE) surgery and all patients should be evaluated for operability candidacy. Despite advancements in PTE technique allowing more segmental-subsegmental surgeries, up to a third of patients with CTEPH may still be considered inoperable. Over the past decade, there have been increasing treatment options for these inoperable CTEPH patients. Balloon pulmonary angioplasty (BPA) is a percutaneous-based interventional treatment option for select CTEPH cases. Early BPA experiences were plagued by high complication rates, but further refinements in technique and equipment pioneered by Japan led to the worldwide spread and adoption of BPA. Multiple centers have shown that patients experience significant improvements in hemodynamics, quality of life, exercise capacity, and survival with BPA treatment. There remain many questions on best practices, but BPA has evolved into a pivotal cornerstone of CTEPH treatment.