Padua prediction score may be inappropriate for VTE risk assessment in hospitalized patients with acute respiratory conditions: A Chinese single-center cohort study.

Background: The Padua Prediction Score (PPS) recommended by the guidelines lacks effective external validation in a Chinese cohort. This study sought to assess the accuracy of the PPS to predict venous thromboembolism (VTE) risk in medical inpatients with acute respiratory conditions. Methods: This consecutive cohort study included 1,574 inpatients from January to August 2019. The occurrence rate of VTE in patients classified at high-risk and low-risk groups according to PPS and Caprini risk assessment model (RAM) was compared. The discriminatory capability of the RAMs was evaluated in all the patients and the subgroup without pharmacological prophylaxis. Reclassification parameters were also used to assess the clinical utility. Results: 170 (10.8%) patients were objectively confirmed as having VTE during hospitalization. The incidence rate of VTE in low-risk patients was 6.3% by PPS, which was significantly higher than that by Caprini RAM (2.6%, p < 0.001). The area under the curve (AUC) for PPS and Caprini RAM was 0.714 (95%CI, 0.672-0.756) and 0.760 (95%CI, 0.724-0.797), respectively (p = 0.003). The AUC of Caprini RAM was larger than PPS even in subgroups without pharmacological prophylaxis (0.774 vs 0.709, p = 0.002). Compared with Caprini RAM, the net reclassification index was estimated at 0.037 (p = 0.436), and integrated discrimination improvement was 0.015 (p = 0.495) by PPS. Conclusions: According to our cohort study, PPS may not be appropriate to predict VTE risk in hospitalized patients with acute respiratory conditions. An accurate, widely applicable, validated RAM needs to be further constructed in Chinese medical inpatients.

The Role of Strain by Cardiac Magnetic Resonance Imaging in Predicting the Prognosis of Patients with Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombotic obstruction of the pulmonary arteries, and right ventricular (RV) dysfunction is a major cause of death. Cardiac magnetic resonance (CMR) is the gold standard for assessing heart wall deformation; therefore, we aimed to determine the prognostic value of CMR strain in patients with CTEPH. Strain derived by CMR was measured at the time of diagnosis in 45 patients with CTEPH, and the relationship between RV strain and prognosis was determined through follow-up. The value of RV strain in the prognostic model was compared with that of pulmonary arterial hypertension (PAH) risk stratification. The RV global peak longitudinal strain (GLS) and global peak circumferential strain (GCS) in CTEPH patients were lower than the normal references of RV strain in the control group. GLS and longitudinal strain in the basal segment were independent risk factors for adverse events (P < .050). Adding CMR parameters to PAH risk stratification improved its predictive power in patients with CTEPH. GLS and GCS scores were impaired in patients with chronic RV overload. RV strain derived by CMR imaging is a promising noninvasive tool for the follow-up of patients with CTEPH.

Analysis of clinical features between active and inactive patients of Takayasu's arteritis with pulmonary arteries involvement.

BACKGROUND: The aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. METHODS: Sixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. RESULTS: Compared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm-5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98-44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10-38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44-34.89), P = 0.016] were independently associated with disease activity. CONCLUSION: Chest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.

Long-term Outcomes and Predictors of Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Endarterectomy.

BACKGROUND: Pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients which can significantly improve symptoms and pulmonary hemodynamics. Therefore, this retrospective study evaluated the long-term outcomes after pulmonary endarterectomy (PEA) and analyze the predictors of long-term outcomes for chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: From 2002-2020, 76 CTEPH patients successfully discharged after PEA in Beijing Chaoyang Hospital were followed-up by scheduled clinical visits or telephone interviews. The follow-up time lasted for 18 years and median time was 7.29 years. RESULTS: The survival rate at 1,3,5,10,15 years postoperatively was 100.00%, 97.10%, 95.40%, 89.80% and 82.90%, respectively. Multivariate logistics regression analysis showed that postoperative mPAP (hazard ratio: 1.144; 95%confidence interval: 1.018-1.285; P = 0.023) was associated with a higher risk of late death, right atrium right and left diameters (hazard ratio: 1.113; 95%confidence interval, 1.006-1.231; P = 0.038) were associated with a higher risk of major adverse events. CONCLUSION: Pulmonary endarterectomy is an effective way to treat CTEPH. Long-term outcome is excellent for patients who undergoing pulmonary endarterectomy who survived from peri-operation time. Postoperative mPAP is a significant prognostic factor for long-term death and right atrium right and left diameters is a significant prognostic factor for major adverse events. That shows patients with high postoperative mPAP and right atrium right and left diameter should be followed up closely.

Single-cell RNA-sequencing and microarray analyses to explore the pathological mechanisms of chronic thromboembolic pulmonary hypertension.

Objective: The present study aimed to explore the pathological mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) using a gene chip array and single-cell RNA-sequencing (scRNA-seq). Materials and methods: The mRNA expression profile GSE130391 was downloaded from the Gene Expression Omnibus database. The peripheral blood samples of five CTEPH patients and five healthy controls were used to prepare the Affymetrix microRNA (miRNA) chip and the Agilent circular RNA (circRNA) chip. The pulmonary endarterectomized tissues from five CTEPH patients were analyzed by scRNA-seq. Cells were clustered and annotated, followed by the identification of highly expressed genes. The gene chip data were used to identify disease-related mRNAs and differentially expressed miRNAs and circRNAs. The protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were constructed for each cell type. Results: A total of 11 cell types were identified. Intersection analysis of highly expressed genes in each cell type and differentially expressed mRNAs were performed to obtain disease-related genes in each cell type. TP53, ICAM1, APP, ITGB2, MYC, and ZYX showed the highest degree of connectivity in the PPI network of different types of cells. In addition, the circRNA-miRNA-mRNA network for each cell type was constructed. Conclusion: For the first time, the key mRNAs, miRNAs, and circRNAs, as well as their possible regulatory relationships, during the progression of CTEPH were analyzed using both gene chip and scRNA-seq data. These findings may contribute to a better understanding of the pathological mechanisms of CTEPH.

Examining the Development of Chronic Thromboembolic Pulmonary Hypertension at the Single-Cell Level.

BACKGROUND: The mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is known to be multifactorial but remains incompletely understood. METHODS: In this study, single-cell RNA sequencing, which facilitates the identification of molecular profiles of samples on an individual cell level, was applied to investigate individual cell types in pulmonary endarterectomized tissues from 5 patients with CTEPH. The order of single-cell types was then traced along the developmental trajectory of CTEPH by trajectory inference analysis, and intercellular communication was characterized by analysis of ligand-receptor pairs between cell types. Finally, comprehensive bioinformatics tools were used to analyze possible functions of branch-specific cell types and the underlying mechanisms. RESULTS: Eleven cell types were identified, with immune-related cell types (T cells, natural killer cells, macrophages, and mast cells) distributed in the left (early) branch of the pseudotime tree, cancer stem cells, and CRISPLD2+ cells as intermediate cell types, and classic disease-related cell types (fibroblasts, smooth muscle cells, myofibroblasts, and endothelial cells) in the right (later) branch. Ligand-receptor interactions revealed close communication between macrophages and disease-related cell types as well as between smooth muscle cells and fibroblasts or endothelial cells. Moreover, the ligands and receptors were significantly enriched in key pathways such as the PI3K/Akt signaling pathway. Furthermore, highly expressed genes specific to the undefined cell type were significantly enriched in important functions associated with regulation of endoplasmic reticulum stress. CONCLUSIONS: This single-cell RNA sequencing analysis revealed the order of single cells along a developmental trajectory in CTEPH as well as close communication between different cell types in CTEPH pathogenesis.

Haemodynamic effects of riociguat in CTEPH and PAH: a 10-year observational study.

BACKGROUND: Long-term treatment with riociguat has been shown to enhance exercise capacity in patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to evaluate the long-term haemodynamic effects of riociguat in patients with PAH and inoperable CTEPH. METHODS: During this single-centre long-term observational study, riociguat was administered at a three-times-daily dose of up to 2.5 mg. The primary outcome was pulmonary vascular resistance (PVR). The secondary outcomes included mean pulmonary arterial pressure (PAP), cardiac index, mortality, clinical worsening events, 6-min walk distance (6MWD) and World Health Organization functional class (WHO FC). RESULTS: 37 patients (CTEPH n=19; PAH n=18) were included. The median follow-up period was 96 months. The survival estimates for all the patients at 1/3/5/8 years were 0.97/0.86/0.72/0.61, without significant differences between patients with CTEPH and PAH. At the final data cut-off, PVR decreased (1232±462 dyn·s·cm-5 versus 835±348 dyn·s·cm-5, p<0.001), cardiac index increased (1.7±0.4 L·min-1·m-2 versus 2.4±0.5 L·min-1·m-2, p<0.001), 6MWD increased by 43.1±59.6 m, and WHO FC improved/stabilised/worsened in 40%/35%/25% of patients versus baseline. Improvement in PAP was not shown. Compared with patients in WHO FC I/II and III/IV at baseline, the 8-year clinical worsening-free survival estimates were 0.51 versus 0.19 (p=0.026). CONCLUSIONS: Riociguat improved PVR and cardiac index for up to 8 years, but not PAP. WHO FC may have certain predictive value for the long-term prognosis.

Cell landscape atlas for patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy constructed using single-cell RNA sequencing.

This study aimed to construct an atlas of the cell landscape and comprehensively characterize the cellular repertoire of the pulmonary endarterectomized tissues of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Five pulmonary endarterectomized tissues were collected. 10× Genomics single-cell RNA sequencing was performed, followed by the identification of cluster marker genes and cell types. Gene Ontology (GO) enrichment analysis was conducted. Seventeen cell clusters were characterized, corresponding to 10,518 marker genes, and then classified into eight cell types, including fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, cysteine rich secretory protein LCCL domain containing 2 (CRISPLD2)+ cell, cancer stem cell, and undefined. The specific marker genes of fibroblast/smooth muscle cell, endothelial cell, T cell/NK cell, macrophage, mast cell, and cancer stem cell were significantly enriched for multiple functions associated with muscle cell migration, endothelial cell migration, T cell activation, neutrophil activation, erythrocyte homeostasis, and tissue remodeling, respectively. No functions were significantly enriched for the marker gene of CRISPLD2+ cell. Our study, for the first time, provides an atlas of the cell landscape of the pulmonary endarterectomized tissues of CTEPH patients at single-cell resolution, which may serve as a valuable resource for further elucidation of disease pathophysiology.

Expression of miR-93-5p as a Potential Predictor of the Severity of Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. METHODS: A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. RESULTS: Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group (P < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI (P < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure. CONCLUSIONS: miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH.

Refractory pleural effusion as a rare complication of pulmonary vascular stenosis induced by fibrosing mediastinitis: a case report and literature review.

Fibrosing mediastinitis (FM) is a progressive, life-threatening disease characterized by extrinsic compression of mediastinal bronchovascular structures, and the clinical manifestations largely depend upon the affected structures. Pleural effusion is rarely reported in patients with FM. We herein describe a 70-year-old man who presented with recurrent breathlessness and refractory left pleural effusion. He was misdiagnosed with and treated for tuberculous pleurisy for several months. Thoracentesis revealed a transudative pleural effusion, and a contrast-enhanced computed tomography scan of the thorax showed an extensive mediastinal soft tissue mass consistent with FM. Pulmonary angiography demonstrated pulmonary artery stenosis on the right side and pulmonary vein stenosis mainly on the left side. After measurement of the pulmonary arterial pressure by right heart catheterization, the patient was diagnosed with pulmonary hypertension associated with FM. He underwent balloon angioplasty and stent implantation of the stenosed pulmonary vessels, which led to long-term improvement in his breathlessness and pleural effusion. Our systematic review of the literature highlights that pleural effusion can be an uncommon complication of FM and requires careful etiological differentiation.

Platelet count trends and response to fondaparinux in a cohort of heparin-induced thrombocytopenia suspected patients after pulmonary endarterectomy.

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.

Possible immune regulation mechanisms for the progression of chronic thromboembolic pulmonary hypertension.

PURPOSE: This study aimed to screen key genes significantly associated with chronic thromboembolic pulmonary hypertension (CTEPH) and predicted suitable drugs for the treatment of CTEPH from the perspective of immune cells. METHODS: The dataset GSE130391 was used for this analysis. Differentially expressed genes (DEGs) between the CTEPH and control groups were screened. Abundance of infiltrating immune cells was analyzed and immune-related DEGs were identified. Next, the circular RNA (circRNA)-micro RNA (miRNA)-mRNA network was constructed, followed by functional enrichment analysis. Then, the protein-protein interaction (PPI) network was constructed and drug-gene interactions were predicted. Finally, miRNA and circRNA prediction results were verified by our previously published studies. RESULTS: Five key immune cell-related DEGs [CD83 molecule (CD83), complement c5a receptor 1 (C5AR1), atypical chemokine receptor 1 (ACKR1), profilin 2 (PFN2), and solute carrier family 2 member 3 (SLC2A3)] were identified. Several circRNA-miRNA-mRNA interactions were obtained, including circ_0022342miR-503-5pSLC2A3 and circ_0002062miR-92b-3p/miR-92a-3pmannosidase alpha class 2A member 1 (MAN2A1). Immune cell for SLC2A3 was eosinophils and for MAN2A1 was regulatory T cells (Tregs). Additionally, Glufosfamide and Kifunensine might be suitable as candidate drugs for CTEPH treatment. CONCLUSIONS: SLC2A3 and MAN2A1 may be important genes for the pathogenesis of CTEPH. Possible immune regulation mechanisms in CTEPH may be circ_0022342miR-503-5pSLC2A3 and circ_0002062miR-92b-3p/miR-92a-3pMAN2A1. These results may be helpful for the diagnosis and treatment of CTEPH from the perspective of immunology.

hsa-miR-106b-5p participates in the development of chronic thromboembolic pulmonary hypertension via targeting matrix metalloproteinase 2.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by elevated pressure in pulmonary arteries. This study was performed to explore the critical miRNAs and genes affecting the pathogenesis of CTEPH. METHODS: GSE56914 dataset (10 CTEPH whole blood samples and 10 control samples) was downloaded from the Gene Expression Omnibus database. Using limma package, the differentially expressed miRNAs (DE-miRNAs) were acquired. After miRNA-target pairs were obtained using miRWalk2.0 tool, a miRNA-target regulatory network was built by Cytoscape software. Using DAVID tool, significantly enriched pathways involving the target genes were identified. Moreover, the protein-protein interaction network and transcription factor-target regulatory network were built by the Cytoscape software. Additionally, quantitative real-time PCR (qRT-PCR) experiments and luciferase assay were conducted to validate miRNA/gene expression and miRNA-target regulatory relationship, respectively. RESULTS: There were 25 DE-miRNAs (8 up-regulated and 17 down-regulated) between CTEPH and control groups. The target genes of has-let-7b-3p, has-miR-17-5p, has-miR-3202, has-miR-106b-5p, and has-miR-665 were enriched in multiple pathways such as "Insulin secretion". qRT-PCR analysis confirmed upregulation of hsa-miR-3202, hsa-miR-665, and matrix metalloproteinase 2 (MMP2) as well as downregulation of hsa-let-7b-3p, hsa-miR-17-5p, and hsa-miR-106b-5p. Luciferase assay indicated that MMP2 was negatively mediated by hsa-miR-106b-5p. CONCLUSIONS: These miRNAs and genes were associated with the pathogenesis of CTEPH. Besides, hsa-miR-106b-5p was involved in the development of CTEPH via targeting MMP2.

Hsa_circ_0046159 is involved in the development of chronic thromboembolic pulmonary hypertension.

The present study was performed to screen for potential molecular biomarkers and to assess the underlying mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) by using sequencing data analysis of microRNAs (miRNAs) and circular RNAs (circRNAs). Total RNA was isolated from peripheral-blood samples from five CTEPH patients and from five normal individuals. Based upon the identification of differentially expressed miRNAs (Affymetrix miRNA chip) and circRNAs (Agilent circRNA chip), target predictions for these differentially expressed miRNAs and functional enrichment analyses of the miRNAs and circRNAs were performed. Subsequently, the miRNA partner predictions of these differentially expressed circRNAs and co-expression analyses of differentially expressed circRNAs and miRNAs were conducted. Based on the results of these analyses, a competing endogenous RNA (ceRNA) network was constructed. Finally, the expression of circRNAs was detected by quantitative real-time PCR (qRT-PCR). Within the miRNA-circRNA regulatory network, hsa_circ_0026480 and hsa_circ_0046159 were predicted to interact with miR-27a-3p and miR-1226-3p, respectively with greater degree. Specially, ATP2A2-that had a ceRNA relationship with hsa_circ_0046159-was predicted as a target of miR-1226-3p. The results of RT-PCR also revealed a significantly increased expression of hsa_circ_0046159 in CTEPH samples than that in normal samples.

Efficacy and Safety of Bronchial Artery Embolization on Hemoptysis in Chronic Thromboembolic Pulmonary Hypertension: A Pilot Prospective Cohort Study.

OBJECTIVES: Managing hemoptysis in chronic thromboembolic pulmonary hypertension can be challenging due to the difficulties in maintaining coagulation homeostasis in affected patients. In this study, we evaluated the efficacy and safety of bronchial artery embolization in treating hemoptysis in chronic thromboembolic pulmonary hypertension patients. DESIGN: Pilot, prospective cohort study. SETTING: A large respiratory medical institute. PATIENTS: From January 1, 2012, to December 31, 2017, hospitalized chronic thromboembolic pulmonary hypertension patients were eligible for inclusion. Patients with pulmonary hypertension caused by other conditions, or who failed to participate in the follow-up were excluded. INTERVENTIONS: Hemoptysis in chronic thromboembolic pulmonary hypertension patients was treated with or without bronchial artery embolization based on whether the bleeding could be stopped with medication alone and patient willingness for bronchial artery embolization treatment. MEASUREMENTS AND MAIN RESULTS: A total of 328 patients diagnosed with chronic thromboembolic pulmonary hypertension were consecutively collected, 317 patients were completed the follow-up. There were 15 chronic thromboembolic pulmonary hypertension patients with hemoptysis in total, and the occurrence rate of hemoptysis in chronic thromboembolic pulmonary hypertension patients was 4.7%. Among the hemoptysis chronic thromboembolic pulmonary hypertension patients, 10 (67%) underwent bronchial artery embolization, and five (33%) were treated with medication only. The median follow-up period for hemoptysis patients was 7.6 months. In patients underwent bronchial artery embolization treatment, oxygenation index and right heart function showed no significant difference between pre bronchial artery embolization and post bronchial artery embolization. Hemoptysis relapse (20% vs 80%; p = 0.025) and hemoptysis-related mortality (0% vs 40%; p = 0.032) were significantly lower, whereas the overall survival (90% vs 40%; p = 0.040) was higher in patients treated with bronchial artery embolization than in patients treated without bronchial artery embolization. CONCLUSIONS: Bronchial artery embolization procedure demonstrated effectiveness and safety to treat hemoptysis in chronic thromboembolic pulmonary hypertension patients at our center, but further controlled studies are needed before it can be considered as an effective therapy for these patients.

Clinical and imaging manifestations of Takayasu's arteritis with pulmonary hypertension: A retrospective cohort study in China.

BACKGROUND: Takayasu's arteritis with pulmonary artery involvement (PTA) is uncommon and part of which may be accompanied by pulmonary hypertension (PH). This study herein investigated the clinical presentation, imaging features, and outcomes in PTA patients with and without PH. METHODS: A total of 57 PTA patients were selected at the Beijing Chao-Yang Hospital from January 2011 to July 2017. Patients were placed into two groups, PTA-with-PH or PTA-without-PH. The clinical characteristics, imaging features, and outcomes of patients in these two groups were investigated. RESULTS: Among the 57 PTA patients, 24 were in the PTA-without-PH group and 33 were in the PTA-with-PH group. The disease duration in PTA-with-PH patients was longer than that of PTA-without-PH patients. The mean follow-up duration of 43 patients was 33.5 ±â€¯20.3 months, while three patients in the PTA-with-PH were deceased. The PTA-with-PH group had significantly higher prevalence of chest tightness and dyspnea, shorter 6-minute walk distance (6MWD) and higher Borg scores after walk than that the PTA-without-PH group. Imaging analyses revealed that patients had five different arterial lesions (stenosis, occlusion, vascular wall thickening, in situ thrombosis, and aneurysm), but aneurysms were only detected in patients in PTA-with-PH patients at 42%. Compared with PTA-without-PH patients, PTA-with-PH patients tended to have occlusion lesions, but less likely to have vascular wall thickening. CONCLUSIONS: Compared with PTA-without-PH patients, PTA-with-PH patients had longer disease duration, more severe symptoms and tended to be deceased during the follow-up time. In addition, PTA-with-PH patients tended to have aneurysm and occlusion vessel lesions.

Pulmonary embolism risk stratification by European Society of Cardiology is associated with recurrent venous thromboembolism: Findings from a long-term follow-up study.

Venous thromboembolism (VTE) recurrence carries significant mortality and morbidity. Accurate risk assessment and effective treatment for patients with acute pulmonary embolism (PE) is important for VTE recurrence prevention. We examined the association of VTE recurrence with risk stratification and PE treatment. We enrolled 627 patients with a first episode of confirmed PE. Baseline clinical information was collected. PE severity was assessed by the European Society of Cardiology's (ESC) risk stratification, the simplified PE Severity Index (sPESI) and the Qanadli score of clot burden. Patients were followed for 1-5 years. The cumulative recurrent VTE and all-cause death were documented. The association between recurrent VTE and risk factors was analyzed. The cumulative incidences of recurrent VTE were 4.5%, 7.3%, and 13.9% at 1, 2, and 5 years of follow-up, respectively. The VTE recurrence was associated with higher (high- and intermediate-) risk stratification predicted by ESC model (HR 1.838, 95% CI 1.318-2.571, P<0.001), as well as with unprovoked PE (HR 2.809, 95% CI 1.650-4.781, P b 0.001) and varicose veins (HR 4.747, 95% CI 2.634-8.557, P<0.001). The recurrence was negatively associated with longer (≥6 months) anticoagulation (HR 0.473, 95% CI 0.285-0.787, P=0.004), especially in patients with higher risk (HR 0.394, 95% CI 0.211-0.736, P=0.003) and unprovoked PE (HR 0.248, 95% CI 0.122-0.504, P<0.001). ESC high-risk and intermediate-risk PE, unprovoked PE and varicose veins increase recurrence risk. Longer anticoagulation treatment reduces recurrence, especially in higher risk and unprovoked PE patients.

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism.

BACKGROUND: Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE). METHODS: In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA). RESULTS: Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH. CONCLUSIONS: CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.

Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance.

BACKGROUND: Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary thromboembolism (PTE), but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated. METHODS: Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP). Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls). RESULTS: Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037) and 95% confidence interval (95% CI, 1.262-3.289) showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G) genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype. CONCLUSIONS: Fibrinogen Aα Thr312Ala (A/G) polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.