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

Aging ◽  
2021 ◽  
Author(s):  
Ran Miao ◽  
Xingbei Dong ◽  
Juanni Gong ◽  
Yidan Li ◽  
Xiaojuan Guo ◽  
...  
Author(s):  
Ran Miao ◽  
Xingbei Dong ◽  
Juanni Gong ◽  
Yidan Li ◽  
Xiaojuan Guo ◽  
...  

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.


2014 ◽  
Vol 12 (4) ◽  
pp. 186-192 ◽  
Author(s):  
David Poch ◽  
Victor Pretorius

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg in the presence of occlusive thrombi within the pulmonary arteries. Surgical pulmonary thromboendarterectomy (PTE) is considered the best treatment option for CTEPH.


2021 ◽  
pp. 204589402110136
Author(s):  
Tailong Zhang ◽  
Weitao Liang ◽  
Longrong Bian ◽  
Zhong Wu

Right heart thrombus (RHT) accompanied by chronic thromboembolic pulmonary hypertension (CTEPH) is a rare entity. RHT may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of RHT is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of RHT with CTEPH that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy (PEA) and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, RHT should be suspected in patients with CTEPH, and simultaneous RHT resection is required along with PEA.


2020 ◽  
Vol 22 (Supplement_F) ◽  
pp. F30-F37
Author(s):  
Stepan Havranek ◽  
Zdenka Fingrova ◽  
David Ambroz ◽  
Pavel Jansa ◽  
Jan Kuchar ◽  
...  

Abstract Atrial fibrillation (AF) and atrial tachycardia (AT) are frequently observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with pulmonary endarterectomy (PEA). Their prevalence and impact on prognosis of patients are not known. We analysed the prevalence of AF/AT and the clinical outcome in 197 patients with CTEPH treated with PEA (median age 62; interquartile range 53–68 years; 62% males). The prevalence of AF/AT was 29% (57 patients). Compared to patients without arrhythmia, the subjects with AF/AT were older [60 (50–67) vs. 62 (57–70) years], manifested an increased size of the left atrium [39 (35–44) vs. 45 (40–50) mm], had a reduced 6-min walking distance [411 (321–506) vs. 340 (254–460) m], and higher pulmonary artery systolic pressure after PEA [38 (30–47) vs. 45 (38–71) mmHg], all results with P-value <0.05. During the follow-up with a median 4.2 (1.6–6.3) years, 45 (23%) patients died. In a multivariate Cox regression model only the male gender [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.15–4.50], a reduced 6-min walking distance (HR 3.67, 95% CI 1.74–7.73), and an increased New York Heart Association class (HR 8.56, 95% CI 4.17–17.60) were associated with mortality (P < 0.05). The prevalence of AF/AT in patients with CTEPH treated with PEA is high. Arrhythmias are associated with reduced functional capacity but not with mortality.


2018 ◽  
Vol 37 (2) ◽  
pp. 250-258 ◽  
Author(s):  
Mareike Lankeit ◽  
Valentin Krieg ◽  
Lukas Hobohm ◽  
Sebastian Kölmel ◽  
Christoph Liebetrau ◽  
...  

2010 ◽  
Vol 299 (4) ◽  
pp. H1083-H1091 ◽  
Author(s):  
Joost Lumens ◽  
Daniel G. Blanchard ◽  
Theo Arts ◽  
Ehtisham Mahmud ◽  
Tammo Delhaas

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with abnormal left ventricular (LV) filling hemodynamics [mitral early passive filling wave velocity/late active filling wave velocity ( E/ A) < 1]. Pulmonary endarterectomy (PEA) acutely reduces pulmonary vascular resistance, resulting in an increase of mitral E/ A. The abolishment of leftward septal bulging and an increase in right ventricular (RV) output are thought to be responsible for the increase of mitral E/ A. In this study, we quantified the separate effects of leftward septal bulging and RV output on LV hemodynamics. In 39 CTEPH patients who underwent PEA, transmitral flow velocities and RV hemodynamic data were obtained pre- and postoperatively. A mathematical model describing the mechanics of ventricular interaction was fitted to the preoperative average values of cardiac output (CO; 4.4 l/min), mean pulmonary artery pressure (mPAP; 50 mmHg), mitral E/ A (0.74), and mean left atrial pressure (mLAP; 9.8 mmHg). Starting from this preoperative reference state with leftward septal bulging, PEA was simulated by changing mPAP and CO to average postoperative values (28 mmHg and 5.7 l/min, respectively). Simulated and postoperatively measured data on E/ A (1.27 vs. 1.48), mLAP (12.6 vs. 11.5 mmHg), and septal curvature (both rightward) were consistent. When an exclusive decrease of mPAP was simulated, mitral E/ A increased 26%, mLAP decreased 16%, and septal curvature became rightward. When an exclusive increase of CO was simulated, mitral E/ A increased 53% and mLAP increased 62%, whereas leftward septal bulging persisted. Thus, our simulations suggest that the increase of mitral E/ A with PEA is caused two-thirds by an increase of RV output and one-third by the abolishment of leftward septal bulging.


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