Proximal Pulmonary Artery Research Articles

Anomalous Right Coronary Artery From the Pulmonary Artery Diagnosed in Pregnancy

A 39-year-old gravida 2, para 1 woman presented for evaluation of palpitations in pregnancy. She was found to have supraventricular tachycardia. The initial echocardiogram demonstrated a color Doppler signal in the proximal pulmonary artery with diastolic-dominant flow, suggestive of coronary flow. She received a diagnosis of anomalous right coronary artery from the pulmonary artery. Her arrhythmia was managed medically. We discuss techniques for risk stratification of cardiac lesions in pregnancy and for the management of anomalous coronary origin from the pulmonary artery. (Level of Difficulty: Intermediate.)

O-1 | 3D Printing of Patient-Specific Intravascular Stents for Congenital Heart Disease – Proof of Concept

Patients with congenital heart disease (CHD) may require stent placement for various vascular stenoses. Multiple stents are used “off-label” for patients with CHD. There is a need for accessible, modifiable and customizable stents for patients with CHD. This study aims to provide proof of concept for patient-specific 3D printed metal stents for CHD. Five hearts of patients with CHD and vascular stenoses were identified from our anonymized model database and 3D printed. Custom stents were designed using SolidWorks and Meshmixer and 3D printed with steel using the Ultimaker S5 Pro printer Metal Expansion Kit. The heart models were digitally reconstructed as if the stenosis was treated, 3D printed and the stents implanted by hand. Five stents were printed and implanted in the models. Diagnoses included: Scimitar syndrome with pulmonary vein baffle stenosis; proximal right pulmonary artery stenosis; left pulmonary artery arising from the aortic arch; left pulmonary artery stenosis; hypoplastic left heart syndrome after Norwood with recoarctation. Stent weight range 1-15g, print time 2-36 minutes, cost $0.13–1.94; these times do not account for the necessary post-processing, which is currently 10 business days. Examples of pre- and post-treated models are shown in the Figure. Utilizing the newest 3D metal printing technology, we were able to generate patient-specific stents and implant them in 3D printed models of CHD. The cost and print time are quite low, however the post-processing time is still quite long. As technology advances further, it may become possible to 3D print patient-specific stents in the cath lab.

Antiproliferative effect of selexipag active metabolite MRE-269 on pulmonary arterial smooth muscle cells from patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a group 4 pulmonary hypertension (PH) characterized by nonresolving thromboembolism in the central pulmonary artery and vascular occlusion in the proximal and distal pulmonary artery. Medical therapy is chosen for patients who are ineligible for pulmonary endarterectomy or balloon pulmonary angioplasty or who have symptomatic residual PH after surgery or intervention. Selexipag, an oral prostacyclin receptor agonist and potent vasodilator, was approved for CTEPH in Japan in 2021. To evaluate the pharmacological effect of selexipag on vascular occlusion in CTEPH, we examined how its active metabolite MRE-269 affects platelet-derived growth factor-stimulated pulmonary arterial smooth muscle cells (PASMCs) from CTEPH patients. MRE-269 showed a more potent antiproliferative effect on PASMCs from CTEPH patients than on those from normal subjects. DNA-binding protein inhibitor (ID) genes ID1 and ID3 were found by RNA sequencing and real-time quantitative polymerase chain reaction to be expressed at lower levels in PASMCs from CTEPH patients than in those from normal subjects and were upregulated by MRE-269 treatment. ID1 and ID3 upregulation by MRE-269 was blocked by co-incubation with a prostacyclin receptor antagonist, and ID1 knockdown by small interfering RNA transfection attenuated the antiproliferative effect of MRE-269. ID signaling may be involved in the antiproliferative effect of MRE-269 on PASMCs. This is the first study to demonstrate the pharmacological effects on PASMCs from CTEPH patients of a drug approved for the treatment of CTEPH. Both the vasodilatory and the antiproliferative effect of MRE-269 may contribute to the efficacy of selexipag in CTEPH.

Benefits of mechanical aspiration of pulmonary artery thrombi regardless of clot location

Key Points Proximal pulmonary embolism reduces trans‐pulmonary flow and induces RV Strain which induces hemodynamic compromise Aspiration Thrombectomy improves pulmonary flow by reducing pulmonary vascular resistance and relieving RV Strain Mechanical aspiration of proximal pulmonary artery clot is beneficial for both main and branch thrombi

Adults with small, unrepaired atrial septal defects have reduced cardiac index during exercise.

Small, unrepaired atrial septal defects are considered a benign lesion with good prognosis. Recently, clinical and register-based studies discovered increased long-term mortality and morbidity. The nature of these findings is not fully understood. Therefore, MRI was performed to evaluate cardiac function at rest and during exercise. Adults with open or spontaneously closed atrial septal defects and healthy, matched controls underwent MRI for evaluation of cardiac chamber volume. Quantitative flow scans measured blood flow in the ascending aorta and the proximal pulmonary artery at rest and during increasing supine exercise. In total, 15 open defects (39 ± 11 years) and 15 matched controls (38 ± 12 years) were included, along with 20 spontaneously closed (36 ± 13 years) and 20 controls (36 ± 11 years). Cardiac chamber volumes and flow measurements at rest were comparable between groups, as were heart rates and workloads during exercise. At maximal exercise, open defects reached 31% lower cardiac index and had 38% higher retrograde flow in the pulmonary artery than their controls, p < 0.01. Shunt ratio remained unchanged during exercise, 1.2 ± 0.2. Closed defects reached 18% lower cardiac index, p = 0.02, with comparable pulmonary retrograde flow. Maximal cardiac index was inversely correlated with increasing age for patients only. Adults with a small, open or spontaneously closed atrial septal defects exhibit markedly lower exercise capacity compared with healthy peers. Moreover, open defects exhibit higher retrograde flows with increasing exercise. Finally, increasing age is related to poorer results in patients but not healthy controls. Longitudinal studies are necessary in order to determine potential accelerated worsening of physical capacity along with age-related changes in patients.

Ruptured pulmonary artery pseudoaneurysm treated with stent graft: case report and literature review

BackgroundHemoptysis is a severe condition, associated with a high mortality rate from asphyxiation. Less than 5% of cases come from the pulmonary arterial circulation and large pseudoaneurysm are rarely treatable by stent graft.Case presentationWe present the case of a 74-year-old man who suffered from a new onset of hemoptysis despite a prior bronchial artery embolization. He underwent a rescue endovascular stent graft placement for a massive hemoptysis caused by a ruptured proximal pulmonary artery pseudoaneurysm. A short review of similar situations is provided.ConclusionSalvage endovascular stent graft placement for a massive hemoptysis caused by a ruptured proximal pulmonary artery pseudoaneurysm is a viable salvage technique for life-threatening hemoptysis.

Collapsed Woman With a D-Shaped Left Ventricle on Echocardiogram

A 45-year-old woman presented to the emergency department with unwitnessed out-of-hospital cardiac arrest with asystole rhythm. After intubation, transesophageal echocardiography was performed to search for possible etiologies of cardiac arrest. It showed a D-shaped left ventricle at the midventricular level in the transgastric short-axis view (Figure A and Video, available at http://www.annemergmed.com). After the return of spontaneous circulation, transesophageal echocardiography revealed the resolution of the D-shaped left ventricle (Figure B). Dilated right ventricle because of cardiac arrest. The right ventricle to left ventricle ratio was described as an echocardiographic sign suggesting pulmonary embolism with high specificity in previous studies.1Fields J.M. Davis J. Girson L. et al.Transthoracic echocardiography for diagnosing pulmonary embolism: a systematic review and meta-analysis.J Am Soc Echocardiogr. 2017; 30: 714-723.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar In our case, right ventricle dilation with septal flattening was also observed during resuscitation, which returned to normal size after the return of spontaneous circulation. In Aagaard's porcine studies,2Aagaard R. Caap P. Hansson N.C. et al.Detection of pulmonary embolism during cardiac arrest—ultrasonographic findings should be interpreted with caution.Crit Care Med. 2017; 45: e695-e702Crossref PubMed Scopus (27) Google Scholar,3Aagaard R. Granfeldt A. Bøtker M.T. et al.The right ventricle is dilated during resuscitation from cardiac arrest caused by hypovolemia: a porcine ultrasound study.Crit Care Med. 2017; 45: e963-e970Crossref PubMed Scopus (32) Google Scholar the right ventricle size showed no correlation with the causes of arrest. The right ventricle dilation might be inherent to cardiac arrest. Our case supported Aagaard’s studies; therefore, the dilated right ventricle noted on the echocardiography during resuscitation must be interpreted cautiously. Other differential diagnoses should be considered if the dilated right ventricle resolves after the return of spontaneous circulation. In patients with cardiac arrest, thrombus visualized in the proximal pulmonary arteries or right heart might be a more specific sign to diagnose pulmonary embolism and guide further treatment, such as thrombolytic therapy.4Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1340) Google Scholar Gastric ulcer perforation was diagnosed following the return of spontaneous circulation by computed tomography. Gastrorrhaphy and drainage of intra-abdominal abscess were done; however, the patient died the next day because of a profound septic shock. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ODMwZGY4ZmNmZjg3MWZkNjRiYzVkNTgyMjQ1YTNhNyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcwOTg5Mzc1fQ.GE5j2RbdtAaHLdnx_AuVeAXfSftnIEpj1OAn9NZU9Stpu06w5LMVtZlgBhaB1tMFs6TOjMwr5LfsP17MhOD7AgBQr4O2BAy1vl0OVBHuhL5TuNK8RFAIVShVmQL_BYFiB4Py1xh8kiU5JsL9kuInpRDAEX4P1ANaxTL9CyTD4X3O9sFEHJLh6LgERT2fq6XjhXu3qODqLCmCDR5S7EOiP8HuU5Mt_PONO5bLGStTYYHOK1vIP7OlT_nLlacBrdeUxJqIHmLdtMZCEkZLFAPedhLGI0Tok-ncrbC-qlUnk1JI2PIYwPtgdKEJrxh6SHIK4D0haEmqAqE7Fbj6EggPDw Download .mp4 (2.92 MB) Help with .mp4 files VideoThe transesophageal echocardiography showing a D-shaped left ventricle at the midventricular level in the transgastric short-axis view during resuscitation, which turned back to a normal shape after the return of spontaneous circulation was achieved.

Abstract 9548: Dual Energy Computed Tomography Perfusion Mapping of Coronary to Pulmonary Collaterals in Chronic Thromboembolic Pulmonary Hypertension

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 pulmonary hypertension where unresolved thromboembolic disease obstructs the pulmonary artery. The resultant lung ischemia commonly leads to bronchopulmonary collateralization thought to lower pulmonary vascular resistance and reduce mortality. Here, we present a rare presentation of coronary-pulmonary collaterals in a 65-year-old former 40-pack year smoker with CTEPH, COPD requiring oxygen, AF, and DHF. Results: Dual-energy computed tomography (DECT) showed complete occlusion of the proximal right pulmonary artery. However, perfused blood volume (PBV) mapping of the DECT study revealed areas of the right lung that were still minimally perfused (Figure 1A, B). Pulmonary angiography confirmed occlusion of the right pulmonary artery (1C) . Subsequent coronary angiography revealed the presence of coronary to pulmonary collaterals that were providing limited perfusion to the right pulmonary circulation from the left circumflex artery (1D) . The patient underwent pulmonary thromboendarterectomy with removal of the clot en bloc without complication (1E) . Post-surgery DECT confirmed restoration of pulmonary arterial circulation and catheterization revealed an excellent hemodynamic response to surgery (1F, G) . Conclusions: DECT-derived PBV revealed significant perfusion to a proximally obstructed lung, hastening the discovery of rarely documented coronary-pulmonary artery collaterals via coronary angiography. We uniquely visualize via perfusion mapping that the collaterals provide an alternate vascular supply distal to the chronic pulmonary arterial obstruction until thromboendarterectomy can conclusively treat the occlusion. The presence of coronary-pulmonary collaterals may share similar pathophysiology to bronchial-pulmonary collaterals and be a positive prognosticator for robust post-operative hemodynamic improvement in CTEPH.

Computational modelling of multi-temporal ventricular-vascular interactions during the progression of pulmonary arterial hypertension.

A computational framework is developed to consider the concurrent growth and remodelling (G&R) processes occurring in the large pulmonary artery (PA) and right ventricle (RV), as well as ventricular-vascular interactions during the progression of pulmonary arterial hypertension (PAH). This computational framework couples the RV and the proximal PA in a closed-loop circulatory system that operates in a short timescale of a cardiac cycle, and evolves over a long timescale due to G&R processes in the PA and RV. The framework predicts changes in haemodynamics (e.g. 68.2% increase in mean PA pressure), RV geometry (e.g. 38% increase in RV end-diastolic volume) and PA tissue microstructure (e.g. 90% increase in collagen mass) that are consistent with clinical and experimental measurements of PAH. The framework also predicts that a reduction in RV contractility is associated with long-term RV chamber dilation, a common biomarker observed in the late-stage PAH. Sensitivity analyses on the G&R rate constants show that large PA stiffening (both short and long term) is affected by RV remodelling more than the reverse. This framework can serve as a foundation for the future development of a more predictive and comprehensive cardiovascular G&R model with realistic heart and vascular geometries.

Morphology and rheology of pulmonary arteries: A relationship with right ventricular function in patients with pulmonary arterial hypertension associated with atrial septal defect?

Qualitative and quantitative hemodynamic flow indexes have been related to right ventricular (RV) function in pulmonary arterial hypertension (PAH), using 4-dimensional flow cardiac magnetic resonance (4D-flow CMR). Little is known in PAH congenital heart disease population characterized by intracardiac shunting. A prospective bi-centric study was conducted in two French referral centers for PAH to assess RV function and anatomical and rheological parameters in the proximal pulmonary arteries (PA) in PAH associated with atrial septal defect (ASD). A multiparametric evaluation, including a complete hemodynamic catheterization and a 4D flow CMR, was performed in 24 patients (50 years [41–55]) with PAH-ASD, of whom 16 (66%) had a persistent left-to-right shunt. Patients were divided into two groups according to the presence ( n = 14) or absence ( n = 10) of RV dysfunction, defined as RV ejection fraction (RVEF) < 45%. Tricuspid annular excursion (TAPSE) was 21 mm [18–26] and RVEF was 37% [27–52]. Mean pulmonary artery pressure was 50 mmHg [39–59] and pulmonary vascular resistance was 8 Wood units [6–8] and 42% were in WHO/NYHA function class III or VI. RV function was correlated with RV-PA coupling (correlation coefficient = −0.91, P <0.0001), PA compliance (correlation coefficient = −0.40, P = 0.04), and PA stiffness index (correlation coefficient = 0.43, P = 0.03). Helicity and vorticity were correlated with PA area, but there was no significant relationship with RV function. Intrinsic parameters were more alterated in the group without RV dysfunction, characterized by a persistent left to right shunt, with a decreased tight PA compliance ( P = 0.01), decreased distensibility ( P = 0.01), decreased pulsatility index ( P = 0.06), increased β-stiffness index ( P = 0.01), and increased elastance ( P = 0.01). In patients with left-to-right shunt, barometric and volumetric overload aggravates proximal PA remodelling with increased PA dilatation and stiffness. Paradoxically, in patients with RV dysfunction, normally associated with end-stage of PAH and right-to-left shunt, this remodelling is significantly less considerable.

Abnormal flow conduction through pulmonary arteries is associated with right ventricular volume and function in patients with repaired tetralogy of Fallot: does flow quality affect afterload?

Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF. Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices. All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%. This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling. • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

Impact of reductive tricuspid ring annuloplasty on right ventricular size, geometry and strain in an ovine model of functional tricuspid regurgitation.

OBJECTIVESReductive ring annuloplasty of the tricuspid annulus represents the contemporary surgical approach to functional tricuspid regurgitation (FTR). We set out to investigate the influence of moderate reductive tricuspid ring annuloplasty on tricuspid regurgitation and right ventricular (RV) size, geometry and strain in an ovine model of chronic FTR.METHODSEight healthy Dorsett male sheep (62.8 + 2kg) underwent a left thoracotomy for placement and tightening of pulmonary artery band to at least double proximal pulmonary artery blood pressure. After 8 weeks of recovery, animals underwent sternotomy, epicardial echocardiography and sonomicrometry crystal implantation. Six crystals were placed around tricuspid annulus and 13 on RV free wall epicardium along 3 parallels defining 3 wall regions (basal, mid and lower) and 1 on the RV apex. All animals underwent beating heart implantation of 26 mm MC3 annuloplasty ring during a second cardiopulmonary bypass run after baseline data acquisition. Simultaneous haemodynamic, sonomicrometry and echocardiography data were acquired at Baseline and after reductive tricuspid ring annuloplasty.RESULTSImplantation of reductive ring annuloplasty resulted in 47 ± 7% annular area reduction (996 ± 152 mm vs 516 ± 52 mm2, P = 0.0002) and significantly decreased RV end-diastolic volume (185 ± 27 vs 165 ± 30 ml, P = 0.02). Tricuspid ring annuloplasty effectively reduced FTR grade (3.75 ± 0.6 vs 0.3 ± 0.5, P = 0.00004) and had little influence on RV function, cross-sectional area, radius of curvature or free wall regional strains.CONCLUSIONSIn adult sheep with 8 weeks of pulmonary artery banding and FTR, tricuspid annulus reduction of 47% with prosthetic ring annuloplasty effectively abolished FTR while maintaining regional RV function and strain patterns.

Embolic Pneumonectomy for the Treatment of Proximal Pulmonary Artery Pseudoaneurysm

Pulmonary artery pseudoaneurysm is an uncommon and potentially fatal abnormality. It has been described from a wide variety of etiologies, including infectious, iatrogenic, neoplastic, congenital, and traumatic causes. There are currently no published consensus guidelines for the diagnostic testing and management of pulmonary artery pseudoaneurysm. This case report presents an uncommon case of pulmonary artery pseudoaneurysm emerging from a non-small cell lung cancer that was successfully managed using coil embolization.

Embolization of a Proximal Pulmonary Artery Pseudoaneurysm in a Cavitary Lung Cancer

Embolization of a Proximal Pulmonary Artery Pseudoaneurysm in a Cavitary Lung Cancer

Safety and Efficacy of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Cancer.

BackgroundUltra-central lung cancer (UCLC) is difficult to achieve surgical treatment. Over the past few years, stereotactic ablative radiotherapy (SABR) or stereotactic body radiotherapy (SBRT) obviously improved the clinical efficacy and survival of UCLC patients. However, the adapted scheme of radiation therapy is still controversial. For this, a single arm retrospective analysis was performed on UCLC patients treated with SBRT.Material and MethodsWe retrospectively studied primary UCLC patients who were treated with SBRT of 56 Gy/6-8f between 2010 and 2018. UCLC was defined as planning target volume (PTV) touching or overlapping the proximal bronchial tree, trachea, esophagus, heart, pulmonary vein, or pulmonary artery within 2 cm around the bronchial tree in all directions.ResultsA total of 58 patients whose median age was 68 years (range, 46-85) were included in our study, 79.3% of whom did not undergo any previous therapy. The median dose of the PTV was 77.8 Gy (range, 43.3-91.8), and the median PTV of tumors was 6.2 cm3 (range, 12.9-265.0). With a median follow-up of 57 months (range, 6-90 months), the median cumulative overall survival (OS) rate was 58 months (range, 2-105). In addition, the 1-year, 2-year and 5-year OS rates were 94.7%, 75.0% and 45.0%, respectively. In our univariable analysis (p=0.020) and multivariate analysis (p=0.004), the OS rate was associated with the PTV. The 5-year OS rates for PTV <53.0 cm3 and PTV ≥53.0 cm3 were 61.6% and 37.4%, respectively. Regarding toxicity after SBRT, there were two cases (3.5%) with grade ≥3 adverse events, of which 1 case died of sudden severe unexplained hemoptysis.ConclusionsPatients with UCLC can benefit from SBRT at a dose of 56 Gy/6-8f. On the other hand, smaller PTV was associated with superior outcomes, and the cure difference needs to be validated by prospective comparative trials.

Hemodynamics of the right ventricle and the pulmonary circulation

Most cardiac diseases affect the left ventricle (LV), with its treatment being the focus of the majority of cardiovascular medical therapies and mechanical support. Many diseases also affect the right ventricle (RV) and pulmonary circulation, either directly or from secondary effects on the LV and systemic circulation. The development of therapies to treat RV failure is critical for the management of many patients with advanced heart and lung disease, but models to develop mechanical therapies to target the RV are currently lacking. While the RV and pulmonary vasculature have many similarities to the LV and systemic vasculature, there are notable differences between them at a morphological and functional level. This results in distinct patterns of coupling between the RV and pulmonary circulation. Models such as the Windkessel use lumped parameters that characterize the mechanical properties of the entire RV and pulmonary circulation. Contemporary computational approaches that have been used to model the pulmonary vasculature rely on patient-derived anatomy for the proximal pulmonary arteries and other approaches, such as fractal-based models for the distal vasculature. At this time, these models are still being optimized and significantly more work will be required to fully implement them and test their utility across multiple patient-derived anatomies. The development of these models for the RV and pulmonary circulation will be critical to address the unmet need of mechanical therapies for disease of the RV and pulmonary circulation.

Distinct Endothelial Cell Populations Characterize the Pulmonary Endarterectomy Specimen in Chronic Thromboembolic Pulmonary Hypertension

<h3>Purpose</h3> Misguided vascular repair is thought to contribute to the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH), yet little is known about endothelial cell (EC) phenotypes in the organized thromboembolic material of patients with CTEPH. Therefore, we sought to characterize ECs from pulmonary endarterectomy (PEA) specimens. <h3>Methods</h3> Human PEA specimens from proximal pulmonary arteries were collected from five CTEPH patients and dissociated for droplet-based single-cell RNA sequencing. Data from three control human lungs was obtained from the Human Lung Cell Atlas (https://hlca.ds.czbiohub.org accessed Sept. 9, 2021). <h3>Results</h3> From the PEA specimens of five CTEPH patients, we obtained transcriptional profiles for 11068 cells representing 20 clusters and 9 cell types. From those, 4 clusters displayed markers of ECs. To identify appropriate control ECs, we assessed markers of endothelial subtype from the Human Lung Cell Atlas and identified markers of pulmonary and bronchial artery ECs. Therefore, we obtained the transcriptional profiles of pulmonary and bronchial artery ECs from the Human Lung Cell Atlas as controls. After standardizing quality control metrics, we merged the data from 2174 control and 1772 CTEPH ECs. Dimension reduction of the merged dataset revealed 12 endothelial clusters (Figure). We note disproportionate distribution of control vs CTEPH ECs across clusters, with a majority of clusters biased towards one condition. Between and within clusters, CTEPH ECs displayed greater expression of TGFβ1, a marker of endothelial-mesenchymal transition (EMT), and P-selectin, a marker of endothelial activation. <h3>Conclusion</h3> Significant endothelial heterogeneity exists in both control and CTEPH ECs. However, we find differences in the composition of EC phenotypes between these two groups. We identify marker genes for CTEPH ECs that contribute to our understanding of EC phenotypes and misguided vascular repair in CTEPH.

High magnesium mitigates the vasoconstriction mediated by different types of calcium influx from monocrotaline-induced pulmonary hypertensive rats.

What is the central question of this study? What is the involvement of Mg2+ in mitigating the vasoconstriction in pulmonary arteries and smaller pulmonary arteries in the monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model? What are the main finding and its importance? Both store-operated Ca2+ entry- and receptor-operated Ca2+ entry-mediated vasoconstriction were enhanced in the MCT-PAH model. High magnesium inhibited vasoconstriction by directly antagonizing Ca2+ and increasing NO release, and this was more notable in smaller pulmonary arteries. Increased extracellular magnesium concentration has been shown to attenuate the endothelin-1-induced contractile response via the release of nitric oxide (NO) from the endothelium in proximal pulmonary arteries (PAs) of chronic hypoxic mice. Here, we further examined the involvement of Mg2+ in the inhibition of vasoconstriction in PAs and distal smaller pulmonary arteries (sPAs) in a monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model. The data showed that in control rats vasoconstriction in sPAs is more intense than that in PAs. In MCT-PAH rats, store-operated Ca2+ entry (SOCE)- and receptor-operated Ca2+ entry (ROCE)-mediated contraction were significantly strengthened. However, there was no upregulation of the vasoconstriction mediated by voltage-dependent calcium entry (VDCE). Furthermore, high magnesium greatly inhibited VDCE-mediated contraction in PAs rather than sPAs, which was the opposite of the ROCE-mediated contraction. Moreover, monocrotaline pretreatment partly eliminated the endothelium-dependent vasodilatation in PAs, which in sPAs, however, was still promoted by magnesium due to the increased NO release in pulmonary microvascular endothelial cells (PMVECs). In conclusion, the findings suggest that both SOCE- and ROCE-mediated vasoconstriction in the MCT-PAH model are enhanced, especially in sPAs. The inhibitory effect of high magnesium on vasoconstriction can be achieved partly by its direct role as a Ca2+ antagonist and partly by increasing NO release in PMVECs.

ERS statement on chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels &lt; 500 μm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/ perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions. This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH. It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Surgical Complexity of Pulmonary Resections Performed for Oligometastatic NSCLC

IntroductionPulmonary resection has been established as an important component of local consolidative therapy (LCT) for oligometastatic NSCLC. However, technical aspects of such surgical procedures have not been well characterized. We sought to review the complexity of operations performed within a large cohort of patients with oligometastatic NSCLC. MethodsWe identified patients treated at a single institution between 2000 and 2017 with stage IV NSCLC, with three or fewer synchronous metastases, and who underwent surgical resection of the primary tumor. Medical records were reviewed, and aspects of surgical complexity were recorded. Descriptive analyses were performed. ResultsAmong 194 patients with oligometastatic NSCLC, 173 (89%) received LCT and 30 (15%) underwent resection of the primary tumor. Thoracotomy was performed in 25 patients (83%), and procedures included 25 (83%) lobectomies, three (10%) pneumonectomies, and two (7%) sublobar resections. Mean blood loss was 200 (50–600) mL, and operative time was 200 (72–492) minutes. Proximal pulmonary artery control was needed in four (15%). Sleeve resection was needed in four (15%). Unplanned procedural change was required in two patients (7%). Chest wall resection occurred in three patients (11%). Lymph nodes were characterized as hard or densely adherent in nine (33%), and operations were described as more difficult than usual in 16 cases (59%). ConclusionsSurgery has emerged as a key strategy for LCT among patients with oligometastatic NSCLC. These operations can be performed safely, yet frequently require advanced techniques and complex resection strategies. As such, health care teams must be prepared for the technical challenges of these cases.