Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Pulmonary hypertension,nephrotic syndrome,and polymyositis due to hepatitis C virus infection:A case report

BACKGROUND Hepatitis C infection not only damages the liver but also often accompanies many extrahepatic manifestations.Incidences of pulmonary hypertension(PH)caused by hepatitis C are rare,and incidences of concurrent nephrotic syndrome and polymyositis are even rarer.CASE SUMMARY Herein we describe the case of a 57-year-old woman who was admitted to our department for intermittent chest tightness upon exertion for 5 years,aggravated with dyspnea for 10 d.After relevant examinations she was diagnosed with PH,nephrotic syndrome,and polymyositis due to chronic hepatitis C infection.A multi-disciplinary recommendation was that the patient should be treated with sildenafil and macitentan in combination and methylprednisolone.During treatment autoimmune symptoms,liver function,hepatitis C RNA levels,and cardiac parameters of right heart catheterization were monitored closely.The patient showed significant improvement in 6-min walking distance from 100 to 300 m at 3-mo follow-up and pulmonary artery pressure drops to 50 mmHg.Long-term follow-up is needed to confirm further efficacy and safety.CONCLUSION Increasing evidence supports a relationship between hepatitis C infection and diverse extrahepatic manifestations,but it is very rare to have PH,nephrotic syndrome,and polymyositis in a single patient.We conducted a literature review on the management of several specific extrahepatic manifestations of hepatitis C.

Cardiac amyloidosis presenting as pulmonary arterial hypertension:A case report

BACKGROUND Pulmonary hypertension is a rare cardiopulmonary disease,with an insidious onset that usually worsens rapidly.Amyloid light chain(AL)amyloidosis is a rare systemic disease caused by extracellular deposition of pathologic,insoluble,and proteinaceous fibrils in organs and tissues;however,it is difficult to diagnose given its varied and nonspecific symptoms.To date,rare cases of amyloidosis with pulmonary hypertension have been reported.Of note,the optimal treatments for cardiac amyloidosis complicated with pulmonary hypertension remain unclear.CASE SUMMARY We report a case of a 51-year-old woman who presented with progressively worsening dyspnea.Transthoracic echocardiography indicated severe pulmonary hypertension.Twenty-seven months after first admission,the patient returned with symptoms of progressive heart failure.A myocardial tissue sample stained with Congo red was positive,and the patient was ultimately diagnosed with AL amyloidosis with cardiac involvement.CONCLUSION Although pulmonary hypertension may be idiopathic,it is frequently associated with other conditions.In rare cases,pulmonary hypertension can be a complication of AL amyloidosis,which should be seriously considered in any adult presenting with nonspecific signs or symptoms of cardiac distress.

Twin pregnancy with sudden heart failure and pulmonary hypertension after atrial septal defect repair: A case report

BACKGROUND Pulmonary arterial hypertension(PAH)in pregnancy is one of the major obstetric complications and is considered a contraindication to pregnancy as it is classified as a class IV risk in the revised risk classification of pregnancy by the World Health Organisation.Pregnancy,with its adaptive and expectant mechanical and hormonal changes,negatively affects the cardiopulmonary circulation in pregnant women.Do patients with repaired simple congenital heart disease(CHD)develop other pulmonary and cardiac complications during pregnancy?Can pregnant women with sudden pulmonary hypertension be treated and managed in time?In this paper,we present a case of a 39-year-old woman who underwent cesarean section at 33 wk'gestation and developed PAH secondary to repaired simple CHD.Our research began by a PubMed search for"pulmonary hypertension"and"pregnancy"and"CHD"case reports.Three cases were selected to review PAH in pregnancy after correction of CHD defects.These studies were reviewed,coupled with our own clinical experience.CASE SUMMARY Herein,a case involving a woman who underwent atrial septal defect repair at the age of 34,became pregnant five years later,and had a sudden onset of PAH and right heart failure secondary to symptoms of acute peripheral edema in the third trimester of her pregnancy.As a result,the patient underwent a cesarean section and gave birth to healthy twins.Within three days after cesarean delivery,her cardiac function deteriorated as the pulmonary artery pressure increased.Effec-tive postpartum management,including diuresis,significant oxygen uptake,vasodilators,capacity and anticoagulants management,led to improvements in cardiac function and oxygenation.The patient was discharged from hospital with a stable recovery and transferred to local hospitals for further PAH treatment.CONCLUSION This case served as a reminder to obstetricians of the importance of pregnancy after repair of CHD.It is crucial for patients with CHD to receive early correction.It suggests doctors should not ignore edema of twin pregnancy.Also,it provides a reference for the further standardization of antenatal,in-trapartum and postpartum management for patients with CHD worldwide.

Rutaecarpine attenuates monocrotaline-induced pulmonary arterial hypertension in a Sprague-Dawley rat model

Background:Pulmonary arterial hypertension presents with obliterative remodeling of the pulmonary arteries and progressive elevation of pulmonary vascular resistance,which increase the risk of right ventricular failure and death.It has been reported in previous studies that rutaecarpine plays a crucial role in anti-inflammatory and antioxidant activities,which may help regulate cell apoptosis and cell proliferation.The purpose of this study was to determine the effects of rutaecarpine in the rat model of monocrotaline-induced pulmonary hypertension.Methods:We induced pulmonary arterial hypertension in adult Sprague-Dawley rats by injecting monocrotaline(60 mg/kg)and then treated with rutaecarpine(40 mg/kg·d)or sildenafil(30 mg/kg·d)(positive control).Subsequently,pulmonary function,inflammation,cytokines and pulmonary vascular remodeling or proliferation were assessed.Results:Rutaecarpine was found to improve monocrotaline-induced mean pulmonary artery pressure,cardiac index,right heart index,right ventricular hypertrophy index,pulmonary artery remodeling and pulmonary function.reverse transcription-quantitative polymerase chain reaction demonstrated a decrease in tumor necrosis factor-α,interleukin-6 and interleukin-1β,whereas western blots a significantly decrease in the expression of nuclear factor kappa-B,endothelin-1,extracellular signal-regulated kinases 1/2,B cell lymphoma-2,Beclin1 and microtubule-associated protein1 light chain 3-II protein,and increase in the expression of Bax,caspase-3 and p62 protein.Conclusion:Rutaecarpine attenuated pulmonary arterial hypertension by inhibiting inflammation,oxidative stress,cell proliferation and autophagy,while promoting apoptosis.

Pulmonary Hypertension Crisis in Patient with Tetralogy of Fallot and Mixed Total Anomalous Pulmonary Vein Connection after the Primary Correction:A Rare Case Report

Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.

“Treat-Repair-Treat”:Management of Left Main Coronary Compression by a Pulmonary Artery Aneurysm in a Patient with Atrial Septal Defect and Significant Pulmonary Hypertension

Left main coronary compression syndrome(LMCS)may complicate pulmonary artery aneurysms(PAA),usually developed in the context of pulmonary arterial hypertension(PAH).We report the case of a 51-year-old female patient with an atrial septal defect(unsuitable for device closure)complicated by a PAA generating a 90%left main stenosis.The significant PAH held us back from immediate surgery.After specific dual PAH-targeted therapy(sildenafil and bosentan),the atrial septal defect could be closed with a unidirectional valved patch;the PAAinduced LMCS was treated by reductive arterioplasty.The postoperative course was uneventful.Follow-up showed clinical improvement,but PAH treatment was still needed.After three months,coronary angiography showed only an insignificant residual left main stenosis,proving that reductive pulmonary arterioplasty was effective in treating LMCS.Any PAA requires further evaluation for LMCS,a dangerous but treatable complication.The“treat-repair-treat”strategy and shunt-closure with a unidirectional valved patch can both improve surgical prospects of LMCS with shunt-related PAH.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography

BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension(CTEPH),approximately 20%-29%of patients exhibit a restrictive pattern on pulmonary function testing.AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area(CSA)in patients with CTEPH.METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019,we evaluated 15 patients with CTEPH who had chest computed tomography(CT)performed at baseline and after at least 6 mo of therapy.We matched the CTEPH cohort with 45 control patients by age,sex,and observation period.CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.RESULTS Total,right lung,and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline(total,P=0.004;right lung,P=0.003;right lower lobe;P=0.01).In the CTEPH group,the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group(total,P=0.01;right lung,P=0.007;right lower lobe,P=0.01;CSA,P=0.0002).There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.CONCLUSION After at least 6 mo of treatment,CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Pulmonary arterial hypertension confirmed by right heart catheterization following COVID-19 pneumonia: A case report and review of literature

BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.

Research progress in the etiology of pulmonary hypertension

Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway

Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid(PA)pretreatment affects PH and pulmonary vascular remodeling in rats.Methods:PH was induced via hypoxia exposure and administration of PA(5 mg/kg per day)in male Sprague-Dawley rats.Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin(HE),a-SMA and Masson staining.MTT assays and EdU staining were used to detect cell proliferation,and apoptosis was analyzed by TUNEL staining.Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keapl-ARE pathway.

Left atrial diameter and atrial fibrillation,but not elevated NT-proBNP,predict the development of pulmonary hypertension in patients with HFpEF

Background The determinants of pulmonary hypertension(PH)due to heart failure with preserved ejection fraction(HFpEF)have been poorly investigated in patients with cardiovascular diseases(CVD).Methods From July 12017 to March 312019,a total of 149 consecutive HFp EF patients hospitalized with CVD were enrolled in this prospective cross-sectional study.A systolic pulmonary artery pressure(PASP)>35 mm Hg estimated by echocardiography was defined as PH-HFp EF.Logistic regression was performed to establish predictors of PH in HFpEF patients.Results Overall,the mean age of participants was 72±11 years,and 74(49.7%)patients were females.A total of 59(39.6%)patients were diagnosed with PH-HFpEF by echocardiography.The left atrial diameter(LAD)was related to the ratio of the transmitral flow velocities/mitral annulus tissue velocities in early diastole(E/E’)and the left ventricular diameter in systole(LVDs).N-Terminal pro B-type natriuretic peptide(NT-proBNP)was not found to be associated with LAD and impaired diastolic or systolic function of the left ventricle.Multivariable logistic regression showed that atrial fibrillation(AF)increased the risk of PH-HFpEF incidence 3.46-fold with a 95%confidence interval(CI)of 1.44–8.32,P=0.005.Meanwhile,LAD≥45 mm resulted in a 3.43-fold increased risk,95%CI:1.51–7.75,P=0.003.However,the significance levels of NT-proBNP,age and LVEF were underpowered in the regression model.Two variables,AF and LAD≥45 mm,predicted the PH-HFpEF incidence(C-statistic=0.773,95%CI:0.695–0.852,P<0.001).Conclusions Two parameters associated with electrical and anatomical remodelling of the left atrium were related to the incidence of PH in HFpEF patients with CVD.

Circular RNAs in pulmonary hypertension:Emerging biological concepts and potential mechanism

Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.

Vascular Metabolic Mechanisms of Pulmonary Hypertension

Pulmonary hypertension(PH)is a severe and progressive disease characterized by increased pulmonary vascular resistance leading to right heart failure and death.In PH,the cellular metabolisms including those of the three major nutrients(carbohydrate,lipid and protein)are aberrant in pulmonary vascular cells.Glucose uptake,glycolysis,insulin resistance,sphingolipid S1P,PGE2,TXA2,leukotrienes and glutaminolysis are upregulated,and phospholipid-prostacyclin and L-arginine-nitric oxide pathway are compromised in lung vascular cells.Fatty acid metabolism is disordered in lung endothelial cells and smooth muscle cells.These molecular mechanisms are integrated to promote PH-specific abnormal vascular cell proliferation and vascular remodeling.This review summarizes the recent advances in the metabolic reprogramming of glucose,fatty acid,and amino acid metabolism in pulmonary vascular remodeling in PH and the mechanisms for how these alterations affect vascular cell fate and impact the course of PH.

Experimental animal models of pulmonary hypertension:Development and challenges

Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

Role of miR-21-5p/FilGAP axis in estradiol alleviating the progression of monocrotaline-induced pulmonary hypertension

Background:Aberrant expression of microRNAs(miRNAs)has been associated with the pathogenesis of pulmonary hypertension(PH).It is,however,not clear whether miRNAs are involved in estrogen rescue of PH.Methods:Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension(IPAH)patients and 12 healthy controls undergoing right heart cath-eterization in Shanghai Pulmonary Hospital.From each sample,5μg of total RNA was tagged and hybridized on microRNA microarray chips.Monocrotaline-induced PH(MCT-PH)male rats were treated with 17β-estradiol(E_(2))or vehicle.Subgroups were cotreated with estrogen receptor(ER)antagonist or with antagonist of miRNA.Results:Many circulating miRNAs,including miR-21-5p and miR-574-5p,were mark-edly expressed in patients and of interest in predicting mean pulmonary arterial pres-sure elevation in patients.The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls.However,miR-574-5p showed no difference in the lungs of MCT-PH rats and controls.miR-21-5p was se-lected for further analysis in rats as E_(2) strongly regulated it.E_(2) decreased miR-21-5p expression in the lungs of MCT-PH rats by ERβ.E_(2) reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats.The abnormal expression of RhoA,ROCK2,Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E_(2) and miR-21-5p antagonist.Conclusions:miR-21-5p level was remarkably associated with PH severity in patients.Moreover,the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E_(2) on MCT-PH through ERβ.

Pulmonary hypertension concurrent with pericardial effusion and superior vena cava syndrome: who is the initiator?

The diagnosis of pulmonary hypertension(PH) should be made by combining clinical manifestations and echocardiographic probability.[1] Following the confirmation of PH, the classification should begin with the more common groups [group 2(PH due to left heart disease) and group 3(PH due to lung diseases and/or hypoxia)], then group 4(chronic thromboembolic PH and other pulmonary artery obstructions) and finally group 1(pulmonary arterial hypertension) and group 5(PH with unclear and/or multifactorial mechanisms).[1] In this case, we demonstrate a rare scenario of obstruction-caused group 4 PH.