Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:Current guidelines for managing pulmonary arterial hypertension(PAH)recommend a risk strati-fication approach.However,the applicability and accuracy of these strategies for PAH associated with congenital heart disease(PAH-CHD)require further validation.This study aims to validate the reliability and predictive accuracy of a simplified stratification strategy for PAH-CHD patients over a three-year follow-up.Additionally,new prognostic variables are identified and novel risk stratification methods are developed for assessing and managing PAH-CHD patients.Methods:This retrospective study included 126 PAH-CHD patients.Clinical and biochemical variables across risk groups were assessed using Kruskal-Wallis and Fisher’s exact tests.Indepen-dent risk factors were identified using ordered logistic regression,while Kaplan-Meier and Cox proportional hazards regression analyses evaluated their impact on all-cause mortality.A new stratification model for the PAH-CHD population was constructed based on these analyses.Results:Significant survival differences across stratified risk groups were observed(p<0.001),validating the effectiveness of the simplified risk stratification method in PAH-CHD patients.Prothrombin activity was a strong independent predictor of adverse outcomes of PAH-CHD patients(Hazard ratio 0.95,p<0.001,C-index 0.70).A model combining N-terminal pro-brain natriuretic peptide,prothrombin activity,albumin,and right atrial area achieved an area under the curve of 0.89 and a C-index of 0.85.Conclusions:The simplified risk stratification method is applicable to PAH-CHD patients.Prothrombin activity is a strong independent predictor of adverse outcomes.A comprehensive risk stratification approach,incorporating both established and novel biomarkers,enhances accessibility and offers predictive efficacy during follow-up for PAH-CHD patients,comparable to established models.

The Potential of Circular RNAs as Biomarkers in Pulmonary Arterial Hypertension Related to Congenital Heart Disease

A particular type of endogenous noncoding RNAs known as circular RNAs(circRNAs)has now become possible biomarkers for several diseases because of their stability and tissue-specific expression patterns.CircRNAs might play a role in various of biological processes.The identification of particular circRNAs dysregulated in pulmonary arterial hypertension(PAH)raises the possibility of these molecules serving as biomarkers for the disease’s early diagnosis and treatment.This review mainly summarizes the role and potential of circRNA as a future biomarker in PAH related to congenital heart disease.This study presented several potential circRNA targets as diagnostic biomarkers for PAH,discussed their biological functions,and addressed the challenges that need to be considered for their application in clinical settings.

Independent prognostic value of lipocalin-2 in congenital heart disease-associated pulmonary artery hypertension

BACKGROUND Timely and accurate evaluation of the patient's pulmonary arterial pressure(PAP)is of great significance for the treatment of congenital heart disease.Currently,there is no non-invasive gold standard method for evaluating PAP.AIM To assess the prognostic value of lipocalin-2(LCN2)in relation to PAP in patients with congenital heart disease associated with pulmonary artery hypertension.METHODS We conducted a retrospective analysis of 69 pediatric patients diagnosed with ventricular septal defects.The patients’clinical and laboratory data were collected.The serum LCN2 concentrations were compared between the pulmonary arterial hypertension(PAH)group and the nonPAH group.The correlation of LCN2 concentration with PAH classification was evaluated using binary logistic regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic potential of LCN2 for PAH.RESULTS Serum LCN2 concentration significantly correlated with patients’mean PAP(r=0.544,P<0.001),but not correlated with creatinine(P=0.446)or blood urea nitrogen(P=0.747).LCN2 levels were significantly correlated with PAH in both univariate[odds ratio(OR)1.107,95%CI:1.033-1.185,P=0.004)]and multivariate regression analysis(OR 1.150,95%CI:1.027-1.288,P=0.015).ROC curve analysis revealed an area under the curve of 0.783 for LCN2.At the cutoff value of 19.42 ng/mL,the sensitivity and specificity of LCN2 for diagnosing PAH is 90.19%and 55.56%,respectively.LCN2 concentration also significantly correlated with the post-repair mean PAP in patients with congenital heart disease(r=0.532,P=0.009).CONCLUSION LCN2 is emerging as a candidate biomarker for assessing PAP in patients with congenital heart disease.Its high sensitivity in diagnosing PAH makes it a valuable tool in patient management.

Salvia Polyphenolates Combined with Doxophylline in the Treatment of Patients with Chronic Pulmonary Heart Disease in the Compensated Stage

Objective:To statistically determine the effect of salvia polyphenolates combined with doxophylline treatment in patients with chronic pulmonary heart disease in the compensated stage.Methods:From January 2023 to January 2024,76 patients with chronic pulmonary heart disease in the compensated stage were selected as research subjects.The patients were divided into a research group and a reference group using a randomized numerical table method.The research group was treated with salvia polyphenolates combined with doxophylline,while the reference group received conventional therapy.The treatment effects of the two groups were compared.Results:The patients in the research group,treated with salvia polyphenolates combined with doxophylline,showed maximal ventilation of 73.26±4.83 L/min,left ventricular ejection fraction of 56.14±1.98%,and total effective treatment rate of 94.74%.These results were better than those of the reference group.The differences between the data of the research group and the reference group were statistically significant(P<0.05).Conclusion:For patients with chronic pulmonary heart disease in the compensated stage,treatment with salvia polyphenolates combined with doxophylline significantly improves maximum ventilation and left ventricular ejection fraction,and also results in a higher total effective treatment rate.

Diagnostic Value of the Padua Score Combined with Thrombotic Biomarker Tissue Plasminogen Activator Inhibitor-1 (tPAI-1) Detection for the Risk of Deep Vein Thrombosis in Patients with Pulmonary Heart Disease

This study explores the diagnostic value of combining the Padua score with the thrombotic biomarker tissue plasminogen activator inhibitor-1(tPAI-1)for assessing the risk of deep vein thrombosis(DVT)in patients with pulmonary heart disease.These patients often exhibit symptoms similar to venous thrombosis,such as dyspnea and bilateral lower limb swelling,complicating differential diagnosis.The Padua Prediction Score assesses the risk of venous thromboembolism(VTE)in hospitalized patients,while tPAI-1,a key fibrinolytic system inhibitor,indicates a hypercoagulable state.Clinical data from hospitalized patients with cor pulmonale were retrospectively analyzed.ROC curves compared the diagnostic value of the Padua score,tPAI-1 levels,and their combined model for predicting DVT risk.Results showed that tPAI-1 levels were significantly higher in DVT patients compared to non-DVT patients.The Padua score demonstrated a sensitivity of 82.61%and a specificity of 55.26%at a cutoff value of 3.The combined model had a significantly higher AUC than the Padua score alone,indicating better discriminatory ability in diagnosing DVT risk.The combination of the Padua score and tPAI-1 detection significantly improves the accuracy of diagnosing DVT risk in patients with pulmonary heart disease,reducing missed and incorrect diagnoses.This study provides a comprehensive assessment tool for clinicians,enhancing the diagnosis and treatment of patients with cor pulmonale complicated by DVT.Future research should validate these findings in larger samples and explore additional thrombotic biomarkers to optimize the predictive model.

Pulmonary Arterial Hypertension Medical Management of the Adult Patient with Congenital Heart Disease

Congenital heart disease(CHD)-associated pulmonary arterial hypertension(PAH)includes a heterogeneous patient population that can be characterized by the underlying cardiac malformation.CHD-associated PAH has an estimated prevalence of 5– 10% in adult patients,with an increasing number of patients surviving to adulthood because of advances in the surgical management and the development of pulmonary arterial hypertension(PAH)-targeted pharmacotherapy.Although limited data exist,targeted PAH pharmacotherapy has proven to be benefi cial in patients with CHD-associated PAH,with observed improvement in functional class,increase in exercise capacity,and improvement in quality of life and cardiopulmonary hemodynamics.Additionally,there has been increasing interest in the“treat-to-close”strategy.PAH-targeted pharmacotherapy may be used to optimize cardiopulmonary hemodynamics so as to improve patients’operability in repairing the cardiac defect.Although there have been signifi cant advances in the management of this disease state in the past 2 decades,mortality remains high,and ongoing clinical trials are needed to better understand the treat-to-close strategy.

Selexipag as Add-on Therapy for Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease:A Single-Center Retrospective Study

Purpose:This study examined the efficacy and safety of selexipag in treating pulmonary arterial hypertension(PAH)associated with congenital heart disease(CHD).Materials and Methods:We conducted a retrospective study of patients with CHD-associated PAH,treated with selexipag since December 2017.Thirteen adult patients(mean age,45.4 years;women,77%)were treated with selexipag as add-on therapy.Baseline characteristics,World Health Organization functional class,6-minute walking distance(6MWD)test results,N-terminal pro-B-type natriuretic peptide levels,echocardiographic data,and incidence of side effects were assessed.Results:The majority of patients(12/13,92.3%)experienced more than one treatment-associated complication;one patient dropped out of the study due to intolerable myalgia.The results of 6MWD test(from 299.2±56.2 m to 363.8±86.5 m,p=0.039)and tricuspid regurgitation(TR)pressure gradient(from 84.7±20.5 mmHg to 61.6±24.0 mmHg,p=0.018)improved and remained improved after selexipag treatment in 12 patients.Based on the results of a non-invasive risk assessment,8(66.7%)patients showed improvement,3(25.0%)showed no interval change,and the status of one patient(8.3%)deteriorated.Moreover,compared to patients treated with a low dosage,patients treated with a medium-to-high dosage showed a greater increase in 6MWD results(88.3±26.4 m vs.55.3±27.6 m,p=0.043)and a greater reduction in the TR pressure gradient(-33.7±10.9 mmHg vs.-12.5±12.0 mmHg,p=0.015).Conclusion:Selexipag is an efficient pulmonary vasodilator as add-on therapy in treating CHD-associated PAH.

NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.

Perioperative Nursing for Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Objectives: To explore the main points of perioperative nursing for adult congenital heart disease with severe pulmonary arterial hypertension. Methods: A retrospective study of 13 patients with congenital heart disease and severe pulmonary arterial hypertension who admitted to the perioperative period of care from January 2018 to December 2019. To prevent perioperative complications of the patients, the focus is on respiratory and circulatory system care, followed by blood coagulation monitoring, digestive system protection and psychological care. Results: All 13 patients passed the perioperative period and were discharged from ICU. Conclusion: Adult congenital heart disease with severe pulmonary arterial hypertension has high perioperative risk, respiratory and circulatory system care is the key.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Clinical Effect of an Improved Post-Operative Feeding Protocol“in Transition”Infants of Congenital Heart Disease with Pulmonary Hypertension

Background:To achieve successful management of infants with congenital heart disease(CHD)together with pulmonary hypertension(PH),postoperative care,especially feeding care is vital in addition to surgery.Postoperative feeding is comprised of three stages:feeding in the intensive care unit,feeding in the general ward and family feeding,in which the general ward is considered as the“transitional stage”.At present,there is little research on the optimal mode of feeding care for the transitional stage,and there is no universally recognized and accepted protocol.Methods:We retrospectively analyzed 114 CHD infants with PH who underwent family-centered(FC)feeding care from July 2017 to December 2018,and prospectively studied 122 CHD infants with the same baseline level who adopted the improved mode,nurse-parent-driven(NPD)feeding mode from January 2019 to June 2020.The feasibility and efficacy of NPD as a“transitional”feeding nursing mode in CHD infants with PH were compared with the FC cohort by observing and analyzing the stress of family caregivers,feedingrelated complications,the proportion of breastfeeding,improvement of nutritional status,acquisition of knowledge and skills of feeding care,inpatient’s satisfaction rating and prognosis.Results:When compared with the FC feeding care,the NPD mode significantly reduced the burden of family caregivers,improved the rate of feeding care knowledge and skills and inpatient’s satisfaction rating,reduced the incidence of improper feeding-related complications,and enhanced the proportion of breastfeeding and nutritional status of infants at the“transitional stage”(all P<0.05).The self-assessment score of care ability of family caregivers and weight gain of children in the NPD group were significantly higher than those in the FC group(all P<0.05)during the follow-up.Conclusions:As a transitional mode of feeding in CHD infants with PH,NPD feeding care is superior to the conventional FC mode,which therefore can be adopted as a standard protocol in clinical practice.

Treatment of patients with bosentan in postoperation of congenital heart disease with pulmonary arterial hypertension:a double-blind,randomized controlled trial

Objective Endothelin is a key role in the pathogenic of pulmonary arterial hypertension. High concentrations of endothelin 1 have been recorded in plasma and lungs of patients with pulmonary artery hypertension associated with congenital heart disease,and the concentrations of endothelin-1 was correlated with severity degree

Transgelin as a potential target in the reversibility of pulmonary arterial hypertension second to congenital heart disease

Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Short-term outcomes in heart failure patients with chronic obstructive pulmonary disease in the community

AIM:To establish the short term outcomes of heart failure(HF)patients in the community who have concurrent chronic obstructive pulmonary disease(COPD).METHODS:We evaluated 783 patients(27.2%)with left ventricular systolic dysfunction under the care of a regional nurse-led community HF team between June 2007 and June 2010 through a database analysis.RESULTS:One hundred and one patients(12.9%)also had a diagnosis of COPD;94% of patients were treated with loop diuretics,83% with angiotensin converting enzyme inhibitors,74% with β-blockers;10.6% with bronchodilators;and 42% with aldosterone an-tagonists.The mean age of the patients was 77.9 ± 5.7 years;43% were female and mean New York Heart Association class was 2.3 ± 0.6.The mean follow-up was 28.2 ± 2.9 mo.β-blocker utilization was markedly lower in patients receiving bronchodilators compared with those not taking bronchodilators(overall 21.7% vs 81%,P < 0.001).The 24-mo survival was 93% in patients with HF alone and 89% in those with both comorbidities(P = not significant).The presence of COPD was associated with increased risk of HF hospitalization [hazard ratio(HR):1.56;95% CI:1.4-2.1;P < 0.001] and major adverse cardiovascular events(HR:1.23;95% CI:1.03-1.75;P < 0.001).CONCLUSION:COPD is a common comorbidity in ambulatory HF patients in the community and is a powerful predictor of worsening HF.It does not however appear to affect short-term mortality in ambulatory HF patients.

Correlation between endothelia cells activation and imbalance of cytokines in pulmonary hypertension of congenital heart disease

Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twenty patients with simple ventricular septal defect (VSD) were chosen as controls, and 30 patients with PH were studied. Plasma levels of ET-1 and NO were measured by radioimmunoassay or colorimetric method. Before cardiopulmonary bypass was established, the specimens from right lung were fixed with formaldehyde solution, embedded with paraffin and stained by SP immunohistochemistry. Intercellular adhesion molecule-1 (ICAM-1) expression was measured through the determination of the light density with computer imaging technology. Results Compared with that of the patients with simple VSD, the light density of ICAM-1 and plasma level of ET-1 increased in patients with PH; but plasma level of NO decreased (P<0.05). Positive correlation was observed between ICAM-1 and ET-1/NO (P<0.05). Conclusion Endothelia cells activation and imbalance of ET-1/NO might play an important role in the development of PH.

Animal models of pulmonary hypertension due to left heart disease

Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.

Effect of ivabradine in the treatment of acute exacerbation of chronic obstructive pulmonary disease with heart failure

Objective: To observe the effectiveness and safety of ivabradine in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and heart failure. Methods:Patients who were admitted to hospital with AECOPD during the period from August 2017 to July 2018. Then those both had heart failure with reduced ejection fraction(HFrEF) and a resting heart rate>70 beats/min were enrolled. A total of 86 cases were screened and completed, which were randomly divided into two groups for treatment. The control group(41 cases) received standard treatments, such as oxygen, anti-infection, anti-spasmodic, hormone, diuretic, ACEI/ARB, recombinant human brain natriuretic peptide (rhBNP), etc. The bisoprolol was given 2.5~5 mg orally once a day to control heart rate, and the test group(45 cases) was further treated with ivabradine 2.5~5 mg orally twice a day on the basis of the control group. The average heart rate, cardiac function, lung function, and 6-minute walking test were compared between the two groups. Results: After treatment, the average heart rate of the test group was lower than the control group, and the heart rate control rate(<70 beats/min%) of the test group was superior to the control group. The level of N-terminal B-type natriuretic peptide(NT-proBNP) in test group was significantly lower than that in control group. The distance of the 6-minute walking test in e test group was significantly longer than that in control group. Conclusion: Ivabradine combined with bisoprolol could help patients with AECOPD and heart failure to further reduce the heart rates, improve heart function and exercise tolerance. Moreover, the therapeutic safety was acceptable during the short term.

Effect of sequential assist-control ventilation on cardio-pulmonary function and systemic inflammatory state of chronic pulmonary heart disease complicated with respiratory failure patients

Objective:To discuss the effect of sequential assist-control ventilation on cardio-pulmonary function and systemic inflammatory state of chronic pulmonary heart disease complicated with respiratory failure patients.Method: A total of 90 cases of chronic pulmonary heart disease complicated with respiratory failure patients, who were treated in our hospital between May, 2012 and Feb., 2016, were selected, and were divided into study group (n=45) and control group (n=45) based on random number table. Patients in control group were given auxiliary - control ventilation. (A/C) treatment during the whole course, while patients in study group were given A/C+BiPAP treatment. Cardio-pulmonary function and serum inflammatory factor content difference was compared inboth groups before and after operation.Results: Before treatment, difference ofcardiac function indicator, ABG level and inflammatory factor content in both groups had no statistical significance. After treatment, cardiac function indicator (PASP, RVd) levels in both groups were lower than before treatment, and EFRV levels were higher than before treatment, and changes in study group were more obvious than that in control group;ABG indicator (PaO2) levels in both groups were higher than before treatment, and PaCO2 levels werelower than before treatment, and changes in study group were more obvious than that in control group;serum inflammatory factor (hs-CRP, IL-6, TNF-α) content in both groups was lower than before treatment, and changes in study group were more obvious than that in control group.Conclusion: sequential assist-control ventilation could optimize the cardio-pulmonary function of chronic pulmonary heart disease complicated with respiratory failure patients and reduce the systemic inflammatory response.

Plasma HGF and OPN as Potential Biomarkers of Pulmonary Arterial Hypertension in Congenital Heart Disease

Objectives:Pulmonary arterial hypertension in congenital heart disease(PAH-CHD)is the most common type of PAH and increases morbidity and mortality in patients with CHD.Right heart catheterization(RHC)is the standard method to diagnose PAH.However,RHC is an invasive and complicated method with relatively high cost.Noninvasive,feasible,and cost-efficient methods are urgently needed.The objective of this study was to evaluate three potential biomarkers of PAH-CHD:Hepatocyte growth factor(HGF),osteopontin(OPN),and suppression of tumorigenicity 2(ST2).Methods:Plasma samples were collected from patients with CHD(n=46)and healthy individuals(n=22)and divided into four groups according to the severity of PAH.The levels of HGF,OPN,and ST2 were then analyzed using an enzyme-linked immunosorbent assay.Correlations between HGF,OPN,ST2,and clinical parameters of PAH-CHD were analyzed.Results:The plasma HGF levels in the moderate to the severe group were significantly higher than those in the mild group,nonPAH group,and healthy control group(p<0.05).Derived from a receiver operating characteristic(ROC)curve analysis,a cut-off value of 356.75 ng/ml for the HGF concentration was able to predict PAH-CHD with 53%sensitivity and 89%specificity.The HGF level was positively related to pulmonary arterial systolic pressure(PASP)(r=0.36,p<0.05)and pulmonary vascular resistance(PVR)(r=0.36,p<0.05).Plasma OPN levels in the mild group were significantly higher than other groups and positively correlated with the pulmonary-systemic shunt ratio(Qp/Qs)(r=0.33,p<0.05).There was no statistically significant between-group difference in plasma soluble ST2(sST2)levels.Conclusion:The plasma HGF level was elevated in PAH-CHD patients and can be used as a potential biomarker.The plasma OPN level was positively correlated with the Qp/Qs.