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Mounting evidence has confirmed that essential hypertension (EH) is closely related to low-grade inflammation, but there is still a lack of in-depth understanding of the state of immune cells in the circulating blood of patients with EH. We analyzed whether hypertensive peripheral blood immune cell balance was destroyed. The peripheral blood mononuclear cells (PBMCs) of all subjects were analyzed using time-of-flight cytometry (CyTOF) based on 42 kinds of metal-binding antibodies. CD45+ cells were categorized into 32 kinds of subsets. Compared with the health control (HC) group, the percentage of total dendritic cells, two kinds of myeloid dendritic cell subsets, one intermediate/nonclassical monocyte subset and one CD4+ central memory T cell subset in the EH group, was significantly higher; the percentage of low-density neutrophils, four kinds of classical monocyte subsets, one CD14lowCD16- monocyte subset, one naive CD4+ and one naive CD8+ T cell subsets, one CD4+ effector and one CD4+ central memory T cell subsets, one CD8+ effector memory T cell subset, and one terminally differentiated γδ T cell subset, decreased significantly in EH. What is more, the expression of many important antigens was enhanced in CD45+ immune cells, granulocytes, and B cells in patients with EH. In conclusion, the altered number and antigen expression of immune cells reflect the imbalanced immune state of the peripheral blood in patients with EH.

The prognosis is poor for patients with pulmonary artery stenosis-associated pulmonary hypertension (PAS-PH). Identifying predictors of prognosis in PAS-PH is crucial to preventing premature death, which has rarely been investigated. We aimed to explore the cardiopulmonary exercise testing (CPET) parameters to predict the prognosis of these patients.We prospectively included all patients with PAS-PH who underwent CPET between September 2014 and June 2021 in Fuwai Hospital (ClinicalTrials.gov ID: NCT02061787). The primary outcome was clinical worsening, including death, rehospitalization for heart failure, or deterioration of PH.Seventy-two patients were included in this study. A median of 2-year follow-up revealed that 18 (25%) patients experienced clinical worsening. The 1-year, 3-year, and 5-year event-free survival rates were 92.5%, 81.7%, and 62.7%, respectively. Patients with clinical worsening demonstrated significantly worse baseline haemodynamics and poorer exercise capacity than their counterparts. Multivariable Cox regression identified that peak OThe prognosis is poor for PAS-PH, and exercise intolerance and ventilation inefficiency are commonly observed. Peak O

Background Patent ductus arteriosus (PDA) can close on its own during childhood. Patent ductus arteriosus with left pulmonary artery (LPA) occlusion is rare. Here, we describe possible aetiologies of this condition and treatment strategies based on recent guidelines. Case summary A 35-year-old man experienced shortness of breath for 20 years. Physical examination revealed pitting oedema, digital clubbing, and bi-phasic murmur along the left sternal border at the 2nd and 3rd intercostal space. Congenital heart disease was suspected. Echocardiography revealed a severely dilated pulmonary trunk and PDA; however, the LPA was not visible. The patient has undergone PDA ligation surgery >30 years ago, which may have caused accidental LPA ligation; however, extreme elevation of pulmonary pressure led to increased difficulties in performing LPA reconstruction and PDA division. Therefore, pulmonary arterial hypertension (PAH) initial combination therapy with parenteral prostanoids was prescribed. The patient’s condition improved gradually. Discussion Inadvertent ligation of the LPA instead of PDA is a rare and usually fatal complication during ductal ligation. Patients who survive this catastrophic complication usually develop the progressive pulmonary vascular disease with increased pulmonary pressure and impaired lung parenchyma resulting in right heart and respiratory failure. Early and regular follow-up with cardiac imaging studies is important to diagnose this complication. Reconstruction of the ligated LPA and PDA late in the disease course is difficult due to the development of pulmonary arterial hypertension. Initial PAH combination therapy may be valuable for relieving the patients’ symptoms at that stage. Heart and lung transplantation can also be considered in suitable patients.

BackgroundDysfunction of autonomic nervous system plays an important role in the development of pulmonary hypertension. The present study aimed to investigate the interaction between balloon pulmonary angioplasty (BPA) and cardiac autonomic function by using heart-rate recovery at 1 min (HRR1) after exercise as a surrogate marker.Methods and ResultsWe retrospectively enrolled 89 consecutive patients with inoperable chronic thromboembolic pulmonary hypertension who underwent BPA from May, 2018 to Jan, 2021. According to hemodynamics at follow-up, patients were categorized as BPA responders if they met one or both of the following criteria: (1) mean pulmonary arterial pressure ≤ 30 mmHg and (2) a reduction of pulmonary vascular resistance ≥ 30%. Compared with baseline, HRR1 tended to increase within 7 days after the first BPA session, and this improvement persisted at follow-up. HRR1 at baseline and at follow-up were associated with well-validated markers of CTEPH severity, including N-terminal pro-brain natriuretic peptide, mean pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, the change of HRR1 from baseline to follow-up was also associated with the change of those variables. After adjustment for confounders, baseline HRR1 was still a strong independent predictor of BPA outcome. Receiver operator characteristic curve analysis showed that the cutoff value for HRR1 in predicting BPA outcome was 19 beats.ConclusionsBPA could significantly improve HRR1, suggesting the alleviation of sympathovagal imbalance. Easily available and non-invasive HRR1 seems to be a useful tool in predicting outcome of BPA and dynamically monitoring the efficacy of BPA.

Background There is no generally accepted comprehensive risk prediction model cooperating risk factors associated with heart failure and pulmonary hemodynamics for patients with pulmonary hypertension due to left heart disease (PH-LHD). We aimed to explore outcome correlates and evaluate incremental prognostic value of pulmonary hemodynamics for risk prediction in PH-LHD. Methods Consecutive patients with chronic heart failure undergoing right heart catheterization were prospectively enrolled. The primary endpoint was all-cause mortality. Individual variable selection was performed by machine learning methods. Cox proportional hazards models were conducted to identify the association between variables and mortality. Incremental value of hemodynamics was evaluated based on the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores. Results A total of 276 PH-LHD patients were enrolled, with a median follow-up time of 34.7 months. By L1-penalized regression model and random forest approach, diastolic pressure gradient (DPG) and mixed venous oxygen saturation (SvO2) were the hemodynamic predictors most strongly associated with mortality (coefficient: 0.0255 and -0.0176, respectively), with consistent significance after adjusted for SHFM [DPG: HR 1.067, 95% CI 1.024–1.113, P = 0.022; SvO2: HR 0.969, 95% CI 0.953–0.985, P = 0.002] or MAGGIC (DPG: HR 1.069, 95% CI 1.026–1.114, P = 0.011; SvO2: HR 0.970, 95% CI 0.954–0.986, P = 0.004) scores. The inclusion of DPG and SvO2 improved risk prediction compared with using SHFM [net classification improvement (NRI): 0.468 (0.161–0.752); integrated discriminatory index (IDI): 0.092 (0.035–0.171); likelihood ratio test: P P Conclusion In PH-LHD, pulmonary hemodynamics can provide incremental prognostic value for risk prediction. Clinical trial registration: NCT02164526 at https://clinicaltrials.gov.

Background and ObjectiveThe association between plasma betaine levels and cardiovascular diseases (CVDs) has been revealed except for pulmonary hypertension (PH). In this study, we aimed to explore the role of betaine in patients with PH.MethodsInpatients with PH at Fuwai Hospital were enrolled after excluding relative comorbidities. Each patient received at least one follow-up through a clinical visit, and the fasting blood was obtained both at the first and second hospitalization for betaine detection. The primary endpoint was defined as composite outcome events and the mean duration was 14.3 (6.9, 21.3) months. The associations of betaine and changes of betaine (Δbetaine) with disease severity and prognosis were explored.ResultsFinally, a total of 216 patients with PH were included and the medians for betaine plasma levels in the total patients group, low betaine, and high betaine groups were 49.8 (39.0, 68.3) μM, 39.0 (33.5, 44.7) μM, and 68.1 (57.8, 88.7) μM, respectively. High betaine was associated with poor World Health Organization Functional Class (WHO-FC), increased N-terminal pro-brain natriuretic peptide (NT-proBNP), low tricuspid annular plane systolic excursion (TAPSE), and cardiac output index even after adjusting for confounders. Patients with high betaine were over twice the risk to receive the poor prognosis than those with a low level [hazard ratio (HR) = 2.080, (95% CI: 1.033–4.188)]. Moreover, the decrease of betaine level after further treatment was positively correlated to ΔNT-proBNP indicating Δbetaine might be an effector of disease severity, and dynamic increase of betaine was also associated with poor prognosis in PH.ConclusionBetaine was associated with disease severity and might be an effector in PH. Patients with increased levels or with dynamic rise of betaine heralded a poor prognosis.

Background: The hemodynamic results of balloon pulmonary angioplasty vary among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies revealed that microvasculopathy accounted for residual pulmonary hypertension after pulmonary endarterectomy, which could be reflected by the diffusing capacity for carbon monoxide (DLCO). We aimed to identify whether the DLCO could predict the BPA response.Materials and Methods: We retrospectively analyzed 75 consecutive patients with inoperable CTEPH who underwent BPA from May 2018 to January 2021 at Fuwai Hospital. According to the hemodynamics at follow-up after the last BPA, patients were classified as “BPA responders” (defined as a mean pulmonary arterial pressure ≤ 30 mmHg and/or a reduction of pulmonary vascular resistance ≥ 30%) or “BPA nonresponders.”Results: At the baseline, BPA responders had significantly higher DLCO values than nonresponders, although the other variables were comparable. In BPA responders, the DLCO decreased after the first BPA session and then returned to a level similar to the baseline at follow-up. Conversely, the DLCO increased constantly from the baseline to follow-up in nonresponders. Multivariate logistic analysis showed that a baseline DLCO of 6% were both independent predictors of an unfavorable response to BPA. Receiver operator characteristic analysis showed that the combination of a baseline DLCO < 70% and ΔDLCO > 6% demonstrated a better area under the curve than either of these two variables used alone.Conclusions: A baseline DLCO < 70% and ΔDLCO > 6% could independently predict unfavorable responses to BPA. Measuring the DLCO dynamically facilitates the identification of patients who might have unsatisfactory hemodynamic results after BPA.

Background: Emerging evidence has showed that serum carbohydrate antigen 125 (CA 125) levels are associated with the severity and prognosis of heart failure. However, its role in pulmonary hypertension remains unclear. This study aimed to investigate the clinical, echocardiographic, hemodynamic, and prognostic associations of CA 125 in pulmonary hypertension.Methods and Results: We conducted a retrospective cohort study of all idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients receiving CA 125 measurement in Fuwai Hospital (January 1, 2014–December 31, 2018). The primary end-point was cumulative 1-year clinical worsening-free survival rate. Linear regression was performed to assess the association between CA 125 and clinical, echocardiographic, and hemodynamic parameters. Cox proportional hazards models were used to assess the association between CA 125 and clinical worsening events. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive performance of CA 125. A total of 231 patients were included. After adjustment, CA 125 still positively correlated with World Health Organization functional class, NT-proBNP, right ventricular end-diastolic diameter, pericardial effusion, mean right atrial pressure and pulmonary arterial wedge pressure; negatively correlated with 6-min walk distance, left ventricular end-diastolic diameter, mixed venous oxygen saturation, and cardiac index. After adjustment, CA 125 > 35 U/ml was associated with over 2 folds increased risk of 1-year clinical worsening. Further, ROC analysis showed that CA 125 provided additional predictive value in addition to the established pulmonary hypertension biomarker NT-proBNP.Conclusion: CA 125 was associated with functional status, echocardiography, hemodynamics and prognosis of pulmonary hypertension.

Background: Four-dimensional automatic right ventricular quantification technology (4D auto-RVQ) is a new method that can simultaneously measure right ventricular (RV) structure and strain. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. We assessed the 4D auto-RVQ to measure right heart structure, function, and hemodynamics in patients with pulmonary hypertension (PHTN) correlated with right heart catheterization (RHC).Methods: We enrolled a prospective cohort of 103 patients with PHTN and 25 healthy controls between September 2017 and December 2018. All patients with PHTN underwent echocardiography and RHC. Patients were included if they underwent two-dimensional (2D) and 4D auto-RVQ echocardiographic sequences on the same day as RHC. We analyzed RV functional indices using 2D and 4D auto-RVQ analyses. We divided patients with PHTN into three groups according to echocardiographic image quality as follows: high (n = 24), average (n = 48), and poor (n = 4). Hemodynamic parameters were measured using RHC, including mean right atrial pressure, mean pulmonary arterial pressure, RV cardiac index (RV-CI), and pulmonary vascular resistance.Results: There were significant differences in most 2D and 4D auto-RVQ parameters between patients with PHTN and healthy controls. Interobserver variability showed significant agreement with 4D auto-RVQ for most measurements except for 4D end-diastolic volume. Indices measured by auto 4D-RVQ in the high-quality image group had a good correlation with RHC but not in the average- and poor-quality image group. Mid-RV diameter showed the best predictive power for the right RV-CI [area under the curve (AUC) 0.935; 95% confidence interval (CI), 0.714–0.997; p < 0.001]. RV end-systolic volume >121.50 mL had a 71.43% sensitivity and a 100% specificity to predict right RV-CI (AUC, 0.890; 95% CI, 0.654–0.986; p < 0.001).Conclusions: 4D auto-RVQ may be used to estimate RV function and some hemodynamic changes compared with RHC in PHTN patients with high image quality. Furthermore, a large sample of the study is needed to evaluate RV function by 4D auto-RVQ in PHTN patients with average image quality.

Right ventricular (RV) function is a powerful predictor of survival in patients with pulmonary hypertension (PH), but noninvasively assessing RV function remains a challenge. The aim of this study was to prospectively compare gated (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) myocardial imaging (gated PET), cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) for the assessment of RV volume and ejection fraction in patients with PH.Twenty-three consecutive patients aged more than 16 years diagnosed with PH were included. All patients underwent gated PET, CMR, and CCT within 7 days. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and right ventricular ejection fraction (RVEF) were calculated by three imaging modalities. RV (18)F-FDG uptake was determined as RV-corrected standardized uptake value (SUV), and the ratio of RV to left ventricular (LV)-corrected SUV (Corrected SUV R/L).Gated PET showed a moderate correlation (r = 0.680, P .001) for RVEDV, good correlation for RVESV (r = 0.757, P .001) and RVEF (r = 0.788, P .001) with CMR, and good correlation for RVEDV (r = 0.767, P .001), RVESV (r = 0.837, P .001), and RVEF (r = 0.730, P .001) with CCT. Bland-Altman analysis revealed systematic underestimation of RVEDV and RVESV and overestimation of RVEF with gated PET compared with CMR and CCT. The correlation between RVESV (r = 0.863, P .001), RVESV (r = 0.903, P .001), and RVEF (r = 0.853, P .001) of CMR and those of CCT was excellent; Bland-Altman analysis showed only a slight systematic variation between CMR and CCT. There were statistically significant negative correlations between RV-corrected SUV and RVEF-CMR (r = -0.543, P .01), Corrected SUV R/L and RVEF-CMR (r = -0.521, P .05), RV-corrected SUV and RVEF-CCT (r = -0.429, P .05), Corrected SUV R/L and RVEF-CCT (r = -0.580, P .01), respectively.Gated PET had moderate-to-high correlation with CMR and CCT in the assessments of RV volume and ejection fraction. It is an available method for simultaneous assessing of RV function and myocardial glucose metabolism in patients with PH.

Introduction: Pulmonary arterial hypertension (PAH) is a relative common complication in patients with congenital heart disease (CHD), affecting both disease progression and prognosis. The pathogenic mechanisms that lead to “irreversible” PAH are therefore poorly understood in subjects with CHD. Hypothesis: The aim of this study was to apply proteomics to discover protein regulations in the lungs of irreversible PAH patients, which could lead to generation of new hypotheses concerning signaling pathways and elucidating the pathophysiology of irreversible PAH. Methods: Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 4 patients with irreversible CHD-PAH, 4 reversible CHD-PAH and 4 control subjects. Result: A total of 133 proteins were differently expressed. The majority of differential expressed proteins were associated with cytoskeleton remodeling, integrin-mediated cell adhesion and migration, endothelial cell contacts, blood coagulation and HDL-mediated reverse cholesterol transport. Novel findings included increased expression of filamin A and caveolin-1 and decreased expression of glutathione S-transferase (GST) family. Filamin A, a major isoform of the filamin family which is a family of cytoskeletal proteins that have been implicated as critical mediators of organ development and cell signaling and migration. In the present study, the density and cellular location of filamin A immunoreactivity was accordant with caveolin-1. The results were confirmed by Western blot and immunohistochemistry. In reversible CHD-PAH and control lung tissue, filamin A and caveolin-1 were prominent in endothelium of pulmonary arteriole. In irreversible CHD-PAH lung tissue, they were prominent in the vascular smooth muscle cell. Conclusions: Label-free proteomics identified differences in the expression of several proteins in the CHD-PAH lung, many of which are relevant to the cell proliferation, differentiation and migration. Increased expression of filamin A and caveolin-1 may be pertinent to the proliferation and migration of vascular smooth muscle cell. Decreased expression of GST indicated impaired anti-oxidative function in irreversible CHD-PAH.

Background Numerous studies have demonstrated that fibroblast growth factor-2 (FGF-2) signaling may play a pivotal role in the development of pulmonary arterial hypertension (PAH). Excessive endothelial FGF-2 contributes to smooth muscle hyperplasia and disease progression. PD173074 is a potent FGF receptor 1 (FGFR-1) inhibitor that displays high activity and selectivity. The aim of this study was to investigate the effects of PD173074 on monocrotaline-induced PAH. We also evaluated whether FGFR-1 inhibition could attenuate bone morphogenetic protein type II receptor (BMPR-II) downregulation in the monocrotaline model. Methods PAH model was established by a single intraperitoneal injection of monocrotaline. And then a daily intraperitoneal injection of PD173074 (20 mg/kg) was administered from day 14 to day 28. Hemodynamic parameters, right ventricular hypertrophy index and morphometry were evaluated at day 28. Western blot and immunohistochemical analyses were used to determine the expression of FGF-2 and bone morphogenetic protein signaling in the lung tissue. Results The expression of FGF-2 and FGFR-1 was upregulated in lung tissue after monocrotaline injection and it was accompanied by hemodynamic changes and pulmonary vascular remodeling. PD173074 treatment ameliorated PAH and vascular remodeling. It decreased ERK1/2 activation and rescued total Akt expression, leading to a reduction in both proliferation and apoptosis in the lung. Besides, PD173074 rescued the expression of BMPR-II and p-Smad 1/5/8. Conclusion These results suggest that PD173074 can alleviate monocrotaline-induced pulmonary arterial hypertension and it may be a useful option for PAH. Our data also suggest a role of FGF-2/bone morphogenetic protein signaling interaction in PAH.

Fibroblast growth factor-2 (FGF-2) signaling plays a pivotal role in the development of pulmonary arterial hypertension (PAH).PD173074 is a potent FGF receptor 1 (FGFR-1) inhibitor that displays high activity and selectivity. The aim of this study was to investigate the effects of PD173074 on