Pulmonary Circulation最新文献

Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect. The 2023 Grover Conference Series reviewed the research landscape to summarize the current state of the art and provide a better understanding of the application of precision medicine to managing pulmonary vascular disease. In particular, the following aspects were discussed: (1) Clinical phenotypes, (2) genetics, (3) epigenetics, (4) biomarker discovery, (5) application of precision biology to clinical trials, (6) the right ventricle (RV), and (7) integrating precision medicine to clinical care. The present review summarizes the content of these discussions and the prospects for the future.

Common variable immunodeficiency (CVID) is a type of primary immunodeficiency that presents as a heterogenous disorder characterized by hypogammaglobinemia, poor response to vaccines, recurrent sinopulmonary infections, and can have noninfectious systemic manifestations. We performed a single-center, retrospective, observational study of five patients with noninfectious complications of CVID. All patients had CVID as defined by the European Society of Immunodeficiencies criteria and had received intravenous immunoglobulin therapy. There were multiple pulmonary manifestations of CVID including frequent pneumonias, bronchiectasis, granulomatous lung disease, and pulmonary hypertension. All our patients were treated with pulmonary vasodilators for severe precapillary pulmonary hypertension along with individualized immunosuppression regimen for interstitial lung disease. Despite treatment for interstitial lung disease and PH, their conditions worsened over 2-3 years with all patients progressing toward organ transplant evaluation. Idiopathic thrombocytopenia and non-cirrhotic portal hypertension were common, with three patients probably suffering from nodular regenerative hyperplasia. Noninfectious complications of CVID can affect different organs and progress despite advanced therapies. Single or multiorgan transplantation is a treatment option for patients with end-stage organ involvement refractory to medical therapy.

Pulmonary artery (PA) flow analysis is crucial for understanding the progression of pulmonary hypertension (PH). We hypothesized that PA flow characteristics vary according to PH etiology. In this study, we used 4D flow cardiovascular magnetic resonance imaging (CMR) to compare PA flow velocity and wall shear stress (WSS) between patients with pulmonary arterial hypertension (PAH) and those with heart failure with preserved ejection fraction and pulmonary hypertension (PH-HFpEF). We enrolled 13 PAH and 15 PH-HFpEF patients. All participants underwent echocardiography, 4D flow CMR, and right heart catheterization. We compared right ventricular outflow tract (RVOT) flow and main pulmonary artery (MPA) hemodynamics, including peak velocity and mean and maximum WSS, between groups. PH-HFpEF patients were older and more likely to have hypertension. PAH patients had higher mean PA pressure (47.8 ± 8.8 vs. 32.9 ± 6.9 mmHg, p < 0.001) and pulmonary vascular resistance (PVR) (8.6 ± 4.6 vs. 2.6 ± 2.2 wood unit, p < 0.001). RVOT systolic notching was more common in PAH patients (8 of 13 vs. 0 of 15), and they had shorter RVOT acceleration time (85.5 ± 20.9 vs. 135.0 ± 21.7 ms, p < 0.001). PAH patients had lower MPA Vmax (0.8 ± 0.2 vs. 1.1 ± 0.4 m/s, p = 0.032), mean WSS (0.29 ± 0.09 vs. 0.36 ± 0.06 Pa, p = 0.035), and maximal WSS (0.99 ± 0.18 vs. 1.21 ± 0.19 Pa, p = 0.011). Anterior MPA analysis confirmed lower WSS in PAH patients. PVR was negatively correlated with MPA mean WSS (r = -0.630, p = 0.002). PAH patients had lower MPA Vmax and lower mean MPA WSS in 4D flow CMR compared to PH-HFpEF patients. These distinct PA flow characteristics suggest that the flow hemodynamics of the PA remodeling process differ depending on the underlying etiology of PH.

Guidelines recommend risk stratification of pulmonary arterial hypertension (PAH) patients to guide management. There are currently several risk stratification scores available, which have largely been validated in various pulmonary hypertension registries in the West but not in Asia. We aim to study the performance of these different risk scores in PAH patients from a multi-ethnic Asian population. A retrospective review of all PAH patients from Jan 2014 to Jun 2021 from a tertiary cardiac center was performed. Mortality outcomes were obtained from national registries. Using the 2022 ESC/ERS, REVEAL Lite 2.0 and COMPERA 2.0 risk scores, patients were classified into different risk strata at baseline and at follow-up and changes in any risk strata recorded. The prognosis of patients based on these factors was compared. A total of 153 patients (mean age: 57 ± 17 years; 117 women; 94 Chinese, 33 Malay, 19 Indian) were included. All three scores showed significant difference in mortality outcomes between the different risk strata both at baseline and at follow-up (p < 0.05), with the highest risk group showing the highest mortality. Patients who worsened to or remained at intermediate/high-risk generally had a worse prognosis than those who remained stable at or improved to low-risk strata. The 2022 ESC/ERS and COMPERA 2.0 risk scores had C-statistics of 0.73 (0.58-0.88) and 0.80 (0.72-0.88), respectively, for predicting 1-year mortality. Serial risk stratification is a useful tool in prognosticating Asian PAH patients and may play an important role in guiding therapeutic management.

The aim of this single-centre retrospective observational study was to evaluate the safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension. Children aged over 5 years who were established on sildenafil plus bosentan were offered to undergo a therapy switch from May 2014 to May 2021 and, if remaining in the service, followed up to May 2024. Children with Eisenmenger syndrome, open intra or extra-cardiac shunt, or with pulmonary hypertension-associated lung disease were excluded. As part of a structured clinical program children were assessed via walk test, echocardiography, cardiac magnetic resonance imaging (CMRI), cardiopulmonary exercise testing, and serum biomarkers. Fifty-two children were included, 33 in the switch group and 19 in the control group. Clinical characteristics at diagnosis and baseline assessments did not differ between groups. All children tolerated the medication switch. Over a median 13.0 [12.0,13.7] week follow-up in the switch group there was a significant improvement in World Health Organization functional class (WHO FC, p < 0.001); reduction in estimated right ventricular systolic pressure by echocardiography of 7 mmHg (p = 0.03) and a 2% increase (p = 0.03) in right ventricular ejection fraction on CMRI. There was a sustained improvement in WHO FC (p < 0.01) in the switch group at medium-term follow-up of 40.9 [35.2,49.3] weeks. Long-term outcome of transplant- or Potts shunt-free survival was comparable between the two groups.

This study aimed to explore the potential causal link between genetic predisposition to various connective tissue diseases (CTDs), namely systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), polymyositis (PM), dermatomyositis (DM), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA), and the incidence of pulmonary arterial hypertension (PAH) utilizing Mendelian randomization (MR). Employing a two-sample MR approach, genetic variants associated with CTDs served as instrumental variables to investigate the exposure-outcome relationship, with GWAS data sourced from the FinnGen Biobank. Comprehensive statistical analyses, including the inverse variance weighted (IVW) method, were conducted, alongside heterogeneity, pleiotropy, and sensitivity tests to ensure the robustness and validity of findings. The results revealed that in the Finnish population, no significant causal associations were identified between PAH and SLE, SS, PM, DM, MCTD, or RA. Notably, a significant association was observed between SSc and an increased risk of PAH (IVW: OR = 1.278, 95% CI = 1.061-1.540, p = 0.010). However, this finding was not replicated in other European populations. These results indicate the unique genetic and pathological pathways underlying SSc-associated PAH, emphasizing the need for tailored screening and management protocols in this patient group.

Pulmonary arterial hypertension (PAH) is a chronic progressive exacerbation of cardiopulmonary vascular disease. The patients' exercise endurance decreased progressively and the survival rate was low. Current basic therapy and targeted drug therapy can improve the quality of life (QoL) of PAH patients, but the long-term efficacy and prognosis are not good. In this study, the female sexual function index (FSFI) scale, Health Promoting Life Style Profile (HPLPII), and emPHasis-10 were used to evaluate PAH patients' sexual function, health-promoting behaviors and QoL. Their correlation and the moderating effect of health promoting behavior were conducted. In total, 306 female patients responded. Age ranged from 18 to 69 years old and the mean age was (38.049 ± 10.686). The average score of sexual function in female PAH patients was (21.703 ± 8.947) points, and the detection rate of sexual dysfunction was 51.307%. The average score of health-promoting behaviors and QoL was (121.915 ± 13.507) points and (17.992 ± 10.245) points respectively. QoL was significantly negatively correlated with sexual function and health-promoting behaviors, while sexual function was significantly positively correlated with health-promoting behaviors. The health-promoting behaviors of female patients with PAH has a moderating effect between sexual function and QoL. The sexual function, health-promoting behaviors and QoL of female PAH patients were all at an general level. Improving the level of health-promoting behaviors could reduce the negative predictive effect of sexual function on QoL.

The hemodynamic definitions of pulmonary hypertension consider resistive loading (pulmonary vascular resistance [PVR]), but there are increasing evidence that pulsatile loading (pulmonary artery compliance [PAC]) has functional and prognostic importance. The aims of the present study on patients with left heart disease, were to evaluate a novel echocardiographic right ventricular (RV) afterload score and to investigate its relation to risk of mortality or implantation of a left ventricular assist device. Patients (n = 220) with left ventricular ejection fraction < 50% consecutively referred for heart transplant or heart failure workup underwent echocardiography and right heart catheterization. Four metrics were included in the afterload score: the systolic pulmonary artery pressure (sPAP_Doppler) and three variables related to pressure reflection in the pulmonary circulation. Two points were allocated for sPAP_Doppler ≥ 60 mmHg and for each pressure reflection variable indicating PVR > 3 Wood units (WU). One point was allocated for sPAP_Doppler 36-59 mmHg and for pressure reflection variables above the upper normal limit. Low afterload was defined as 0-to-1 points, intermediate as 2-to-4 points, and high as 5-to-8 points. There were in-between the groups significant differences in PAC and PVR. A 5-point RV dysfunction score showed with stepwise increased RV afterload more severe dysfunction. Unadjusted hazard ratio for endpoint was 3.34 (1.69-6.79) for intermediate score, and 5.11 (2.52-10.40) for patients with high score. In conclusion, in patients with severe heart failure, a novel echocardiographic RV afterload score is related to increased pulsatile and resistant load, more severe RV dysfunction, and increased risk of adverse outcome.

Balloon pulmonary angioplasty (BPA) is now a widely accepted treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but it still faces the problem of high complications. Herein, we report a rare case of severe vagal response during the BPA of a total occlusion lesion in a patient with CTEPH. The patient experienced acute chest pain and dyspnea, accompanied by a significant decrease in heart rate and blood pressure. After administering atropine, the patient's symptoms rapidly subsided. This case highlights the potential for vascular and pleural injury with chest pain, which can lead to severe vagal response during the BPA procedures. To minimize this risk, avoiding guide wire-induced injury to the pleura situated distal to the target vessel is crucial.

Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described. The objective of this study was to define the role of the hepcidin-ferroportin axis on the phenotype of PAEC and to study potential PAEC-PASMC interactions relevant to the pathogenesis of pulmonary vascular remodeling and PAH. PAECs treated with hepcidin, or interleukin-6 were investigated for both ferroportin and hepcidin release and regulation using immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMCs treated with conditioned media from hPAEC treated with hepcidin was investigated using the xCELLigence system and other tools. We demonstrate in this study that PAECs express ferroportin; hepcidin treatment of PAECs resulted in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs caused PASMCs to down-regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limited these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses. This study confirms that the hepcidin ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECs with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering potential novel therapeutic targets.