Pulmonary Circulation最新文献

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.

Patients with borderline pulmonary hypertension (PH) often experience shortness of breath or exacerbation of PH during exercise, known as exercise-induced PH. However, the pathogenesis of exercise-induced post-capillary PH (post-EIPH) and its treatment strategies remain unclear. Recent guidelines and consensus documents have highlighted the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in heart failure and chronic kidney disease (CKD). This study aimed to investigate the effects of SGLT2 inhibitors in patients with post-EIPH and CKD. This single-center prospective cohort study enroled 10 patients with CKD (age, 68 years; female, 60%) who exhibited post-EIPH between 1 July 2022 and 31 December 2023. Post-EIPH was defined as a pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope > 2 and peak PCWP during exercise ≥ 25 mmHg measured by catheterization. The patients received SGLT2 inhibitor treatment for 6 months. At rest, patients with post-EIPH had borderline-PH (21.5 ± 1.8 mmHg), with preserved left and right ventricular function. SGLT2 inhibitors treatment significantly reduced the PCWP/CO slope during exercise (3.9 ± 1.2 vs. 2.4 ± 1.2 mmHg/L/min, p = 0.013) and improved the 6-min walking distance (489.9 ± 80.2 vs. 568.3 ± 91.9 m, p = 0.014). Magnetic resonance imaging revealed a lower left ventricular global longitudinal strain in patients with post-EIPH, which was increased by SGLT2 inhibitor treatment (-13.8 ± 2.0 vs. -17.3 ± 2.0%, p = 0.003). SGLT2 treatment inhibitors mitigated post-EIPH hemodynamic abnormalities and exercise intolerance, suggesting their potential as its therapeutic option.

The right ventricular stroke work index (RVSWI) reflects the active work of the right ventricle (RV), but its clinical usefulness is not yet fully known in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to evaluate the correlation of RVSWI to clinical parameters, the presence of comorbidities and response to therapy. We performed a retrospective observational study of 54 patients (PAH: N = 30, CTEPH: N = 24) and control patients (N = 11), and collected clinical data including RVSWI and comorbidities at baseline. We also compared changes in the parameters of the four-strata mortality risk score at follow-up (median time of 12 months) after the initiation of therapy between patients with low- (<1450 mmHg*mL/m², N = 18) and high-RVSWI values (≥1450 mmHg*mL/m², N = 19). RVSWI at diagnosis was higher in PAH/CTEPH compared to control subjects (1408 ± 391 vs. 704 ± 140 mmHg*mL/m², p < 0.001, mean ± standard deviation, t-test), but did not differ between PAH and CTEPH patients (1406 ± 342 vs. 1409 ± 470 mmHg*mL/m², p = 0.98). Patients without comorbidities had higher RVSWI than those with comorbidities (N = 23: 1522 ± 400 vs. N = 31: 1323 ± 384 mmHg*mL/m², p = 0.04), which was also found in PAH (p < 0.001), but not in CTEPH (p = 0.37). A greater improvement in the four-strata mortality risk score (p < 0.05) and a trend for a larger reduction in N-terminal proB-type natriuretic peptide concentration (p = 0.06) were observed in the high-RVSWI subgroup than in the low-RVSWI patients at follow-up. In PAH and CTEPH, RVSWI provides additional information on RV function in comorbidities, and it may predict response to specific therapy. Regular monitoring of RVSWI may aid in optimizing therapy selection and timing.

Pulmonary veno-occlusive disease (PVOD) is a lethal variant of pulmonary hypertension. The degree of pulmonary arterial involvement varies. Here, we compare two PVOD patients who were transplanted at 8 years of age, whereof one is a homozygous EIF2AK4 mutation carrier. Tissue was imaged with synchrotron-based micro-CT and the results were compared with clinical data and sectioned tissue was analyzed with histology, immunohistochemistry, immunofluorescence, and in situ hybridization. Chest CT of the noncarrier exhibited scattered poorly defined ground-glass opacities and marked septal lines, whereas the mutation carrier showed numerous nodular centrilobular ground-glass opacities and sparse septal lines. The noncarrier developed pulmonary edema with vasodilators and 3D imaging combined with histology showed severe obstruction of interlobular septal veins and medial hypertrophy of pulmonary arteries, but no arterial or arteriolar intimal fibrosis. In contrast, the mutation carrier exhibited only mild intimal fibrosis in interlobular septal veins but severe arterial and arteriolar remodeling, including intimal fibrosis, tortuous course of arterioles, muscularization extending to the alveolar duct level and multiple vascular lumens within the same pulmonary arterial adventitia. Both patients had focally thickened alveolar septa with areas of pulmonary capillary hemangiomatosis (PCH) which colocalized with increased capillary muscularization, tenascin C expression, and deposition, as well as with matrix metalloproteinase-9 (MMP9)/CD45 positive cells. In conclusion, synchrotron-based phase-contrast micro-CT is valuable for understanding vascular remodeling. Significant differences were observed between heritable and sporadic PVOD, which may influence management strategies.

Pulmonary hypertension (PH) is a frequent complication of chronic lung disease (CLD). However, PH is difficult to diagnose early since accompanying symptoms overlap and are similar to those of the underlying CLD. In most cases the PH is mild to moderate and therefore physical signs may be absent or subtle. This consensus paper provides insight into the clues that might suggest the presence of occult PH in patients with CLD. An overview of current diagnostic tools and emerging diagnostic technologies is provided as well as guidance for the work-up and diagnosis of PH in patients with CLD.