Pulmonary Circulation最新文献

Overnight inpatient monitoring is common following balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). We describe our institutional experience in same-day discharge (SDD) after BPA. Across 78 BPA sessions, there were only 2 (2.6%) admissions for hemoptysis with no reperfusion lung injury or deaths at 30 days.

Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution.

Long-term hypoxia is one of the main causes of pulmonary vascular remodeling in pulmonary hypertension (PH) associated with congenital heart disease (CHD) children. Endothelial to mesenchymal transition (EndMT) is an important pathological basis of pulmonary vascular remodeling in PH. We observed that Fibronectin 1 (FN1) had strong protein-protein interactions with both Thrombospondin 1 (THBS1) and Transglutaminase 2 (TGM2) in PH with venous peripheral bloods samples from pediatric patients and healthy children. LungMAP CellCards and heatmaps of human PAEC in PH patients and lung tissues in hypoxia induced PH mice model were used to show that THBS1 and FN1 were significantly elevated. We studied the relationship between THBS1 and FN1 in vivo, by using SUHX-induced PH mice model, and in vitro, by using hypoxia-induced human PAEC. The results showed that hypoxia could result in EndMT and inhibiting THBS1 could reverse EndMT in vivo and in vitro, verifying our transcriptome results. Taken together, our research demonstrated that THBS1 could mediate hypoxia driven EndMT of PH, providing a new insight of research in the pathophysiology of PH.

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan (n = 28) or placebo (n = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; p = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo (p = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in combination with the clinical Curaçao criteria to confirm the diagnosis. HHT can be complicated by significant pulmonary vascular disease including pulmonary arteriovenous malformations, pulmonary arterial hypertension and high output cardiac failure. These are associated with substantial morbidity and mortality and therefore timely diagnosis is important to mitigate complications and optimise preventative strategies. This article outlines important advances in our understanding of the pathobiology of HHT and current recommendations regarding the diagnosis and screening of HHT with a specific focus on adult patients with pulmonary vascular disease. Important therapeutic advances, novel therapies on the horizon and unmet needs are also explored.

Congenital heart defects (CHDs) represent one of the most prevalent categories of neonatal defects, and maternal dietary patterns have been linked to the risk of these conditions. Branched-chain amino acids (BCAAs), particularly leucine, are essential for various metabolic and physiological processes involved in heart development. In this study, we examined the molecular mechanisms through which elevated levels of leucine induce defects in cardiac microvascular endothelial cells. We collected plasma samples from healthy controls and neonatal patients with CHDs, employed a high-leucine diet for pregnant female mice, and applied high-leucine treatment in human cardiac microvascular endothelial cells (HCMECs). The impacts of high-leucine levels on WD Repeat Containing Planar Cell Polarity Effector (WDPCP)/MAPK signaling axis were investigated in the cell and animal models. We reported heightened plasma leucine levels in neonatal patients with CHDs and observed that a high-leucine diet in pregnant mice was associated with reduced expression of WDPCP and attenuated MAPK/ERK signaling. High-leucine treatment in HCMECs impaired epithelial-mesenchymal transition (EMT) and cell migration; however, overexpression of WDPCP or activation of MAPK exhibited a rescue effect. The upregulation of endomucin (EMCN) under high-leucine conditions contributed to the impaired EMT and migratory capacity of HCMECs, and the WDPCP/MAPK signaling axis regulated EMCN overexpression in response to high-leucine treatment. High levels of leucine in neonatal patients with CHDs may inhibit the WDPCP/MAPK axis, leading to an increase in EMCN expression that undermines the function of cardiac microvascular endothelial cells. These findings suggest the potential of targeting the WDPCP/MAPK axis as an intervention strategy for neonatal CHDs.

Right ventricular (RV) (dys)function determines outcomes in pulmonary hypertension (PH). We previously found that asymmetric RV myocardial work (MW) corresponds with inefficient RV function in experimental PH models. We therefore aimed to investigate regional distribution of RV MW and its correlation with catheter hemodynamics in children with PH. RV MW was calculated by longitudinal strain and simultaneous catheter pressure measurements in 14 patients with PH. Wasted MW was defined as the ratio of inappropriate myocardial lengthening to favorable shortening work. Segment-wise and averaged MW and wasted MW were evaluated at baseline and during pulmonary vasodilation therapy with oxygen and nitric oxide, and their relationship to hemodynamic measurements was analyzed. We found that MW was higher for the lateral wall than the septum: 1013 ± 374 mmHg · % versus 532 ± 190 mmHg · % at baseline. Wasted MW ratio did not differ significantly between wall regions. Pulmonary vasodilators slightly reduced mean pulmonary artery pressure and was accompanied by a more symmetrical MW distribution. Averaged MW correlated with the rate of RV pressure development (dP/dt maximum) and decay (dP/dt minimum) at all conditions (p  $\le$  0.047). The results suggest that MW contribute to, and may be used as a marker of, systolic and diastolic efficiency in the PH RV.

Our prospective study investigates the 3-year trajectory of disease-specific quality of life (QoL) using the PEmb-QoL questionnaire, functional performance via 6-min walk tests, and the 5-year survival following acute pulmonary embolism (PE) and explores their association with patient demographics and clinical characteristics. We highlight that PE-specific QoL improves over time despite no significant changes in cardiopulmonary performance.

Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β-hydroxylase (DβH) inhibition with BIA 21-5337 improved right ventricular (RV) function or remodeling in pressure overload-induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21-5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate-reducing effects of BIA 21-5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure-volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21-5337 reduced adrenal gland DβH activity and 24-h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end-of-study, there were no differences in RV function or RV remodeling between BIA 21-5337 and vehicle-treated rats. In conclusion, treatment with BIA 21-5337 did not have any beneficial-nor adverse-effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity.