Cheng Wang

Background: The mechanisms underlying stroke recurrence after patent foramen ovale (PFO) closure for secondary prevention remain poorly understood. This study evaluated incomplete device apposition (IDA) using cardiac CT angiography (CTA) and investigated its association with stroke recurrence. Methods: In this prospective cohort study conducted at four centres in China (2020–2026), 233 patients (mean age: 37.01±6.73 years; 48.9% male) without known vascular risk factors were included from 382 consecutive candidates who underwent transcatheter PFO closure with follow-up ≥6 months. Cardiac CTA at 6 months post closure assessed the presence, location and extent of IDA defined as a gap between the left disc and the interatrial septum. Recurrent stroke and new-onset symptoms (atrial tachyarrhythmia, migraine headache, chest pain/discomfort) were recorded and their associations with IDA were analysed. Results: IDA was observed in 55.8% of patients predominantly at the anterior-inferior rim (93.4%). IDA was significantly associated with larger and longer PFOs, larger devices and greater in vivo device thickness (p < 0.001 for all). During a median follow-up of 20.00 (IQR 18.00–24.00) months, patients with IDA had a higher risk of recurrent stroke (log-rank p = 0.022) and new-onset symptoms (log-rank p < 0.001). In eight patients who underwent repeat CTA, device apposition remained stable after 6-month closure. Pathological validation was available in one patient with severe chest pain/discomfort and a well-apposed device had sufficient endothelialisation. Conclusion: IDA is common after PFO closure and is associated with increased risks of recurrent stroke and new-onset symptoms. Preventive strategies warrant further investigation. Trial registration number: NCT04686253 .

Selenium deficiency is implicated in pulmonary arterial hypertension (PAH). This study investigated the effects of sodium selenite (SSE) on PAH and its underlying mechanisms. In a monocrotaline-induced PAH rat model, SSE treatment significantly improved right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and vascular remodeling. It reduced collagen deposition and partially restored the expression of Collagen 1 and SM22α. SSE upregulated glutathione peroxidase 3 (GPX3) expression and attenuated oxidative stress, as evidenced by enhanced SOD activity and decreased MDA levels. In vitro, SSE inhibited H₂O₂ and angiotensin II-induced proliferation, oxidative stress, and phenotypic switching in pulmonary artery smooth muscle cells (PASMCs), while upregulating GPX3 at both mRNA and protein levels. These findings demonstrate that SSE alleviates PAH by enhancing GPX3-mediated antioxidant defense and suppressing vascular remodeling, supporting its potential as a therapeutic strategy for PAH.

Purpose ePWV and BMI are closely related to the prediction of new-onset diabetes. The aim of this study was to evaluate the impact and predictive value of the combination of estimate pulse wave velocity (ePWV) and body mass index (BMI) on new-onset diabetic patients.Methods A secondary analysis of a cohort study conducted by rich health care was performed with a total of 211833 eligible subjects enrolled. Logistic regression analysis was used to identify factors influencing the occurrence of diabetes, and ROC curve analysis was used to evaluate the predictive value of ePWV, BMI, and their combination on new-onset diabetes.Results During a mean follow-up period of 3.12 years, 3000 men (1.41%) and 1174 women (0.55%) were diagnosed with diabetes. Logistic regression analysis showed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and history of diabetes in the family were high-risk factors for new-onset diabetes. Compared with using ePWV or BMI alone, the combined ePWV and BMI had a higher area under the receiver operating characteristic curve of 0.822.Conclusion The elevation of ePWV and BMI levels is an independent risk factor for new-onset diabetes, and the combination of ePWV and BMI can better predict new-onset diabetes compared to using either indicator alone.

Background. Strain analysis of cardiac magnetic resonance (CMR) is critical for the diagnosis and prognosis of heart failure (HF) with preserved ejection fraction (HFpEF). Our study aimed to identify the diagnostic and prognostic value of strain analysis revealed by CMR in HFpEF. Methods. Participants in HFpEF and control were recruited according to the guideline. Baseline information, clinical parameters, blood samples were collected, and echocardiography and CMR examination were performed. Various parameters, including global longitudinal strain, global circumferential strain (GCS) and global radial strain in left ventricle (LV), right ventricle (RV), and left atrium, were measured from CMR. Receiver operator curve (ROC) was established to evaluate the diagnostic and prognostic value of strains in HFpEF. Results. Seven strains, with the exception of RVGCS, were employed to generate ROC curves after t-test. All strains had significant diagnostic value for HFpEF. The area under curve (AUC) of LV strains was greater than 0.7 and the AUC of the combined analysis of LV strains was 0.858 (95% confidence interval (CI): 0.798–0.919, sensitivity: 0.713, specificity: 0.875, ), indicating that they had a higher diagnostic value than individual LV strains. However, individual strains had no predictive value in identifying end-point events in HFpEF, the AUC of coanalysis of LV strains was 0.722 (95% CI: 0.573–0.872, sensitivity: 0.500, specificity: 0.959, ), indicating its prognostic relevance. Conclusion. Individual strain analysis in CMR may be useful for diagnosing HFpEF, the combination of LV strain analysis had the highest diagnostic value. Moreover, the prognostic value of individual strain analysis in predicting HFpEF outcome was not satisfactory while the combined usage of LV strain analysis was prognostically valuable in HFpEF outcome prediction.

We aimed to research the role of right ventricular strain parameters (RVSP) quantified by cardiac magnetic resonance feature tracking (CMR-FT) in the early assessment of right ventricular (RV) function in patients with pulmonary arterial hypertension associated with atrial septal defect (PAH–ASD). From September 2017 to May 2021, we retrospectively enrolled 41 patients with PAH–ASD and 20 healthy controls. All subjects underwent CMR-FT, and right heart catheterization was conducted in patients with PAH–ASD. The relationship between RVSP and RV functional parameters was subjected to correlation analysis, and intragroup correlation coefficient (ICC) and Bland–Altman plots were used to assess the consistency. The subjects were divided into three groups: Group A (controls; n = 20), Group B (PAH–ASD, RVEF ≥ 45%; n = 14), and Group C (PAH–ASD, RVEF < 45%; n = 27). Compared with healthy controls, the RV global longitudinal strain (GLS) in Group B was significantly decreased (− 19.68 ± 2.72% vs. − 25.21 ± 3.6%, P < 0.05). In RVEF-preserved PAH–ASD patients (Group B), compared with patients with GLS ≤ − 20%, patients with GLS > − 20% also had significantly elevated right ventricular end-diastolic pressure (RVEDP) [8 (6.5–8.25) mmHg vs. 4.5 ± 1.64 mmHg, P < 0.05]. RV GLS had a moderate to strong correlation with RVEF, RVESVi, RVEDVi, RVEDP, and NT-proBNP (P < 0.05). ICC and Bland–Altman plots showed good intragroup and intergroup consistency in radial, circumferential and longitudinal strains of RV. In conclusion, it is feasible to quantify RV strain in patients with PAH–ASD by CMR-FT, and GLS is valuable for the early assessment of RV dysfunction in patients with PAH–ASD.

Pulmonary arterial hypertension (PAH) is characterized by cardiac remodelling. Glutaminolysis plays a crucial role in PAH‐induced remodelling. The metabotropic glutamate receptor 5 (mGluR5) may mediate this process. This study investigated whether or not the blockade of mGluR5 may attenuate PAH‐induced pathological cardiac remodelling. Pulmonary arterial hypertension was induced by intraperitoneally injecting male Sprague‐Dawley (SD) rats with 60 mg/kg of monocrotaline (MCT). 3‐((2‐Methyl‐4‐thiazolyl)ethynyl)pyridine (MTEP) (10 mg/kg intraperitoneally) was used as a therapeutic intervention to block mGluR5. Cardiac functions were assessed with right heart catheterization and electrocardiography. Alterations in protein expressions and inflammatory markers were investigated using western blot and enzyme‐linked immunosorbent assay (ELISA), respectively. Increased right ventricular systolic pressure (RSVP), elevated protein expressions of mGluR5, collagen types I and III and cartilage intermediate layer protein 1 (CILP1), enhanced phosphorylation of phosphatidylinositol 3‐kinase (PI3K), AKT and p38 mitogen‐activated protein kinase (P38MAPK), increased angiopoietin 2 (Ang 2) and vascular endothelial growth factor‐α (VEGF) protein expressions and elevated serum levels of interleukin 6 (IL‐6) and tumour necrotic factor α (TNF‐α) were observed in MCT‐induced PAH rats. MTEP improved hemodynamics and right ventricular hypertrophy. MTEP also attenuated MCT‐induced elevations in the protein expressions of mGluR5, collagen types I and III, CILP1, Ang 2 and VEGF and decreased PI3K, AKT and P38MAPK phosphorylations and inflammatory cytokine levels. Metabotropic glutamate receptor 5 blockade using MTEP ameliorates PAH‐induced pathological right cardiac remodelling via inhibiting the signalling cascade involving PI3K/AKT, P38MAPK, Ang 2 and VEGF.

Toll-like receptor 4 (TLR4) are important in inflammation and regulating vascular smooth muscle cells (VSMCs) proliferation, which are related to atherosclerosis and restenosis. We have investigated the mechanisms involved in Lipopolysaccharide (LPS)-induced proliferation of VSMCs. Stimulation of rat aortic VSMCs with LPS significantly increases the proliferation of VSMCs. This effect is regulated by Rac1 (Ras-related C3 botulinum toxin substrate l), which mediates the activation of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathways. Inhibition of Rac1 activity by NSC23766 is associated with inhibition of Akt activity. Treatment with NSC23766 or LY294002 significantly decreases LPS-induced TLR4 protein and mRNA expression. The data show that positive feedback regulation of proliferation in VSMCs is mediated through the TLR4/Rac1/Akt pathway.