Selenium supplementation elevated SELENBP1 to inhibit fibroblast activation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease induced by abnormal activation of pulmonary adventitial fibroblasts (PAFs) in the early stage. The association between selenium deficiency and PAH is not yet fully understood. In this study, we found that the serum selenium content of PAH patients was significantly lower than that of healthy volunteers in two independent cohorts. Moreover, PAH patients with lower selenium levels may present poorer prognosis. Prophylactic selenium supplementation could effectively improve hemodynamics and pulmonary vascular remodeling in monocrotaline-induced pulmonary hypertension rat models. Mechanistically, selenium supplementation restored the level of selenium binding protein 1 (SELENBP1) which could exert an antagonistic effect on PAF activation. The rescue assay further proved that selenium supplementation worked in a SELENBP1-dependent manner. These findings demonstrated that selenium deficiency is an important risk factor in PAH, and the selenium-SELENBP1 axis represents a promising target for PAH prevention.

Association between early central venous pressure measurement and all-cause mortality in critically ill patients with heart failure: A cohort of 11,241 patients.

Background: The timing of central venous pressure (CVP) measurement may play a crucial role in heart failure management, yet no studies have explored this aspect. Methods: Clinical information pertaining to patients in critical condition with a diagnosis of heart failure was retrieved from the MIMIC-IV database. The association between initial measurements of central venous pressure (CVP) and the incidence of mortality from all causes was analyzed using the Cox proportional hazards approach. Subgroup analysis and propensity score matching were conducted for sensitivity analyses. Results: This study included 11,241 participants (median age, 75 years; 44.70 % female). Utilizing restricted cubic spline and Kaplan-Meier survival analyses, it was determined that prognostic outcomes were better when CVP was measured within the initial 5-h window. Multivariate-adjusted 1-year (HR: 0.69; 95 % CI: 0.61-0.77), 90-day (HR: 0.70; 95 % CI: 0.62-0.80), and 30-day (HR: 0.67; 95 % CI: 0.57-0.78) all-cause mortalities were significantly lower in patients with early CVP measurement, which was proved robustly in subgroup analysis. Subsequent to the application of propensity score matching, a cohort of 1536 matched pairs was established, with the observed mortality rates continuing to be significantly lower among participants who underwent early CVP assessment. Conclusions: Early CVP measurement (within 5 h) demonstrated an independent correlation with a decrease in both immediate and extended all-cause mortality rates among patients in critical condition suffering from heart failure.

A Novel Postconditioning Approach Attenuates Myocardial Ischaemia-Reperfusion Injury in Rats.

Background: Ischaemia-reperfusion injury (IRI) is the damage that occurs when blood flow is restored to a tissue or organ after a period of ischaemia. Postconditioning is a therapeutic strategy aimed at reducing the tissue damage caused by IRI. Postconditioning in rodents is a useful tool to investigate the potential mechanisms of postconditioning. Currently, there is no convenient approach for postconditioning rodents. Methods: Rats were subjected to a balloon postconditioning procedure. A balloon was used to control the flow in the vessel. This allowed for easy and precise manipulation of perfusion. Evans blue and triphenyltetrazolium chloride (TTC) double staining were used to determine the infarct size. Apoptosis in the myocardium was visualised and quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was performed to assess the expression of key apoptotic proteins, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X (Bax), and cleaved caspase-3. Results: The balloon control approach to postconditioning provided accurate control of coronary blood flow and simplified the postconditioning manipulation. Infarct size reduction was observed in IRI rats after post-conditioning. There was a decrease in cardiac apoptosis in IRI rats after conditioning, as detected by TUNEL staining. IRI rats showed increased Bcl-2 levels and decreased Bax and cleaved caspase-3 levels in the myocardium. Conclusions: Postconditioning was successfully applied in rats using this novel approach. Postconditioning with this approach reduced infarct size and apoptosis in the area at risk.

Association of sarcopenia with the long-term risk of atrial fibrillation: A prospective cohort study.

The relationship between sarcopenia and the long-term risk of atrial fibrillation (AF) remains unclear. This study recruited a large prospective Caucasian cohort from the UK Biobank. Participants were assessed at baseline with handgrip strength and muscle mass and were categorized into groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia. Kaplan-Meier method and Cox proportional hazards model were used to explore the association between sarcopenia and the incidence of AF. The genetic predisposition of AF was assessed by polygenic risk score. Sensitivity analyses were performed to validate the results. A total of 384,433 participants with a median age of 58 years and 54.3% women were enrolled in this study. There were 24,007 cases of new-onset AF over a median follow-up of 12.56 years. The groups of non-sarcopenia, probable sarcopenia, and confirmed sarcopenia accounted for 22,290 (6.1%), 1665 (9.2%), and 52 (11.9%) cases, respectively. Compared with the non-sarcopenia group, participants with probable sarcopenia or confirmed sarcopenia had an 8% (95% CI, 1.03-1.14) or 61% (95% CI, 1.23-2.12) higher risk of AF incidence. The findings remained robust in multiple sensitivity analyses, such as subgroup analysis and further adjustment of genetic predisposition. Notably, the association between sarcopenia and a high AF risk was more pronounced in younger participants, women, and those with valvular heart disease. In conclusion, sarcopenia was associated with a high long-term risk of AF in Caucasians, supporting sarcopenia as a new independent risk factor of AF.

Biolimus-coated versus paclitaxel-coated balloons for coronary in-stent restenosis (BIO ASCEND ISR): a randomised, non-inferiority trial.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).

Association between red blood cell distribution width and the all-cause mortality of patients with aortic stenosis: A retrospective study.

BACKGROUND: It is essential to assess the risk stratification of patients with aortic stenosis (AS). OBJECTIVE: To clarify the predictive value of red blood cell distribution width (RDW) in AS patients using a large cohort from the MIMIC-IV database. METHODS: Restricted cubic spline, the Kaplan-Meier method, and logistic and Cox regression analyses were used to explore the association between RDW and all-cause mortality in AS patients. Multivariate adjustments, propensity score matching and weighting, and subgroup analysis were conducted to exclude confounding factors. Receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were drawn to evaluate the predictive performance of RDW. RESULTS: 1,148 patients with AS were included. Their death risks gradually increased with the elevation of RDW. Multivariate-adjusted 90-day (OR: 2.12; HR: 1.90; p = 0.001) and 1-year (OR: 2.07; HR: 1.97; p < 0.001) all-cause mortalities were significantly higher in patients with RDW≥14.7 %, which remained robust after propensity score matching and subgroup analysis. For AS patients with high RDW, those < 75 years old had higher death risks than those ≥ 75 years old. The area under the ROC curve of RDW were 0.741 and 0.75 at 90-day and 1-year follow-ups, respectively, exhibiting comparable performance to acute physiology score III and outperforming other critical illness scores in predicting the prognosis of AS patients. DCA curves also illustrated that RDW had a wide range of net benefits. CONCLUSIONS: High RDW was independently associated with increased 90-day and 1-year all-cause mortalities of AS patients, with strong predictive capability of prognosis.

Integrated bioinformatics analysis and experimental animal models identify a robust biomarker and its correlation with the immune microenvironment in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) represents a substantial global risk to human health. This study aims to identify diagnostic biomarkers for PAH and assess their association with the immune microenvironment through the utilization of sophisticated bioinformatics techniques. Methods: Based on two microarray datasets, differentially expressed genes (DEGs) were detected, and hub genes underwent a sequence of machine learning analyses. After pathways associated with PAH were assessed by gene enrichment analysis, the identified genes were validated using external datasets and confirmed in a monocrotaline (MCT)-induced rat model. In addition, three algorithms were employed to estimate the proportions of various immune cell types, and the link between hub genes and immune cells was substantiated. Results: Using SVM, LASSO, and WGCNA, we identified seven hub genes, including (BPIFA1, HBA2, HBB, LOC441081, PI15, S100A9, and WIF1), of which only BPIFA1 remained stable in the external datasets and was validated in an MCT-induced rat model. Furthermore, the results of the functional enrichment analysis established a link between PAH and both metabolism and the immune system. Correlation assessment showed that BPIFA1 expression in the MCP-counter algorithm was negatively associated with various immune cell types, positively correlated with macrophages in the ssGSEA algorithm, and correlated with M1 and M2 macrophages in the CIBERSORT algorithm. Conclusion: BPIFA1 serves as a modulator of PAH, with the potential to impact the immune microenvironment and disease progression, possibly through its regulatory influence on both M1 and M2 macrophages.

A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Association of Cardiovascular Health with the Incidence of Venous Thromboembolism: A Prospective Study of 275,149 Participants from the UK Biobank.

BACKGROUND: The Life's Essential 8 (LE8) score, recently proposed by the American Heart Association, represents a new paradigm for evaluating cardiovascular health (CVH). We aimed to explore the association between CVH, estimated using LE8, and venous thromboembolism (VTE) incidence. METHODS: A total of 275,149 participants were recruited from the UK Biobank and divided into high (LE8 score ≥ 80), moderate (LE8 score < 80 but ≥ 50), and low (LE8 score < 50) CVH groups. Restricted cubic spline analysis, the Kaplan-Meier method, and the Cox proportional hazards model were used to explore the association between CVH and VTE. The genetic predisposition to VTE was assessed with a polygenic risk score. Sensitivity analyses were performed to validate the results. RESULTS: During a median follow-up of 12.56 years, VTE developed in 506 (4.09%), 6,069 (2.78%), and 720 (1.66%) participants with low, moderate, and high CVH levels, respectively. Compared with the low CVH group, participants in the moderate and high CVH groups had a 23% (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.71-0.85) and 41% (HR: 0.59; 95% CI: 0.52-0.66) lower risk of VTE, respectively, after adjusting for demographic characteristics, medical history, socioeconomic status, and genetic predisposition. This association remained robust in multiple sensitivity analyses. Higher CVH levels led to a more pronounced reduction in the risk of VTE in females and could appreciably offset the genetic risk of VTE. CONCLUSION: Higher CVH levels were significantly associated with a lower incidence of VTE, encouraging efforts to increase LE8 scores in individuals.

Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets.

N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein-protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future.

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension.

INTRODUCTION: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable. METHODS: Both active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan-Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards. RESULTS: Of 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46-0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p < 0.0001), 6MWD improvements of + 84 m (p < 0.0001), and a reduction in NT-proBNP of - 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV. CONCLUSION: Initial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01560637.

Comparison of Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Small Vessel Disease (from the Dissolve SVD Randomized Trial).

The Dissolve drug-coated balloons (DCBs) is a new-generation DCB coated with paclitaxel of balloon surface, with midchain triglyceride excipient. Although the use of DCBs is a promising technique, little is known about the the clinical efficacy of the novel Dissolve DCB in coronary small vessel disease. This study was a prospective, randomized, multicenter, noninferiority trial comparing the Dissolve DCB with the Resolute drug-eluting stent (DES) in patients with a reference vessel diameter ≥2.25 and ≤2.75 mm. Patients with a reference vessel diameter ≥2.00 and <2.25 mm were enrolled in the very small vessel registry. The angiographic and clinical follow-up were planned at 9 months and 1 year in all patients, respectively. The primary end point was 9-month in-segment percentage diameter stenosis. A total of 247 patients with small vessel disease from 10 Chinese sites were included (Dissolve DCB, n = 118; Resolute DES, n = 129); 30 patients were treated with the DCB in the very small vessel cohort. The 9-month in-segment percentage diameter stenosis was 31.2 ± 2.0% with Dissolve DCB versus 26.1 ± 2.1% with Resolute DES; the 1-sided 97.5% upper confidence limit of the difference was 10.3% (p for noninferiority = 0.0002). At 12 months, the DCB and DES groups were associated with similar rates of target lesion failure (8.5% vs 6.1%, p = 0.28) and major adverse cardiac and cerebrovascular events (20.9% vs 13.6%, p = 0.12). In conclusion, the Dissolve DCB was noninferior to the Resolute DES for the primary end point of 9-month in-segment percentage diameter stenosis in this multicenter, head-to-head, randomized trial (a safety and efficacy study of Dissolve In Treatment Of Coronary Small Vessel Disease; NCT03376646).

Clinical features and long-term survival in idiopathic pulmonary arterial hypertension with thyroid dysfunction: insights from a national multicentre prospective study.

Background: Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction. Methods: A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2-5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex. Results: In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment. Conclusion: IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.

Novel lncRNA LNC_000113 Drives the Activation of Pulmonary Adventitial Fibroblasts through Modulating PTEN/Akt/FoxO1 Pathway.

The activation of pulmonary adventitial fibroblasts (PAFs) is one of the key components of pulmonary arterial remodelling in pulmonary arterial hypertension (PAH). Emerging evidence indicates that lncRNAs may play fibrotic roles in a range of diseases. In this present study, we identified a novel lncRNA, LNC_000113, in pulmonary adventitial fibroblasts (PAFs) and characterised its role in the Galectin-3-induced activation of PAFs in rats. Galectin-3 led to elevated expression of lncRNA LNC_000113 in PAFs. The expression of this lncRNA was primarily PAF enriched. A progressive increase in lncRNA LNC_000113 expression was observed in rats with monocrotaline (MCT)-induced PAH rats. Knockdown of lncRNA LNC_000113 cancelled the Galectin-3's fibroproliferative effect on PAFs and prevented the transition of fibroblasts to myofibroblasts. The loss-of-function study demonstrated that lncRNA LNC_000113 activated PAFs through the PTEN/Akt/FoxO1 pathway. These results propose lncRNA LNC_000113 drives the activation of PAFs and promotes fibroblast phenotypic alterations.

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with unclear underlying molecular mechanisms and limited therapeutic options. This study aimed to explore the role of core fucosylation and the only glycosyltransferase FUT8 in PAH. We observed increased core fucosylation in a monocrotaline (MCT)-induced PAH rat model and isolated rat pulmonary artery smooth muscle cells (PASMCs) treated with platelet-derived growth factor-BB (PDGF-BB). We found that 2-fluorofucose (2FF), a drug used to inhibit core fucosylation, improved hemodynamics and pulmonary vascular remodeling in MCT-induced PAH rats. In vitro, 2FF effectively restrains the proliferation, migration, and phenotypic switching of PASMCs and promotes apoptosis. Compared with controls, serum FUT8 concentration in PAH patients and MCT-induced rats was significantly elevated. FUT8 expression appeared increased in the lung tissues of PAH rats, and the co-localization of FUT8 with α-SMA was also observed. SiRNA was used to knockdown FUT8 in PASMCs (siFUT8). After effectively silencing FUT8 expression, phenotypic changes induced in PASMCs by PDGF-BB stimulation were alleviated. FUT8 activated the AKT pathway, while the admission of AKT activator SC79 could partially counteract the negative effect of siFUT8 on the proliferation, apoptotic resistance, and phenotypic switching of PASMCs, which may be involved in the core fucosylation of vascular endothelial growth factor receptor (VEGFR). Our research confirmed the critical role of FUT8 and its mediated core fucosylation in pulmonary vascular remodeling in PAH, providing a potential novel therapeutic target for PAH.

Long non-coding RNA PVT1 regulates atherosclerosis progression via the microRNA-106b-5p/ACSL4 axis.

Long non-coding RNAs (lncRNAs) have been associated with atherosclerosis (AS), but the role of lncRNA PVT1 in this disease is still unknown. However, lncRNA PVT1 was found to be significantly upregulated in the serum of AS patients. In vitro experiments using human vascular endothelial cells (HUVECs) showed that oxidized low-density lipoprotein (ox-LDL) treatment enhanced PVT1 expression and impeded HUVEC proliferation, which could be reversed by PVT1 knockdown or miR-106b-5p mimics. Additionally, knockdown of PVT1 and overexpression of miR-106b-5p inhibited the increase of iron content, MDA level, lipid ROS, ACSL4, and PTGS2 in ox-LDL-induced HUVECs, as well as the decrease of GSH and GPX4. We also found that PVT1 knockdown reduced lipid deposition, atherosclerotic plaque number, and size in ApoE-/- mice. These results suggest that PVT1 plays a crucial role in AS progression by regulating the miR-106b-5p/ACSL4 axis in HUVECs, and may therefore be a potential therapeutic target for AS.

A Randomized Comparison of 2 Different Drug-Coated Balloons for In-Stent Restenosis.

BACKGROUND: Although use of drug-coated balloons (DCB) is a promising technique, little is known about the clinical efficacy of the Dissolve DCB in drug-eluting stent (DES) in-stent restenosis (ISR). OBJECTIVES: This study sought to evaluate the efficacy and safety of the Dissolve DCB in patients with DES ISR. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing Dissolve DCB with SeQuent Please DCB in patients with DES ISR. Angiographic and clinical follow-up was planned at 9 months in all patients. The primary endpoint was 9-month in-segment late loss. RESULTS: A total of 260 patients with ISR from 10 Chinese sites were included (Dissolve DCB, n = 128; SeQuent Please DCB, n = 132). Nine-month in-segment late loss was 0.50 ± 0.06 mm with Dissolve DCB vs 0.47 ± 0.07 mm with SeQuent Please DCB; the 1-sided 97.5% upper confidence limit of the difference was 0.18 mm (P for noninferiority = 0.03). Rates of target lesion failure and binary restenosis were numerical higher in the Dissolve DCB cohort compared with the SeQuent Please DCB cohort at 9 months (17.5% vs 10.7%; P = 0.12; 23.4% vs 16.4%; P = 0.19, respectively). At 9 months, major adverse cardiac and cerebrovascular events occurred in 36 patients (28.3%) vs 30 patients (22.9%) in the Dissolve DCB and SeQuent Please DCB groups, respectively. CONCLUSIONS: In this head-to-head randomized trial, the Dissolve DCB was noninferior to the SeQuent Please DCB for 9-month in-segment late loss. However, Dissolve DCB with its numerical increase in target lesion failure and binary restenosis warrants assessment in larger clinical trials (A Safety and Efficacy Study of Dissolve™ in Treatment of Coronary In-Stent Restenosis; NCT03373695).

Characteristics, treatments and survival of pulmonary arterial hypertension associated with congenital heart disease in China: Insights from a national multicenter prospective registry.

BACKGROUND: The purpose of this registry was to provide insights into the characteristics, treatments and survival of patients with PAH-CHD in China. METHODS: Patients diagnosed with PAH-CHD were enrolled in this national multicenter prospective registry. Baseline and follow-up data on clinical characteristics, PAH-targeted treatments and survival were collected. RESULTS: A total of 1060 PAH-CHD patients (mean age 31 years; 67.9% females) were included, with Eisenmenger syndrome (51.5%) being the most common form and atrial septal defects (37.3%) comprising the most frequent underlying defect. Approximately 33.0% of the patients were in World Health Organization functional class III to IV. The overall mean pulmonary arterial pressure and pulmonary vascular resistance were 67.1 (20.1) mm Hg and 1112.4 (705.9) dyn/s/cm5, respectively. PAH-targeted therapy was utilized in 826 patients (77.9%), and 203 patients (19.1%) received combination therapy. The estimated 1-, 3-, 5-, and 10-year survival rates of the overall cohort were 96.9%, 92.9%, 87.6% and 73.0%, respectively. Patients received combination therapy had significantly better survival than those with monotherapy (p = 0.016). NT-proBNP >1400 pg/ml, SvO2 ≤ 65% and Borg dyspnea index ≥ 3 and PAH-targeted therapy were independent predictors of mortality. Hemoglobin > 160g/L was a unique predictor for mortality in Eisenmenger syndrome. CONCLUSIONS: Chinese PAH-CHD patients predominantly exhibit Eisenmenger syndrome and have significantly impaired exercise tolerance and right ventricular function at diagnosis, which are closely associated with long-term survival. PAH-targeted therapy including combination therapy showed a favorable effect on survival in PAH-CHD. The long-term survival of Chinese CHD-PAH patients remains to be improved.

10-year survival of pulmonary arterial hypertension associated with connective tissue disease: insights from a multicentre PAH registry.

OBJECTIVES: To report the 10-year survival rate and prognostic factors of pulmonary arterial hypertension associated with CTD (CTD-PAH) patients, to compare treatment and survival between patients enrolled before and after 2015, and to validate the discrimination of the recommended four-strata model in predicting 10-year survival at follow-up in Chinese CTD-PAH patients. METHODS: This study was derived from a Chinese national multicentre prospective registry study from 2009 to 2019. Medical records were collected at baseline and follow-up, including PAH-targeted therapy and binary therapy (both CTD and PAH-targeted therapy). RESULTS: A total of 266 CTD-PAH patients were enrolled and the 10-year survival rate was 59.9% (median follow-up time: 4.85 years). Underlying CTD (SSc), baseline 6-min walking distance and SaO2 were independent risk factors for 10-year survival. The proportion of patients receiving PAH-targeted combination therapy increased from 10.1% (2009-2014) to 26.5% (2015-2019) and that of binary therapy increased from 14.8% to 35%. The 1-year survival rate increased from 89.8% (2009-2014) to 93.9%, and the 3-year survival rate increased from 80.1% (2009-2014) to 86.5% (both P > 0.05). The four-strata strategy performed well in predicting 10-year survival at follow-up (C-index = 0.742). CONCLUSION: The 10-year survival rate of CTD-PAH patients was reported for the first time. The 10-year prognosis was poor, but there was a tendency for more standardized treatment and better survival in patients enrolled after 2015. The recommended four-strata model at follow-up can effectively predict 10-year survival in CTD-PAH patients.