Atherosclerosis, a primary cause of ischemic diseases, is driven by excessive oxidative stress. Edaravone Dexborneol, a clinically used antioxidant, has demonstrated potent protective effects in cerebral ischemia. However, its role in atherosclerosis remains unexplored. In the present study, atherosclerosis models were constructed using Apoe-/- mice fed a high-fat diet. Edaravone Dexborneol treatment significantly attenuated aortic atherosclerosis progression, evidenced by reduced advanced plaque burden and improved hemodynamic parameters at the aortic root. The treatment also suppressed oxidative stress, leading to decreased low-density lipoprotein (LDL) oxidation and reduced oxidized LDL accumulation in aortic tissues and endothelial cells. Mechanistically, RNA sequencing and Western blot analyses revealed that Edaravone Dexborneol alleviates oxidative damage by activating peroxisome proliferator-activated receptor gamma (PPARγ) and up-regulating paraoxonase 1 (PON1) expression. In human umbilical vein endothelial cells, PON1 knockdown partially abolished the antioxidant effects of Edaravone Dexborneol, while PPARγ inhibition reversed its induction of PON1. Furthermore, the combination of Edaravone Dexborneol with rosuvastatin exhibited synergistic anti-atherogenic effects superior to rosuvastatin alone. In conclusion, Edaravone Dexborneol attenuates atherosclerosis via the PPARγ/PON1 pathway, highlighting its potential as an antioxidant-based therapeutic strategy for atherosclerotic disease.

BACKGROUND:The novel thin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) demonstrated safety and efficacy in a nonrandomized first-in-human study. OBJECTIVES:The objective of this study was to compare the IBS with contemporary metallic cobalt chromium everolimus-eluting stents (CoCr-EES) in patients with coronary artery disease. METHODS:IRONMAN-II was a prospective, multicenter, single-blinded, noninferiority randomized trial across 36 centers in China. Eligible patients had myocardial ischemia and 1 or 2 de novo target lesions. Patients were randomly assigned (1:1) to IBS or CoCr-EES, with allocation masked. Optical coherence tomography (OCT) was performed in the first 25 participant pairs. Clinical follow-up was scheduled at 1, 6, and 12 months, and annually to 5 years, with angiographic and OCT follow-up at 2 years. The primary endpoint was 2-year angiographic in-segment late lumen loss (LLL). Powered secondary endpoints included target vessel quantitative flow ratio (QFR) and OCT-derived cross-sectional mean flow area. Other secondary endpoints included target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target vessel revascularization), the patient-oriented composite endpoint (all-cause death, MI, or any revascularization), their individual components, and device thrombosis. RESULTS:Between March 10 and December 13, 2022, 518 patients were randomized to IBS (n = 259) or CoCr-EES (n = 259). At 2 years, lesion-level in-segment LLL was 0.28 (0.52) mm with IBS and 0.23 (0.43) mm with CoCr-EES (difference: 0.08 mm; 95% CI: -0.02 to 0.18; Pnoninferiority = 0.03). Mean QFR was 0.90 (0.13) with IBS and 0.92 (0.09) with CoCr-EES (difference: -0.02; 95% CI: -0.04 to 0; Pnoninferiority = 0.05). Mean OCT flow area was 6.92 (3.48) mm2 with IBS and 6.64 (2.44) mm2 with CoCr-EES (difference: 0.27; 95% CI: -0.09 to 0.63; Pnoninferiority < 0.0001). Two-year target lesion failure occurred in 7.4% of IBS patients and 5.4% of CoCr-EES patients (HR: 1.37; 95% CI: 0.69-2.73; P = 0.37). No significant between-group differences in the rates of patient-oriented composite endpoint, death, or MI were present between the 2 groups. No scaffold thromboses occurred in the IBS group, whereas 1 stent thrombosis occurred with CoCr-EES. Binary restenosis and revascularization rates were higher with IBS, however, most such events were non-ischemia-driven. CONCLUSIONS:In IRONMAN-II, the sirolimus-eluting IBS was noninferior to CoCr-EES for 2-year in-segment LLL, QFR, and OCT-derived flow area. Clinical event rates were also comparable between groups although non-ischemia-driven revascularization rates were higher after IBS. Longer-term follow-up is necessary to demonstrate whether late benefits are realized after complete IBS resorption. (A Clinical Investigation to Evaluate the Safety and Efficacy of IBS in Patients With Coronary Artery Disease; NCT05206084).

Previous preclinical studies suggested that Shexiang Tongxin Dropping Pill (STDP) would be effective for coronary slow flow phenomenon (CSFP), but its clinical efficacy and safety remain uncertain. A multicenter, randomized, controlled phase IV trial was implemented to enroll 200 participants diagnosed with angina and CSFP between July 2016 and August 2020 to examine the drug's effectiveness and safety. The analysis revealed that corrected TIMI frame count (CTFC) values in left anterior descending (LAD) and left circumflex (LCX) arteries in STDP group could be decreased, respectively (both p < 0.01), whereas no significant changes were seen with placebo; between group differences were significant for both LAD (p = 0.008) and LCX (p = 0.044). Furthermore, STDP was well tolerated. Taken together, the results demonstrated STDP could significantly improve coronary blood flow and maintain an excellent safety profile, making it a favorable option in clinic for angina patients with CSFP. Trial registration: The trial was registered in Chinese Clinical Trial Registry (ID: ChiCTR-IPR-16008950).

OBJECTIVE:To investigate the mechanism by which agmatine alleviates sepsis-induced intestinal injury through the inhibition of intestinal pyroptosis. METHODS:1) Bioinformatic analysis: Dataset GSE13904 was selected from the gene expression omnibus (GEO) database, gene ontology (GO), Kyoto encyclopedia of genes and genomes database (KEGG), and protein-protein interaction (PPI) analyses were performed to analyze transcriptomic changes in the blood of sepsis patients. 2) Animal experiments: Ten C57BL/6J mice were randomly divided into a sham group (laparotomy only without ligation) and a sepsis-induced intestinal injury model group [cecal ligation and puncture (CLP)], with 5 mice in each group. Mice were euthanized 48 hours after successful modeling, and ileal tissues were harvested. The expression of immunoglobulin superfamily containing leucine rich repeat (ISLR) in the intestinal tissues of mice was detected by quantitative polymerase chain reaction (qPCR) and Western blotting. 3) Cell experiments: ICE-6 cells were divided into the following groups: control group (cultured in complete medium), lipopolysaccharide (LPS) group (cultured in complete medium containing 10 mg/L lipopolysaccharide, LPS), LPS+agmatine group (treated with 120 μmol/L agmatine on the basis of the LPS group), and an LPS+agmatine+siRNA-ISLR group [transfected with small interfering RNA (siRNA)-ISLR on the basis of the LPS + agmatine group]. Furthermore, cells transfected with siRNA negative control (siRNA-NC) were used to verify the silencing effect of siRNA-ISLR on the ISLR gene. ICE-6 cells were divided into a control group, an LPS group, an LPS+agmatine group, and an LPS+agmatine+Aconine group [treated with 0.25 mmol/L Aconine, a nuclear factor-κB (NF-κB) signaling activator, on the basis of the LPS + agmatine group]. The expression levels of ISLR, NOD-like receptor protein 3 (NLRP3), interleukin-1β (IL-1β), and caspase-1 in cells from each group were detected by qPCR and Western blotting. The levels of IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the cell supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:1) Bioinformatic analysis: GO, KEGG, and PPI analyses of dataset GSE13904 revealed abnormal expression of multiple molecules in sepsis patients, among which ISLR expression was significantly decreased. 2) Animal experiments: The expression levels of ISLR in the intestinal tissue of mice in the sepsis-induced intestinal injury model group were significantly lower than those in the sham group [ISLR mRNA (2-ΔΔCt): 0.52±0.12 vs. 1.02±0.21; ISLR/GAPDH: 0.55±0.01 vs. 1.00±0.01, both P < 0.05], which was consistent with the trend observed in the bioinformatic analysis; therefore, ISLR was selected as the target molecule for functional and mechanistic investigation. 3) Cell experiments: Compared with the control and siRNA-NC groups, ISLR expression was downregulated in the siRNA-ISLR group, confirming successful specific knockdown of the ISLR gene. Compared with the control group, ISLR expression was significantly downregulated in the LPS group, while the expression of NLRP3, IL-1β, and caspase-1 was significantly upregulated, and the levels of IL-6, IL-1β, and TNF-α in the supernatant were significantly increased (all P < 0.05), indicating successful establishment of the LPS-induced injury model. Compared with the LPS group, ISLR expression was significantly upregulated in the LPS+agmatine group [ISLR mRNA (2-ΔΔCt): 0.98±0.17 vs. 0.48±0.11, ISLR/GAPDH: 0.95±0.08 vs. 0.71±0.05], while the expression of NLRP3, IL-1β, and caspase-1 was significantly downregulated, and the levels of IL-6, IL-1β, and TNF-α in the supernatant were significantly decreased (all P < 0.05). Compared with the LPS+agmatine group, ISLR expression was significantly downregulated in both the LPS+agmatine+siRNA-ISLR group [ISLR mRNA (2-ΔΔCt): 0.62±0.20 vs. 0.98±0.17, ISLR/GAPDH: 0.68±0.03 vs. 0.95±0.08] and the LPS+agmatine+Aconine group [ISLR mRNA (2-ΔΔCt): 0.28±0.05 vs. 0.97±0.31, ISLR/GAPDH: 0.61±0.03 vs. 0.93±0.03], while the expression of NLRP3, IL-1β, and caspase-1 was significantly upregulated, and the levels of IL-6, IL-1β, and TNF-α in the supernatant were significantly increased (all P < 0.05), suggesting that the effects of agmatine were reversed by either siRNA-ISLR or the NF-κB signaling activator. CONCLUSIONS:Agmatine may alleviate sepsis-induced intestinal cell injury by inhibiting intestinal cell pyroptosis, potentially through regulating NF-κB signaling via ISLR.

Cardiac organoids (COs) are platforms for disease modeling and regenerative medicine, yet inadequate vascularization still limits their function and longevity. This review examines how biomaterial properties-porosity, elasticity, surface chemistry, and bioactivity-regulate endothelial cell behavior and vascular network formation, thereby shaping progress in organoid vascularization. We survey natural, synthetic, and composite systems (e.g., collagen, fibrin, polyethylene glycol [PEG] hydrogels, and poly(ε-caprolactone) [PCL] scaffolds) used to promote vascularization. We also summarize fabrication strategies to improve perfusion, including micro/nanopatterning, scaffold design, and delivery of pro-angiogenic factors, and we outline technical routes for spatially patterned vasculature such as three-dimensional (3D) bioprinting and microfluidics. Ongoing challenges include degradation mismatch and incomplete integration. Future work should emphasize stimuli-responsive and bioactive materials, as well as standardized, scalable scaffold platforms, to strengthen reproducibility and translational efficiency. These directions will help optimize the vascular microenvironment of organoids, enhance functional maturation, and broaden applications in disease modeling, drug evaluation, and regenerative repair.

BACKGROUND:Atrial fibrillation (AF) is a common cardiac arrhythmia that is characterized by atrial electrical remodeling. The P2X7 receptor (P2X7R), an ATP-gated ion channel, has been implicated in cardiovascular pathologies; however, its role in atrial electrical remodeling remains unclear. This study investigated whether inhibition of P2X7R could mitigate isoproterenol (ISO)-induced atrial electrical remodeling in rats and explored the underlying mechanisms. METHODS:Two gene expression profiles related to AF (GSE79768 and GSE10598) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. Mendelian randomization (MR) investigated the causal relationship between P2X7R expression and AF. Enrichment analysis was also conducted. An animal model was established via intraperitoneal injection of ISO for 2 weeks. The rats were divided into three groups: control (CTL), ISO, and ISO + Brilliant Blue G (BBG). Cardiac electrophysiological parameters were assessed using programmed electrical stimulation. Myocardial fibrosis and hypertrophy were evaluated using Sirius Red and Wheat Germ Agglutinin staining, respectively. P2X7R abundance was assessed using immunofluorescence, and relevant proteins were detected by Western blotting. RESULTS:GEO2R and MR analyses indicated a correlation between P2X7R expression and AF. Rats in the ISO group exhibited increased P2X7R levels, abnormal cardiac electrophysiology, altered ion channel protein expression, myocardial hypertrophy, and fibrosis. Enrichment analysis indicated that oxidative stress responses might be involved, and Western blotting showed significantly elevated levels of NOX, CaMKII, and associated proteins. BBG (P2X7R inhibitor) treatment mitigated these effects. CONCLUSIONS:P2X7R was associated with AF, and inhibition of P2X7R curbed electrical and structural remodeling in ISO-induced AF, potentially via the NOX/CaMKII pathway.

An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.

Right ventricular (RV) failure and malignant arrhythmia are determinants of the prognosis of pulmonary arterial hypertension (PAH). Transient receptor potential vanilloid type 2 (TRPV2) is involved in the development of heart failure, whereas its role in PAH deserves further exploration. This study aimed to explore whether TRPV2 contributes to SU5416/hypoxia (SuHx)-induced ventricular remodeling and arrhythmias, and its possible mechanisms. Haemodynamic measurements, electrocardiogram, ventricular electrophysiological protocol, Wheat germ agglutinin (WGA) staining, hematoxylin and eosin (H&E) staining, Masson trichrome staining, immunofluorescence, real-time quantitative PCR (qPCR) and western blot were performed. Meanwhile, small interfering RNA (siRNA) for targeting TRPV2 or β-catenin was used to further verify the potential mechanism of TRPV2. In the SuHx-induced PH rat model, TRPV2 inhibitor tranilast significantly reduced mean pulmonary artery pressure (mPAP) and pulmonary vascular remodeling; relieved ventricular remodeling, myocardial fibrosis, and hypertrophy; shortened the prolongation of QT, QTc, Tpeak-Tend interval, effective refractory period (ERP) and action potential duration (APD); reduced susceptibility to ventricular fibrillation (VF). TRPV2 inhibition restored calcium homeostasis, attenuated ion channel and connexin remodeling (Kv4.3, Kv4.2, Kv1.5, Kir3.1, Kir3.4, KCNK3, Cx40 and Cx43), prevented autonomic dysfunction, reduced ventricular fibrosis, and inflammatory cytokines; In the hypoxia-induced H9c2 model, siRNA for targeting TRPV2 or β-catenin improved ion channel remodeling. TRPV2 inhibition suppressed the IGF1-mediated Wnt/β-catenin signaling pathway. Our data support TRPV2 inhibition prevents PH-induced right ventricular remodeling and VF susceptibility; TRPV2 can serve as a therapeutic target for PH-induced VF.

Abdominal aortic aneurysm (AAA) is a common degenerative disease of the abdominal aorta, which can result in extremely high mortality owing to the rupture of the abdominal aorta. The activation of IL-7R has been shown to modulate the inflammatory responses, which play an important role in the progression of AAAs. However, the mechanism of IL-7/IL-7R axis in AAAs is still unclear. This study aims to investigate the effects of IL-7R on AAAs and the underlying mechanisms involved. Wild-type C57BL/6 and IL-7R knockout mice were used as experimental subjects. ELISA analysis, histological staining, western blotting and qPCR were performed to explore effects of IL-7R deficiency in the formation and development of elastase-induced AAAs. Transwell, CCK8, and immunofluorescence assays detected the migration and polarization of RAW264.7 macrophages in vitro. We demonstrated that IL-7R was elevated in mice with AAAs. Blocking IL-7R can inhibit the formation of AAAs and reduce aortic dilatation, elastic layer degradation, and inflammatory cell infiltration. Knockout of IL-7R suppressed the migration, infiltration and M1 polarization of macrophages. Moreover, inhibition of the NF-κB signaling pathway by BAY 11-7082 attenuated the macrophage-mediated inflammatory responses caused by IL-7R overexpression. In short, this study showed that IL-7R promotes the infiltration and migration of macrophages by regulating M1 macrophage polarization, possibly in part via activation of the NF-κB pathway, which may be associated with the development of AAAs.

The global burden of atrial fibrillation (AF) and atrial flutter (AFL), major contributors to stroke and heart failure, has substantially increased since 1990 due to aging populations and improved chronic disease survival. This study analyzed global, regional, and national trends in AF/AFL prevalence, incidence, mortality, and disability-adjusted life years (DALYs) among those aged ≥ 65 years (1990–2021), stratified by age, sex, and socioeconomic development index (SDI). The Global Burden of Disease (GBD) 2021 dataset provided data on AF/AFL. The analysis included age standardization, average annual percentage change (AAPC) calculations, frontier analysis, and decomposition analysis to quantify the contributions of demographic and epidemiological changes. Global AF/AFL cases in those aged ≥ 65 years increased significantly (1990–2021), with a 203.91

Doxorubicin (DOX) is an anthracycline with potent antitumor properties and rare yet serious cardiotoxic side effects that limit its clinical application. The sigma-1 receptor is a stress-triggered chaperone often dysregulated in diseases and has known cardioprotective effects. Although its anti-oxidative stress and anti-apoptotic effects have been demonstrated, its effectiveness in DOX-induced cardiotoxicity has never been explored. This study investigated the potential role of the activated sigma-1 receptor in a DOX-induced murine cardiotoxicity model to elucidate the receptor's mechanism of action. We established the model in C57BL/6 mice by daily intraperitoneal injections of fluvoxamine (Flv) for 4 consecutive weeks to activate the receptor and by weekly intraperitoneal injections of DOX at 5 mg/kg for 3 weeks. We performed in vitro experiments using cardiomyocytes of neonatal Sprague–Dawley rats to verify the protective effect of the sigma-1 receptor. We found that sigma-1 expression in the heart decreased in the DOX-treated mice, and activating the receptor with Flv improved cardiac function. Moreover, Flv pretreatment inhibited cardiomyocyte apoptosis and endoplasmic reticulum stress and increased the expression of the Bcl2 apoptosis regulator (Bcl2), effectively alleviating the pathophysiological manifestations in mice. In addition, activating the receptor exerted cardioprotective effects by modulating endoplasmic reticulum stress through the PRKR-like endoplasmic reticulum kinase (PERK) signaling pathway. It also reduced mitochondrial and endoplasmic reticulum contact and alleviated mitochondrial calcium overload through the IP3R-VDAC1-MCU signaling pathway. In conclusion, our study emphasizes the therapeutic potential of activating sigma-1 receptors against DOX-induced cardiotoxicity, suggesting sigma-1 receptors as potential therapeutic targets for this disease.

Left atrial thrombus (LAT) poses a significant risk for stroke and other thromboembolic complication in patients with atrial fibrillation (AF). This study aimed to evaluate the incidence and predictors of LAT in patients with paroxysmal AF, utilizing machine learning techniques based on data from the Chinese Atrial Fibrillation study. A large-scale multi-center retrospective study was conducted involving patients diagnosed with non-valvular paroxysmal AF. LAT incidence was assessed, and potential risk factors were analyzed. Machine learning algorithms, including decision tree, random forest, AdaBoost, k-Nearest Neighbor, and logistic regression, were employed to develop a predictive model for LAT. Of the 49,515 patients with paroxysmal AF, 1,058 patients (2.1

β-adrenergic receptors (βARs) play significant roles in regulating Ca2+ signaling in cardiac myocytes, thus holding a key function in modulating heart performance. βARs regulate the influx of extracellular Ca2+ and the release and uptake of Ca2+ from the sarcoplasmic reticulum (SR) by activating key components such as L-type calcium channels (LTCCs), ryanodine receptors (RyRs) and phospholamban (PLN), mediated by the phosphorylation actions by protein kinase A (PKA). In cardiac myocytes, the presence of β2AR provides a protective mechanism against potential overstimulation of β1AR, which may aid in the restoration of cardiac dysfunctions. Understanding the Ca2+ regulatory signaling pathways of βARs in cardiac myocytes and the differences among various βAR subtypes are crucial in cardiology and hold great potential for developing treatments for heart diseases.

The incidence of aortic dissection (AD) is steadily increasing, driven by the rising prevalence of chronic conditions such as hypertension and the global aging of the population. Oxidative stress emerges as a pivotal pathophysiological mechanism contributing to the progression of AD. Oxidative stress triggers apoptosis in vascular smooth muscle cells, reshapes the extracellular matrix (ECM), and governs ECM degradation and remodeling, subsequently impacting aortic compliance. Furthermore, oxidative stress not only facilitates the infiltration of macrophages and mononuclear lymphocytes but also disrupts the integral structure and functionality of endothelial cells, thereby inducing endothelial cell dysfunction and furthering the degeneration of the middle layer of the aortic wall. Investigating antioxidants holds promise as a therapeutic avenue for addressing AD.

Background: The recent randomized controlled trials studying intracranial atherosclerotic stenosis (ICAS) have used digital subtraction angiography (DSA) to quantify stenosis and enroll patients. However, some disadvantages of DSA such as invasive features, contrast agent overuse, and X-ray radiation overexposure, were not considered in these studies. This study aimed to explore whether computed tomography angiography (CTA) with semi -automatic analysis could be an alternative method to DSA in quantifying the absolute stenotic degree in clinical trials. Methods: Patients with 50-99% ICAS were consecutively screened, prospectively enrolled, and underwent CTA and DSA between March 2021 and December 2021 at 6 centers. This study was registered at www. chictr.org.cn (ChiCTR2100052925). The absolute stenotic degree of ICAS on CTA with semi -automatic analysis was calculated by several protocols using minimal/maximum/mean diameters of stenosis and reference site from a semi -automatic analysis software. Intraclass correlation coefficient (ICC) was used to evaluate the reliabilities of quantifying stenotic degree on CTA. The optimal protocol for quantifying ICAS on CTA was explored. The agreements of quantifying ICAS in calcified or non -calcified lesions and 50-69% or 70-99% stenosis on CTA and DSA were assessed. Results: A total of 191 participants (58.8 +/- 10.7 years; 148 men) with 202 lesions were enrolled. The optimal protocol for quantifying ICAS on CTA was calculated as (1 - the minimal diameter of stenosis/the mean diameter of reference) x 100% for its highest agreement with DSA [ICC, 0.955, 95% confidence interval (CI): 0.944-0.966, P<0.001]. Among the 202 lesions, 80.2% (162/202) exhibited severe stenosis on DSA. The accuracy of CTA in detecting severe ICAS was excellent (sensitivity =95.1%, positive predictive value =98.1%). The agreements between DSA and CTA in non -calcified lesions (ICC, 0.960 vs. 0.849) and severe stenosis (ICC, 0.918 vs. 0.841) were higher than those in calcified lesions and moderate stenosis. Conclusions: CTA with semi -automatic analysis demonstrated an excellent agreement with DSA in quantifying ICAS, making it promising to replace DSA for the measurement of absolute stenotic degree in clinical trials.

BACKGROUND It is unclear whether advances in management of acute coronary syndrome (ACS) and introduction of novel oral anticoagulants have changed outcomes in patients with ACS with concomitant atrial fi brillation (AF). OBJECTIVE This study aimed to examine the incidence of AF in patients admitted for ACS and to evaluate its association with adverse outcomes, given the recent advances in management of both diseases. METHODS Natural language processing search algorithms identified fi ed AF in patients admitted with ACS across 13 Northwell Health Hospitals from 2015 to 2021. Hierarchical generalized linear mixed modeling was used to assess the association between AF and in-hospital mortality, bleeding, and stroke outcomes; marginal Cox regression modeling was used to assess the association between AF and postdischarge mortality. RESULTS Of 12,315 patients admitted for ACS, 3018 (24.5%) had AF with 1609 (53.3%) newly diagnosed. AF patients more commonly received anticoagulation with an oral anticoagulant (80.4% vs 12.3%) or heparin (61.9% vs 56.9%), had lengthier intensive care unit stay (72 vs 49 hours), and underwent fewer percutaneous coronary interventions (31.9% vs 53.1%). In-hospital bleeding, stroke, and mortality were higher in the AF group (15.3% vs 5.0%, 7.4% vs 2.4%, and 6.9% vs 2.1%, respectively). AF was an independent risk factor for all in-hospital outcomes (odds ratios of 2.5, 2.7, and 2.0 for bleeding, stroke, and mortality, respectively) as well as for postdischarge mortality (hazard ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSION AF is present in 25% of ACS patients and increases risk of in-hospital and postdischarge adverse outcomes. Additional data are required to direct optimal management.

Background: We previously described the mortality associated with cardiac injury in patients with coronavirus disease 2019 (COVID-19). The activation of immune and thrombotic biomarkers at admission, and their ability to predict cardiac injury and mortality patterns in COVID-19, remains unclear. Methods: This retrospective cohort study included 170 patients with COVID-19 with cardiac injury at the time of admission to Tongji Hospital in Wuhan between January 29, 2020, and March 8, 2020. The temporal evolution of inflammatory cytokines, coagulation markers, clinical treatment, and mortality were analyzed. Continuous variables are expressed as median (interquartile range). The Mann-Whitney test was used for two-group comparisons, whereas the Kruskal-Wallis test was used for comparisons among three groups. Categorical variables are expressed as proportions and percentages, and Fisher’s exact test was used to compare differences. A multivariate regression model was used to predict in-hospital death. A simple linear regression analysis was applied to examine the correlation between baseline biomarkers and peak cTnI levels. Results: Of the 170 patients, 60 (35.3%) died early (<21 d), and 61 (35.9%) died after a prolonged stay. The admission laboratory findings correlating with early death were elevated interleukin 6 (IL-6) (P < 0.0001), tumor necrosis factor-α (P = 0.0025), and C-reactive protein (P < 0.0001). We observed the trajectory of biomarker changes in patients after admission hospitalization, and determined that early mortality was associated with a rapidly increasing D-dimer level, and gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models indicated that the risk of death was associated with immune and thrombotic pathway activation. Elevated admission cTnI levels were associated with elevated IL-6 (P = 0.03) and D-dimer (P = 0.0021) levels. Conclusion: In patients with COVID-19 with cardiac injury, IL-6 and D-dimer levels at admission predicted subsequently elevated cTnI levels and early death, thus highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury.

BACKGROUND:The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES:The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS:The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS:Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS:Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.