HE4 Serum Levels are Associated with Poor Prognosis in Patients with Acute Heart Failure Combined with Chronic Kidney Disease.

Purpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD. Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People's Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death. Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65-79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300-3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003-1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels>276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤276.15 pmol/L (Log rank test: χ2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626-3.906, P < 0.001). Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD.

Factors associated with the delay in informed consent procedures of patients with ST-segment elevation myocardial infarction and its influence on door-to-balloon time: a nationwide retrospective cohort study.

Background and Objectives: ST-segment elevation myocardial infarction (STEMI) is the deadliest and most time-sensitive acute cardiac event. However, failure to achieve timely informed consent is an important contributor to in-hospital delay in STEMI care in China. We investigated the factors associated with informed consent delay in patients with STEMI undergoing percutaneous coronary intervention (PCI) and the association between the delay and door-to-balloon time. Methods: We conducted a nationally representative retrospective cohort study using patient data reported by hospital-based chest pain centers from 1 January 2016 to 31 December 2020. We applied generalized linear mixed models and negative binomial regression to estimate factors independently predicting informed consent delay time. Logistic regressions were fitted to investigate the association of the informed consent delay time and door-to-balloon time, adjusting for patient characteristics. Results: In total, 257, 510 patients were enrolled in the analysis. Mean informed consent delay time was 22.4 min (SD = 24.0), accounting for 39.3% in door-to-balloon time. Older age (≥65 years) was significantly correlated with informed consent delay time (RR: 1.034, P = 0.001). Compared with ethnic Han patients, the minority (RR: 1.146, P < 0.001) had more likelihood to extend consent giving; compared with patients who were single, longer informed consent time was found in married patients (RR: 1.054, P = 0.006). Patients with intermittent chest pain (RR: 1.034, P = 0.011), and chest pain relief (RR: 1.085, P = 0.005) were more likely to delay informed consent. As for transfer modes, EMS (RR: 1.063, P < 0.001), transfer-in (RR: 1.820, P < 0.001), and in-hospital onset (RR: 1.099, P = 0.002) all had positive correlations with informed consent delay time compared to walk-in. Informed consent delay was significantly associated with prolonged door-to-balloon time (OR: 1.002, P < 0.001). Conclusion: Informed consent delay is significantly associated with the door-to-balloon time which plays a crucial role in achieving better outcomes for patients with STEMI. It is essential to shorten the delay time by identifying and intervening modifiable factors that are associated with shortening the informed consent procedure in China and other countries.

Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.

Autophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62-Keap1-Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co-IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62-Keap1-Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

AIMS: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. METHODS AND RESULTS: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%). CONCLUSIONS: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.

Platelet-derived growth factor subunit-B mediating the effect of dickkopf-1 on acute myocardial infarction risk: a two-step Mendelian randomization study.

Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.

Investigating the causal effect of Dickkopf-1 on coronary artery disease and ischemic stroke: a Mendelian randomization study.

Epidemiological investigations have indicated a correlation between elevated plasma levels of Dickkopf-related protein 1 (DKK1) and the presence of atherosclerosis. However, the exact causal relationship of DKK1 with the development of coronary artery disease (CAD) and ischemic stroke (IS) remains unclear. To address this gap, our study aimed to explore their causal association using a two-sample Mendelian randomization (MR) approach. We obtained summary statistics from genome-wide association studies (GWAS) meta-analyses conducted by Folkersen et al. and Nikpay et al., which included data from 21,758 individuals for DKK1 and 42,096 cases of CAD. Additionally, we obtained data from the FinnGen biobank analysis round 5, which included 10,551 cases of IS. Eight MR methods were employed to estimate causal effects and detect directional pleiotropy. Our findings demonstrated that genetic liability to DKK1 was associated with increased risks of CAD (odds ratio [OR]: 1.087; 95% confidence interval [CI]: 1.024-1.154; P = 0.006) and IS (OR: 1.096; 95% CI: 1.004-1.195; P = 0.039). These results establish a causal link between genetic liability to DKK1 and elevated risks of CAD and IS. Consequently, DKK1 may represent a promising therapeutic target for the prevention and treatment of CAD and IS.

Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia.

Background: Myocardial infarction (MI) is a type of severe coronary artery disease (CAD) that can lead to heart failure and sudden cardiac death. The prevalence of heart failure globally is estimated at 1%-2%, of which ∼60% of cases are the consequence of MI as the primary cause. At present, several disease-causing genes have been identified that may be responsible for MI, such as autophagy-related 16-like 1 (ATG16L1) and RecQ-like helicase 5 (RECQL5). Methods: In this study, we enrolled a Chinese family with MI, CAD, and stroke hemiplegia. Whole-exome sequencing was applied to analyze the genetic lesion of the proband. Sanger sequencing was used to validate the candidate mutation in five family members and 200 local control cohorts. Results: After data filtering, we detected a novel mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 in the proband. Sanger sequencing further validated that the novel mutation was existent in the affected individuals, including the proband's younger sister and her mother, and absent in the other healthy family members and 200 local control cohorts. Furthermore, bioinformatics analysis confirmed that the novel mutation, located in a highly evolutionarily conserved site, was predicted to be deleterious and may change the hydrophobic surface area and aliphatic index of RECQL5. Conclusion: Here, we report the second mutation (NM_004259: c.1247T>C/p.I416T) of RECQL5 underlying MI and CAD by whole-exome sequencing. Our study expanded the spectrum of RECQL5 mutations and contributed to genetic diagnosis and counseling of MI and CAD.

m6A regulator-mediated RNA methylation modification patterns are involved in the regulation of the immune microenvironment in ischaemic cardiomyopathy.

The role of RNA N6-methyladenosine (m6A) modification in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains largely unclear. This study first identified differential m6A regulators between ICM and healthy samples, and then systematically evaluated the effects of m6A modification on the characteristics of the immune microenvironment in ICM, including the infiltration of immune cells, the human leukocyte antigen (HLA) gene, and HALLMARKS pathways. A total of seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were identified using a random forest classifier. A diagnostic nomogram based on these seven key m6A regulators could effectively distinguish patients with ICM from healthy subjects. We further identified two distinct m6A modification patterns (m6A cluster-A and m6A cluster-B) that are mediated by these seven regulators. Meanwhile, we also noted that one m6A regulator, WTAP, was gradually upregulated, while the others were gradually downregulated in the m6A cluster-A vs. m6A cluster-B vs. healthy subjects. In addition, we observed that the degree of infiltration of the activated dendritic cells, macrophages, natural killer (NK) T cells, and type-17 T helper (Th17) cells gradually increased in m6A cluster-A vs. m6A cluster-B vs. healthy subjects. Furthermore, m6A regulators, including FTO, YTHDC1, YTHDF3, FMR1, ZC3H13, and RBM15 were significantly negatively correlated with the above-mentioned immune cells. Additionally, several differential HLA genes and HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. These results suggest that m6A modification plays a key role in the complexity and diversity of the immune microenvironment in ICM, and seven key m6A regulators, including WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15, and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop immunotherapy strategies with a higher level of accuracy for patients with a significant immune response.

Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram.

The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including MNS1, FRZB, OGN, and LUM, and four downregulated DEGs, SERP1NA3, RNASE2, FCN3 and SLCO4A1, were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.

Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation.

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.

Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome: The H-REPLACE Randomized Equivalence and Noninferiority Trial.

Importance: Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective: To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants: This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions: Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures: The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results: Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. Conclusions and Relevance: In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration: ClinicalTrials.gov Identifier: NCT03363035.

Clinical performance and quality measures for heart failure management in China: the China-Heart Failure registry study.

AIMS: Heart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China. METHODS AND RESULTS: Following the results of China-HF stage I (2012-2015), the second stage of the China-HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China-HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US-based Get with The Guidelines-Heart Failure (GWTG-HF) registries. In total, 34 938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China-HF stage II was higher than that in the China-HF stage I, but generally lower than GWTG-HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin-angiotensin-system inhibitors, and 82.2% beta-blockers. Implantable cardioverter-defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG-HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization. CONCLUSIONS: Despite significant improvements in the use of guideline-recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

Effects of USF1 SNPs and SNP-Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population.

Background: Upstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China. Methods: Six USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD. Results: The genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C-rs2774276G-rs2516839A and rs3737787C-rs2774276G-rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C-rs2774276G-rs2516839A and rs3737787T-rs2774276C-rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05-0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (p I < 0.001). The expression levels of the USF1 mRNA, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1ß, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1ß, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01). Conclusion: Sex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1ß, TNF-α, and IL-6.

Statistical Analysis of IABP-Surgery Data with the Co-use of Anticoagulants, Pulse of Dorsalis Pedis Artery, D-Dimer Data, and Coagulation Function.

Data analysis was performed on IABP (intra-aortic balloon pump) patients for the use of anticoagulants, pulse of dorsalis pedis artery, D-dimer data, and coagulation function. According to the differential diagnosis of 52 patients admitted to hospital, data on the use of anticoagulants, dorsalis pedis artery pulsation, D-dimer data, and coagulation function were collected. These data were analyzed by using a nonparametric test, linear regression analysis, adjustment effect analysis, and chi-square test. Some findings of the analysis included: (1) There were differences in the dorsalis pedis artery pulsation of samples from different sexes, all of which were significant. (2) Coagulation function has a significant positive relationship with D-dimer. (3) When the D-dimer affects the prognosis, the regulatory variable (dorsalis pedis artery pulse) is at different levels, and the influence amplitude has significant differences. (4) Samples taken with different anticoagulants all showed significant differences in the dorsalis pedis artery pulsation.

Association Between Circulating Cell-Free DNA Level at Admission and the Risk of Heart Failure Incidence in Acute Myocardial Infarction Patients.

Plasma cell-free DNA (cfDNA) was elevated in patients with acute myocardial infarction (AMI) or heart failure (HF). However, whether cfDNA could serve as a predictor for risk of HF after AMI remains unknown. In this study, we conducted a pilot prospective cohort study in which 98 AMI patients were enrolled from a single center to assess the association between cfDNA levels at admission and risk of HF in an AMI population. Patients with cfDNA above the median level (14.39 ng/mL) showed higher low-density lipoprotein cholesterol, cardiac troponin I (cTnI), and soluble suppression of tumorigenicity 2 (sST2) levels compared with patients below the median. cfDNA was positively correlated with cTnI (r = 0.377, p < 0.001) and sST2 (r = 0.443, p < 0.001). Within a median follow-up of about 345 days, 46 patients (52.6%) developed HF. Multivariate Cox analysis showed that a higher cfDNA (above the cutoff value: 9.227 ng/mL) was an effective risk predictor (C-index = 0.74, 95% confidence interval [CI]: 0.733-0.748) for HF incidence after AMI (adjusted hazard ratio [HR]: 2.805; 95% CI: 1.087-7.242; p = 0.033). Moreover, a linear association was observed between cfDNA and risk of HF incidence adjusted for by age, gender, and history of chronic kidney disease (p for linear trend = 0.044). Taken together, the cfDNA levels at admission are associated with the incidence of HF in AMI patients. A positive correlation between cfDNA and the fibrotic factor sST2 was proved, but the underlying mechanisms require further study.

Impact of the COVID-19 Pandemic on ST-Elevation Myocardial Infarction Management in Hunan Province, China: A Multi-Center Observational Study.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) care in China. Methods: We conducted a multicenter, retrospective cohort study in Hunan province (adjacent to the epidemic center), China. Consecutive patients presenting with STEMI within 12 h of symptom onset and receiving primary percutaneous coronary intervention, pharmaco-invasive strategy and only thrombolytic treatment, were enrolled from January 23, 2020 to April 8, 2020 (COVID-19 era group). The same data were also collected for the equivalent period of 2019 (pre-COVID-19 era group). Results: A total of 610 patients with STEMI (COVID-19 era group n = 286, pre-COVID-19 era group n = 324) were included. There was a decline in the number of STEMI admissions by 10.5% and STEMI-related PCI procedures by 12.7% in 2020 compared with the equivalent period of 2019. The key time intervals including time from symptom onset to first medical contact, symptom onset to door, door-to-balloon, symptom onset to balloon and symptom onset to thrombolysis showed no significant difference between these two groups. There were no significant differences for in-hospital death and major adverse cardiovascular events between these two groups. Conclusion: During the COVID-19 pandemic outbreak in China, we observed a decline in the number of STEMI admissions and STEMI-related PCI procedures. However, the key quality indicators of STEMI care were not significantly affected. Restructuring health services during the COVID-19 pandemic has not significantly adversely influenced the in-hospital outcomes.

Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH). METHODS: A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments. RESULTS: Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone. CONCLUSIONS: Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.

Ultrasound-targeted microbubble destruction (UTMD)-mediated miR-150-5p attenuates oxygen and glucose deprivation-induced cardiomyocyte injury by inhibiting TTC5 expression.

BACKGROUND: Cardiomyocyte injury is a typical feature in cardiovascular diseases. Changes in cardiomyocytes strongly affect the progression of cardiovascular diseases. This work aimed to investigate the biological function and potential mechanism of action of miR-150-5p in cardiomyocytes. METHODS AND RESULTS: A myocardial ischemia (MI) injury rat model was constructed to detect miR-150-5p and tetratricopeptide repeat domain 5 (TTC5) expression during heart ischemia injury. Primary cardiomyocytes were isolated for in vitro study. CCK-8 assays were used to detect cardiomyocyte viability. Western blots were used to detect TTC5 and P53 expression. qPCR was utilized to measure RNA expression of miR-150-5p and TTC5. The TUNEL assay was used to determine cell apoptosis. ELISA was used to determine cytokine (TNF-α, IL-1ß, IL-6, and IL-8) levels in heart tissues and cell culture supernatants. A dual-luciferase reporter assay was carried out to verify the binding ability between miR-150-5p and TTC5. Oxygen-glucose deprivation (OGD) treatment significantly inhibited cell viability. Ultrasound-targeted microbubble destruction (UTMD)-mediated uptake of miR-150-5p inverted these results. Additionally, UTMD-mediated uptake of miR-150-5p retarded the effects of OGD treatment on cell apoptosis. Besides, UTMD-mediated uptake of miR-150-5p counteracted the effects of OGD treatment on the inflammatory response by regulating cytokine (TNF-α, IL-1ß, IL-6, and IL-8) levels. For the mechanism of the protective effect on the heart, we predicted and confirmed that miR-150-5p bound to TTC5 and inhibited TTC5 expression. CONCLUSIONS: UTMD-mediated uptake of miR-150-5p attenuated OGD-induced primary cardiomyocyte injury by inhibiting TTC5 expression. This discovery contributes toward further understanding the progression of primary cardiomyocyte injury.

MicroRNA-325-3p Targets Human Epididymis Protein 4 to Relieve Right Ventricular Fibrosis in Rats with Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) usually causes right ventricular dysfunction, which is closely related to cardiac fibrosis. But cardiac fibrosis mechanism remains unclear. Our purpose was to explore microRNA-325-3p (miR-325-3p)/human epididymis protein 4's (HE4) role in the occurrence and development of right ventricular fibrosis in PAH. METHODS: The right ventricular fibrosis model of rats with PAH was constructed, and miR-325-3p was overexpressed to explore miR-325-3p's effect on myocardial fibrosis in rats with PAH. Pearson correlation coefficient examined the correlation between HE4 and miR-325-3p. We separated and identified the primary rat myocardial fibroblasts from the heart tissue. Then, the Ang II-treated myocardial fibroblast fibrosis model was constructed. miR-325-3p mimics and si-HE4 and oe-HE4 cell lines were constructed to investigate miR-325-3p and HE4 effects on myocardial cell fibrosis. Then, we added PI3K inhibitor LY294002 to study the effects of HE4 in cell fibrosis by the PI3K/AKT pathway. Starbase was used to predict miR-325-3p and HE4 binding sites. Dual-luciferase reporter assay verified whether miR-325-3p and HE4 were targeted. RESULTS: Overexpression of miR-325-3p alleviated myocardial fibrosis in rats with PAH. Pearson correlation coefficient showed that HE4 was negatively correlated with miR-325-3p expression. Starbase predicted that miR-325-3p had binding sites with HE4. Dual-luciferase reporter assay demonstrated that miR-325-3p targeted HE4. Overexpression of miR-325-3p downregulated HE4 and inhibited myocardial fibroblast fibrosis. HE4 knockdown inhibited myocardial fibroblast fibrosis. HE4 promoted myocardial fibroblast fibrosis and activated the PI3K/AKT pathway. In addition, HE4 affected myocardial fibroblast fibrosis through the PI3K/AKT pathway. CONCLUSIONS: miR-325-3p could target HE4 to relieve right ventricular fibrosis in rats with PAH. This study could provide new targets and strategies for right ventricular fibrosis in PAH.