Global LEADR pivotal trial results.

BACKGROUND: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform. OBJECTIVE: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead. METHODS: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively. RESULTS: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD). CONCLUSION: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

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.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS: Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS: In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS: Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04179669.

Effects of adding biochar on the preservation of nitrogen and passivation of heavy metal during hyperthermophilic composting of sewage sludge.

Hyperthermophilic composting (HTC) is regarded as an effective method for processing sewage sludge. The aim of the study was to investigate effects of using biochar as an amendment on the preservation of nitrogen and passivation of heavy metal during the HTC process of sewage sludge. Results showed that HTC improved the fermentation efficiency and the compost maturity by increases in the temperature and germination index (GI) value, and decreases in the moisture and C/N ratio compared to conventional thermophilic composting. HTC process and the biochar addition resulted in a decrease of the nitrogen loss compared with the control pile during composting by promoting transforming ammonium into nitrite nitrogen. Adding biochar to composting inhibited the transformation of Cu, Zn and Pb into more mobile speciation compared to the control pile although their contents increased during composting, which lead to reduction in availability of heavy metals. Thus, HTC process with the addition of biochar is viable for the reduction of the nitrogen losses and mobility of heavy metal in compost.Implications: The treatment of sewage sludge is imminent due to its threat to general health and ecosystems. This work represents the effects of adding biochar on the preservation of nitrogen and passivation of heavy metal during hyperthermophilic composting of sewage sludge. Our results indicate that the additions of biochar and hyperthermophilic composting engendered the several of positive effects on the preservation of nitrogen and passivation of heavy metal. Thus, HTC process with the addition of biochar is viable for the reduction of the nitrogen losses and mobility of heavy metal in compost.

Percutaneous transhepatic access for catheter ablation of a patient with heterotaxy syndrome complicated with atrial fibrillation: A case report.

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias, and radiofrequency catheter ablation is the most effective treatment strategy. The inferior vena cava (IVC) is a common approach for radiofrequency ablation of AF. However, this approach may not be applied to some cases such as chronic venous occlusions, surgical ligation of the IVC, and heterotaxy syndrome (HS). CASE SUMMARY: A 68-year-old man with HS suffered from severely symptomatic persistent AF for 9 years, and we successfully ablated by percutaneous transhepatic access. CONCLUSION: In patients without femoral vein access, the use of the hepatic vein for pulmonary vein isolation is a viable alternative for invasive electrophysiology procedures.

Sestrin2 Is Increased in Calcific Aortic Disease and Inhibits Osteoblastic Differentiation in Valvular Interstitial Cells via the Nuclear Factor E2-related Factor 2 Pathway.

ABSTRACT: Sestrin2 (Sesn2) is involved in the progression of cardiovascular diseases, such as hypertension and myocardial infarction. This study aimed to examine Sesn2 expression in human calcific aortic valve disease (CAVD) and explore its possible mechanisms by which Sesn2 participates in this process. CAVD and normal aortic valves were collected. Sesn2 expression and sources were examined, and the results showed that Sesn2 expression was increased in aortic valves from patients with CAVD and was mainly secreted by macrophages. Additionally, U937 macrophages were pretreated with si-Sesn2 or cDNA-Sesn2 and further treated with oxidized low-density lipoprotein (ox-LDL); M1 macrophages and their markers were measured, and we found that pretreatment with si-Sesn2 increased ox-LDL-induced M1 macrophage polarization and marker mRNA levels, whereas pretreatment with cDNA-Sesn2 had the opposite effects. In ox-LDL-treated U937 macrophages, oxidative stress levels were increased in the si-Sesn2 pretreatment group and further increased by si-Nrf2 treatment, whereas oxidative stress levels were decreased in the cDNA-Sesn2 pretreatment group and significantly reversed by ML385, a specific Nrf2 inhibitor. The effects of Sesn2 on ox-LDL-induced oxidative stress and the osteogenic differentiation of ox-LDL-induced valvular interstitial cells (VICs) was examined by down-regulating Nrf2 pathway. When U937 macrophages were co-cultured with VICs, downregulation of Sesn2 increased ox-LDL-induced osteogenic differentiation in VICs, whereas overexpression of Sesn2 exerted the opposite effects. Our study suggests that Sesn2 is increased in CAVD aortic valves and may participate in the development of CAVD by regulating oxidative stress via the Nrf2 pathway.

Prevalence and risk of atrial fibrillation in China: A national cross-sectional epidemiological study.

Background: Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China. Methods: Study data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results. Findings: A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval [CI] 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 [95% CI 1·38-1·46]; p < 0·001), men (1·34 [1·24-1·45]; p < 0·001), hypertension (1·22 [1·12-1·33]; p < 0·001), coronary heart disease (1·44 [1·28-1·62]; p < 0·001), chronic heart failure (3·70 [3·22-4·26]; p < 0·001), valvular heart disease (2·13 [1·72-2·63]; p < 0·001), and transient ischaemic attack/stroke (1·22 [1·04-1·43]; p = 0·013). Interpretation: The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden. Funding: This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).

Biolimus-Coated Balloon in Small-Vessel Coronary Artery Disease: The BIO-RISE CHINA Study.

BACKGROUND: Drug-coated balloons are a safe and effective option for patients undergoing percutaneous coronary intervention, but prior randomized studies have exclusively used paclitaxel-coated devices. OBJECTIVES: The aim of this study was to assess for the first time the safety and efficacy of a novel biolimus-coated balloon (BCB) in patients with small-vessel coronary disease. METHODS: In a prospective trial conducted at 10 centers in China, 212 patients with small-vessel native coronary disease (reference vessel diameter 2.0-2.75 mm, lesion length ≤25 mm) were randomized to receive a BCB or an uncoated balloon. The primary endpoint was in-segment late lumen loss at 9 months. RESULTS: In the per-protocol population, angiographic late lumen loss at 9 months was 0.16 ± 0.29 mm in the BCB group vs 0.30 ± 0.35 mm with the plain balloon (P = 0.001). Late luminal enlargement (positive remodeling) occurred in 29.7% of patients in the BCB group vs 9.8% of patients with plain balloons (P = 0.007). In the full analysis set population, after 12 months, target lesion failure rates were 6.7% in the BCB group vs 13.9% with the plain balloon (HR: 0.47; 95% CI: 0.19-1.16), and rates of the patient-oriented clinical outcome were 14.3% with the BCB vs 21.8% with the plain balloon (HR: 0.64; 95% CI: 0.33-1.24). CONCLUSIONS: In this first-in-human study, a novel BCB showed superior efficacy to plain balloon angioplasty in patients with small-vessel coronary disease undergoing percutaneous coronary intervention. Positive vascular remodeling was more frequent, and there was a trend toward improved clinical outcomes. (A Randomized Trial of a Biolimus-Coated Balloon Versus POBA in Small Vessel Coronary Artery Disease [Brave]; NCT03769623).

Research progress of biomarkers in early detection of chemotherapy-induced cardiotoxicity.

With the advances of drug therapy, the prognosis of cancer patients has seen remarkable improvements, and cancer-related mortality has decreased significantly. However, the followed drug-related cardiotoxicity becomes a serious threat to patients' living quality and survival rate. Cardiovascular toxicity associated with some chemotherapy drugs is reversible and dose-dependent. If early identification is possible, early cardiovascular protection measures or adjustment of chemotherapy regimens can be taken to improve the prognosis of patients. Therefore, early prevention and monitoring of chemotherapy-related cardiotoxicity are critical for cancer patients and survivors. Among them, biomarkers are an important method for the early identification of myocardial injury.

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

NEW FINDINGS: What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. ABSTRACT: Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6 mg kg-1  day-1 ), or placebo for 30 days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

Increased plasma sestrin2 concentrations in patients with chronic heart failure and predicted the occurrence of major adverse cardiac events: A 36-month follow-up cohort study.

BACKGROUND: Previous study had demonstrated that sestrin2 (Sesn2) expression was increased in human failing heart. Although, the circulating Sesn2 concentrations in patients with chronic heart failure (CHF) remains unknown. This study investigated plasma Sesn2 concentrations in patients with CHF and the role between Sesn2 and the occurrence of major adverse cardiac events. METHODS: A total of 80 control subjects and 220 CHF patients were enrolled and the Sesn2 concentrations of each sample were measured. Additionally, the occurrence of major adverse cardiac events in each CHF patient were followed prospectively for 36 months. RESULTS: Increased plasma Sesn2 concentrations were found in CHF patients and gradually increased from New York Heart Association (NYHA) functional class II to IV. The Sesn2 concentrations were positively correlated with N-terminal B-type natriuretic peptide (NT-pro BNP) but negatively correlated with left ventricular ejection fraction (LVEF) in CHF patients. The ROC curve suggested that Sesn2 had a certain value in predicting major adverse cardiac events during CHF patients, although, the predictive role of Sesn2 is not as good as NT-pro BNP. In addition, the multivariate Cox hazard analysis was performed after the CHF patients were divided into 3 groups (low, middle, and high) base on the plasma Sesn2 concentrations category, and the results showed that both high and middle Sesn2 concentrations increased the incidence of major adverse cardiac events when compared with low Sesn2 group. Furthermore, CHF patients with major adverse cardiac events showed higher Sesn2 concentrations when compared with CHF without major adverse cardiac events. The Kaplan-Meier analysis was performed after the CHF patients were divided into 2 groups according to the median Sesn2 concentrations and the results revealed that patients with high Sesn2 concentrations had a higher risk of major adverse cardiac events compared with those with low Sesn2. CONCLUSIONS: Plasma Sesn2 concentrations were increased in CHF patients and positively correlated with the severity of CHF. Increased Sesn2 concentrations significantly increased the occurrence of major adverse cardiac events and suggested poor outcome in CHF patients.

Linc01230, transcriptionally regulated by PPARγ, is identified as a novel modifier in endothelial function.

Evidence is growing that PPARγ could improve the bioavailability of NO in pathological conditions to maintain endothelial function by activating Akt/eNOS pathway. LincRNAs participate in regulating development of cardiovascular diseases. Although investigations have been made to delineate the function of PPARγ and lincRNAs, little is known about the regulation relationship between them, especially in endothelial cells. In this study, we not only verified that PPARγ could antagonize the adverse effects brought from ox-LDL, but also found a novel factor related to PPARγ, named linc01230. According to our study, PPARγ transcriptionally regulated linc01230 by specifically combining with two binding regions, which have superposition effect, in the upstream of linc01230 promoter. In addition, linc01230 reduced ox-LDL induced endothelial dysfunction and affected the phosphorylation of Akt. These results conclude linc01230 as a novel modifier in PPARγ-mediated activation of Akt in endothelial function.

Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by Suppressing Autophagy via the LPA3/AKT/mTOR Pathway.

Background: Lysophosphatidic acid (LPA), as a phospholipid signal molecule, participates in the regulation of various biological functions. Our previous study demonstrated that LPA induces cardiomyocyte hypertrophy in vitro; however, the functional role of LPA in the post-infarct heart remains unknown. Growing evidence has demonstrated that autophagy is involved in regulation of cardiac hypertrophy. The aim of the current work was to investigate the effects of LPA on cardiac function and hypertrophy during myocardial infarction (MI) and determine the regulatory role of autophagy in LPA-induced cardiomyocyte hypertrophy. Methods: In vivo experiments were conducted in Sprague-Dawley rats subjected to MI surgery or a sham operation, and rats with MI were assigned to receive an intraperitoneal injection of LPA (1 mg/kg) or vehicle for 5 weeks. The in vitro experiments were conducted in H9C2 cardiomyoblasts. Results: LPA treatment aggravated cardiac dysfunction, increased cardiac hypertrophy, and reduced autophagy after MI in vivo. LPA suppressed autophagy activation, as indicated by a decreased LC3II-to-LC3I ratio, increased p62 expression, and reduced autophagosome formation in vitro. Rapamycin, an autophagy enhancer, attenuated LPA-induced autophagy inhibition and H9C2 cardiomyoblast hypertrophy, while autophagy inhibition with Beclin1 siRNA did not further enhance the hypertrophic response in LPA-treated cardiomyocytes. Moreover, we demonstrated that LPA suppressed autophagy through the AKT/mTOR signaling pathway because mTOR and PI3K inhibitors significantly prevented LPA-induced mTOR phosphorylation and autophagy inhibition. In addition, we found that knockdown of LPA3 alleviated LPA-mediated autophagy suppression in H9C2 cardiomyoblasts, suggesting that LPA suppresses autophagy through activation of the LPA3 and AKT/mTOR pathways. Conclusion: These findings suggest that LPA plays an important role in mediating cardiac dysfunction and hypertrophy after a MI, and that LPA suppresses autophagy through activation of the LPA3 and AKT/mTOR pathways to induce cardiomyocyte hypertrophy.

Circulating soluble corin as a potential biomarker for cardiovascular diseases: A translational review.

Corin is a type II transmembrane serine protease that is highly expressed in the heart and plays a physiological role in the activation of natriuretic peptides. Corin is expressed primarily in myocytes, and it can enter the circulation. Circulating soluble corin has been found to be associated with various cardiovascular diseases, such as hypertension, heart failure, myocardial infarction, preeclampsia, and stroke. All these findings indicate that circulating soluble corin has the potential to be a sensitive and specific biomarker for risk prediction and prognostic assessment of cardiovascular diseases. However, there are certain challenges hindering the incorporation of circulating soluble corin into clinical practice. To provide new ideas based on the use of corin for risk prediction, prognostic assessment, and clinical treatment of cardiovascular diseases and to promote the implementation of corin as a routine laboratory index, we summarize the latest studies of the association between corin and cardiovascular diseases in recent years and offer some prospective proposals for future research on corin in this review.

Oxidative stress impairs myocyte autophagy, resulting in myocyte hypertrophy.

NEW FINDINGS: What is the central question of this study? Does oxidative stress induce impairment of autophagy that results in myocyte hypertrophy early after pressure overload? What is the main finding and its importance? In cultured myocytes, hydrogen peroxide decreased autophagy and increased hypertrophy, and inhibition of autophagy enhanced myocyte hypertrophy. In rats with early myocardial hypertrophy after pressure overload, myocyte autophagy was progressively decreased. The antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol prevented the decrease of myocyte autophagy and attenuated myocyte hypertrophy early after pressure overload. These findings suggest that oxidative stress impairs myocyte autophagy that results in myocyte hypertrophy. ABSTRACT: Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces an impairment of autophagy that results in myocyte hypertrophy. H9C2 cardiomyocytes pretreated with the autophagy inhibitor 3-methyladenine were exposed to 10 and 50 µm hydrogen peroxide (H2 O2 ) for 48 h. Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation. The animals were killed 24, 48 or 72 h after surgery. In a separate group, the AAC and sham-operated rats randomly received the antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol for 72 h. In H9C2 cardiomyocytes, H2 O2 decreased the ratio of microtubule-associated protein light chain 3 (LC3) II to LC3 I and increased P62 and phosphorylated ERK (p-ERK) proteins and myocyte surface area. 3-Methyladenine further increased H2 O2 -induced p-ERK expression. In rats after AAC, the heart to body weight ratio was progressively increased, the LC3 II/I ratio was progressively decreased, p62 and p-ERK expression was increased, and expression of Beclin1, Atg5 and Atg12 was decreased. N-Acetyl-cysteine or tempol prevented the decreases in the LC3 II/I ratio and Beclin1 and Atg5 expression and attenuated the increases in LV wall thickness, myocyte diameter and brain natriuretic peptide expression in AAC rats. In conclusion, oxidative stress decreases Beclin1 and Atg5 expression that results in impairment of autophagy, leading to myocyte hypertrophy. These findings suggest that antioxidants or restoration of autophagy might be of value in the prevention of early myocardial hypertrophy after pressure overload.