Search

Abstract Background Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. Methods We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (

Abstract Aims This study investigated the S2I2N0–3 score, a simple tool comprising stroke history, insulin‐treated diabetes, and N‐terminal pro‐brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Analysing 890 GUIDE‐IT HFrEF trial participants, we stratified them by baseline S2I2N0–3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90 days) and extended periods (median follow‐up of 15 months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2I2N0–3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2I2N0–3 score was associated with a higher risk of short‐ and long‐term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03–1.98; long term: HR 1.18, 95% CI 1.02–1.38], all‐cause death (HR 1.52, 95% CI 1.12–2.07; HR 1.18, 95% CI 1.03–1.36), HF hospitalization (HR 1.39, 95% CI 1.20–1.62; HR 1.18, 95% CI 1.06–1.31), any hospitalization (HR 1.19, 95% CI 1.06–1.34; HR 1.09, 95% CI 1.00–1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21–1.60; HR 1.17, 95% CI 1.06–1.30). The S2I2N0–3 demonstrated reliable prognostic value, with C‐indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z‐statistics, net reclassification index, and integrated discrimination improvement, the S2I2N0–3 showed comparable predictive power for all outcomes during both short‐ and long‐term follow‐ups. Conclusions The S2I2N0–3 risk score had modest predictive values for both short‐ and long‐term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.

Background In the past decade, the biological functions of various RNA modifications in mammals have been uncovered. N4‐acetylcytidine (ac4C), a highly conserved RNA modification, has been implicated in human diseases. Despite this, the involvement of RNA ac4C modification in cardiac physiology and pathology remains incompletely understood. NAT10 (N‐acetyltransferase 10) stands as the sole acetyltransferase known to catalyze RNA ac4C modification. This study aims to explore the role of NAT10 and ac4C modification in cardiac physiology and pathology. Methods and Results Cardiac‐specific knockout of NAT10, leading to reduced RNA ac4C modification, during both neonatal and adult stages resulted in severe heart failure. NAT10 deficiency induced cardiomyocyte apoptosis, a crucial step in heart failure pathogenesis, supported by in vitro data. Activation of the p53 signaling pathway was closely associated with enhanced apoptosis in NAT10‐deficient cardiomyocytes. As ac4C modification on mRNA influences translational efficiency, we employed ribosome footprints coupled with RNA sequencing to explore genome‐wide translational efficiency changes caused by NAT10 deficiency. We identified and validated that the translational efficiency of Kmt5a was suppressed in NAT10 knockout hearts due to reduced ac4C modification on its mRNA. This finding was consistent with the observation that Kmt5a protein levels were reduced in heart failure despite unchanged mRNA expression. Knockdown of Kmt5a in cardiomyocytes recapitulated the phenotype of NAT10 deficiency, including increased cardiomyocyte apoptosis and activated p53 signaling. Finally, overexpression of Kmt5a rescued cardiomyocyte apoptosis and p53 activation induced by NAT10 inhibition. Conclusions Our study highlights the significance of NAT10 in cardiomyocyte physiology, demonstrating that NAT10 loss is sufficient to induce cardiomyocyte apoptosis and heart failure. NAT10 regulates the translational efficiency of Kmt5a, a key mediator, through mRNA ac4C modification during heart failure.

Abstract 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

In order to improve the shear performance of reinforced concrete beams and improve the shear bearing capacity of concrete beams, the author proposes a scheme based on flax fiber cloth to strengthen the shear performance of reinforced concrete beams, by studying the effects of different treatment methods and preparation process parameters on the mechanical and interfacial properties of composites, the improvement mechanism of the mechanical and interfacial properties of flax fiber composites was revealed, and through the high performance of flax fiber and its composite materials, the bearing characteristics and failure modes of reinforced concrete beams reinforced with flax fiber cloth, verification of the increase in shear capacity and the effectiveness of structural reinforcement of reinforced concrete beams reinforced with flax fiber cloth. Experimental results show that: After the reinforced concrete beam was reinforced with nano-TiO2-grafted flax fiber cloth, its shear bearing capacity reached 653 kN, and the mid-span limit deflection value of the concrete beam reached 14.6 mm, which was greatly increased by about 6.3 mm compared with the unreinforced one. Conclusion: The reinforced concrete beam reinforced with flax fiber cloth should not only meet the bearing capacity requirements, but also meet the ductility requirements of the structure.

Abstract 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.

Abstract Aims Liver fibrosis scores (LFSs) are non‐invasive and effective tools for estimating cardiovascular risks. To better understand the advantages and limitations of currently available LFSs, we determined to compare the predictive values of LFSs in heart failure with preserved ejection fraction (HFpEF) for primary composite outcome, atrial fibrillation (AF), and other clinical outcomes. Methods and results This was a secondary analysis of the TOPCAT trial, and 3212 HFpEF patients were enrolled. Five LFSs, namely, non‐alcoholic fatty liver disease fibrosis score (NFS), fibrosis‐4 score (FIB‐4), BARD, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and Health Utilities Index (HUI) scores were adopted. Cox proportional hazard model and competing risk regression model were performed to assess the associations between LFSs and outcomes. The discriminatory power of each LFS was evaluated by calculating the area under the curves (AUCs). During a median follow‐up of 3.3 years, a 1‐point increase in the NFS [hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.04–1.17], BARD (HR 1.19; 95% CI 1.10–1.30), and HUI (HR 1.44; 95% CI 1.09–1.89) scores was associated with an increased risk of primary outcome. Patients with high levels of NFS (HR 1.63; 95% CI 1.26–2.13), BARD (HR 1.64; 95% CI 1.25–2.15), AST/ALT ratio (HR 1.30; 95% CI 1.05–1.60), and HUI (HR 1.25; 95% CI 1.02–1.53) were at an increased risk of primary outcome. Subjects who developed AF were more likely to have high NFS (HR 2.21; 95% CI 1.13–4.32). High levels of NFS and HUI scores were a significant predictor of any hospitalization and hospitalization for heart failure. The AUCs for the NFS in predicting primary outcome (0.672; 95% CI 0.642–0.702) and incident of AF (0.678; 95% CI 0.622–0.734) were higher than other LFSs. Conclusions In light of these findings, NFS appears to have superior predictive and prognostic utility compared with AST/ALT ratio, FIB‐4, BARD, and HUI scores. Clinical trial registration: (https://clinicaltrials.gov). Unique identifier: NCT00094302.

Abstract Aims This study aims to evaluate the prognostic value of mean corpuscular haemoglobin concentration (MCHC) on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results We analysed HFpEF participants from the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline data (n = 1747). Patients were grouped into hypochromia or non‐hypochromia group according to a MCHC cut‐off level of 330 g/L. Cox proportional hazard model was used to explore the prognostic value of hypochromia on the long‐term clinical outcomes (the primary endpoint [composite of cardiovascular mortality, HF hospitalization and aborted cardiac arrest], any‐cause and HF hospitalization, all‐cause and cardiovascular mortality). Patients were further stratified according to baseline estimated glomerular filtration rate (eGFR) to explore the impact of renal dysfunction on the prognostic value of hypochromia. Baseline hypochromia was prevalent (n = 662, 37.9%) and strongly associated with worse clinical outcomes. In patients with worse renal function (eGFR

Abstract Background Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. Methods Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. Results Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19–1.72, P

Abstract It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short‐ and long‐term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women; mean age, 68.8 years), we assessed the risk of 30‐day, 1‐year, and long‐term (> 1 year) mortality with 1‐SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow‐up of 4.1 years, 1341 patients died. The 30‐day, 1‐year, and long‐term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable‐adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long‐term mortality (hazard ratio, 1.11; 95% CI, 1.02‐1.22; p = .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long‐term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04–1.29; p = .007) and .89 (95% CI, .80–.99; p = .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1‐year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all‐cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.

Abstract Background Obesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous. Methods Latent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared. Results Two subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P = 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40–0.70, P

Abstract Background Current guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients. Methods We systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model. Results A total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86–0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71–0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69–0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70–0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88–0.92), and ACS (HR = 0.86, 95% CI: 0.76–0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results. Conclusions Our current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year. Registration The study protocol was registered to PROSPERO (CRD42021295405).

Abstract Aims The aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment. Methods and results A swap‐stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment. Three phenotypes of HFpEF were identified. Phenotype 1 was the youngest with low burden of co‐morbidities. Phenotype 2 was the oldest with high prevalence of atrial fibrillation, pacemaker implantation, and hypothyroidism. Phenotype 3 was mostly obese and diabetic with high burden of other co‐morbidities. Compared with phenotype 1, phenotypes 2 (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.14–1.89; P = 0.003) and 3 (HR: 2.35; 95% CI: 1.80–3.07; P

Background: There has been an increasing use of transcatheter tricuspid valve repair (TTVR) recently. However, the periprocedural, short-term, and long-term outcomes of TTVR remain unclear. Objectives: To determine the clinical outcomes in patients with significant tricuspid regurgitation undergoing TTVR. Design: Systematic review and meta-analysis. Data Source and Methods: The systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and EMBASE were searched for clinical trials and observational studies until March 2022. Studies reporting the incidence of clinical outcomes after TTVR were included. The clinical outcomes included periprocedural, short-term (in-hospital or within 30 days), and long-term (>6-month follow-up) outcomes. The primary outcome was all-cause mortality whereas the secondary outcomes included technical success, procedural success, cardiovascular mortality, rehospitalization for heart failure (HHF), major bleeding, and single leaflet device attachment. The incidence of these outcomes across studies was pooled by a random-effects model. Results: A total of 21 studies with 896 patients were included. A total of 729 (81.4%) patients underwent isolated TTVR while only 167 (18.6%) patients underwent combined mitral and tricuspid valve repair. Over 80% of the patients used coaptation devices while approximately 20% used annuloplasty devices. The median follow-up duration was 365 days. Technical and procedural success was high at 93.9% and 82.1%, respectively. The pooled perioperative, short-term, and long-term all-cause mortality for patients undergoing TTVR was 1.0%, 3.3%, and 14.1%, respectively. The long-term cardiovascular mortality rate was 5.3% while the HHF rate was 21.5%. Major bleeding and single leaflet device attachment were two major complications, accounting for 14.3% and 6.4%, respectively, during long-term follow-up. Conclusion: TTVR is associated with high procedural success and low procedural and short-term mortality. However, all-cause mortality, cardiovascular mortality, and HHF rates remain high during long-term follow-up. Registration: PROSPERO (CRD42022310020).

Abstract Chronic heart failure is the end stage of cardiac diseases. With a high prevalence and a high mortality rate worldwide, chronic heart failure is one of the heaviest health-related burdens. In addition to the standard neurohormonal blockade therapy, several medications have been developed for chronic heart failure treatment, but the population-wide improvement in chronic heart failure prognosis over time has been modest, and novel therapies are still needed. Mechanistic discovery and technical innovation are powerful driving forces for therapeutic development. On the one hand, the past decades have witnessed great progress in understanding the mechanism of chronic heart failure. It is now known that chronic heart failure is not only a matter involving cardiomyocytes. Instead, chronic heart failure involves numerous signaling pathways in noncardiomyocytes, including fibroblasts, immune cells, vascular cells, and lymphatic endothelial cells, and crosstalk among these cells. The complex regulatory network includes protein–protein, protein–RNA, and RNA–RNA interactions. These achievements in mechanistic studies provide novel insights for future therapeutic targets. On the other hand, with the development of modern biological techniques, targeting a protein pharmacologically is no longer the sole option for treating chronic heart failure. Gene therapy can directly manipulate the expression level of genes; gene editing techniques provide hope for curing hereditary cardiomyopathy; cell therapy aims to replace dysfunctional cardiomyocytes; and xenotransplantation may solve the problem of donor heart shortages. In this paper, we reviewed these two aspects in the field of failing heart signaling cascades and emerging therapeutic strategies based on modern biological techniques.

Abstract Aims Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) had distinct haemodynamic characteristics in the setting of acute heart failure. The aim of our study is to evaluate the differential response to aggressive diuresis in HFrEF and HFpEF. Methods and results Patients in the Diuretic Optimization Strategies Evaluation trial with left ventricular ejection fraction measurement were included (n = 300) and classified into HFrEF [left ventricular ejection fraction (LVEF)

Abstract Background Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). Methods Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was 20 ms. Results The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

BackgroundMetabolic syndrome is a pre-diabetes condition that is associated with increased cardiovascular morbidity and mortality. We aimed to explore how exercise capacity, cardiac structure, and function were affected in patients with metabolic syndrome.MethodsOutpatients with echocardiography and exercise stress test combined with impedance cardiography (ETT + ICGG) results available from Nov 2018 to Oct 2020 were retrospectively enrolled. Echocardiographic, ETT + ICG profiles, and exercise performance were compared between patients with metabolic syndrome and the ones without. Sensitivity analyses were performed excluding patients without established coronary heart disease and further 1:1 paired for age and gender, respectively. Multiple linear regression was used to find out related predictors for maximal metabolic equivalents (METs).ResultsThree hundred and twenty-third patients were included, among whom 97 were diagnosed as metabolic syndrome. Compared to patients without metabolic syndrome, echocardiography showed that patients with metabolic syndrome had a significantly lower E/A ratio (p < 0.001). Besides, they have larger left atrium, larger right ventricle, and thicker interventricular septum (all p < 0.001), but similar left ventricular ejection fraction (P = 0.443). ICG showed that patients with metabolic syndrome had significantly higher stroke volume at rest and maximum (p < 0.001), higher left cardiac work index at rest and maximum (p = 0.005), higher systemic vascular resistance (SVR) at rest (p < 0.001), but similar SVI (p = 0.888). During exercise, patients with metabolic syndrome had lower maximal METs (p < 0.001), and a higher proportion suffering from ST-segment depression during exercise (p = 0.009). Sensitivity analyses yielded similar results. As for the linear regression model, 6 independent variables (systolic blood pressure, BMI, E/A ratio, the height of O wave, the peak value of LCWi, and the baseline of SVR) had statistically significant effects on the maximal METs tested in exercise (R = 0.525, R2 = 0.246, P < 0.001).ConclusionPatients with metabolic syndrome had significant structural alteration, apparent overburden of left ventricular work index, pre-and afterload, which may be the main cause of impaired exercise tolerance.

BackgroundTo evaluate the safety and efficacy of hybutimibe plus atorvastatin for lipid control in hypercholesterolemia patients with atherosclerotic cardiovascular disease risk equivalent.MethodsIn this double-blind phase III study, we 1:1 randomly assigned 255 hypercholesterolemia patients with atherosclerotic cardiovascular disease to receive hybutimibe plus atorvastatin or placebo plus atorvastatin. The primary endpoint was the rate of change of plasma low-density lipoprotein-cholesterol (LDL-C) level at 12 weeks from baseline. The secondary endpoints were plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), non-HDL-C, apoprotein (Apo) B, and 2-, 4-, 8-, and 12-week Apo A1 levels change rate and rates of change of plasma LDL-C levels at 2, 4, and 8 weeks from baseline.ResultsFrom April 2016 to January 2018, 128 in the hybutimibe plus atorvastatin group and 125 in the atorvastatin group were included in modified intention-to-treat (mITT) analysis. After 12 weeks of treatment, LDL-C level changed from 2.61 mmol/L (±0.30) at baseline to 2.18 mmol/L (±0.45) in the hybutimibe plus atorvastatin group and from 2.58 (±0.31) mmol/L to 2.40 (± 0.46) mmol/L in the atorvastatin group (P < 0.0001), in mITT. The change rate in the hybutimibe plus atorvastatin group was significantly higher than that in the atorvastatin group (P < 0.0001); the estimated mean rates of change were −16.39 (95% confidence interval: −19.04, −13.74) and −6.75 (−9.48, −4.02), respectively. Consistently, in per-protocol set (PPS) analysis, the rate of change of LDL-C in the hybutimibe plus atorvastatin group was significantly higher than that in atorvastatin group. Significant decreases in the change rates of non-HDL-C, TC, and Apo B at 2, 4, 8, and 12 weeks (all P < 0.05) were observed for hybutimibe plus atorvastatin, while the differences were not significant for HDL-C, TG, and Apo-A1 (all P > 0.05). During the study period, no additional side effects were reported.ConclusionsHybutimibe combined with atorvastatin resulted in significant improvements in LDL-C, non-HDL-C, TC, and Apo B compared with atorvastatin alone. The safety and tolerability were also acceptable, although additional benefits of hybutimibe plus atorvastatin were not observed compared with atorvastatin alone in HDL-C, TG, and Apo-A1.

Summary: Background: In the current practice, graft ischaemia and reperfusion injury (IRI) is considered an inevitable component in organ transplantation, contributes to compromised organ quality, inferior graft survival and limitations in organ availability. Among all the donor organs, the heart is most vulnerable to IRI and the tolerated ischaemic time is the shortest. Methods: By combining adapted surgical techniques and normothermic machine perfusion (NMP), we performed the first case of ischaemia-free beating heart transplantation (IFBHT) in man. The donor heart was procured after an in situ NMP circuit was established, then underwent ex situ NMP and implanted under NMP support. The post-transplant graft function was monitored. Findings: The donor heart was procured, preserved, and implanted under a continuously perfused, normothermic, oxygenated, beating state. During ex situ NMP, the donor heart beat with sinus rhythm and adequate ventricular contraction, consumed oxygen and lactate, suggesting a good cardiac function. The dynamic electrocardiogram demonstrated an absence of ischaemic injury of the donor heart during the entire procedure. The echocardiogram showed an immediate graft function with a left ventricle ejection fraction (LVEF) of 70%. The patient was discharged on post-transplantation day 20 and was followed up for 8 months with normal cardiac function and life. Interpretation: This study shows the feasibility of IFBHT procedure, which might be able to completely avoid graft IRI, has thus the potential to improve transplant outcome while increasing organ utilization. Funding: This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial International Cooperation Base of Science and Technology.

Abstract Background Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. Methods Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. Results A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40–1.77; P

Abstract Background The C2HEST score has been validated for predicting AF in the general population or post-stroke patients. We aimed to assess whether this risk score could predict incident AF and other clinical outcomes in heart failure with preserved ejection fraction (HFpEF) patients. Methods A total of 2202 HFpEF patients without baseline AF in the TOPCAT trial were stratified by baseline C2HEST score. Cox proportional hazard model and competing risk regression model was used to explore the relationship between C2HEST score and outcomes, including incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The discriminative ability of the C2HEST score for various outcomes was assessed by calculating the area under the curve (AUC). Results The incidence rates of incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization were 1.79, 0.70, 3.81, 2.42, 15.50, and 3.32 per 100 person-years, respectively. When the C2HEST score was analyzed as a continuous variable, increased C2HEST score was associated with increased risk of incident AF (HR 1.50, 95% CI 1.29–1.75), as well as increased risks of all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The AUC for the C2HEST score in predicting incident AF (0.694, 95% CI 0.640–0.748) was higher than all-cause death, cardiovascular death, any hospitalization, or HF hospitalization. Conclusions The C2HEST score could predict the risk of incident AF as well as death and hospitalization with moderately good predictive abilities in patients with HFpEF. Its simplicity may allow the possibility of quick risk assessments in busy clinical settings.

Abstract Aims The aim of the study was to explore the risk factors and evaluate the prognostic implication of pulmonary hospitalization on heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results We performed a secondary analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). A total of 1714 patients with HFpEF were analysed in our study. In the multivariate Cox proportional hazards regression analysis, history of chronic obstructive pulmonary disease (COPD), smoking, bone fracture after the age of 45, and previous HF hospitalization were identified as independent risk factors for pulmonary hospitalization. To evaluate the prognostic significance of pulmonary hospitalization, patients were categorized into five groups according to the causes of their first hospitalization. The all‐cause and cardiovascular (CV) mortality risks in these five groups were compared using time‐varying Cox proportional hazards model. Compared with patients without hospitalization during follow‐up, those with pulmonary hospitalization were associated with a 204% increase [hazard ratio (HR) 3.04, 95% confidence interval (CI) 2.07–4.47, P

IntroductionPatients with incomplete revascularization (ICR) tend to develop refractory angina despite optimal medical therapy. The Compound Danshen Dripping Pills (CDDP) is a widely used antianginal drug in China and is shown to significantly alleviate myocardial ischemia. Previous studies showed dose-efficacy tendency when increasing doses of CDDP. This study aims to investigate the efficacy and safety of intensive doses of CDDP in patients with refractory angina with ICR.Methods and AnalysisThe INCODER study is a multicenter, double-blind, randomized controlled, superiority trial. We plan to recruit 250 patients aged 18–85 years with a diagnosis of refractory angina with ICR. Patients will be randomized (1:1) to intensive treatment group (CDDP 20 pills three times per day) or standard treatment group (10 pills CDDP and 10 pills placebo three times per day). Patients will have a 6-week medication period and be followed up every 2 weeks. The primary endpoint is the change of total exercise time from baseline to week 6 as assessed by cardiopulmonary exercise testing (CPET). Secondary endpoints include changes in the frequency of angina, Canadian Cardiovascular Society angina class, nitroglycerin use, Seattle Angina Questionnaire scores, peak oxygen uptake (VO2 peak) and other parameters as measured by CPET, and the levels of plasma C-reactive protein, homocysteine, and N-terminal pro-B-type natriuretic peptide. Safety events related to CDDP use will be monitored.Ethics and DisseminationThe research had been approved by the Clinical research and laboratory animal ethics committee of the First Affiliated Hospital, Sun Yat-sen University ([2019]65). The results will be reported through peer-reviewed journals, seminars, and conference presentations.Trial Registration Numberwww.chictr.org.cn (ChiCTR2000032384). Registered on 27 April 2020.

Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body’s needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation for the prevention of heart disease progression.

Cardiac remodeling is the critical process in heart failure due to many cardiovascular diseases including myocardial infarction, hypertension, cardiovascular disease and cardiomyopathy. However, treatments for heart failure focusing on cardiac remodeling show relatively limited effectiveness. In recent decades, epitranscriptomic modifications were found abundantly present throughout the progression of cardiac remodeling, and numerous types of biochemical modifications were identified. m6A modification is the methylation of the adenosine base at the nitrogen-6 position, and dysregulation of m6A modification has been implicated in a wide range of diseases. However, function of m6A modifications still remain largely unknown in cardiac diseases, especially cardiac remodeling. LncRNAs are also shown to play a vital role in the pathophysiology of cardiac remodeling and heart failure. The crosstalk between lncRNAs and m6A modification provides a novel prospective for exploring possible regulatory mechanism and therapeutic targets of cardiac remodeling. This review summarizes the role of m6A modification in cardiac remodeling in the current researches.

Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m6A modification of 18S rRNA at position A1832, has been shown to regulate the efficiency of mRNA translation during the differentiation of ES cells and the growth of cancer cells. It remains unknown whether and how METTL5 regulates cardiac hypertrophy. In this study, we have generated a mouse model, METTL5-cKO, with cardiac-specific depletion of METTL5 in vivo. Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocytes was further confirmed with both gain- and loss-of-function approaches in primary cardiomyocytes. Mechanically, METTL5 can modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptomic shift during cardiac hypertrophy. Altogether, our study may uncover an important translational regulator of cardiac hypertrophy through m6A modification.

Abstract Background Secondhand smoke (SHS) exposure is a well-established cardiovascular risk factor, yet association between SHS and prognosis of heart failure remains uncertain. Method Data were obtained from the US National Health and Nutrition Examination Surveys III from 1988 to 1994. Currently nonsmoking adults with a self-reported history of heart failure were included. Household SHS exposure was assessed by questionnaire. Participants were followed up through December 31, 2011. Cox proportional-hazards models were used to assess the association of household SHS exposure and mortality risk. Potential confounding factors were adjusted. Results Of 572 currently nonsmoking patients with heart failure, 88 were exposed to household SHS while 484 were not. There were totally 475 deaths during follow-up. In univariate analysis, household SHS was not associated with mortality risk (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.76–1.26, p = 0.864). However, after adjustment for demographic variables, socioeconomic variables and medication, heart failure patients in exposed group had a 43% increase of mortality risk compared with those in unexposed group (HR: 1.43, 95% CI: 1.10–1.86, p = 0.007). Analysis with further adjustment for general health status and comorbidities yielded similar result (HR: 1.47, 95% CI: 1.13–1.92, p = 0.005). Conclusion Household SHS exposure was associated with increased mortality risk in heart failure patients.

Abstract Background Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. Methods We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. Results A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28–2.57, p

Background: Eosinophilic granulomatosis with polyangitis manifested as myocardial infarction with non-obstructed coronary arteries (MINOCA) is rarely reported.Case: We report a 43-year-old male patient without any cardiovascular risk factors presenting with acute chest pain. Electrocardiogram was suggestive of acute anterior and inferior myocardial infarction. MINOCA was confirmed based on significant elevated cardiac troponin and normal coronary arteries. Cardiac magnetic resonance (CMR) imaging revealed extended late gadolinium enhancement (LGE). Further diagnosis of eosinophilic granulomatosis with polyangitis (EGPA) was based on clinical manifestations and auxiliary examination. Subsequent immunosuppressive therapy led to regression of symptoms and significant resolution of LGE on CMR.Conclusion: Our case highlights that EGPA can be a rare cause of MINOCA. CMR is useful for differentiation diagnosis and evaluation of cardiac involvement.

Aims: The aim of the study was to determine the associations of weight loss or gain with all-cause mortality risk in heart failure with preserved ejection fraction (HFpEF).Methods and Results: Non-lean patients from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist study were analyzed (n = 1,515). Weight loss and weight gain were defined as a decrease or increase in weight ≥5% between baseline and 1 year. To determine the associations of weight change and mortality risk, we used adjusted Cox proportional hazards models and restricted cubic spline models. The mean age was 71.5 (9.6) years. Weight loss and gain were witnessed in 19.3 and 15.9% patients, respectively. After multivariable adjustment, weight loss was associated with higher risk of mortality (HR 1.42, 95% CI 1.06–1.89, P = 0.002); weight gain had similar risk of mortality (HR 0.98, 95% CI 0.68–1.42, P = 0.932) compared with weight stability. There was linear relationship between weight change and mortality risk. The association of weight loss and mortality was different for patients with and without diabetes mellitus (interaction p = 0.009).Conclusion: Among patients with HFpEF, weight loss was independently associated with higher risk of all-cause mortality, and weight gain was not associated with better survival.Clinical Trial Registration:https://clinicaltrials.gov, Identifier: NCT00094302.

Aims: To investigate the relationship between body-weight fluctuation and risks of clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).Methods and Results:We measured intra-individual variations in body weight from baseline and follow-up visits in 1,691 participants with HFpEF from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. The primary endpoint was any cardiovascular events (a composite of death from cardiovascular disease, non-fatal myocardial infarction, aborted cardiac arrest, or hospitalization for HF). The body-weight fluctuation was measured according to average successive variability and high variability was defined as greater than or equal to the median. After adjustment for risk factors, mean body weight and weight change, each increase of 1 standard deviation in body-weight variability was significantly associated with increased risks of any cardiovascular events (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.15–1.33, P < 0.001). Patients with high variability had a 47% increased risk of any cardiovascular events and 27% increased risk of all-cause death compared with those with low variability. Such association was similar among patients with New York Heart Association functional class I/II vs. III/IV, obesity vs. non-obesity, and weight loss, gain vs. stability (the P-values for interaction were all insignificant).Conclusion: Among patients with HFpEF, body-weight fluctuation was associated with increased risks of cardiovascular events independent of traditional cardiovascular risk factors, and regardless of HF severity, baseline weight or weight change direction.Clinical Trial Registration: Aldosterone antagonist therapy for adults with heart failure and preserved systolic function (TOPCAT), https://clinicaltrials.gov, identifier [NCT00094302].

Cardiac remodeling occurs after the heart is exposed to stress, which is manifested by pathological processes such as cardiomyocyte hypertrophy and apoptosis, dendritic cells activation and cytokine secretion, proliferation and activation of fibroblasts, and finally leads to heart failure. Circular RNAs (circRNAs) are recently recognized as a specific type of non-coding RNAs that are expressed in different species, in different stages of development, and in different pathological conditions. Growing evidences have implicated that circRNAs play important regulatory roles in the pathogenesis of a variety of cardiovascular diseases. In this review, we summarize the biological origin, characteristics, functional classification of circRNAs and their regulatory functions in cardiomyocytes, endothelial cells, fibroblasts, immune cells, and exosomes in the pathogenesis of cardiac remodeling.

Abstract ᅟ The present study comprised 17,096 Chinese hypertensive dyslipidemia patients who received lipid-lowering treatment for > 3 months in order to investigate blood pressure (BP) as well as low-density lipoprotein cholesterol (LDL-C) goal attainment rates in Chinese hypertensive dyslipidemia patients on antidyslipidemia drugs. The factors that interfered with BP, or BP and LDL-C goal attainment rates and antihypertensive treatment patterns, were analyzed. In total, 89.9% of the 17,096 hypertensive dyslipidemia patients received antihypertensive medications mainly consisting of a calcium channel blocker (CCB) (48.7%), an angiotensin receptor antagonist (ARB) (25.4%) and an angiotensin-converting enzyme inhibitor (ACEI) (15.1%). In cardiology departments, usage rates of β-blockers (19.2%) were unusually high compared to other departments (4.0–8.3%), whereas thiazide diuretics were prescribed at the lowest rate (0.3% vs 1.2–3.6%). The overall goal attainment rates for combined BP and LDL-C as well as BP or LDL-C targets were 22.9, 31.9 and 60.1%, respectively. The lowest BP, LDL-C and BP combined with LDL-C goal attainment rates were achieved in endocrine departments (19.9, 48.9 and 12.4%, respectively). Combination therapies showed no benefit particularly for BP goal achievement. A multivariate logistic regression analysis showed that age < 65 years, alcohol consumption, diabetes, coronary heart disease (CHD), cerebrovascular disease (CVD), chronic kidney disease (CKD), body mass index (BMI) ≥ 28 kg/m2 and not achieving total cholesterol goals were independent predictors for achieving BP, LDL-C or combined BP and LDL-C goals. In summary, the BP and LDL-C goal achievement rates in Chinese dyslipidemia outpatients with hypertension were low, especially in endocrine departments. Combination therapies were not associated with improvement of the goal achievement rates. Trial registration Clinical trial registration number NCT01732952

Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients.Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08–1.26; ALP: adjusted HR, 1.12; 95% CI 1.04–1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02–1.31; ALP: adjusted HR, 1.16; 95% CI 1.05–1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12–1.33; ALP: adjusted HR, 1.12; 95% CI 1.03–1.23).Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.

Heart failure is the terminal outcome of the majority of cardiovascular diseases, which lacks specific diagnostic biomarkers and therapeutic targets. It contributes to most of cardiovascular hospitalizations and death despite of the current therapy. Therefore, it is important to explore potential molecules improving the diagnosis and treatment of heart failure. MicroRNAs (miRNAs) are small non-coding RNAs that have been reported to be involved in regulating processes of heart failure. After the discovery of miRNAs in exosomes, the subcellular distribution analysis of miRNAs is raising researchers' attention. Growing evidence demonstrates that exosomal miRNAs may be promising diagnostic and therapeutic molecules for heart failure. This review summarizes the role of exosomal miRNAs in heart failure in the prospect of molecular and clinical researches.

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

Background: Heart failure with preserved ejection fraction (HFpEF) affects women more frequently than men. However, data on sex-specific associations of adverse health outcomes and left ventricular structure and function and with microalbuminuria in patients with HFpEF are scarce.Methods: In 1,334 participants enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial, we estimated the sex-specific multivariable-adjusted risk and LV traits with urine microalbumin/creatine ratio (ACR), using Cox or linear regression.Results: In total, 604 (45.3%) were women. In multivariable-adjusted analyses, a doubling of ACR in both men and women was associated with higher posterior (+0.014 cm, p = 0.012/+0.012 cm, p = 0.033) wall thickness and left ventricular mass index (+2.55 mg/m2, p = 0.004/+2.45 mg/m2, p = 0.009), whereas was also associated with higher septal (+0.018 cm, p = 0.002) and left atrial volume index (+1.44 mL/m2, p = 0.001) in men. ACR was a key predictor of all-cause (HR, 1.11; p = 0.006) and cardiovascular (HR, 1.17; p = 0.002) death in women, whereas in men ACR was associated with HF hospitalization (HR, 1.23; p < 0.001), any hospitalization (HR, 1.06; p = 0.006), and myocardial infarction (HR, 1.19; p = 0.017). The interactions of sex with ACR were significant for hospitalization for heart failure and any hospitalization (p ≤ 0.034).Conclusions: Outcomes and cardiac structure and function in patients with HFpEF appear to be influenced by ACR that vary according to sex. In men, ACR was significant associated with LV diastolic function, hospitalization, and myocardial infarction, whereas in women was associated with mortality.

Background Data on the association of systolic and diastolic blood pressure with the structure and function of failing hearts with preserved ejection fraction (EF) are sparse. Methods and Results This analysis included 935 patients with heart failure (49.4% women; mean age, 69.9 years) with preserved EF (≥45%) enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial before initiation of randomized therapy. Left ventricular (LV) structure (dimensions, wall thickness, and mass index), diastolic function (left atrial volume index, transmitral blood flow, and mitral annular velocities), and systolic function (EF and longitudinal strain) were assessed echocardiographically. In multivariable‐adjusted analyses, association sizes expressed per 1‐SD (14.8–mm Hg) increment in systolic blood pressure were 0.020 cm (P=0.003) and 0.018 cm (P=0.004) for LV septal and posterior wall thickness, respectively, and 2.42 mg/m2 (P=0.018) for LV mass index. The corresponding associations with diastolic blood pressure were nonsignificant (P≥0.067). In similarly adjusted analyses, the association sizes expressed per 1‐SD (10.7–mm Hg) increment in diastolic blood pressure were −0.15 for E/A (P

Introduction Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with coronary artery disease. However, rates of lipid-lowering medication adherence are far from ideal. Reducing dosage frequency from multiple dosing to once-daily dosing may improve patients’ medication adherence. Xuezhikang (XZK), an extract of Chinese red yeast rice, contains a family of naturally occurring statins and is traditionally prescribed as 600 mg two times per day. A comParative Efficacy study of XZK (APEX study) is designed to test the hypothesis that XZK prescribed 1200 mg once per day (OD group) is non-inferior to 600 mg two times per day (TD group) in patients with hypercholesterolaemia.Methods and analysis The APEX study is a multicentre, prospective randomised controlled, open-label, non-inferiority study. We plan to recruit 316 patients aged ≥18 years with a diagnosis of mild to moderate hypercholesterolaemia for primary prevention. Patients will be randomised (1:1) to OD group and TD group. The OD group take XZK 1200 mg once per day after dinner while TD group take a traditional dose of 600 mg, two times per day after meals. Participants will have an 8-week medication period and be followed up at weeks 0, 4 and 8. The primary end point is the mean percentage change from baseline to week 8 in serum LDL-C. Secondary end points are safety and lipid-lowering effect on other lipoproteins and compliance. Data analyses will be on the intention-to-treat principle using non-inferiority analysis.Ethics and dissemination The research had been approved by the Clinical Research and Laboratory Animal Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University ((2017)286). The results will be reported through peer-reviewed journals, seminars and conference presentations.Trial registration number ChiCTR-IIR-17013660.

Background/Aims: Cyr61-cysteine-rich protein 61 (CCN1/CYR61) is a multifunctional matricellular protein involved in the regulation of fibrogenesis. Animal experiments have demonstrated that CCN1 can inhibit cardiac fibrosis in cardiac hypertrophy. However, no study has been conducted to assess the relation between serum CCN1 and prognosis of acute heart failure (AHF). Methods: We measured the serum CCN1 levels of 183 patients with AHF, and the patients were followed up for 6 months. The associations between CCN1 levels and some clinical covariates, especially left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), atrial fibrillation and age, were estimated. The AHF patients were followed up for 6 months. The endpoint was all-cause mortality. Kaplan-Meier curve analysis and multivariable Cox proportional hazards analysis were employed to evaluate the prognostic ability of CCN1. We used calibration, discrimination and reclassification to assess the mortality risk prediction of adding CCN1. Results: Serum CCN1 concentrations in AHF patients were significantly increased compared with those in individuals without AHF (237 pg/ml vs. 124.8 pg/ml, p< 0.001). CCN1 level was associated with the level of NT-proBNP (r=0.349, p< 0.001) and was not affected by LVEF, eGFR, age or atrial fibrillation in AHF patients. Importantly, Kaplan-Meier curve analysis illustrated that the AHF patients with serum CCN1 level > 260 pg/ ml had a lower survival rate (p< 0.001). Multivariate Cox hazard analysis suggests that CCN1 functions as an independent predictor of mortality for AHF patients (LgCCN1, hazard ratio 5.825, 95% confidence interval: 1.828-18.566, p=0.003). In addition, the inclusion of CCN1 in the model with NT-proBNP significantly improved the C-statistic for predicting death (0.758, p< 0.001). The integrated discrimination index was 0.019 (p< 0.001), and the net reclassification index increased significantly after addition of CCN1 (23.9%, p=0.0179). Conclusions: CCN1 is strongly predictive of 6-month mortality in patients with AHF, suggesting serum CCN1 as a promising candidate prognostic biomarker for AHF patients.

Finite-state model predictive control (FS-MPC) is computationally expensive, as it uses all voltage vectors available for prediction and estimation. This paper proposes a novel finite-state model-based predictive current control (MPCC) scheme to overcome the drawbacks of FS-MPC. A reference frame based on the prediction of the current locus when a zero-voltage vector is employed is established to reduce the computational requirements; specifically, only one zero-voltage vector must be predicted compared with the seven required in conventional FS-MPC. The selection of the optimal voltage vector is based on the direction of the current locus in the established reference frame instead of a cost function, which is necessary and time consuming in conventional FS-MPC. Zero-voltage vectors are also selected by contrasting the distance between the reference and predictive currents to reduce the torque ripple of the proposed method. Simulation and experimental results are presented and confirm the efficient performance of the proposed MPCC.

This paper proposes an improved continuous-time model predictive control (CTMPC) of permanent magnetic synchronous motors (PMSMs) for a wide-speed range, including the constant torque region and the flux-weakening (FW) region. In the constant torque region, the mathematic models of PMSMs in dq-axes are decoupled without the limitation of DC-link voltage. However, in the FW region, the mathematic models of PMSMs in dq-axes are cross-coupled together with the limitation of DC-link voltage. A nonlinear PMSMs mathematic model in the FW region is presented based on the voltage angle. The solving of the nonlinear mathematic model of PMSMs in FW region will lead to heavy computation load for digital signal processing (DSP). To overcome such a problem, a linearization method of the voltage angle is also proposed to reduce the computation load. The selection of transiting points between the constant torque region and FW regions is researched to improve the performance of the driven system. Compared with the proportional integral (PI) controller, the proposed CTMPC has obvious advantages in dealing with systems’ nonlinear constraints and improving system performance by restraining overshoot current under step torque changing. Both simulation and experimental results confirm the effectiveness of the proposed method in achieving good steady-state performance and smooth switching between the constant torque and FW regions.

BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) transplantation is a promising approach for myocardium repair. Promotion of ASCs migration and survival is the key for improving ASCs efficiency. SDF-1α is a critical factor responsible for ASCs migration and survival. Atorvastatin (Ator) is capable of up-regulating SDF-1α. Therefore, we're going to investigate whether ASCs migration and survival could be improved with atorvastatin. METHODS: In vitro study, cardiomyocytes were subjected to anoxia-reoxygenation injury and subsequently divided into different groups: group blank control, Ator, Ator plus L-NAME (A+L-NAME) and Ator plus AMD3100 (A+AMD3100).When migration analysis completed, cardiomyocytes were used for subsequent analyses. In vivo study, rats underwent ischemia-reperfusion injury were assigned into different groups corresponding to in vitro protocols. ASCs were transplanted on the seventh day of atorvastatin therapy. Seven days later, the rates of migration, differentiation and apoptosis were evaluated. RESULTS: Compared with other groups, ASCs migration in vitro was significantly improved in group Ator, which was dependent on SDF-1α/CXCR-4 coupling. Results of in vivo study were consistent with that of in vitro study, further supporting the notion that the efficacy of atorvastatin on ASCs migration improvement was related to SDF-1α/CXCR-4 axis. Higher vessel density in group Ator might be another mechanism responsible for migration improvement. Concomitantly, apoptosis was significantly reduced in group Ator, whereas no significant difference of differentiation was found. CONCLUSION: Migration and survival of ASCs could be improved by atorvastatin under ischemia-reperfusion injury, which were ascribed to SDF-1α/CXCR-4 axis.