Revisiting the diagnostic and prognostic significance of high-frequency QRS analysis in cardiovascular diseases: a comprehensive review.

Cardiovascular diseases (CVDs) present a significant global public health threat, contributing to a substantial number of cases involving morbidity and mortality. Therefore, the early and accurate detection of CVDs plays an indispensable role in enhancing patient outcomes. Decades of extensive research on electrocardiography at high frequencies have yielded a wealth of knowledge regarding alterations in the QRS complex during myocardial ischemia, as well as the methodologies to assess and quantify these changes. In recent years, the analysis of high-frequency QRS (HF-QRS) components has emerged as a promising non-invasive approach for diagnosing various cardiovascular conditions. Alterations in HF-QRS amplitude and morphology have demonstrated remarkable sensitivity as diagnostic indicators for myocardial ischemia, often surpassing measures of ST-T segment changes. This comprehensive review aims to provide an intricate overview of the current advancements, challenges, and prospects associated with HF-QRS analysis in the field of CVDs.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Association of Pre-PCI Blood Pressure and No-Reflow in Patients with Acute ST-Elevation Coronary Infarction.

Background: Previous studies have established blood pressure (BP) as a pivotal factor influencing no-reflow following primary percutaneous coronary intervention (PCI) in patients with ST-elevation acute coronary infarction (STEMI). However, no relevant study has been conducted to investigate the optimal range of BP associated with the lowest risk of no-reflow among STEMI patients so far. Therefore, our objective was to evaluate the association between pre-PCI BP and the occurrence of no-reflow in patients with STEMI. Method: We included 1025 STEMI patients undergoing primary PCI. The BP pre-PCI was categorized into 20-mmHg increments. Logistic models were employed to assess the association of no-reflow with systolic blood pressure (SBP) or diastolic blood pressure (DBP). Three sensitivity analyses were conducted to further confirm the robustness of the association between blood pressure and no-reflow. Results: SBP or DBP exhibited a U-shaped curve association with no-reflow. No-reflow was higher in patients with lower SBP (<100 mmHg) (adjusted hazard ratio (OR) 3.64, 95% confidence interval (CI) 1.84,7.21; p < 0.001) and lower DBP (<60 mmHg) (OR 3.28, 95% CI 1.63,6.49; p < 0.001) [reference: 120 ≤SBP <140; 80 ≤DBP <100 mmHg], respectively. Furthermore, no-reflow was higher in patients with higher SBP (≥160 mmHg) (OR 2.07, 95% CI 1.27,3.36; p = 0.003) and DBP (≥100 mmHg) (OR 3.36, 95% CI 2.07,5.46; p < 0.001), respectively. The results of sensitivity analyses were consistent with the above findings. Conclusion: Maintaining a pre-PCI SBP within the range of 120 to 140 mmHg and a DBP within the range of 80 to 100 mmHg may be confer benefits to patients with STEMI in no-reflow.

A Prediction Model Based on Systemic Immune-Inflammatory Index Combined with Other Predictors for Major Adverse Cardiovascular Events in Acute Myocardial Infarction Patients.

Objective: To evaluate the prognostic value of the systemic immune-inflammatory index (SII) for predicting in-hospital major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) and establish a relevant nomogram. Methods: This study included 954 AMI patients. We examined three inflammatory factors (SII, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR)) to see which one predicts in-hospital MACEs better. The predictors were subsequently screened using bidirectional stepwise regression method, and a MACE nomogram was constructed via logistic regression analysis. The predictive value of the model was evaluated using the area under the curve (AUC), sensitivity and specificity. In addition, the clinical utility of the nomogram was evaluated using decision curve analysis. We also compared the nomogram with the Global Registry of Acute Coronary Events (GRACE) scoring system. Results: 334 (35.0%) patients had MACEs. The SII (AUC =0.684) had a greater predictive value for in-hospital MACEs in AMI patients than the PLR (AUC =0.597, P<0.001) or NLR (AUC=0.654, P=0.01). The area under the curve (AUC) of the SII-based multivariable model for predicting MACEs, which was based on the SII, Killip classification, left ventricular ejection fraction, age, urea nitrogen (BUN) concentration and electrocardiogram-based diagnosis, was 0.862 (95% CI: 0.833-0.891). Decision curve and calibration curve analysis revealed that SII-based multivariable model demonstrated a good fit and calibration and provided positive net benefits than the model without SII. The predictive value of the SII-based multivariable model was greater than that of the GRACE scoring system (P<0.001). Conclusion: SII is a promising, reliable biomarker for identifying AMI patients at high risk of in-hospital MACEs, and SII-based multivariable model may serve as a quick and easy tool to identify these patients.

Genetic Association of Lipid-Lowering Drugs with Aortic Aneurysms: A Mendelian Randomization Study.

AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. RESULTS: The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, p = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, p = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, p = 1.78 × 10-04). PCSK9 (Proprotein convertase subtilisin/kexin type 9) and CETP (Cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, p = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, p = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSIONS: This study provides causal evidence for the genetic association between lipid-lowering drugs and aortic aneurysms. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

This Mendelian Randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms. Key findings High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.

Safety and efficacy of the DragonFly system for transcatheter valve repair of degenerative mitral regurgitation: one-year results of the DRAGONFLY-DMR trial.

BACKGROUND: Severe degenerative mitral regurgitation (DMR) can cause a poor prognosis if left untreated. For patients considered at prohibitive surgical risk, transcatheter edge-to-edge repair (TEER) has become an accepted alternative therapy. The DragonFly transcatheter valve repair system is an innovative evolution of the mitral TEER device family to treat DMR. AIMS: Herein we report on the DRAGONFLY-DMR trial (ClinicalTrials.gov: NCT04734756), which was a prospective, single-arm, multicentre study on the safety and effectiveness of the DragonFly system. METHODS: A total of 120 eligible patients with prohibitive surgical risk and DMR ≥3+ were screened by a central eligibility committee for enrolment. The study utilised an independent echocardiography core laboratory and clinical event committee. The primary endpoint was the clinical success rate, which measured freedom from all-cause mortality, mitral valve reintervention, and mitral regurgitation (MR) >2+ at 1-year follow-up. RESULTS: At 1 year, the trial successfully achieved its prespecified primary efficacy endpoint, with a clinical success rate of 87.5% (95% confidence interval: 80.1-92.3%). The rates of major adverse events, all-cause mortality, mitral valve reintervention, and heart failure hospitalisation were 9.0%, 5.0%, 0.8%, and 3.4%, respectively. MR ≤2+ was 90.4% at 1 month and 92.0% at 1 year. Over time, left ventricular reverse remodelling was observed (p<0.05), along with significant improvements in the patients' functional and quality-of-life outcomes, shown by an increase in the New York Heart Association Class I/II from 32.4% at baseline to 93.6% at 12 months (p<0.001) and increased Kansas City Cardiomyopathy Questionnaire (KCCQ) score of 31.1±18.2 from baseline to 12 months (p<0.001). CONCLUSIONS: The DRAGONFLY-DMR trial contributes to increasing evidence supporting the safety and efficacy of TEER therapy, specifically the DragonFly system, for treating patients with chronic symptomatic DMR 3+ to 4+ at prohibitive surgical risk.

Associations of serum carotenoids with visceral adiposity index and lipid accumulation product: a cross-sectional study based on NHANES 2001-2006.

BACKGROUND: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP. METHODS: The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors. RESULTS: In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (ß) and 95% CI was - 0.98 (- 1.34, - 0.62) for α-carotene, - 1.39 (- 1.77, - 1.00) for ß-carotene, - 0.79 (- 1.18, - 0.41) for ß-cryptoxanthin, - 0.68 (- 0.96, - 0.39) for lutein/zeaxanthin, and - 0.88 (- 1.50, - 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between ß-carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments. CONCLUSION: This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding.

Association between serum Klotho concentration and hyperlipidemia in adults: a cross-sectional study from NHANES 2007-2016.

Objective: The Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults. Methods: The study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships. Results: In our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86-0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58-0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects. Conclusion: This study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.

Pregnancy-induced physiological hypertrophic preconditioning attenuates pathological myocardial hypertrophy by activation of FoxO3a.

Previous studies show a woman's pregnancy is correlated with post-reproductive longevity, and nulliparity is associated with higher risk of incident heart failure, suggesting pregnancy likely exerts a cardioprotection. We previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning (PHP) can also protect the heart against subsequent pathological hypertrophic stress. We aimed to clarify the phenomenon of PHP and its mechanisms. The pluripara mice whose pregnancy-induced physiological hypertrophy regressed and the nulliparous mice underwent angiotensin II (Ang II) infusion or transverse aortic constriction (TAC). Echocardiography, invasive left ventricular hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. Silencing or overexpression of Foxo3 by adeno-associated virus was used to investigate the role of FoxO3a involved in the antihypertrophic effect. Compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang II infusion, or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with PHP. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3ß (p-GSK3ß)/ß-catenin/Cyclin D1. Silencing or overexpression of Foxo3 attenuated or enhanced the anti-hypertrophic effect of PHP in mice with pathological stimulation. Our findings demonstrate that PHP confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3ß pathway.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Long-Chain Acyl Carnitines Aggravate Polystyrene Nanoplastics-Induced Atherosclerosis by Upregulating MARCO.

Exposure to micro- and nanoplastics (MNPs) is common because of their omnipresence in environment. Recent studies have revealed that MNPs may cause atherosclerosis, but the underlying mechanism remains unclear. To address this bottleneck, ApoE-/- mice are exposed to 2.5-250 mg kg-1 polystyrene nanoplastics (PS-NPs, 50 nm) by oral gavage with a high-fat diet for 19 weeks. It is found that PS-NPs in blood and aorta of mouse exacerbate the artery stiffness and promote atherosclerotic plaque formation. PS-NPs activate phagocytosis of M1-macrophage in the aorta, manifesting as upregulation of macrophage receptor with collagenous structure (MARCO). Moreover, PS-NPs disrupt lipid metabolism and increase long-chain acyl carnitines (LCACs). LCAC accumulation is attributed to the PS-NP-inhibited hepatic carnitine palmitoyltransferase 2. PS-NPs, as well as LCACs alone, aggravate lipid accumulation via upregulating MARCO in the oxidized low-density lipoprotein-activated foam cells. Finally, synergistic effects of PS-NPs and LCACs on increasing total cholesterol in foam cells are found. Overall, this study indicates that LCACs aggravate PS-NP-induced atherosclerosis by upregulating MARCO. This study offers new insight into the mechanisms underlying MNP-induced cardiovascular toxicity, and highlights the combined effects of MNPs with endogenous metabolites on the cardiovascular system, which warrant further study.

Diagnostic performance of angiography-derived fractional flow reserve analysis based on bifurcation fractal law for assessing hemodynamic significance of coronary stenosis.

OBJECTIVES: Blood flow into the side branch affects the calculation of coronary angiography-derived fractional flow reserve (FFR), called Angio-FFR. Neglecting or improperly compensating for the side branch flow may decrease the diagnostic accuracy of Angio-FFR. This study aims to evaluate the diagnostic accuracy of a novel Angio-FFR analysis that considers the side branch flow based on the bifurcation fractal law. METHODS: A one-dimensional reduced-order model based on the vessel segment was used to perform Angio-FFR analysis. The main epicardial coronary artery was divided into several segments according to the bifurcation nodes. Side branch flow was quantified using the bifurcation fractal law to correct the blood flow in each vessel segment. In order to verify the diagnostic performance of our Angio-FFR analysis, two other computational methods were taken as control groups: (i) FFR_s: FFR calculated by delineating the coronary artery tree to consider side branch flow, (ii) FFR_n: FFR calculated by just delineating the main epicardial coronary artery and neglecting the side branch flow. RESULTS: The analysis of 159 vessels from 119 patients showed that our Anio-FFR calculation method had comparable diagnostic accuracy to FFR_s and provided significantly higher diagnostic accuracy than that of FFR_n. In addition, using invasive FFR as a reference, the Pearson correlation coefficients of Angio-FFR and FFRs were 0.92 and 0.91, respectively, while that of FFR_n was only 0.85. CONCLUSIONS: Our Angio-FFR analysis has demonstrated good diagnostic performance in assessing the hemodynamic significance of coronary stenosis by using the bifurcation fractal law to compensate for side branch flow. CLINICAL RELEVANCE STATEMENT: Bifurcation fractal law can be used to compensate for side branch flow during the Angio-FFR calculation of the main epicardial vessel. Compensating for side branch flow can improve the ability of Angio-FFR to diagnose stenosis functional severity. KEY POINTS: • The bifurcation fractal law could accurately estimate the blood flow from the proximal main vessel into the main branch, thus compensating for the side branch flow. • Angiography-derived FFR based on the bifurcation fractal law is feasible to evaluate the target diseased coronary artery without delineating the side branch.

Insights into the toxicological effects of nanomaterials on atherosclerosis: mechanisms involved and influence factors.

Atherosclerosis is one of the most common types of cardiovascular disease and is driven by lipid accumulation and chronic inflammation in the arteries, which leads to stenosis and thrombosis. Researchers have been working to design multifunctional nanomedicines with the ability to target, diagnose, and treat atherosclerosis, but recent studies have also identified that nanomaterials can cause atherosclerosis. Therefore, this review aims to outline the molecular mechanisms and physicochemical properties of nanomaterials that promote atherosclerosis. By analyzing the toxicological effects of nanomaterials on cells involved in the pathogenesis of atherosclerosis such as vascular endothelial cells, vascular smooth muscle cells and immune cells, we aim to provide new perspectives for the prevention and treatment of atherosclerosis, and raise awareness of nanotoxicology to advance the clinical translation and sustainable development of nanomaterials.

Reactive oxygen species-induced long intergenic noncoding RNA p21 accelerates abdominal aortic aneurysm formation by promoting secretary smooth muscle cell phenotypes.

Whether long noncoding RNAs participate in the formation of abdominal aortic aneurysms (AAAs) through the regulation of SMC phenotypic switching is unknown. lincRNA-p21 induced by reactive oxygen species (ROS) is likely functionally associated with SMC phenotypic switching. We thus investigated the role of lincRNA-p21 in SMC phenotypic switching-associated AAA formation and its underlying mechanisms. An analysis of human and mouse abdominal aortic samples revealed that the lincRNA-p21 levels were significantly higher in AAA tissue. Stimulation with hydrogen peroxide upregulated the expression of lincRNA-p21 in a dose-dependent manner and converted SMCs from a contractile phenotype to a synthetic, proteolytic, and proinflammatory phenotype in vitro. Moreover, lincRNA-p21 promoted fracture of elastic fibres, reconstruction of the vascular wall, and AAA formation in vivo by modulating SMC phenotypic switching in two mouse models of AAA induced by angiotensin II or porcine pancreatic elastase (PPE) perfusion. Using a bioinformatics prediction method and luciferase reporter gene assays, we further proved that lincRNA-p21 sponged miR-204-5p to release the transcriptional activity of Mekk3 and promoted the NF-κB pathway and thereby played a role in the SMC phenotypic switch and AAA formation. The ROS levels were positively correlated with the lincRNA-p21 levels in human and mouse AAA tissues. The knockdown of lincRNA-p21 in a PPE-induced mouse AAA model increased the miR-204-5p levels and reduced the expression of Mekk3, whereas lincRNA-p21 overexpression had the opposite effect. Collectively, the results indicated that ROS-induced lincRNA-p21 sponges miR-204-5p to accelerate synthetic and proinflammatory SMC phenotypes through the Mekk3/NF-κB pathway in AAA formation. Thus, lincRNA-p21 may have therapeutic potential for AAA formation.

Circ-Ddx60 contributes to the antihypertrophic memory of exercise hypertrophic preconditioning.

INTRODUCTION: We previously reported a phenomenon called exercise hypertrophic preconditioning (EHP), the underlying mechanisms of which need further clarification. OBJECTIVES: We aimed to investigate whether circular RNAs (circRNAs) are involved in EHP. METHODS: CircRNA sequencing of myocardial tissue was performed in male C57BL/6 mice with EHP and sedentary. Bioinformatics analysis and Sanger sequencing were used to screen hub circRNA expression and to detect full-length circRNAs, respectively. Loss-of-function analyses were conducted to assess the effects of circ-Ddx60 (c-Ddx) on EHP. After 21 days of swimming training or resting, mice underwent transverse aortic constriction (TAC) or sham surgery. Echocardiography, invasive hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. The presence of interaction between c-Ddx and proteins was investigated using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS). RESULTS: In this study, we identified a novel circRNA, named c-Ddx that was preferentially expressed in myocardial tissue and significantly up-regulated in EHP mice. Silencing of c-Ddx attenuated the antihypertrophic effect of EHP and worsened heart failure in mice that underwent TAC. ChIRP-MS and molecular docking analysis validated the combination of c-Ddx and eukaryotic elongation factor 2 (eEF2). Mechanistically, c-Ddx silencing inhibited the increase of phosphorylation of eEF2 and its upstream AMP-activated protein kinase (AMPK) induced by EHP. CONCLUSIONS: C-Ddx contributes to the antihypertrophic memory of EHP by binding and activating eEF2, which would provide opportunity to search new therapeutic targets for pathological hypertrophy of heart.

Association between triglyceride-glucose index and worsening renal function in the elderly.

Background: Triglyceride-glucose (TyG) index is a simple marker of insulin resistance. However, insufficient data is available on whether the TyG index is associated with worsening renal function (WRF) in the elderly. Therefore, this study was designed to explore the association between the TyG index and WRF based on a community elderly cohort. Methods: In this study, 7,822 elderly (aged ≥ 65 years) adults from southern China were enrolled and divided into four groups according to the TyG index quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Additional endpoints included a decline in eGFR of 30% and 40% during the follow-up period. Results: During the median 2.04 year follow-up period, 1,541 (19.7%) participants developed CKD. After adjusting for confounding factors, multivariable Cox regression models revealed significant associations between TyG index and incident CKD (HR per SD increase, 1.21; 95% CI: 1.14-1.29), a decline in eGFR of 30% (HR per SD increase, 1.38; 95% CI: 1.26-1.50), and decline in eGFR of 40% (HR per SD increase, 1.42; 95% CI: 1.24-1.63). Furthermore, compared with those in Q1, participants in Q4 demonstrated a higher risk of developing CKD (HR, 1.59; 95% CI: 1.35-1.88). These positive associations remained consistent across different subgroup populations. Conclusion: Our study suggests a positive and independent association between the TyG index and WRF in the elderly.

A novel and effective ECG method to differentiate right from left ventricular outflow tract arrhythmias: Angle-corrected V2S.

Background and aims: Standard 12-lead electrocardiogram (ECG) patterns combined with the anatomical cardiac long-axis angle revealed by chest X-ray can prevent the influence of cardiac rotation, physical shape, and lead position, so it may be an ideal means to predict the origin of the outflow tract (OT) ventricular arrhythmias (OTVAs) for ablation procedures. The study explores the value of this strategy in identifying the origin of OTVA. Methods: This study was conducted using a retrospective cohort and a prospective cohort of consecutive patients at two centers. The anatomical cardiac long-axis angle was calculated by measuring the angle between the cardiac long-axis (a line joining the apex to the midpoint of the mitral annulus) and the horizontal plane on a chest X-ray. The V2S angle was calculated as the V2S amplitude times the angle. We ultimately enrolled 147 patients with symptomatic OTVAs who underwent successful radiofrequency catheter ablation (RFCA) (98 women (66.7%); mean age 46.9 ± 14.7 years; 126 right ventricular OT (RVOT) origins, 21 left ventricular OT (LVOT) origins) as a development cohort. The new algorithm was validated in 48 prospective patients (12 men (25.0%); mean age 48.0 ± 15.8 years; 36 RVOT, 12 LVOT origins). Results: Patients with RVOT VAs had greater V2S, long-axis angle, and V2S angle than patients with LVOT VA (all P < 0.001). The cut-off V2S angle obtained by receiver operating characteristic (ROC) curve analysis was 58.28 mV° for the prediction of RVOT origin (sensitivity: 85.7%; specificity: 95.2%; positive predictive value: 99.1%; negative predictive value: 52.6%). The AUC achieved using the V2S angle was 0.888 (P < 0.001), which was the highest among all indexes (V2S/V3R: 0.887 (P < 0.016); TZ index: 0.858 (P < 0.001); V1-2 SRd: 0.876 (P < 0.001); V3 transition: 0.651 (P < 0.001)). In the prospective cohort, the V2S angle had a high overall accuracy of 93.8% and decreased the procedure time (P = 0.002). Conclusion: V2S angle can be a novel measure that can be used to accurately differentiate RVOT from LVOT origins. It could help decrease ablation duration and radiation exposure.

Noninvasive photoacoustic computed tomography/ultrasound imaging to identify high-risk atherosclerotic plaques.

PURPOSE: Noninvasive detection of high-risk plaques is still challenging. In this study, we aimed to noninvasively assess αvß3-integrin expression using a customed photoacoustic (PA) computed tomography (PACT)/ultrasound (US) system in atherosclerotic lesions of varying degrees of severity and to explore its potential value for detecting high-risk plaques. METHODS: We constructed αvß3-integrin-targeted ultrasmall gold nanorods (AuNRs) with cyclo Arg-Gly-Asp (cRGD) and tested their properties. Employing C57BL/6 J (wild-type, WT) mice and apolipoprotein E gene knockout (ApoE-/-) mice fed either a chow diet or a high-fat/high-cholesterol diet (HFHCD), we established varying degrees of lesion severity. In vivo PACT/US imaging was performed to assess αvß3-integrin expression in the 4 groups by cRGD-AuNRs. Further histopathologic examination was conducted to evaluate the plaque vulnerability indicators. RESULTS: The data showed that cRGD-AuNRs exhibited excellent photothermal conversion capacity, stability, targeting ability, and biocompatibility. The immunohistochemical results indicated that αvß3-integrin was upregulated with increasing aggravation of the lesions. In vivo PACT/US imaging showed good consistency with αvß3-integrin expression. Notably, ApoE-/- mice fed a HFHCD showed an abrupt PA intensity increase compared with the other groups. The histopathologic examination verified that the atherosclerotic plaques of ApoE-/- mice fed the HFHCD developed unstable phenotypes. Correlation analysis showed that PA intensity was mainly related to inflammation and angiogenesis among all of the indicators. CONCLUSION: Our data indicated that αvß3-integrin is an effective indicator of plaque instability, and noninvasive PACT/US molecular imaging assessment of αvß3-integrin holds promise in detecting high-risk plaques.

Impact of the caFFR-Guided Functional SYNTAX Score on Ventricular Tachycardia/Fibrillation Development in Patients With Acute Myocardial Infarction.

Aims: To explore the relationship between the severity of coronary artery disease (CAD) and the occurrence of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with acute myocardial infarction (AMI). Methods: We retrospectively enrolled 705 patients with AMI, who were hospitalized and underwent percutaneous coronary intervention (PCI), in Nanfang Hospital from July 2017 to July 2020. Logistic regression analysis and backward stepwise approach were taken to select the correlation factors. The left and the receiver operating characteristic curves (ROC) analysis were plotted to observe the discriminative power of the SYNTAX score (SS)/caFFR-guided functional SS (FSScaFFR) on the incident VT/VF. Results: About 58 (8.2%) patients experienced life-threatening VT/VF. The FSScaFFR (OR: 1.155; 95% CI: 1.047 to 1.273; p = 0.004) was an independent predictor of VT/VF after AMI. The ROC analysis showed that the discriminative power of FSScaFFR on the incident VT/VF was significantly better than SS (0.759 vs.0.695, p < 0.0001). Patients with VT/VF were categorized into 2 groups according to the interval between the onset of AMI and the VT/VF. The logistic regression analysis revealed that FSScaFFR was a significant independent correlation of early- and late-VT/VF. Conclusion: The incident VT/VF in patients with AMI is closely associated with the severity of CAD evaluated by SS and FSScaFFR. Compared to SS, FSScaFFR has a higher correlation with VT/VF, and FSScaFFR was demonstrated to be an independent correlation factor of incident VT/VF after AMI.

The Association Between the Frequency of Annual Health Checks Participation and the Control of Cardiovascular Risk Factors.

Background: General health checks can help in controlling cardiovascular risk factors. However, few studies have investigated whether regular participation in annual health checks could further improve the control of cardiovascular risk factors compared with intermittent participation. Therefore, our study aimed to explore the association between the frequency of annual health check participation and the control of cardiovascular risk factors. Methods: Residents aged ≥ 65 years or having chronic diseases (hypertension or diabetes) from 37 communities of Guangzhou, Guangdong, who participated in the Basic Public Health Service project between January 2015 and December 2019, were enrolled and divided into 3 groups ("Sometimes," "Usually," and "Always") according to their frequencies of annual health check participation. Multivariable linear regression models were performed to assess the association between the frequency of annual health check participation and the control of cardiovascular risk factors. A subgroup analysis stratified by gender was also conducted. Results: In total, 9,102 participants were finally included. Significant differences were identified between groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and serum creatinine. After fully adjusting for confounding factors, residents who always participated in the annual health check tended to have lower SBP (ß = -4.36, 95% CI: -5.46; -3.26, p < 0.001), fasting glucose (ß = -0.27, 95% CI: -0.38; -0.15, p < 0.001), and total cholesterol (ß = -0.19, 95% CI: -0.26; -0.13, p < 0.001), compared with those who attended sometimes. Furthermore, gender did not alter these associations. Conclusion: A higher frequency of annual health check participation was associated with lower SBP, fasting glucose, and total cholesterol.