AIMS:The study investigated the predictive value of serum soluble ST2 (sST2) and left atrial strain parameters for left ventricular systolic dysfunction (LVSD), and the correlation analysis with corresponding indicators in patients with chronic coronary syndrome (CCS). METHODS:A total of 135 patients with CCS who presented to the Cardiology Department Zhongda hospital and underwent echocardiographic examinations from January 2025 to December 2025 were ultimately included. Based on two-dimensional speckle tracking echocardiography, left ventricular global longitudinal strain and left atrial strain were measured within 72 h of CCS diagnosis, and the patients were categorized into two groups: LV GLS > -17%, LVSD group; and LV GLS≤-17%, non- LVSD group. Baseline data were collected from all patients and compared between the two groups. The correlation between sST2 and LA parameters in CCS patients was evaluated using Spearman correlation.  Based on the results of the multivariate logistic regression analysis, a predictive model for LVSD in CCS patients was established. RESULTS:In the LVSD group, sST2 levels, early diastolic mitral inflow velocity (E)/ early diastolic mitral annular velocity (e') ratio, left atrial volume index (LAVI), and left atrial stiffness index (LASI) were increased. In the CCS patients, sST2, E/e', LAVI, and LASI demonstrated good correlation. sST2 and LASI were independent predictors for diagnosing LVSD in patients with CCS. ROC curve analysis showed that ST2 and LASI had diagnostic value for left ventricular systolic dysfunction in patients with CCS. CONCLUSION:This study found that in patients with CCS complicated by LVSD, sST2 levels were elevated, left atrial strain parameters were impaired, and a certain correlation was observed between the two. Furthermore, we investigated whether sST2 and LASI are independent predictors for diagnosing LVSD in CCS patients. By combining these two indicators, a diagnostic model can be constructed.

Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is characterized by the frequent co-occurrence of obesity, central adiposity, insulin resistance, type 2 diabetes mellitus, and low-grade inflammation. How these exposures sustain myocardial remodeling remains uncertain. One-carbon metabolism provides a plausible biochemical interface between nutrient stress and epigenetic regulation: S-adenosylmethionine (SAM) donates methyl groups, whereas S-adenosylhomocysteine (SAH) inhibits methyltransferases. Altered nicotinamide N-methyltransferase (NNMT) flux, homocysteine-related SAH retention, and metabolic regulation of DNA methyltransferase (DNMT) and ten-eleven translocation (TET) enzymes could therefore reshape DNA methylation and hydroxymethylation. Direct human evidence remains sparse: available HFpEF methylation data are blood-derived rather than myocardial, and cardiac or adjacent models support individual components of the framework but not a continuous disease-specific pathway. We therefore view DNA methylation as a context-dependent regulatory layer that may amplify or stabilize inflammatory, fibrotic, and metabolic programs rather than as a uniform initiating cause. Accordingly, translational studies should prioritize compartment-specific target engagement, reversibility, and biomarker-guided patient selection rather than assume a role for methylation-directed therapy.

A 76-year-old female with rheumatic heart disease presented with progressive dyspnea 12 years after dual surgical bioprosthetic valve replacement (mitral: 25 mm; aortic: 21 mm). Diagnostic imaging revealed severe stenosis of both prostheses, with a mitral valve area of 0.8 cm2 and an aortic valve area of 1.06 cm2, complicated by a risk of left ventricular outflow tract obstruction (neo-left ventricular outflow tract obstruction area: 110 mm2). Given the high surgical risk, simultaneous transfemoral transcatheter aortic and mitral valve-in-valve implantation was performed using Edwards Sapien 3 valves. The Laceration of the Anterior Mitral leaflet to Prevent left ventricular Outflow Obstruction (LAMPOON) technique was employed to prophylactically divide the anterior bioprosthetic leaflet, preventing left ventricular outflow tract obstruction. Post-procedural recovery was uncomplicated, and echocardiography demonstrated restored valve function; the mitral mean gradient was 3 mmHg and the aortic mean gradient was 10 mmHg. This case demonstrates the feasibility of dual valve-in-valve therapy for patients with complex bioprosthetic degeneration.

Background: Vascular calcification (VC) is an inflammatory disease driven by aberrant cellular processes in which macrophages play an important role. The A disintegrin and metalloproteinase 8 (ADAM8) protein is an important regulatory factor in macrophages and contributes to the development of inflammatory diseases. However, the relationship between ADAM8 and VC remains unknown. Thus, this study aimed to investigate the role of macrophage ADAM8 in VC. Methods: Plasma ADAM8 levels were compared between patients with and without aortic calcification. Immunofluorescence staining of human aortic tissue samples was performed to assess differences in ADAM8 expression between calcified and non-calcified tissues. Macrophage-specific Adam8 knockout mice (Adam8flox/flox, Lyz2-Cre; KO) and the corresponding control mice (Adam8flox/flox; Flox) were generated using CRISPR/Cas9 technology. Additionally, the adeno-associated virus AAV6-F4/80-Adam8 was employed to achieve macrophage-specific overexpression. The relationship between macrophage ADAM8 and VC was studied in a VC mouse model of chronic kidney disease (CKD) by comparing VC severity between groups. Results: Plasma ADAM8 levels were elevated in patients with aortic calcification. Immunofluorescence staining of human aortic samples suggested that VC was associated with ADAM8-positive macrophage infiltration and ADAM8 released by macrophages. In mice, macrophage-specific Adam8 knockout attenuated the development of CKD-associated VC, whereas macrophage-specific ADAM8 overexpression reversed the VC phenotype. Conclusion: ADAM8 levels are elevated in patients with aortic calcification and are associated with macrophage infiltration into vascular tissue and ADAM8 release, leading to increased VC. These findings identify ADAM8 as a promising novel therapeutic target for preventing VC.

BACKGROUND:Calcified coronary lesions present challenges during percutaneous coronary intervention, often impeding successful stent delivery and expansion. Rotational atherectomy (RA) facilitates plaque modification in such cases. However, clinical performance of a novel RA system remains unclear. OBJECTIVES:This noninferiority study evaluated the safety and efficacy of the novel system. METHODS:This trial included 2 prospective phases, a first-in-human (FIH) study and a pivotal randomized controlled trial. In the FIH study, 15 patients underwent percutaneous coronary intervention with the novel RA system, and clinical success was assessed. In pivotal trial, 224 patients with calcified lesions were randomized to receive RA using either the novel (n = 111) or established (n = 113) system, followed by stenting. The primary endpoint was freedom from major adverse cardiovascular events (MACEs), a composite of cardiac death, myocardial infarction, and target vessel revascularization, at 30 days. Secondary endpoints included MACEs at 12 months and quantitative imaging analyses. RESULTS:All FIH patients achieved clinical success. In pivotal study, the median follow-up time was 349.5 (IQR: 343, 359) days. Freedom from MACEs at 30 days was 97.3% (108 of 111 vs 110 of 113; 95% CI: 92.3%-99.4% vs 92.4%-99.5%) in both groups (P for noninferiority <0.0001). At 12 months, MACEs remained low in both groups (2.7%; 95% CI: 0.9%-8.1% vs 2.7%; 95% CI: 0.9%-8.0%; P = 1.0000). Postprocedural minimal stent area was similar on intravascular ultrasound between the 2 groups (5.29 ± 1.20 vs 5.29 ± 1.47 mm2, P = 0.9921). CONCLUSIONS:The novel RA system demonstrated noninferior safety and efficacy to established system, offering an effective alternative for the treatment of complex calcified coronary lesions. (CorOnary atheRectomy system in patiEnts with Coronary arTery calcification (CORECT); NCT05447585).

Obesity is closely associated with arterial stiffening and pathological vascular remodeling, yet its key molecular mechanisms remain incompletely understood. The endocrine function of adipocytes reveals the significance in regulating vascular diseases. This study investigated the adipocyte-derived serine protease inhibitor A3c (Serpina3c) in regulating vascular extracellular matrix (ECM) homeostasis and vascular smooth muscle cell (VSMC) phenotypic switching during obesity-related vascular injury. Serpina3c expression was significantly reduced in perivascular and epididymal adipose tissue in high-fat diet (HFD)-fed mice. Serpina3c deficiency exacerbated arterial stiffening and impaired vascular reactivity in HFD-fed mice, accompanied by ECM disorganization and VSMC switching toward a synthetic phenotype. Conversely, adipocyte-specific restoration of Serpina3c in perivascular/epididymal fat effectively reversed these abnormalities. Mechanistically, adipocyte-derived Serpina3c bound to the ADAMTS4 proteinase domain and inhibited its enzymatic activity, leading to decreased fibronectin cleavage. The reduction in fibronectin fragments suppressed integrin-mediated activation of the AKT1/NF-κB signaling pathway, ultimately maintaining ECM homeostasis and preventing the transition of VSMCs to a synthetic phenotype. Accordingly, the impaired vascular reactivity in HFD-fed Serpina3c knockout mice was rescued by an ADAMTS4 antagonist. Clinically, aneurysmal tissues from patients with a high body mass index showed decreased co‑localization of Kallistatin (the human homolog of Serpina3c) with ADAMTS4, alongside more severe aneurysmal progression and arterial structural damage. In summary, this study identifies the adipokine Serpina3c as a novel endogenous inhibitor of ADAMTS4 that limits ECM proteolysis and VSMC synthetic switching by attenuating fragmented fibronectin-mediated AKT1/NF-κB signaling. Targeting Serpina3c provides a new therapeutic approach for obesity-related arterial remodeling.

BackgroundRecent epidemiological studies have shown that heart failure (HF) can lead to an increased incidence of cancer. However, there is limited information regarding how HF promotes cancer development. We attempted to clarify the potential role of miR-221/222-3p dysregulation in HF in promoting cancer through comprehensive application of various bioinformatics tools and in vitro validation.MethodsVarious bioinformatics tools, including TargetScanHuman, the Human microRNA (miRNA) tissue atlas, RNA structure, miRNET, DAVID, Enrichr, FunRich, STRING, MalaCards, miRcancer, OncoLnc, miRTargetLink, GEPIA, the cBioportal, the GEO database, and Cytoscape, were comprehensively applied. Twenty patients with coronary artery disease (CAD) admitted to Zhongda Hospital, Southeast University, were enrolled in this study. The patients were divided into HF and non-HF groups. Serum (5% in complete medium) from patients with or without HF was added to the HT-29 cell culture medium. Inhibitors of miR-221/222-3p were constructed. EdU kits and CCK8 kits were used for proliferation detection. Western blotting was used to measure the level of PCNA. qRT-PCR was used to measure the levels of miR-221/222-3p.ResultsmiR-221/222-3p was widely distributed in various tissues and organs, including the heart. The PPI network revealed that miR-221/222-3p was closely associated with HF, whereas the KEGG pathway analysis indicated that the functions of miR-221/222-3p were mainly cancer-related. The Cytoscape analysis indicated that miR-221/222-3p act as key regulators of the progression of several common malignant tumors through their target mRNAs. In vitro experiments showed that miR-221/222-3p was elevated in the serum of HF patients and in human colon cancer cells (HT-29) treated with HF serum. HF serum promoted the proliferation of HT-29 cells, which was reversed by miR-221/222-3p inhibitors.ConclusionmiR-221/222-3p may be an important link between HF and cancer, as they are upregulated in HF and thus promote cancer.

Climate change has amplified the variability and intensity of cold weather, contributing to a growing health burden. Cold exposure serves as a significant, yet preventable, environmental trigger for acute chest pain–related life-threatening cardiovascular diseases (CVDs), such as acute coronary syndrome, acute aortic dissection, and pulmonary embolism. This scientific statement synthesizes multidisciplinary evidence from meteorology, environmental epidemiology, basic science, and clinical research to offer an updated evaluation of the impact of cold exposure on these acute chest pain-related life-threatening CVDs. The evidence consistently demonstrates that cold weather significantly increases the incidence of such events, often with delayed effects lasting several days to weeks. Vulnerable groups, including the elderly, individuals with chronic conditions, and those of lower socioeconomic status, are particularly at risk. Data also suggest that interventions, including central heating, integrated health warning systems, and appropriate personal protective measures, can effectively mitigate the associated risks. Based on this evidence, the statement provides expert consensus recommendations across clinical, policy, and behavioral domains. Strengthening prevention and response to cold-related cardiovascular risks is essential for building climate-resilient health systems and mitigating the health impacts of climate change.

This article describes the case of a middle-aged woman who developed recurrent in-stent restenosis (ISR) due to metal allergy. The first ISR occurred after implantation of a nickel-rich Medtronic Endeavor Resolute stent (35% nickel, 35% cobalt, and 20% chromium). A skin patch test revealed a strong nickel allergy (++), with no allergic reaction to cobalt. Nickel allergy was considered to be the cause of the first ISR. Then, a drug-coated balloon platinum-chromium alloy stent was implanted, and ISR occurred again during follow-up. The article discusses this special case and clinically relevant management options. This case highlights a scenario with refractory in-stent restenosis persisting despite various treatment strategies, including stents with different metal components, drug-coated balloons, and intensive drug therapy.

BACKGROUND:Sarcopenia and dyslipidemia are established as independent risk factors for cardiovascular disease (CVD). AIMS:The study aims to investigate the joint effect of sarcopenia and lipid parameters on the risk of self-reported cardiovascular disease in individuals with different stages of glucose metabolism. METHODS:This study included 9053 China Health and Retirement Longitudinal Study (CHARLS) 2015 participants aged ≥ 45 years without baseline CVD. Using multivariable logistic regression, it assessed sarcopenia-lipid-CVD event links, stratified by glucose metabolism. Risk reclassification used combined sarcopenia-lipid status. Restricted cubic splines detected non-linear lipid-CVD relationships. Receiver operating characteristic curves (ROC) evaluated lipid metric accuracy. RESULTS:A total of 1074 participants (11.9%) reported new-onset CVD. Joint exposure analysis identified synergistic effects: sarcopenia combined with elevated lipid parameters (except HDL-C) conferred the highest CVD risk, particularly in normoglycemic (NGR) and prediabetic (Pre-DM) subgroups (p < 0.001), but not in Type 2 diabetics (p > 0.05). ROC analysis revealed modest discriminative ability of non-traditional indices compared with conventional parameters across glycometabolic strata. Atherogenic Coefficient demonstrated relatively consistent, yet limited, predictive capability across glycometabolic states and may warrant consideration as a potential lipid biomarker for CVD risk assessment. CONCLUSIONS:The findings highlight the coexposure effects between sarcopenia and lipid parameters on cardiovascular diseases, especially for individuals with normal glucose regulation and prediabetes.

BackgroundThe risk factors of bleeding related to dual or triple therapy in patients with atrial fibrillation after percutaneous coronary intervention (PCI) are not fully explored. We addressed this issue on patients enrolled in the MANJUSRI trial.MethodsData of patients assigned to the dual therapy group (ticagrelor + warfarin, Dual group) and the triple group (clopidogrel + aspirin + warfarin, Triple group) in the MANJUSRI trial were analyzed. Multivariate regression analysis was used to determine the risk factors of bleeding among enrolled patients.ResultsThe incidence of overall bleeding at 6 months was 36.49% in the dual group and 35.62% in the triple group (P > 0.05). Multivariate cox regression analysis showed that alcohol consumption was positively correlated with overall bleeding in the total cohort (OR = 3.905, P = 0.001) and in the dual therapy group (OR = 4.643, P = 0.034). Age was positively associated with overall bleeding risk (OR = 1.059, P = 0.032), while body mass index was negatively associated with overall bleeding risk (OR = 0.911, P = 0.048) in the triple therapy group.ConclusionsAlcohol consumption increased the risk of overall bleeding after PCI in atrial fibrillation patients, especially in patients treated with warfarin and ticagrelor. Aging also increased bleeding risk in the whole cohort. Lower body weight contributed significantly to increased risk of overall bleeding in AF patients post PCI receiving combined clopidogrel, aspirin and warfarin medications. Above factors should be considered in terms of individualized anticoagulation management in AF patients post PCI aiming to reduce their bleeding risk.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT02206815, identifier NCT02206815.

Background and purpose: Matching the anti-proliferative drug effect with endothelial healing after drug-eluting stent (DES) implantation may help reduce cardiac events, especially stent thrombosis. A previous PIONEER II optical coherence tomography (OCT) sub-study demonstrated significantly better 1-month strut coverage with the novel healing-targeted BuMA Supreme DES, which was designed with a drug elution period of 4 to 6 weeks after implantation, compared with the XIENCE everolimus eluting stent (EES). This clinical trial aimed to evaluate whether the early endothelial healing observed in previous OCT sub-study would translate into improved intermediate-term angiographic and short-term clinical outcomes. Methods: PIONEER II was a multicenter, prospective, tandem clinical trial conducted in China. It was part of a series of clinical investigations of the BuMA Supreme DES, together with PIONEER I in Europe and PIONEER III in the United States, Canada, Europe, and Japan. The efficacy and safety of the BuMA Supreme DES were evaluated in patients with de novo coronary artery lesions. Results: From December 2015 to March 2018, 459 patients were randomly assigned to the randomized controlled trial (RCT) arm and received either the BuMA Supreme DES (n = 226) or the BuMA biodegradable polymer sirolimus-eluting stent (BP-SES; n = 233). In addition, 819 patients were enrolled in the objective performance criteria (OPC) arm. In the RCT arm, the BuMA Supreme DES was non-inferior to the BuMA BP-SES with respect to 9-month in-stent late lumen loss (LLL), with values of 0.23 ± 0.37 mm and 0.27 ± 0.36 mm, respectively (difference: −0.046 mm, 95% confidence interval: −0.107 to 0.015; P < 0.001 for non-inferiority). Furthermore, the BuMA Supreme DES demonstrated significantly lower values for secondary angiographic endpoints, including in-segment LLL and in-stent/in-segment diameter stenosis, compared with the BuMA BP-SES. In the OPC arm analysis, which combined patients from the BuMA Supreme group of the RCT arm with patients enrolled in the single-arm cohort, the 1-year target lesion failure rate was 4.17%. Both primary endpoints met the pre-specified non-inferiority criteria. Conclusion: The BuMA Supreme DES was non-inferior to the BuMA BP-SES with respect to 9-month in-stent LLL and was associated with the expected target lesion failure rate and a low incidence of stent thrombosis at 1-year follow-up.

Obesity has emerged as one of the most critical global health challenges. However, current anti-obesity pharmacotherapies are limited by suboptimal efficacy and significant side effects. White adipose tissue (WAT) browning may contribute to ameliorating obesity. In this study, a water-soluble lipophilic second near-infrared region (NIR-II) photothermal agent, CPDT-BBT-N (BTN), which specifically targets lipid droplets (LDs) and accumulates in adipocytes, was developed. Upon NIR irradiation, BTN induced a strong photothermal effect, enabling localized mild hyperthermia that specifically triggers white adipocyte browning with high efficiency and minimal off-target effects. WAT browning markedly accelerated the burning of the excessive fat accumulated in adipocytes. Notably, this intervention also showed systemic metabolic benefits. In high-fat diet (HFD)-induced obese mice, the BTN + NIR treatment attenuated weight gain by 20%, reduced subcutaneous WAT mass by 43%, and decreased visceral fat mass by 35%. Furthermore, it significantly reduced serum cholesterol (38%), triglycerides (30%), insulin (30%), and glucose levels (35%) while improving insulin sensitivity. Mechanistically, mild thermal stimulation promoted calcium influx in adipocytes, upregulating the expression of the thermogenic protein UCP1, enhancing mitochondrial oxidative respiration, and facilitating lipid catabolism. Together, these findings provide a novel and feasible strategy for effectively and safely managing obesity.

Accurately identifying coronary vulnerable plaque that would cause major adverse clinical events based on morphological characteristics remains a major clinical challenge. Plaque biomechanics are closely associated with plaque rupture and could assist in rupture risk stratification to identify high-risk coronary plaques for potential intervention. In vivo optical coherence tomography images of 40 coronary plaques from 40 patients with coronary artery disease were acquired and categorized into three groups according to their morphological characteristics: stable, vulnerable, and ruptured plaques. Finite element analysis was performed to obtain the peak stress value over the fibrous cap and shoulder region denoted as critical plaque wall stress (CPWS). A rupture risk stratification scheme was proposed based on the CPWS value to classify three plaque groups from biomechanical perspective, and its agreement rate with morphological classification was calculated. Ruptured and vulnerable plaques exhibited significant higher CPWS values than stable ones while no significant difference was found between ruptured and vulnerable plaques. The biomechanical risk stratification scheme was formed using 150 kPa and 230 kPa as threshold values for CPWS to classify three types of plaques, and its agreement rates with morphological classification were 17/20, 5/10, and 7/10 for stable, vulnerable, and ruptured plaques, respectively. This biomechanical scheme holds the potential to accurately stratify the rupture risk of coronary plaques as demonstrated by reasonable concordance with morphological classification. Discrepancy between two classifications highlights the unique value of biomechanical scheme, when integrated with morphological classification, in preventing unnecessary interventions and detecting rupture-prone plaques.

BackgroundStent implantation in vessels with moderate/severe coronary tortuosity is associated with increased rates of target vessel failure due to higher rates of target vessel-related myocardial infarction or ischemia-driven target vessel revascularization. Local wall shear stress (WSS) changes might contribute to this phenomenon. This study investigates the impact of stenting on the hemodynamic environment of tortuous coronary arteries in a numerical simulation model.Materials and methodsA numerical simulation model was established to explore the characteristics of hemodynamic parameters before and after simulated stent implantation in tortuous coronary vessels. The numerical simulation model is composed of four tortuous arcs. By controlling the curvature of these arcs, three groups with different tortuosity were formed. Four different stenosis degrees (40%, 50%, 60%, and 70%) were formed by changing the diameter of the third arc in each group. Finally, 12 models with different degrees of stenosis and tortuosity were analyzed.ResultsThe velocity and WSS were reduced in proportion to increased stenosis after stent implantation in tortuous segments mimicking tortuous coronary vessels with low, medium, and high tortuosity.ConclusionOur results indicate that further reduced WSS in tortuous coronary vessels post stenting might lead to increased endothelial dysfunction, vascular inflammation, and neointimal hyperplasia, all of which facilitate the formation of in-stent restenosis, especially in tortuous coronary vessels with severe stenosis.

Objective: To investigate the anti-atherosclerosis effect of chikusetsusaponin IV (CSIV) against high-fat diet-induced atherosclerosis in rats. Methods: A high-fat diet was used for the induction of atherosclerosis in rats, and the rats received oral CSV or atorvastatin. The body weight, organ weights, food intake, calorie intake, lipid parameters, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)/mevalonate ratio, collagen, free fatty acid, cardiac parameters, apolipoprotein (A and B), antioxidant parameters, inflammatory cytokines, and inflammatory parameters were assessed. The mRNA expressions of interleukin-1 beta (IL-beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-17, PI3K, AKT, and mTOR were estimated. Results: CSV significantly modulated food intake, body weight, organ weight (liver, kidney, and heart), and calories (P<0.05). Total cholesterol, triglycerides, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, cardiovascular risk index-1, and cardiovascular risk index-2 were decreased, while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSV group (P<0.05). Besides, CSV significantly restored the level of HMG-CoA/mevalonate ratio, collagen, free fatty acid, cardiac parameters (creatinine kinase-MB, lactate dehydrogenase, cTnT, cTnI), apolipoprotein (apolipoprotein A and apolipoprotein B), antioxidant parameters (MDA, CAT, GPx, GSH, SOD), inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-10), inflammatory parameters (COX-2, TGF-beta, NF-kappa B), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1. CSV also decreased the mRNA expression of IL-1 beta, TNF-alpha, IL-6, IL-17, PI3K, AKT, and mTOR. Conclusions: This study showed the anti-atherosclerosis effect of CSV against high-fat diet-induced atherosclerosis in rats via alteration of NF-kappa B/COX-2 and PI3K/AKT/mTOR signaling pathway.