Transcatheter Edge-to-Edge Repair (TEER) is a therapeutic option established for older patients with heart failure and concomitant mitral regurgitation. Frailty is associated with prognosis after transcatheter valve interventions. However, despite clinical potential, evidence for gait speed as a simplified prognostic marker in patients undergoing TEER remains insufficient.

This study aimed to investigate the association between preoperative gait speed and mid- to long-term mortality after TEER.

We conducted a single-center retrospective cohort study of 97 patients (mean age: 78.9 ± 8.7 years; 56.7% male) who survived the first 7 days after TEER and had available preoperative gait speed data. Preoperative gait speed was assessed, and clinical data were obtained from medical records. Cox regression analysis was performed to elucidate the association between preoperative gait speed and mortality.

In Cox proportional hazards models, higher gait speed (per 0.1 m/s increase) was associated with lower mortality after adjustment for the Society of Thoracic Surgeons risk score and handgrip strength (hazard ratio: 0.81; 95% confidence interval: 0.68-0.97; p = 0.02). In time-dependent receiver operating characteristic curve analysis, gait speed showed moderate discriminative ability for mortality, with area under the curve values of 0.749 at 1 year and 0.710 at 2 years. A gait speed of 0.8 m/s was used as an exploratory threshold for survival stratification, and patients with gait speed < 0.8 m/s had lower survival than those with gait speed ≥ 0.8 m/s (log-rank p < 0.01).

Lower preoperative gait speed was associated with higher mid- to long-term mortality after TEER. Preoperative gait speed may provide clinically useful information for exploratory risk stratification, although the cutoff-based findings require external validation.

Background: Traditional cardiovascular risk models often overlook "residual risk" driven by psychopathological factors. This study investigates the exploratory prognostic baseline associations of Type D personality (TDP) and specific symptomatic dimensions with long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We conducted a retrospective case study based on hospital records evaluating 221 patients with confirmed CAD. Anatomical complexity was quantified via the SYNTAX Score (SS). Psychological profiling utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1026 days using multivariate Cox proportional hazards models. Results: Over a mean follow-up of 1026 days, the overall all-cause mortality rate was 33.0% (n=73). TDP prevalence was 19.0% (n=42) and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; p<0.001). In the adjusted psychological model, baseline anxiety symptom severity presented an exploratory, borderline relationship with survival (HR = 0.941; p=0.049), with the 95% confidence interval upper bound reaching the null threshold (1.000), suggesting a potential, hypothesis-generating "Anxiety Paradox". The psychological model demonstrated variations in descriptive validation indices (C-index = 0.624) compared to a baseline model integrating trait metrics and anatomical severity (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress (r=0.493). Conclusions: TDP components and granular psychological tracks show significant baseline associations with coronary anatomical distributions, while anxiety dimensions present an exploratory relationship with long-term survival. Given the lack of adjustment for major clinical determinants of mortality (such as age, comorbidities, or ventricular function), these findings must be interpreted strictly as hypothesis-generating and exploratory.

Background: Cardiovascular (CV) risk estimation is usually based on the assessment of classic risk factors and the extent of coronary artery stenosis. However, a substantial rate of acute coronary syndromes (ACS) and sudden cardiac deaths (SCD) is observed in patients with high-risk atherosclerotic plaques (HRP), even in the absence of significant stenosis. Therefore, this study aimed to evaluate the predictive value of traditional clinical risk factors for the presence of HRP in patients scheduled for coronary computed tomography (CCT). Methods: This single-center study included 123 patients undergoing CCT for suspected coronary artery disease (CAD). Atherosclerotic plaque morphology (HRP) and the degree of coronary artery stenosis (CAD-RADS categories) were assessed in all the patients. CV risk factors, including LDL serum levels and CT Calcium score (CS), were analyzed. Results: The study cohort was mostly males (54.5%), with an average age of 60.40 ± 12.45 years and typical risk factors: hypertension (70%), diabetes (22%), obesity (30%), and smoking (20%). Most patients (88%) were found to have coronary atherosclerosis with nonobstructive disease (CAD-RADS 1-2) in 39% of patients. HRP was confirmed in over one-fifth of the participants (22%), with half of the patients in the CAD-RADS 2 category. There were no differences in CV risk factors between patients with and without HRP in CCT. No significant clinical predictor of HRP in CCT was identified. Conclusions: CV risk factors do not predict HRP in CCT, which may underestimate the real risk of ACS and SCD.

Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) are ligand-activated nuclear transcription factors that orchestrate key metabolic and immuno-inflammatory networks governing hepatic homeostasis. By regulating fatty acid oxidation, insulin signaling, bile acid metabolism, and hepatic stellate cell activation, PPARs integrate metabolic and inflammatory cues central to the pathogenesis of chronic liver disorders. Chronic liver diseases (CLDs) constitute a major and growing global health burden. Metabolic dysfunction-associated steatotic liver disease (MASLD), now affecting up to one-third of the adult population worldwide, is closely linked to type 2 diabetes, cardiovascular disease, and major liver-related events. In parallel, chronic immune-mediated cholestatic liver diseases continue to pose important therapeutic challenges. Although ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), and several second-line therapeutic options are now available, a substantial proportion of patients exhibit an incomplete biochemical response, while effective disease-modifying therapies for primary sclerosing cholangitis (PSC) remain lacking. Across etiologies, persistent metabolic stress, immune-mediated injury, and maladaptive fibrogenesis represent convergent pathogenic pathways. In MASLD, PPAR agonists have shown promising effects on steatosis, necroinflammatory activity, and fibrosis regression in randomized clinical trials, positioning them among the most advanced pharmacological strategies currently under investigation. In cholestatic liver diseases, selective and dual PPAR agonists have demonstrated significant improvements in cholestasis, pruritus, and markers of disease activity, supporting their role as second-line or adjunctive therapy. This review critically appraises the current preclinical and clinical evidence on the role of PPARs in CLDs, delineates the underlying molecular mechanisms, and discusses future therapeutic perspectives. Although the available evidence is encouraging, most clinical studies have primarily demonstrated improvements in surrogate biochemical and histological endpoints rather than hard clinical outcomes. Ongoing phase III trials and long-term outcome studies will be essential to define the role of PPAR agonists within future therapeutic algorithms for CLDs.

Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a leading causes of premature death, yet treatment options remain limited. In this study, we developed the easily accessible engineered exosomes for treatment of DMD-associated cardiomyopathy and explored the underlying mechanisms in DmdΔ4 mice, a model harboring hot spot mutation in the dystrophin gene.

DmdΔ4 mice and their cardiomyopathy phenotype were confirmed by Sanger sequencing, pathological staining, flow cytometry, immunoblotting, single-cell sequencing and echocardiographic analysis. Engineered exosomes, exosomes- cardiac homing peptide (Exo-CHP), were synthesised and characterised by click chemistry and miRNA sequence, separately. The targeted ability and the therapeutic effects of Exo-CHP were studied in vitro and in vivo. Primary cardiomyocytes were used to study the underlying mechanism of Exo-CHP.

DmdΔ4 mice showed an obvious cardiomyopathy-associated phenotype. Exo-CHP can target myocardium and mitigate pathological progression of cardiomyopathy in DmdΔ4 mice. The therapeutic effects of intravenously delivered Exo-CHP significantly reduced myocardial inflammation, fibrosis and improved the mice's cardiac function. The rescue effects were mediated through the regulation of gene expression at the transcriptomic level, prevention of dystrophin protein complex degradation, and inhibition of intracellular calcium influx and calpain protease activity. The miR-21 knockdown Exo-CHP can counteract the protective effects of Exo-CHP on the calcium content and membrane integrity of primary DmdΔ4-derived cardiomyocytes.

Our study demonstrated the feasibility, efficacy and the possible mechanism of mesenchymal stromal cell-derived engineered exosomes, positioning them as a potential cell-free intervention for DMD-associated cardiomyopathy.

Cardiac arrhythmias remain a leading cause of cardiovascular morbidity and mortality worldwide. Although conventional antiarrhythmic drugs are effective, their use is constrained by proarrhythmic risks and extracardiac toxicity. Wenxin Keli (WXKL), a traditional Chinese medicine (TCM) formula, has demonstrated antiarrhythmic properties in preclinical and clinical studies with a reportedly favorable safety profile. This article provides a critical synthesis of WXKL's pharmacological mechanisms, including ion channel modulation (INa, ICaL, Ito), calcium handling, and calcium/calmodulin-dependent protein kinase II signaling, with explicit appraisal of translational limitations. Clinical trial evidence and meta-analyses for atrial fibrillation (AF), premature ventricular contractions, and other indications were systematically evaluated, with detailed discussion of effect sizes, heterogeneity, and methodological quality. Key challenges unique to WXKL as a TCM-derived product-formulation variability, quality control limitations, and regulatory approval pathways-are analyzed in depth. A prioritized research agenda is proposed to address evidence gaps. *These authors contributed equally to this work and share first authorship.

Hypertension remains the leading global contributor to cardiovascular mortality. Although renal denervation (RDN) has demonstrated efficacy, the central neurobiological mechanisms sustaining its sympathoinhibitory effects remain unclear. We investigated whether RDN modulates the ATP and P2X7R (P2X7 receptor)/PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) signaling axis in the hypothalamic paraventricular nucleus to attenuate neuroinflammation and blood pressure.

Eight-week-old male spontaneously hypertensive rats were randomly assigned to either sham surgery or RDN (combined physical/chemical ablation; n=8 per group). Systolic blood pressure was longitudinally monitored using tail-cuff plethysmography. Cardiac target-organ injury was assessed using hematoxylin-eosin and Masson's trichrome staining. ATP levels, P2X7R expression, and PI3K/Akt phosphorylation in the paraventricular nucleus were quantified by ELISA, Western blotting, and immunofluorescence. A selective P2X7R antagonist (HY-50697/A-740003) was used for pharmacological validation.

RDN significantly reduced systolic blood pressure in spontaneously hypertensive rats (from 210.3 to 143.2 mm Hg, P<0.0001) and markedly ameliorated left ventricular hypertrophy and myocardial fibrosis. Mechanistically, RDN substantially decreased ATP concentrations in the paraventricular nucleus (from 406.81 to 292.98 nmol/L, P<0.0001), downregulated P2X7R protein expression, and suppressed pathological activation of the PI3K/Akt signaling pathway, accompanied by reduced proinflammatory cytokine production. Pharmacological inhibition of P2X7R functionally phenocopied the antihypertensive and central anti-inflammatory effects induced by RDN.

RDN was associated with reduced blood pressure and attenuation of central ATP-related neuroinflammatory signaling, beyond peripheral sympathetic disruption. The ATP/P2X7R/PI3K/Akt axis may represent a candidate pathway linking renal signaling to central sympathetic regulation, warranting further investigation as a potential mechanistic target in resistant hypertension.

BACKGROUND Congenital absence of the right coronary artery (RCA) is a rare anomaly often identified incidentally. We report a case of transient left ventricular systolic dysfunction followed by recovery of ejection fraction and new-onset mitral chordal rupture, which became the primary driver of pronounced N-terminal pro-B-type natriuretic peptide (NT-proBNP) elevation. The coexistence of 2 distinct pathologies complicated causal attribution; we discuss proposed mechanisms while recognizing their limitations. CASE REPORT A 58-year-old woman presented with exertional chest pain. At initial admission, she exhibited sinus tachycardia, elevated NT-proBNP (910 pg/mL), and reduced left ventricular ejection fraction (LVEF; 43% [M-mode]) with hypokinesis of the anterior wall and anteroseptum. Symptoms improved with anti-ischemic therapy. Three weeks later, LVEF recovered to 56% (biplane Simpson method), but NT-proBNP increased to 2440 pg/mL. Echocardiography revealed rupture of a small chord of the anterior mitral leaflet with mild-to-moderate regurgitation and elevated filling pressures (E/e'=13.8). Coronary angiography demonstrated congenital absence of the RCA ostium, with an enlarged left circumflex artery supplying the RCA territory and no evidence of atherosclerotic stenosis. Retrospective quantitative mitral regurgitation indices from archived images were examined. Management was conservative; symptoms resolved and NT-proBNP levels decreased during follow-up. CONCLUSIONS In patients with rare coronary anomalies, newly acquired common valvular disease may dominate the clinical presentation. Transient systolic dysfunction and subsequent chordal rupture occurred in our patient; a direct causal relationship remains speculative. Multimodality imaging is essential to accurately attribute hemodynamic changes and guide therapy. Long-term surveillance of coronary anatomy and valve function is recommended.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal-fetal crosstalk, mediated largely through placental function, coordinates the transfer of metabolic, endocrine, and immune signals that are essential for normal cardiac and vascular development. Disruptions in maternal physiology-including metabolic disorders, hypertensive conditions, inflammation, and environmental stress-can perturb this communication network and alter the intrauterine milieu. These changes induce persistent modifications in cardiomyocyte growth, endothelial function, and key regulatory pathways, thereby contributing to long-term cardiovascular risk. Emerging studies highlight that cardiovascular programming is governed by interconnected mechanisms involving epigenetic regulation, mitochondrial function, immune signaling, and intercellular communication. This review synthesizes current evidence on how maternal-fetal crosstalk shapes cardiovascular development beyond genetic determinants and provides an integrated framework linking early-life exposures to lifelong cardiovascular health.