Search Results (328)

Soluble growth stimulation protein form of interleukin-1 receptor-like 1 (ST2) may signal myocardial stress, and elevated ST2 blood levels are associated with adverse outcomes in adult heart disease. Data on ST2 in children with congenital heart disease (CHD) is limited. This study explored ST2 in newborns and older children with atrial septal defect (ASD), as this represents a common CHD type that remains clinically challenging to recognize in childhood with slowly evolving symptoms. A case–control study was carried out in newborn ASD cases versus controls measuring ST2 on dried blood spot samples and additionally in pediatric ASD cases versus controls on venous blood together with cardiac magnetic resonance before and after treatment. ST2 was higher in newborns with ASD (n = 19) compared to controls (n = 93); (p < 0.01). Receiver operating characteristics to diagnose newborn ASD by ST2 showed an area under the curve of 0.848. Levels of ST2 decreased in pediatric ASD (n = 16) after treatment (p = 0.014). Lower left ventricular ejection fraction correlated with higher ST2 levels before (r = −0.348) and after treatment (r = −0.497). Elevated ST2 in newborns may aid early ASD diagnosis. Levels of ST2 in pediatric ASD decrease after treatment, and higher levels are associated with lower left ventricular ejection fraction, warranting further study. Full article

Background: The endothelial activation and stress index (EASIX), derived from the serum lactate dehydrogenase, creatinine, and platelet counts, is a composite biomarker for endothelial dysfunction and systemic stress. It has been developed to predict clinical outcomes in hematologic malignancies. This study aimed to investigate the EASIX’s predictive role in contrast-induced nephropathy (CIN) and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 1552 patients with STEMI who underwent primary PCI were retrospectively included. The patients were divided into two groups: CIN (+) and CIN (−). Baseline demographic, laboratory, clinic, and procedural variables were compared between the two groups. Logistic regression analysis was performed to identify independent predictors of CIN and in-hospital mortality, while receiver operating characteristic (ROC) curves were used to determine the optimal EASIX cut-off values. Results: CIN developed in 7.6% (n = 118) of the study population, and these patients had significantly increased EASIX scores. Those with CIN were older and exhibited higher rates of diabetes mellitus, chronic kidney disease (CKD), and decreased left ventricular ejection fraction (LVEF) (all p < 0.001). In multivariable analysis, age (OR 1.053), CKD (OR 1.338), reduced LVEF (OR 0.965), and EASIX (OR 2.467) independently predicted CIN. EASIX > 0.93 demonstrated strong discriminatory ability (AUC 0.785; sensitivity 72% and specificity 72%). EASIX also independently predicted in-hospital mortality (OR 3.592), with an optimal cut-off > 0.88 (AUC 0.774). Conclusions: By integrating markers of renal function, endothelial activation, and systemic stress, EASIX may serve as a useful and reliable indicator for predicting CIN development and in-hospital mortality in STEMI patients undergoing primary PCI. Full article

Obesity is a chronic, highly prevalent disease affecting nearly one-third of the global population and represents a major independent risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Excess adiposity—especially visceral and epicardial adipose tissue (EAT)—acts as an active endocrine and immune organ, promoting chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and adverse myocardial remodeling. Expanded EAT exerts both paracrine inflammatory effects and mechanical constraint on the myocardium, contributing to diastolic dysfunction, microvascular impairment, atrial arrhythmogenesis, and elevated filling pressures despite preserved systolic function. Evidence demonstrates a dose–response relationship between increasing body mass index and incident HF. Clinically, obesity-related HFpEF is characterized by concentric left ventricular hypertrophy, impaired relaxation, increased plasma volume, reduced exercise tolerance, and relatively low natriuretic peptide levels, complicating diagnosis. HF management includes traditional treatment with diuretics, renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. These agents widely remain foundational as they primarily target hemodynamic and neurohormonal pathways in HF. In contrast, sodium–glucose cotransporter 2 inhibitors consistently reduce HF hospitalizations across the ejection fraction spectrum, while glucagon-like peptide-1 receptor agonists and dual incretin therapies (e.g., tirzepatide) promote substantial weight loss, improve symptoms, and demonstrate promising anti-remodeling effects in obesity-related HFpEF. Recognizing obesity-driven HF as a distinct cardiometabolic entity supports an integrated therapeutic strategy combining structured weight reduction with guideline-directed HF polypharmacotherapy to address both hemodynamic burden and upstream adiposity-related mechanisms. Full article

Background: Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure with preserved ejection fraction, resulting from myocardial deposition of misfolded amyloid fibrils derived predominantly from transthyretin (ATTR wild-type [ATTRwt] or variant [ATTRv]) or immunoglobulin light chains (AL). Despite advances in noninvasive imaging and disease-modifying therapies, delayed diagnosis remains common, and clinically actionable molecular biomarkers for early detection, phenotypic discrimination, and therapeutic monitoring are limited. MicroRNAs (miRNAs), small noncoding regulators of post-transcriptional gene expression, have emerged as key modulators of cardiovascular remodeling and systemic amyloid biology. Methods: We performed a comprehensive review of experimental, translational, and clinical studies to evaluate the role of miRNAs in transthyretin and light-chain cardiac amyloidosis, incorporating data from myocardial tissue analyses, circulating miRNA profiling, and mechanistic studies in cellular and animal models. Results: Dysregulated miRNA networks contribute to amyloid-induced cardiac injury by modulating mitochondrial energetics, oxidative stress, inflammation, fibrosis, proteostasis, and neurocardiac signaling. Specific miRNAs, including members of the miR-21, miR-29, and miR-30 families, as well as miR-150-5p and miR-339, have been associated with amyloid burden, adverse myocardial remodeling, plasma cell biology, and disease severity. Distinct circulating and tissue miRNA signatures differentiate transthyretin from light-chain cardiac amyloidosis and correlate with functional status, heart failure biomarkers, and clinical outcomes. Conclusions: MiRNAs represent promising diagnostic and prognostic biomarkers in cardiac amyloidosis and offer mechanistic insights into disease pathogenesis. Integration of miRNA profiling with multimodality imaging and emerging RNA-based therapeutics may enable earlier diagnosis and support precision management of amyloid-related heart failure. Full article

Heart failure (HF) with reduced ejection fraction is a systemic disorder that extends beyond cardiac dysfunction and involves peripheral organs, particularly skeletal muscle. Exercise intolerance and fatigue are the hallmark manifestations of HF that strongly predict morbidity and mortality. Accumulating evidence suggests that intrinsic skeletal muscle abnormalities are key contributors to exercise intolerance in HF. In HF, skeletal muscle undergoes metabolic remodeling characterized by shifts in fiber type composition, mitochondrial dysfunction, and increased oxidative stress. Mitochondrial dysfunction, characterized by decreased mitochondrial density, impaired biogenesis, and reduced respiratory capacity, further compromises skeletal muscle performance. These alterations impair adenosine triphosphate (ATP) generation via oxidative phosphorylation, forcing reliance on less efficient anaerobic glycolysis. The resulting metabolic shift exacerbates early lactate accumulation, muscle fatigue, and diminished exercise capacity. In parallel, an increase in oxidative and carbonyl stress, along with a decrease in antioxidant defenses as well as derangements in pathways that remove toxic lipid peroxidation, heightens oxidative and carbonyl stress perpetuating injury and establishing a vicious cycle of progressive muscle dysfunction. Thus, metabolic remodeling in skeletal muscle represents a central determinant of exercise intolerance in HF. While exercise training remains the most effective strategy to restore skeletal muscle health and exercise tolerance, emerging therapies offer novel avenues for intervention. Future research should focus on elucidating the molecular mechanisms underlying skeletal muscle dysfunction and developing therapies that restore metabolic integrity and functional capacity in HF. Full article

Achieving high density in complex powder metallurgy components like spur gears is often hindered by friction-induced density gradients and ejection defects. This study investigates a novel elastic die system designed to mitigate these issues through controlled radial deformation. Spur gears were compacted using Ancorsteel 2000 powder under pressures of 400–700 MPa, utilizing a tapered elastic sleeve to apply radial compression. Green and sintered densities were measured, while porosity distribution was quantified via image analysis. Additionally, a 3D finite element simulation using FORGE software was conducted to model the thermo-mechanical behavior and stress distribution during the process. Experimental trials demonstrated that the elastic relaxation of the sleeve enabled free ejection of the compacts without requiring an extraction force. Image analysis confirmed a homogenous porosity distribution across the gear teeth, and higher die pre-stressing strokes were found to correlate with increased sintered density. Finite element modeling accurately predicted critical stress concentrations of 700 MPa at the die–sleeve interface and validated the strain distribution. The results confirm that elastic die technology effectively eliminates ejection friction and improves density uniformity in complex gears, offering a viable solution for reducing tool wear and manufacturing defects in high-precision powder metallurgy. Full article

Objectives: The current study presents a sequential strategy for the development of directly compressible powder formulations relying on Design of Experiments (DoE) and Compactibility-Ejection stress plots. Methods: Compression analysis was used to evaluate the impact of changing the sort of microcrystalline cellulose (MCC), dicalcium phosphate (DCP), the diluent ratio, lubricant type, and the inclusion of an API from different suppliers. Results: The effect of DCP particle size on the ejection stress was efficiently mitigated in the placebo formulations by lubrication. However, the initial differentiation between sorts was highlighted at a smaller scale when the active pharmaceutical ingredient (API) was included in the formulation. For MCC, the tensile strength was positively correlated with the level of plasticity and tabletability capacity of different sorts. The particle size was a critical attribute for the API, influencing the detachment and ejection stress values. Fine particles (d50 = 30 µm) presented increasing stress values once the compression force rose, while for coarser particles (d50 = 50 µm) these effects were limited. Conclusions: Material-related variability must be understood to design products and processes with adequate performance. The proposed strategy enables early identification of critical material attributes, supporting rational formulation and supplier selection to ensure consistent quality during manufacturing. Full article

Background: Despite advances in reperfusion strategies, long-term major adverse cardiac and cerebrovascular events (MACCE) remain frequent after ST-elevation myocardial infarction (STEMI). Practical risk stratification tools applicable at presentation are therefore needed. We investigated the prognostic value of a simple composite index integrating age, blood urea nitrogen, and left ventricular ejection fraction (Age×BUN/LVEF) for predicting long-term MACCE in STEMI patients treated with primary percutaneous coronary intervention (PCI). Methods: This retrospective, single-center cohort study included 313 consecutive STEMI patients undergoing primary PCI between 2020 and 2024. The Age×BUN/LVEF (AGEBUNeFR) index was calculated using age and admission blood urea nitrogen values and left ventricular ejection fraction assessed during index hospitalization. The primary outcome was long-term MACCE, defined as a composite of all-cause mortality, recurrent myocardial infarction, repeat revascularization, stroke, and heart failure hospitalization. The median follow-up was 2.24 years (interquartile range 1.40–3.06). Results: During follow-up, 93 patients (29.7%) experienced MACCE. The AGEBUNeFR index was independently associated with MACCE after multivariable adjustment (adjusted HR 1.028 per unit increase, 95% CI 1.016–1.040; p < 0.001). Time-varying analyses demonstrated a dynamic prognostic effect, with significant associations in the early post-PCI period (p = 0.002) and a pronounced re-emergence of risk during late follow-up (>36 months; p < 0.001). Conclusions: The AGEBUNeFR index is a simple, readily available, and powerful predictor of long-term MACCE in STEMI patients undergoing primary PCI. By integrating age, renal/hemodynamic stress, and cardiac function, this composite index provides dynamic and incremental prognostic information beyond conventional clinical models, supporting its potential role as a practical tool for long-term risk stratification after STEMI. Full article

Background: Atrial fibrillation (AF) is frequently encountered in patients presenting with acute coronary syndrome (ACS); however, its clinical significance beyond being a simple rhythm disturbance remains debated. We hypothesized that AF at presentation may be associated with a high-risk clinical profile characterized by hemodynamic instability and increased inflammatory and ischemic activity. Methods: This single-center, retrospective observational study included consecutive adult patients with acute coronary syndrome admitted to a tertiary cardiology center between January 2022 and December 2024. Patients were classified into two groups according to cardiac rhythm at presentation: AF and sinus rhythm. Baseline demographic characteristics, hemodynamic parameters, laboratory biomarkers, validated risk scores, and revascularization strategies were compared between groups. Multivariable logistic regression analysis was performed to evaluate whether AF was independently associated with a high-risk presentation, primarily defined by elevated GRACE risk score, reduced left ventricular ejection fraction, and increased inflammatory markers. Results: A total of 158 patients were included, of whom 50 (31.6%) presented with atrial fibrillation (mean age 71.2 ± 11.4 years, 46% female). Compared with patients in sinus rhythm, those with AF had significantly higher GRACE risk scores, lower left ventricular ejection fraction, faster heart rate, and higher white blood cell counts and peak high-sensitivity troponin levels. These associations remained significant after multivariable adjustment. Patients with AF also showed a numerically higher prevalence of severe angina at presentation. Conclusions: In patients presenting with ACS, atrial fibrillation is associated with a high-risk hemodynamic profile accompanied by increased inflammatory and ischemic activity. Rather than being an incidental finding, AF may represent a clinically relevant marker of acute cardiovascular stress and may contribute to early risk stratification in this setting. Full article

Pulmonary hypertension (PH) is a complex condition in which early diagnosis remains challenging, particularly in patients with exertional symptoms and normal or borderline resting haemodynamics. Although right heart catheterisation is the diagnostic gold standard, transthoracic echocardiography is the recommended first-line non-invasive test. However, resting echocardiography provides only a static assessment and may underestimate disease severity in early or latent pulmonary vascular disease due to preserved pulmonary vascular compliance and adaptive right ventricular responses. Because pulmonary haemodynamics are intrinsically flow-dependent, pathological abnormalities may only emerge during increased cardiac output. Stress echocardiography, performed using exercise or pharmacological stress, enables dynamic evaluation of pulmonary pressure responses, cardiac output augmentation, right ventricular contractile reserve, and ventricular interaction. Increasing evidence indicates that stress echocardiography can unmask abnormal pulmonary pressure–flow relationships, impaired pulmonary vascular reserve, and reduced right ventricular–pulmonary arterial coupling that are not apparent at rest, thereby improving functional and haemodynamic characterisation in selected patients. This Diagnostic Review outlines the physiological basis for stress echocardiographic assessment of pulmonary circulation, proposes practical recommendations for patient selection and testing protocols, and provides a framework for interpretation centered on pressure–flow relationships rather than absolute pulmonary pressure thresholds. Particular attention is given to clinical scenarios with high diagnostic yield, including unexplained exertional dyspnoea, systemic sclerosis, suspected heart failure with preserved ejection fraction, at-risk relatives of patients with pulmonary arterial hypertension, selected athletes, and paediatric populations. Stress echocardiography should not be considered a standalone diagnostic test for PH but, when performed in experienced centers and integrated within structured diagnostic pathways, it represents a valuable non-invasive adjunct to guide referral for invasive haemodynamic confirmation. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy. Full article

Background: Heart failure (HF) is a clinical syndrome that involves multiple interconnected pathways. Circulating biomarkers in HF emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy. The aim of the present study was to evaluate circulating levels of biomarkers in elderly patients with improved HF ejection fraction, previously with left ventricular ejection fraction (LVEF) <40%, after six months of drug therapy optimisation. Methods: We enrolled 100 HFimpEF outpatients. All patients provided medical history and underwent physical examination at baseline and after six months of follow-up. The serum values of circulating biomarkers were assessed with an ELISA test. Proteomic analysis was performed on serum samples collected from a subset of 13 patients at baseline and after six months of follow-up. Results: At follow-up, we observed significant improvements in glycometabolic, renal and inflammatory profiles (p < 0.001). Proteomic analysis revealed selective changes in key cardiovascular (CV)-related proteins, such as insulin-like growth factor-binding protein 4 (IBP4), thrombospondin-4 (TSP4), intercellular adhesion molecule 1 (ICAM1), and syndecan-4 (SDC4). Conclusions: This study demonstrates significant improvements across multiple CV biomarkers after six months of therapy optimisation in HFimpEF patients, providing evidence for comprehensive therapeutic effects targeting inflammation, oxidative stress, neurohormonal activation, and thrombotic risk. Full article

Ice accretion along aircraft leading edges, particularly at stagnation line parting strips, remains difficult to remove using conventional electrothermal anti-icing systems. These systems require continuous high-power heating to maintain the stagnation region above the melting point, often exceeding 10–12 kW/m². This study introduces an Ice Cavitation Deicer (ICD) that removes ice through rapid, localized cavitation generated within a thin melt layer formed at the ice–surface interface. In the proposed approach, a short pulse of electric current melts a 1–10 µm interfacial layer and causes a cavitation impulse of approximately 1–10 MPa. This impulse ejects the stagnation-line ice in a direction normal to the surface, often against the external airflow, enabling the immediate aerodynamic removal of the remaining ice. Analytical modeling based on the energy conservation principle was used to determine the optimal foil geometry, thermal pulse parameters, thermal stress, and material selection. Experiments with various metallic foils and substrate materials validated the predicted ejection behavior. The impulses were sufficient to fracture and eject ice 1–10 mm thick. The observed ice fragment velocities varied from 1 m/s to 10 m/s. Compared with conventional thermal anti-icing, the ICD concept reduces power consumption by approximately two orders of magnitude while offering rapid and reliable leading-edge deicing. The low power requirements, rapid response, and compatibility with thin-foil heater architectures make ICD a promising technology for both conventional and electrified aircrafts, UAVs, rotorcrafts, and other platforms where power availability is limited. This manuscript presents the first theoretical and experimental research on the ICD method and is a concept-proof work. Further research and development are required before the ICD is ready to be tested in flight. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a key contributor to the development of heart failure with preserved ejection fraction in individuals with obesity. This study aimed to investigate whether MASLD and diastolic dysfunction are independently associated with abdominal obesity through shared metabolic and oxidative mechanisms. We conducted a cross-sectional study in a tertiary university hospital including patients aged ≥ 50 years with obesity and MASLD. Clinical, anthropometric, biochemical, and oxidative stress parameters were collected, and hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (FibroScan^®). Patients were stratified according to the presence or absence of echocardiographic diastolic dysfunction. A total of 73 patients was included in the analysis and 27.4% had diastolic dysfunction. Patients with diastolic dysfunction were older and had higher body weight, body mass index (BMI) and waist circumference. Markers of hepatic steatosis, including fatty liver index (FLI) and controlled attenuation parameter (CAP), were higher in patients with diastolic dysfunction, whereas fibrosis measures were not. CAP was independently associated with diastolic dysfunction after adjustment for age and sex, but this association was lost after further adjustment for waist circumference, suggesting a mediating role of central adiposity. Plasma glutathione was inversely associated with FLI, but oxidative stress markers were not associated with diastolic dysfunction or steatosis severity. In conclusion, in patients ≥ 50 years with MASLD and obesity, diastolic dysfunction was common and closely related to abdominal obesity, highlighting MASLD as a multisystem condition with early cardiac involvement. Full article

Exercise training has demonstrated potential benefits in addressing the adverse effects of cardiovascular diseases, particularly myocardial infarction (MI). This study analyzed the cardioprotective effects of moderate exercise before and after MI in rats subjected to isoproterenol (ISO)-induced heart damage. Wistar rats were assigned to five groups: controls (CTRL), isoproterenol-treated (ISO), swimming before ISO (PRE + ISO), swimming after ISO (ISO + POST), and swimming both before and after ISO (PRE + ISO + POST). Cardiac function was assessed through echocardiography, while oxidative stress markers, Heme Oxygenase-1 (HO-1) and Myeloperoxidase (MPO), were quantified using biochemical assays and enzyme-linked immunosorbent assay (ELISA). Statistical analyses were conducted by one-way analysis of variance (ANOVA), accompanied by Tukey’s post hoc test. Exercise performed post-MI and both pre- and post-MI significantly reduced ISO-induced infarct size and improved left ventricular function (stroke volume (SV), ejection fraction (EF), and Tei index). HO-1 protein concentration and HO enzyme activity were restored, while swim training reduced the activity of MPO compared to the ISO group. Moderate exercise training, when appropriately timed, provides cardioprotection against ISO-induced myocardial damage by reducing oxidative stress and cardiac dysfunction. Full article