Search Results (4,401)

Acute Myocardial Infarction (AMI) is a critical cardiac condition that poses a substantial threat to myocardial function. Expedient diagnosis of AMI is paramount and relies on serological assays for rapid and accurate quantification of relevant biomarkers. Electrochemical sensors have emerged as promising candidates for this application, owing to their accessibility, operational simplicity, and high specificity. In this study, we developed a paper-based electrochemical immunosensor to detect cardiac troponin I in serum and saliva specimens. The electrode was fabricated using screen-printing technology with photographic paper as the substrate, employing graphite-based ink, nail polish, and acetone as the solvent. A quasi-reference electrode was constructed using silver powder-based ink, nail polish, and acetone. The immunosensor was prepared by modifying the working electrode with gold nanoparticles (AuNP) functionalized with cardiac troponin I antibodies (anti-cTnI) and bovine serum albumin (BSA). This modified electrode was subsequently used to detect the troponin I antigen. The analyses were performed in 0.1 mol L⁻¹ phosphate buffer medium, pH 7.00, in the presence of 5.0 mmol L⁻¹ of the potassium ferrocyanide probe. The immunosensor exhibited a sensitivity of 0.006 µA/fg mL⁻¹, a limit of detection of 9.83 fg mL⁻¹, and a limit of quantification of 32.79 fg mL⁻¹. Specificity studies conducted in the presence of other macromolecules demonstrated minimal interference, with relative standard deviations (RSD) below 5.00%, indicating a specific interaction with troponin I. Furthermore, the immunosensor demonstrated excellent reproducibility and stability. Upon application to serum and saliva samples, the immunosensor presented recoveries of approximately 99–105%, suggesting its potential applicability in clinical analyses. Full article

Background/Objectives: Pacemaker-associated heart failure (PaHF) is a recognized complication of chronic ventricular pacing, yet its long-term incidence and prognostic impact remain incompletely defined. Previous studies on PaHF have been largely limited by small sample sizes, single-center designs, and insufficient long-term or time-dependent analyses. We aimed to evaluate the incidence, clinical predictors, and mortality risk of PaHF in a nationwide real-world cohort. Methods: Using the Korean National Health Insurance Service database, we identified 32,216 patients who underwent de novo pacemaker implantation between 2008 and 2019 without prior heart failure. Results: During a median follow-up of 3.8 years, 4170 patients (12.9%) developed new-onset PaHF and 6184 (19.2%) died. PaHF was independently associated with increased all-cause mortality (adjusted hazard ratio [HR]: 3.11, 95% confidence interval [CI]: 2.93–3.32, p < 0.001), even after accounting for immortal-time bias and relevant covariates. The incidence of PaHF and its associated mortality risk both peaked within the first six months post implantation and remained persistently elevated throughout follow-up; notably, PaHF-associated mortality showed a late resurgence. Sensitivity and subgroup analyses consistently demonstrated higher mortality among patients with PaHF across a wide range of clinical characteristics. Conclusions: In this large, nationwide cohort, the development of PaHF was associated with a substantial and sustained increase in mortality risk following pacemaker implantation. Given the persistent and dynamic nature of this risk, longitudinal monitoring of cardiac function and individualized pacing strategies may be warranted to mitigate long-term adverse outcomes. Additionally, these findings provide real-world benchmarks to guide future pacing strategies and surveillance efforts. Full article

Background: PLACK syndrome is an ultra-rare autosomal recessive disorder caused by biallelic loss-of-function variants in CAST, which encodes calpastatin, an endogenous inhibitor of calpains. The syndrome is classically defined by peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads. Although the phenotype has been largely restricted to dermatological manifestations, emerging reports suggest dilated cardiomyopathy (DCM) as a systemic complication. Methods: We investigated five affected children from three sibships of an extended consanguineous family. Clinical evaluation and genome sequencing (GS) followed by segregation analysis of the targeted mutation test (TMT) were performed. Histopathological examination of an explanted heart was conducted in one child who underwent heart transplantation. Results: All affected children exhibited typical dermatological features of PLACK syndrome. Four developed severe DCM, two of whom required orthotopic heart transplantation. GS, performed in three affected children, identified a novel homozygous frameshift variant in CAST (NM_001750.7:c.1177dup, p.Arg393Profs*4), which segregated with the disease within the family. No additional plausible variants in known cardiomyopathy-associated genes were detected. Histopathological examination of the explanted heart demonstrated hypertrophied cardiomyocytes with nuclear enlargement, hyperchromasia, and fibrosis. Conclusions: Our findings expand the phenotypic spectrum of PLACK syndrome to include severe DCM and suggest CAST deficiency as a novel cause of recessively inherited cardiomyopathy. The favorable short-term outcome following transplantation highlights a potential therapeutic option. Given the possibility of age-dependent penetrance, lifelong cardiac surveillance is for the affected individuals suggested. To emphasize cardiomyopathy as a critical and underrecognized component of the syndrome, we propose the consideration of modifying the acronym to PLACK-C. Full article

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. It is believed that children with JIA have lower cardiopulmonary capacity and worse exercise tolerance. The gold standard for assessing physical fitness is aerobic fitness, commonly referred to as the maximum or peak oxygen uptake volume (peakVO₂) measured during a maximum load exercise test. Reduced aerobic fitness may play a key role in predicting the health of JIA patients as it has been associated with cardiovascular diseases and increased adult mortality. Methods: The aim of this study was to assess the oxygen capacity of adolescents with JIA along with other cardiopulmonary parameters in order to determine a group of patients with increased risk of developing cardiovascular diseases in comparison with healthy individuals. Patients were assessed based on parameters such as age, sex, type of JIA, laboratory parameters, physical activity, and treatment. Results: Patients with JIA had lower median values of peakVO₂ (29.05 vs. 38.02 mL/min/kg, p < 0.001), as well as other crucial cardiopulmonary parameters, such as O₂ pulse, minute ventilation, oxygen uptake efficiency slope, and cardiac output than in the healthy control group. The ventilatory anaerobic threshold was achieved earlier and at lower VO₂ values in children with JIA (p = 0.0001). Children with JIA also had lowered respiratory parameters such as maximal voluntary ventilation (p = 0.0031) and tidal volume (p = 0.0002). Patients who were physically active (moderate-intensity physical activity lasting at least 60 min per day) had significantly higher peakVO₂ (p = 0.0099) and ΔVO₂/ΔWR relationship (p = 0.0041) values than JIA patients who were not physically active. Conclusions: Children with JIA show moderate to severe physical impairment. Reduced physical fitness and a low level of activity might be associated with further deterioration of patient’s condition, which might contribute to increased risk of cardiovascular disease, social exclusion and deterioration of quality of life in this group of patients. Exercise programs that improve aerobic fitness and increase muscle strength should be individualized and modified based on the individual needs and capabilities of the patient. Full article

Cardiopulmonary bypass (CPB) can lead to cardiac damage due to oxidative stress (OS) and inflammation in heart failure (HF). We tested the hypothesis that preoperative HF patients with reduced ejection fraction (HFrEF) subjected to CBP have higher levels of OS and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) in heart and plasma and in those that develop postoperative AF (pAF) as a clinical outcome. HF was categorized for preoperative left ventricular EF: preserved (HFpEF > 50%, n = 27) and reduced EF (HFrEF ≤ 40%, n = 25). Samples of atrial tissue, pericardial fluid, and plasma were collected at surgery to assess NLRP3 expression; 3-nitrotyrosine (3-NT), thiobarbituric acid reaction (TBARS), and nuclear factor erythroid 2-related factor 2 (Nrf2) in atrial tissue; NLRP3, IL-1β, and IL-18 expression in pericardial fluid; and antioxidant capacity, 8-isoprostanes, and malondialdehyde (MDA) in plasma. Reactive oxygen species, 3-NT, and NLRP3 in atrial tissue were determined by immunohistochemistry in a subset of pAF patients. Plasma and atrial tissue 3-NT and MDA were higher in HFrEF compared with HFpEF. Lipid peroxidation products were higher in both plasma and atrial tissue in pAF (n = 29), compared to sinus rhythm (SR) (n = 23). In HFrEF patients, the values of tissue ROS, 3-NT, and NLRP3 were higher than in HFpEF patients. In addition, the expression levels of NLRP3, IL-1β, and IL-18 were higher in atrial tissue and pericardial fluid in HFrEF. Patients with preoperative HFrEF showed higher OS in plasma and the expression of NLRP3, ROS, and 3-NT in atrial tissue biopsies and pericardial fluid. This finding suggests a potential pharmacologic therapy for pAF and clinical complications due to CPB. Full article

Acute myocardial infarction (MI) is a major cardiovascular event and a leading cause of mortality worldwide. Beyond the initial ischemic injury, the inflammatory and immune responses play pivotal roles in both tissue damage and subsequent healing. While the anti-inflammatory strategies targeting neutrophil-driven injury have demonstrated potential in limiting early cardiac damage, growing evidence highlights the critical role of innate immune cells beyond the acute phase. Neutrophils, traditionally associated with tissue injury, also contribute to the resolution of inflammation and initiate key repair processes. Monocytes and macrophages follow a dynamic trajectory, transitioning from pro-inflammatory to reparative states, and play essential roles in debris clearance, angiogenesis, and scar formation. In the early inflammatory phase of acute MI, immune cells such as neutrophils and monocytes are rapidly recruited and activated. While they initially amplify inflammation through the release of pro-inflammatory mediators, their subsequent transition toward anti-inflammatory and reparative phenotypes helps limit tissue damage by clearing necrotic debris from the infarcted area and contributes to the resolution of inflammation. Accumulating evidence reveals a complex crosstalk between neutrophils and macrophages post-MI, with resident macrophages being involved in neutrophil recruitment, and neutrophil-derived signals participating in monocyte recruitment and macrophage polarization, thereby coordinating the spatial and temporal phases of cardiac repair. Understanding how neutrophil-derived mediators influence macrophage responses and whether macrophage-secreted factors reciprocally modulate neutrophil behavior opens promising pathways for developing targeted therapies to limit adverse remodeling following MI. Therefore, this review aims to (i) provide an overview of the roles of neutrophils and monocytes/macrophages in the pathophysiology of myocardial infarction, (ii) explore the mechanisms of communication, particularly via neutrophil-derived secreted factors, that influence monocyte/macrophage function and impact post-MI inflammation, repair, and remodeling, and (iii) highlight the potential therapies interfering with inflammation and neutrophil/macrophage cross-talk. Full article

Background: Arteriovenous fistula (AVF) in patients with end-stage renal disease (ESRD) can lead to high-output heart failure (HOHF). There is limited data on the incidence and outcomes of HOHF in patients with AVF. Objective: The main goal of our study was to determine the incidence and prevalence of HOHF [diagnosed via right heart catheterization (RHC)] in chronic kidney disease (CKD)/ESRD patients with AVF. We also aimed to evaluate the clinical determinants of the development of HOHF in this group. Methods: We conducted a retrospective cohort study at the University of Kansas Medical Center from January 2011 to December 2023. Patients with CKD/ESRD with AVF who underwent RHC after AVF creation were included in the study. HOHF was defined as a cardiac index (CI) ≥ 4.0 L/min/m², measured either with the Fick or the Thermodilution method. Bivariate and multivariable regression analyses were performed to identify independent predictors of HOHF in this population. Results: Out of 84 patients with AVF, 34 patients met established inclusion and exclusion criteria. Ten out of thirty-four patients (29.4%) developed HOHF. Hemoglobin (Hb) was significantly lower in the HOHF group than the non-HOHF group (10.16 vs. 11.52 g/dL; p = 0.02). Patients with HOHF had significantly elevated CI when compared with the non-HOHF group (CI Fick: 4.54 vs. 2.91 L/min/m², p < 0.001). Similar mortality was observed in the HOHF and non-HOHF groups. After multivariant regression analysis, Hb was an independent predictor of HOHF (HR 0.86, 95% CI: 0.76–0.98, p =< 0.01). Conclusions: HOHF is common in patients with AVF; nearly 1/3 (29.4%) of the patients developed HOHF, confirmed with RHC. Low Hb was found to be an independent predictor of HOHF. Further larger studies are needed to confirm these findings and establish an early detection protocol to detect and treat this condition. Full article

The rapid development of Generative Adversarial Networks (GANs) has transformed medical image processing, enabling realistic image synthesis, augmentation, and restoration. This study presents a comparative evaluation of three representative GAN architectures, Pix2Pix, SPADE GAN, and Wasserstein GAN (WGAN), across multiple medical imaging tasks, including segmentation, image synthesis, and enhancement. Experiments were conducted on three benchmark datasets: ACDC (cardiac MRI), Brain Tumor MRI, and CHAOS (abdominal MRI). Model performance was assessed using Fréchet Inception Distance (FID), Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index (SSIM), Dice coefficient, and segmentation accuracy. Results show that SPADE-inpainting achieved the best image fidelity (PSNR ≈ 36 dB, SSIM > 0.97, Dice ≈ 0.94, FID < 0.01), while Pix2Pix delivered the highest segmentation accuracy (Dice ≈ 0.90 on ACDC). WGAN provided stable enhancement and strong visual sharpness on smaller datasets such as Brain Tumor MRI. The findings confirm that no single GAN architecture universally excels across all tasks; performance depends on data complexity and task objectives. Overall, GANs demonstrate strong potential for medical image augmentation and synthesis, though their clinical utility remains dependent on anatomical fidelity and dataset diversity. Full article

Background/Objectives: Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal and cardiac muscle degeneration driven by inflammation and fibrosis, ultimately leading to cardiomyopathy and premature death. Deramiocel, an allogeneic cell therapy composed of cardiosphere-derived cells (CDCs), has demonstrated potent anti-fibrotic and immunomodulatory effects in preclinical models and clinical trials, including HOPE-2 and its open-label extension (HOPE-2 OLE), where Deramiocel treatment significantly attenuated progression of skeletal and cardiac muscle dysfunction. Methods: CDCs in Deramiocel were cultured to generate CM enriched with secreted exosomes and factors, which was subsequently applied to primary human dermal fibroblasts (HDFs). Following co-culture, ex-pression of collagen type I alpha 1 (COL1A) and collagen type III alpha 1 (COL3A) was measured by qRT-PCR. Non-conditioned media serves as a control in the assay. Reduction in COL1A and COL3A expression therefore provides a direct and clinically relevant measure of the anti-fibrotic activity of Deramiocel. Results: A novel in vitro potency assay was developed to quantify the anti-fibrotic activity of Deramiocel. Conditioned media (CM) from over one hundred Deramiocel manufacturing lots significantly suppressed expression of collagen type I alpha 1 (COL1A) and collagen type III alpha 1 (COL3A) in primary human dermal fibroblasts compared with non-conditioned media controls, establishing a robust, reproducible readout of anti-fibrotic activity. The effect was dose-dependent and abrogated by sequential depletion of exosomes and soluble proteins, implicating both as critical mediators of Deramiocel’s mechanism of action. Importantly, CDCs in Deramiocel lots classified as potent by this assay were shown to exert a clinically meaningful benefit in DMD patients in the HOPE-2 and HOPE-2 OLE studies. Conclusions: This assay represents a mechanistically informative, therapeutically relevant, reproducible, scalable, and regulatory-compliant approach for assessing Deramiocel potency, enabling consistent manufacturing, and facilitating the continued development of Deramiocel as a disease-modifying therapy for DMD. Full article

Background: Non-cardiac organ failure is a severe complication following acute myocardial infarction (AMI), particularly among patients with concomitant arrhythmia. This study aimed to identify risk factors at admission that were associated with in-hospital non-cardiac organ failure. Methods: This case–control study enrolled AMI patients hospitalized for treatment with any type of arrhythmia. Patients were divided into the complication group and the control group based on the development of non-cardiac organ failure. Relaxed least absolute shrinkage and selection operator (LASSO) logistic regression and multivariate logistic regression were performed to identify risk factors, which were subsequently used to develop a predictive model. Shapley Additive Explanation (SHAP) values were applied to enhance model interpretability. Results: A total of 668 patients were enrolled, including 59 individuals in the complication group. After LASSO-logistic and multivariate logistic regression, five independent risk factors were identified and ranked by their SHAP values: Killip class III/IV [odds ratio (OR)] = 2.409, 95% confidence interval (CI): 1.246–4.657, p = 0.009], fibrin degradation products [OR = 1.029, 95% CI: 1.009–1.049, p = 0.003], N-terminal pro-B-type natriuretic peptide [OR = 1.000, 95% CI: 1.000–1.000, p = 0.002], type 2 diabetes mellitus [OR = 1.888, 95% CI: 1.005–3.546, p = 0.048], and cardiogenic shock [OR = 3.443, 95% CI: 1.463–8.089, p = 0.005]. The model demonstrated good discriminative ability with an area under the curve of 0.790 (95% CI: 0.720–0.861). Internal validation showed a calibration slope of 0.953 and a Brier score of 0.067, indicating strong overall predictive accuracy. Conclusions: This study identified five independent risk factors associated with in-hospital non-cardiac organ failure in AMI patients with arrhythmia. The nomogram might assist in early risk stratification, ultimately improving clinical outcomes in high-risk AMI patients with arrhythmia. Full article

In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM. Full article

Changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage are caused by disruptions in ATP supply and/or demand in the heart. These disruptions may affect myocardial energetics and, consequently, cardiac function and mechanics. Increased cardiac inorganic phosphate levels and decreased myocardial ATP levels are the outcomes of this decrease in purine nucleotide levels. Both modifications can immediately affect cellular mechanical work and tension development. Depletion of cardiac nucleotides and compromised myocardial mechanical function are linked to both acute myocardial ischemia and decompensatory remodelling of the myocardium in heart failure. Theoretically, in both acute ischemia and chronic high-demand situations associated with the development of heart failure, an imbalance in the breakdown, salvage, and synthesis of purine nucleotides results in a net loss of purine nucleotides. It was found that the use of nucleotide precursors can be a potentially effective approach to diminishing ischemia–reperfusion damage. The scope of this article is to review knowledge of the effect of purine nucleotide precursors such as D-ribose, AICAR, inosine, hypoxanthine, and adenine on myocardial ischemia–reperfusion injury and highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with ischemia–reperfusion injury by these molecules. Full article

Background: Heart failure (HF), as the end stage of various cardiac diseases, alters blood flow to key organs responsible for drug clearance. This can lead to unpredictable and often suboptimal drug exposure, creating a critical need for quantitative tools to guide precise dosing in this vulnerable population. Methods: This study aimed to establish a whole-body physiologically based pharmacokinetic (PBPK) model for characterizing drug pharmacokinetics in both healthy subjects and patients across the HF severity spectrum. Eight commonly used drugs (digoxin, furosemide, bumetanide, torasemide, captopril, valsartan, felodipine and midazolam) for treating HF and its comorbidities were selected. Following successful validation against clinical data from healthy subjects, the PBPK model was extrapolated to HF patients. Pharmacokinetics of the eight drugs in 1000 virtual HF patients were simulated by replacing tissue blood flows and compared using clinical observations. Results: Most of the observed concentrations were encompassed within the 5th–95th percentiles of simulated values from 1000 virtual HF patients. Predicted area under the concentration–time curve and maximum plasma concentration fell within the 0.5~2.0-fold range relative to clinical observations. Sensitivity analysis demonstrated that intrinsic renal clearance, unbound fraction in blood, muscular blood flow, and effective permeability coefficient significantly impact plasma exposure of digoxin at a steady state. Oral digoxin dosing regimens for HF patients were optimized via the validated PBPK model to ensure that steady-state plasma concentrations in all HF patients remain below the toxicity threshold (2.0 ng/mL). Conclusions: A PBPK model was successfully developed to predict the plasma concentration–time profiles of the eight tested drugs in both healthy subjects and HF patients. Furthermore, this model may also be applied to guide digoxin dose optimization for HF patients. Full article

Coronary Artery Disease (CAD), mainly due to the progressive development of atherosclerotic plaques, is one of the world’s leading causes of mortality and morbidity. A significant percentage of initial events (around 30%) remain fatal to this day despite significant advances in the diagnosis and treatment of cardiovascular diseases (CVDs). Early detection and risk stratification are therefore essential. In this study, we adopted a multi-omics approach integrating transcriptomic (RNA-seq) and epigenomic (ATAC-seq) profiling of peripheral blood mononuclear cells (PBMCs) from a cohort of individuals undergoing clinically indicated cardiac computed tomography angiography (CCTA) to uncover potential novel molecular markers of CAD. We identified 39 genes consistently dysregulated across all CAD subtypes. ATAC-seq analysis revealed distinct chromatin accessibility patterns at CAD-associated loci, with a predominance of quiescent and transcriptionally active states. Validation in an independent cohort confirmed the expression patterns of key Differentially Expressed Genes (DEGs), such as Claudin 18 (CLDN18), supporting the robustness of our findings. Consequently, the integration of multi-omics data allowed us to identify a core gene signature and regulatory patterns associated with disease severity, offering potential biomarkers for clinical risk stratification in patients with CAD. Full article

Chronic alcohol misuse is the leading cause of non-ischemic dilated cardiomyopathy, and the molecular mechanisms underlying the development of alcohol-associated cardiomyopathy (ACM), particularly regarding sex-specific susceptibility and mitochondrial contributions, are not fully known. In this study, we utilized a preclinical model of chronic + binge ethanol consumption to investigate sex differences in disease severity and mitochondrial function. Male and female C57BL/6J mice were fed ethanol or control liquid diets for 30 days, with 2 binge episodes on days 10 and 30. Cardiac morphology was assessed via echocardiography and cardiac function via left ventricular pressure–volume catheterization. Mitochondrial function was evaluated ex vivo using Seahorse XF analysis, ATP luminescence, and AmplexTM Red fluorescence in isolated ventricular mitochondria. Ethanol feeding induced significant cardiac dysfunction and increased transcriptional expression of inflammatory and fibrotic markers in males, while these effects were not seen in females. Despite these sex-specific cardiac effects, mitochondrial respiration, ATP production, collagen protein expression, and oxidative stress were not significantly altered following alcohol exposure in either sex. Further investigation is warranted to assess the potential role of ovarian hormones in this female cardioprotection against chronic + binge ethanol. Full article