Search Results (250)

The cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age- and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations. Full article

The growing frequency of extreme weather, earthquakes, fires, and environmental hazards underscores the need for real-time monitoring and predictive management at the urban scale. Conventional three-dimensional spatial information systems, which rely on orthophotos and ground surveys, often suffer from computational inefficiency and data overload when processing large and heterogeneous datasets. To address these limitations, this study introduces a three-dimensional GeoHash-based geocoding algorithm designed for lightweight, real-time, and attribute-driven digital twin operations. The proposed method comprises five integrated steps: generation of 3D GeoHash grids using longitude, latitude, and altitude coordinates; integration with GIS-based urban 3D models; level optimization using the Shape Overlap Ratio (SOR) with a threshold of 0.90; representative object labeling through weighted volume ratios; and altitude correction using DEM interpolation. Validation using a testbed in Sillim-dong, Seoul (10.19 km²), demonstrated that the framework achieved approximately 9.8 times faster 3D modeling performance than conventional orthophoto-based methods, while maintaining complete object recognition accuracy. The results confirm that the 3D GeoHash framework provides a unified spatial key structure that enhances data interoperability across querying, visualization, and simulation. This approach offers a practical foundation for operational digital twins, supporting high-efficiency 3D mapping and predictive disaster management toward resilient and data-driven urban systems. Full article

Myxomatous mitral valve disease (MMVD) is the most prevalent cardiac disorder in small and toy breed dogs, with the Cavalier King Charles Spaniel (CKCS) showing exceptionally high predisposition and early onset of the disease. MMVD is characterized by progressive mitral valve degeneration, volume overload, and eventual development of congestive heart failure (CHF). Given the strong hereditary component in CKCS, considerable research has focused on elucidating the genetic basis of MMVD in this breed. This review article summarizes the current state of knowledge on the phenotypic features, inheritance, and candidate loci potentially responsible for early onset and severe course of the disease. The pathogenesis of the disease, its classification, and the effects of breeding programs aimed at reducing the occurrence of MMVD have been described. Key findings include associations between MMVD severity and polymorphisms in genes such as NEBL, ACE, CDK6, HEPACAM2, COL5A1, and FAH, as well as evidence implicating dysregulated TGF-β signaling, serotonin signaling, and extracellular matrix remodeling pathways. The current state of knowledge on the role of miRNA in the pathogenesis of MMVD was also summarized. Despite these findings, no specific high-penetrating mutation has been identified. MMVD is a complex, polygenic condition shaped by regulatory variants and breed-specific genetic bottlenecks. Comparative studies underscore the translational relevance of canine MMVD to human mitral valve disease, while genomic insights may be basis for the future selective breeding strategies and therapeutic approaches. Further large-scale, integrative studies combining genomics, transcriptomics, and functional validation are needed to clarify disease mechanisms and support targeted treatment in CKCS as well as the development of new breeding strategies and programs. Full article

Basic physiology and molecular mechanisms accounting for the maldistribution of fluid that is characteristic of the “third fluid space” (V_t2) have been known for several decades but have been poorly integrated into the clinical literature. Today, the maldistribution can be quantified and simulated in living humans by using volume kinetic mathematics, which introduces possibilities to validate interventions designed to mitigate the pathophysiology. Fluid accumulation in V_t2 occurs both in fluid overload and inflammation, and both are largely influenced by interstitial fluid pressure. This is normally slightly sub-atmospheric but increases during volume loading to eventually exceed the ambient air pressure, whereby the loss of vacuum allows pools of fluid to appear in the interstitial gel. Opening of V_t2 due to fluid overload can be delayed/minimized by lowering the infusion rate, hemorrhage, and the use of hyper-oncotic fluid. Accumulation of fluid in V_t2 during acute inflammation and tissue injury can be explained by disruption of the cell–matrix interactions that actively regulate the interstitial pressure. Inflammatory mediators, mostly tissue cytokines, cause release of tensile forces that disrupt integrin-dependent adhesion between interstitial fibroblasts and collagen fibers. This disruption causes the interstitial space to expand, which results in a deep negative (suction) pressure. These events can be modulated by α-trinositol and insulin. Full article

Chronic inter-dialytic volume overload and uremic inflammation activate TGF-β/Smad3 and p38 MAPK pathways, inducing connective tissue growth factors (CCN2/CTGF)-mediated fibrosis and NT-proBNP secretion from over-stretched cardiomyocytes. The combined rise in CTGF and NT-proBNP reflects myocardial fibrosis, stiffness and remodeling, predicting cardiovascular (CV) death in maintenance hemodialysis (MHD) patients. From molecular pathology to clinical translation, circulating CCN2/CTGF and NT-proBNP levels and bio-clinical data among MHD patients were measured in this prospective cohort. Multivariate Cox regression analysis identified independent predictors of mortality, which were incorporated into a composite risk-score model. The predictive performance for all-cause, CV, and sudden cardiac death (SCD) was assessed using receiver operating characteristic (ROC) survival analysis. CCN2/CTGF, NT-proBNP, age, serum albumin, MHD vintage, high-sensitivity C-reactive protein, smoking, and diabetes mellitus were significant predictors. The integrated model yielded areas under the curve of 0.91 for all-cause mortality, 0.88 for CV mortality, and 0.87 for SCD. Integrated complementary biomarkers and clinical parameters significantly improve mortality risk prediction in MHD patients. This synergistic model provides clinicians with a robust tool for early CV screening, individualized intervention, and precision management for high-risk populations. Full article

Background: This retrospective cross-sectional study evaluated the association of the global wall thickness index (GTI), derived from cardiovascular magnetic resonance (CMR), with demographic, clinical, and imaging findings, as well as heart failure history in transfusion-dependent thalassemia (TDT) patients. Methods: We analyzed 1154 TDT patients (52.9% female, 37.46 ± 10.67 years) from the Extension-Myocardial Iron Overload in Thalassemia project and 167 healthy controls (54.5% female, 36.33 ± 15.78 years). The CMR protocol included the T2* technique for the assessment of iron overload, cine imaging for the assessment of left ventricular (LV) function and size, and late gadolinium enhancement (LGE) imaging for the detection of replacement myocardial fibrosis (in the subset of 366 patients who underwent contrast administration). GTI (in mm/m²) was calculated from LV mass and end-diastolic volume. Results: GTI discriminated TDT patients from controls better than the LV end-diastolic volume index. Among TDT patients, GTI was higher in males, in those with diabetes, and in those with severe myocardial iron overload (cardiac T2* < 10 ms), but was unrelated to age, hemoglobin and ferritin levels, splenectomy, hepatic and pancreatic T2* values, LV ejection fraction, and fibrosis. GTI showed a diagnostic performance comparable to global heart T2* and superior to LV ejection fraction in identifying patients with prior heart failure. Conclusions: GTI is elevated in TDT patients compared with healthy controls. Male sex and severe myocardial iron overload are key determinants of GTI in TDT. Increased GTI is linked to a history of heart failure, supporting its role as a complementary tool to conventional CMR indices. Full article

Background: Prostate cancer is the most frequent malignancy in men, with an incidence of 21% of all diagnosed tumors in this population in Spain. Between 10 and 20% of patients with prostate cancer develop castration-resistant prostate cancer (CRPC). Abiraterone is widely used in CRPC and metastatic prostate cancer, but data on its renal safety are limited. Methods: We performed a single-center, retrospective observational study including patients with advanced prostate cancer who initiated abiraterone between January 2013 and July 2024 at Hospital Clínico San Carlos (Madrid, Spain). Patients were followed until December 2024. Renal events were defined as acute kidney injury (AKI), electrolyte imbalance, new onset or worsening hypertension (HTN), and/or volume overload. Risk factors and associations with mortality were analyzed using multivariate models. Results: Seventy-nine patients were included (mean age 76 ± 9.5 years; 70.9% CRPC; 89.9% metastatic disease). Median follow-up was 17 months. Renal events occurred in 63.3% of patients. Independent risk factors were metastatic disease (OR 13.335; 95% CI 1.418–124.444; p < 0.0235) and HTN (OR 3.336; 95% CI 1.091–10.206; p < 0.0347). Electrolyte imbalance occurred in 36.7% of patients. AKI developed in 30.4% of patients, of whom 50% progressed to chronic kidney disease. New/worsening HTN occurred in 25.5%, and volume overload occurred in 16.5%. Abiraterone discontinuation due to renal events was rare (4%). At the end of follow-up, 18.9% of patients had died. In a multivariate Cox analysis, AKI was identified as an independent predictor of mortality [HR 3.044 (95% CI 1.001–9.260); p = 0.05]. Conclusions: Renal events are common in patients treated with abiraterone, especially in those with metastatic disease and hypertension. AKI independently predicted mortality. Close monitoring of renal function and blood pressure is essential in this population. Full article

Background: Diabetic ketoacidosis (DKA) in patients with kidney failure receiving dialysis presents a formidable clinical challenge. Standard DKA protocols, designed for patients with preserved renal function, often fail in this cohort and can be unsafe when applied without modification. Patients are at risk of iatrogenic fluid overload, dyskalaemia, and hypoglycaemia due to altered insulin kinetics, impaired gluconeogenesis, and the absence of osmotic diuresis. Purpose: This narrative review aims to synthesise current understanding of DKA pathophysiology in dialysis patients, delineate distinct clinical phenotypes, and propose individualised management strategies grounded in physiology-based reasoning, comparative guideline insights, and consensus-supported literature. Methods: We searched PubMed/MEDLINE, Embase, and Google Scholar (January 2004–June 2024) for adult dialysis populations, using terms spanning DKA, kidney failure, insulin kinetics, fluid balance, and cerebral oedema. Reviews, observational cohorts, guidelines, consensus statements, and physiology papers were prioritised; case reports were used selectively for illustration. Evidence was weighted by physiological plausibility and practice relevance. Nephrology-led authors aimed for a pragmatic, safety-first synthesis, seeking and integrating contradictory recommendations. Conclusions: Our findings highlight the critical need for a nuanced approach to fluid management, a tailored insulin strategy that accounts for glucose-insulin decoupling and prolonged insulin half-life, and careful consideration of potassium and acidosis correction. We emphasise the importance of recognising specific volume phenotypes (hypovolaemic, euvolaemic, hypervolaemic) to guide fluid therapy, and advocating the judicious use of variable-rate insulin infusions (‘dry insulin’) to mitigate fluid overload. We also show that service-level factors are critical. Dialysis-specific pathways, interdisciplinary training, and quality improvement metrics can reduce iatrogenic harm. By linking physiology with workflow adaptations, this review provides a physiologically sound, bedside-oriented map for navigating this complex emergency safely and effectively. In doing so, it advances an individualised model of DKA care for dialysis-dependent patients. Full article

Background: Patent ductus arteriosus (PDA) in dogs causes persistent left-to-right shunting, leading to pulmonary overcirculation, left heart volume overload, and potential congestive heart failure. Accurate assessment of fluid imbalance is essential but challenging with conventional echocardiography or biomarkers. Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), may serve as a non-invasive marker of extracellular fluid distribution and cellular integrity. Objectives: This study aimed to evaluate PhA as an indicator of thoracic fluid imbalance in dogs with PDAby analyzing its correlation with pulmonary velocity (PV) and end-diastolic volume (eV), as well as its responsiveness to surgical correction. In addition, we assessed the relationships between PhA and echocardiographic structural indices (LA/Ao, TDI Sep E/Em, TDI Lat E/Em) and examined the influence of the measurement region. Methods: PhA was measured at 5, 50, and 250 kHz in 30 PDA-affected and 15 healthy dogs, with electrode placement across thorax, trunk, and abdomen. Echocardiography evaluated PV, eV, and PDA-specific structural parameters. Results: Thoracic PhA at 5 kHz was significantly reduced in PDAdogs, strongly correlated with PV and moderately with eV. Postoperative measurements showed progressive PhA recovery. Only TDI Lat E/Em correlated with mid-frequency PhA, while other structural indices showed minimal association. Thoracic PhA was lower than trunk or abdominal values, indicating that thoracic measurements may better capture localized extracellular fluid changes in PDAcompared with other regions. Conclusion: Thoracic PhA at 5 kHz effectively reflects extracellular fluid changes in PDA, complements structural echocardiography, and tracks postoperative fluid normalization. Its non-invasive nature supports clinical utility for monitoring hemodynamic burden and therapeutic response. Full article

Pressure overload in non-treated or resistant hypertension (HTN) increases the risk of heart failure (HF) as well as the occurrence of fatal ventricular arrhythmias and stroke-provoking atrial fibrillation (AF), while perturbed connexin-43 (Cx43) and Cx40 might be involved. In addition, kidney dysfunction may facilitate hemodynamic volume overload and congestive HF. We investigated the impact of volume overload on Cx43 and Cx40 in right and left heart atria of hypertensive pressure overloaded Ren-2 transgenic (TGR) strain and normotensive Hannover Sprague Dawley (HSD) rats, as well as the efficacy of renin–angiotensin blockade with trandolapril and losartan. Key novel findings revealed lower levels of Cx43 and Cx40 proteins in left as well as right heart atria in pressure overloaded hypertensive rats compared to normotensive rats. There was a significant decrease in Cx43 and Cx40 proteins due to volume overload in both atria of normotensive as well as hypertensive rats. Treatment with trandolapril increased Cx43 and Cx40 levels in right and left heart atria of normotensive as well as hypertensive volume overloaded rats. While losartan increased Cx43 and did not affect Cx40 in left and right heart atria of volume overloaded rats. Findings of this study point out that right heart atria of normotensive as well as hypertensive rats are more susceptible to volume overload comparing to the left heart atria. Trandolapril attenuated pro-arrhythmic downregulation of Cx43 and Cx40 in atria of volume overloaded normotensive as well as hypertensive rats. This fact as well as examining AF inducibility requires further investigation. Full article

An atrial septal defect (ASD) is the most common congenital heart defect (CHD) diagnosed in adulthood. It is characterized by significant anatomical heterogeneity and complications that evolve over time. While often asymptomatic in children, the signs of adverse effects of ASD increase with age, including a greater risk of heart failure, stroke, atrial fibrillation (AF), and reduced life expectancy. ASD is traditionally considered a right-heart lesion due to long-term complications such as arrhythmias, right-sided heart failure, thromboembolism, and, in a subset of patients, pulmonary arterial hypertension (PAH). The pathophysiology of atrial shunts also affects the left heart due to volume overload and adverse ventriculo-ventricular interaction. Early diagnosis of interatrial septal anomalies is essential to prevent hemodynamic consequences and/or thromboembolic events. Electrocardiographic (ECG) findings play a crucial role in this early diagnosis. This narrative review aims to update clinicians on the latest evidence regarding the pathophysiological link between ASD and cardiac rhythm disorders, the nuances of optimal diagnostics, treatment options (surgical, interventional, pharmacological), and the need for long-term follow-up for patients with ASD. The review will determine the risk of conduction disorders compared to a healthy population and to compare the prevalences of conduction disorders, mortality, and pacemaker use in patients with closed ASDs versus those with open ASDs. Full article

Hypertension is a major risk factor for heart failure. Acetylation of p53 is known to regulate its activities. We have previously identified that p53 acetylation is required for cardiac remodeling in a mouse model of pressure overload-induced heart failure. Acetylation mutant p53 (p53aceKO) mice have been shown to have the ability to regulate SIRT3 KO-induced cardiac fibrosis. In the present study, we hypothesized that p53aceKO mice would exhibit cardiac protection and blunt cardiac fibrosis when subjected to Ang-II-induced hypertension. Control and p53aceKO mice received either a micro-osmotic pump implant administering Ang-II for 28 days or a sham procedure. Blood pressure was measured weekly, and echocardiography was performed every two weeks. Mice were euthanized and hearts were processed for histological analysis. While both control and p53aceKO mice receiving Ang-II exhibit increased systolic and diastolic blood pressures, control mice also demonstrate increases in ejection fraction and fractional shortening compared to the sham, while p53aceKO mice do not. Furthermore, control mice receiving Ang-II exhibit decreased left ventricular diameter and volume at end-systole and end-diastole, as well as thickening of both the anterior and posterior walls, while p53aceKO mice exhibit no significant changes in any of these parameters. Additionally, p53aceKO mice do not exhibit the Ang-II infusion-induced cardiac fibrosis seen in control mice treated with Ang-II. Mutation of p53 acetylation is protective against Ang-II infusion-induced cardiac fibrosis and dysfunction in mice. Acetylated p53 may, therefore, be a novel therapeutic target to address complications in the heart associated with hypertension. Full article

Left ventricular (LV) hypertrabeculation is increasingly recognized as a phenotype that may reflect physiological adaptation, particularly in athletes exposed to chronic overload, although its functional relevance remains uncertain. This study evaluated the prevalence of excessive trabeculation and its physiological correlation with LV remodeling. We conducted a single-center, cross-sectional study involving 320 Olympic-level athletes without cardiovascular disease. All underwent cardiac magnetic resonance (CMR). Hypertrabeculation was defined by the Petersen criteria. Athletes meeting these criteria were classified as hypertrabeculated and compared with non-hypertrabeculated matched for age, sex, and sport category. LV morphology, function, strain parameters, and hemodynamic forces (HDFs) were analyzed. Hypertrabeculation was identified in 9% of the cohort. No significant differences were observed between groups for training exposure (p = 0.262), body surface area (p = 0.762), LV volumes (end-diastolic volume indexed p = 0.397 end-systolic volume indexed p = 0.118), ejection fraction (p = 0.101), mass (p = 0.919), sphericity index (p = 0.419), myocardial wall thickness (p = 0.394), tissue characterization (T1 mapping p = 0.366, T2 mapping p = 0.833), global longitudinal strain (GLS p = 0.898), global circumferential strain (GCS p = 0.219), or HDFs. All values were within the normal range. In our cohort, LV hypertrabeculation, evaluated by CMR, was relatively common but not associated with structural or functional abnormalities, supporting its interpretation as a benign variant in asymptomatic athletes with normal cardiac function. Full article

Background/Objectives: This study examined the efficacy of essential amino acid (EAA) supplementation on changes in behavior and hippocampal neurotrophin, dopaminergic and serotonergic markers to a volume overload stress resembling an overtraining syndrome. Methods: Thirty-two 3-month-old male C57Bl/6J mice were randomized into four groups: Resistance training (RT), resistance training with overtraining (RTO), resistance training with overtraining and EAA (RTOEAA), or control. Mice in RTOEAA received EAA supplementation (1.5 g·kg·day⁻¹), while the other groups received a sham treatment. A 5-week resistance training protocol was employed. Training volume was increased two-fold during the final two weeks for RTO and RTOEAA to cause the OTS. EAA intervention for RTOEAA occurred during the OTS. Results: A significant decline in the maximum resistance carrying load in RTO compared to RT (p = 0.002) and RTOEAA (p = 0.029) confirmed that the animals in that group were overtrained. Significantly greater average latency times for RTO compared to RT (p = 0.009) and C (p = 0.05) indicated that the OTS caused spatial memory deficits in animals that were not supplemented. These latter changes may have been related to the significant declines in brain derived neurotrophic (BDNF) expression and elevations in dopamine 1 receptor (D1R) expressions. Increased resiliency for RTOEAA may have been related to the effect of EAA on stimulating significant increases in the expression of hippocampal tyrosine receptor kinase B (TrkB) and serotonin receptors (5-HT1A). Conclusions: EAA supplementation during a resistance model of overtraining appeared to provide increased resiliency to OTS by maintaining neurotrophin expression and enhancing serotonergic adaptation. Full article

Hypertensive heart disease (HHD) is characterized by pressure overload-induced cardiac remodeling, in which mitochondrial dysfunction has emerged as a central contributor to pathophysiology. Mitochondria occupy roughly one-third of the volume of a cardiomyocyte and serve as the primary source of ATP for the constantly active heart, while also regulating calcium homeostasis, redox balance, and apoptotic signaling. Chronic hypertension imposes energetic and oxidative stress on cardiomyocytes, disrupting mitochondrial structure and function. Key mitochondrial quality control processes including organelle fusion–fission dynamics, biogenesis, and mitophagy become dysregulated in HHD, leading to impaired energy production and heightened cell injury. This unstructured review discusses the physiological roles of mitochondria in cardiac muscle and examines how altered mitochondrial dynamics contribute to hypertensive cardiac damage. We detail mechanisms of mitochondrial dysfunction in HHD, such as excessive fission, cristae disruption, and oxidative stress, and how these changes are exacerbated by aging. Age-related mitochondrial remodeling such as loss of cristae and decreased organelle volume may synergistically worsen hypertensive cardiac injury. We further integrate findings from recent studies in animal and human models, including advanced three-dimensional ultrastructural analyses and molecular investigations that illuminate new aspects of mitochondrial network organization, the mitochondrial contact site and cristae organizing system (MICOS), cristae maintenance complex, and quality control pathways in HHD. Understanding mitochondrial dysfunction in HHD reveals potential therapeutic avenues targeting mitochondrial quality and dynamics to preserve cardiac function in hypertension. Full article