Search Results (403)

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Background: Cardiovascular diseases (CVD) are major contributors to global morbidity and mortality, and their association with cognitive impairment has gained increasing attention. Recent studies indicate that the prevalence of post-myocardial infarction (MI) cognitive impairment ranges from 22% to 37%, with attention being one of the most frequently affected domains. Moreover, novel approaches, such as normobaric hypoxic training in cardiac rehabilitation, show potential in improving both cardiovascular and cognitive outcomes. Aim: This narrative review aims to synthesize current evidence on the role of hypoxia in the development of cognitive dysfunction among patients with cardiac diseases, emphasizing shared mechanisms along the heart–brain axis. Methods: We performed a narrative search of PubMed, Scopus, and Web of Science databases using the keywords “hypoxia”, “cognitive impairment”, “myocardial infarction”, “heart failure”, and “CABG surgery”. We included original studies, reviews, and meta-analyses published between 2000 and up to the present in English. Priority was given to peer-reviewed human studies; animal models were included when providing mechanistic insights. Exclusion criteria included case reports, conference abstracts, and non-peer-reviewed sources. Narrative reviews, while useful for providing a broad synthesis, carry an inherent risk of selective bias. To minimize this limitation, independent screening of sources and discussions among multiple authors were conducted to ensure balanced inclusion of the most relevant and high-quality evidence. Results: Hypoxia contributes to cognitive decline through multiple pathophysiological pathways, including blood–brain barrier disruption, white matter degeneration, oxidative stress, and chronic neuroinflammation. The concept of “cardiogenic dementia”, although not yet formally classified, highlights cardiac-related contributions to cognitive impairment beyond classical vascular dementia. Clinical assessment tools such as the Stroop test, Trail Making Test (TMT), and Montreal Cognitive Assessment (MoCA) are useful in detecting subtle executive dysfunctions. Both pharmacological treatments (ACE inhibitors, ARBs) and innovative rehabilitation methods (including normobaric hypoxic training) may improve outcomes. Conclusions: Cognitive impairment in cardiac patients is common, clinically relevant, and often underdiagnosed. Routine cognitive screening after cardiac events and integration of cognitive rehabilitation into standard cardiology care are recommended. Future studies should incorporate cognitive endpoints into cardiovascular trials. Full article

Recent advances in wearable sensing technology have enabled simultaneous measurement of heart activity and body movement using devices equipped with both ECG recording and 3-axis accelerometers. This study examined whether transient heart rate (HR) responses to physical activity can be accurately characterized under free-living conditions. Continuous RR interval data and activity levels derived from accelerometer signals were analyzed using a multivariate autoregressive (MVAR) model. Results from 12 male participants showed a strong correlation between predicted and observed HR responses (r² = 0.93, r = 0.96, p < 0.001). These findings indicate that up to 93% of transient HR dynamics associated with daily physical activity can be explained by the model. While these results are preliminary due to the limited sample size, the approach provides a promising framework for the noninvasive, continuous monitoring of cardiovascular responses in everyday health and wellness applications. Full article

Reactive sulfur species (RSS)—hydrogen sulfide (H₂S), low-molecular-weight persulfides/polysulfides and protein persulfidation—constitute a third redox axis alongside ROS and RNS. Nanomolar H₂S, produced by trans-sulfuration (CBS/CSE) and 3-MST, is oxidized by sulfide–quinone reductase to persulfides that fuel the respiratory chain while curbing superoxide. Reversible persulfidation reprograms cysteine sensors in metabolism (GAPDH), inflammation (NLRP3, p47^phox) and transcription (Keap1/NRF2), linking RSS to energy balance, vasodilation, innate immunity and neuroplasticity. Disrupted sulfur signaling—deficit or overload—contributes to heart failure, sarcopenia, neurodegeneration, cancer and post-COVID syndromes. Therapeutically, slow-release donors (SG1002, GYY4137), mitochondria-targeted vectors (AP39), photo- or thiol-activated “smart” scaffolds, diet-derived polysulfides/isothiocyanates and microbiota engineering aim to restore the protective RSS window. Key challenges are a narrow therapeutic margin and real-time quantification of persulfide fluxes. Harnessing RSS therefore offers a route to rebalance redox homeostasis across diverse chronic diseases. Full article

Background: A subset of patients with chronic dyspepsia exhibits palpable upper abdominal hardness and systemic symptoms like headache, chest discomfort, neck/shoulder stiffness, fatigue, and depression. In traditional Korean medicine (TKM), this symptom complex is referred to as Damjeok syndrome (痰积症候群, DJS). Although DJS is frequently observed in TKM practice, it lacks a clear case definition and biological mechanism, limiting its integration in gastroenterology research and evidence-based practice. Clarifying its clinical and biological features is essential to understand its pathophysiology and clinical significance. Methods: This case–control study aimed to characterize DJS by comparing 16 female patients diagnosed with DJS and 15 age-matched healthy females as controls. A female-only cohort was selected to reflect the higher prevalence of chronic dyspepsia in women and reduce biological variability. Clinical characteristics and potential DJS-specific biomarkers were evaluated through complete blood count (CBC), serum biochemical tests, heart rate variability (HRV) for autonomic function, and plasma 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite linked to gastrointestinal motility and autonomic regulation. Results: The DJS group had a mean disease duration of 58.0 ± 46.2 months, with epigastric fullness and underlying abdominal hardness as primary complaints. Postprandial distress syndrome (PDS) was the most common (43.8%) dyspepsia subtype, often combined with epigastric pain syndrome (EPS). Extra-gastrointestinal symptoms such as headache/fatigue (87.5%) and anxiety/depression (81.3%) were highly prevalent. Neutrophil counts were significantly lower in the DJS group (p = 0.01), while other hematological or biochemical markers showed no differences (p > 0.1). HRV analysis revealed decreased parasympathetic activity (RMSSD and HF, p < 0.1), and plasma 5-HIAA levels were significantly elevated compared to healthy controls (p = 0.01). Conclusions: DJS aligns with functional gastrointestinal disorders (FGIDs), sharing psychosomatic symptoms and reduced parasympathetic activity, suggesting gut–brain axis dysregulation. However, distinct features like palpable upper abdominal hardness and elevated plasma 5-HIAA levels indicate that DJS may represent a unique subtype within the category of FGIDs. These findings highlight the need for larger, well-designed studies to further elucidate the pathophysiology of DJS. Full article

BPAF (Bisphenol AF), one of the primary substitutes for BPA (Bisphenol A), is widely used in the production of plastics, optical fibers, and other materials. During the use of these products, BPAF inevitably enters the environment and exerts toxic effects on animal growth, development, reproduction, immunity, neurology, and genetics. This study employed marine medaka (Oryzias melastigma) as the experimental model to evaluate the toxicological impacts of BPAF on early development. Embryos were exposed to four BPAF concentrations (0, 1 μg/L, 10 μg/L, and 100 μg/L) for 14 days (embryonic to larval stages), followed by phenotypic measurements, behavioral analysis, and gene expression detection. The results demonstrated that BPAF exposure induced developmental malformations and reduced survival rates in marine medaka embryos, with embryo survival negatively correlated with BPAF concentrations. Additionally, BPAF significantly decreased embryonic heart rates, and the 100 μg/L BPAF group exhibited prolonged embryo hatching time and reduced hatching success. In newly hatched larvae, BPAF exposure led to decreased body length, reduced heart rates, and significant suppression of swimming activity, characterized by increased resting time and reduced swimming distance. BPAF exposure altered the expression levels of genes associated with cardiovascular function (e.g., tbx2b, arnt2), the HPT axis (e.g., tg, dio3a, trh, trhr2, tpo), and neurodevelopment (e.g., ache, elavl3, gfap) in the medaka larvae. These transcriptional perturbations are proposed as potential molecular mechanisms underlying the observed phenotypic effects, including reduced heart rates and suppressed swimming behavior in the study. Molecularly, BPAF exposure significantly disrupted the expression of genes related to the cardiovascular system, HPT axis, and nervous system. Full article

CD44, a multi-isoform adhesion receptor for hyaluronic acid (HA), plays a crucial role in regulating cell interactions with the extracellular matrix, cell migration, differentiation, and survival in both physiological and pathological contexts. Accumulating experimental evidence suggests that CD44 is not merely a passive marker of mesenchymal cell activation but rather an active signaling hub driving fibrosis in many organs, including the lung, skin, heart, and liver. Its involvement in fibroblast differentiation into myofibroblasts, as well as induction of the invasive phenotype of these cells, shows striking analogies to the mechanisms of epithelial-to-mesenchymal transition (EMT) known from cancer progression. In this paper, we discuss both the molecular mechanisms of CD44-dependent signaling (including through EGFR, MAPK/ERK, CaMKII, lipid rafts, and Smad) and the influence of its modulation (knockout, antibodies, blockade of HA synthesis) on the course of fibrosis in in vitro and in vivo models. In addition, we present the influence of environmental pollutants—such as heavy metals, particulate matter, endocrine disruptors, and microplastics—on the activation of the HA-CD44 axis in connective tissue, with particular emphasis on their role in the induction of chronic inflammation, EMT, and extracellular matrix deposition. The collected evidence suggests that CD44 serves as a central integrator of inflammatory and fibrogenic signals, and its pharmacological modulation may represent a novel therapeutic strategy for treating fibrotic diseases and chronic inflammatory conditions. Full article

Background: The mitral valve apparatus is a complex system that requires sufficient function of all involved structures. Previous studies have demonstrated that ventricular remodeling can cause displacement of subannular structures, including the papillary muscles, which in turn promotes the development of mitral regurgitation. Furthermore, in such cases, annuloplasty alone is often insufficient to restore optimal valve function. Instead, additional reconstruction of the subannular apparatus is associated with improved clinical outcomes. Our study aimed to analyze the topography of the papillary muscles in the mitral valve complex and their relevance for mitral valve function. Methods: In 148 patients who underwent both cardiac computed tomography (CT) and echocardiography, the position of the papillary muscles within the left ventricle was assessed. CT scans were evaluated in end-diastolic four-chamber view, two-chamber view, and short-axis view. CT analysis involved determining the position of the papillary muscles based on a modified left ventricular segmentation scheme, which subdivided the original segments into “a” and “b” subsegments in a counterclockwise manner. Furthermore, the midventricular diameter, ventricular length, as well as the angle between the papillary muscle (PM) and the left ventricular wall, were measured. Comorbidities were assessed. The presence of mitral regurgitation (MR) and ejection fraction was determined based on echocardiographic data. Echocardiography was conducted either as part of initial cardiological assessments or during follow-up examinations. For detailed statistical analysis, the patients were divided into the following groups: control group, MR-only group, coronary heart disease (CHD)-only group, and combined CHD and MR subgroup. Results: Mitral regurgitation was significantly correlated with age (p < 0.001) and hypertension (r = 0.1900, p = 0.0208), and in the MR-only subgroup, additionally with atrial fibrillation (r = 0.2426, p = 0.0462). The length (p < 0.001) and internal diameter (p < 0.001) of the left ventricle were significantly larger in men than in women. Different positions of the papillary muscles were identified. Segment 7a was significantly correlated with MR in the combined CHD and MR subgroup. In normal-sized ventricles, patients with MR and papillary muscle in 12a (p = 0.0095) or 10a (p = 0.0460) showed a significantly larger angle than patients without MR (overall dataset). Conclusions: Assessment of papillary muscle position is essential in diagnosing mitral regurgitation and should guide the consideration of subannular repair during surgical treatment. Full article

Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies is primarily attributable to the complex and heterogeneous pathophysiology underlying HFpEF. The hallmark of HFpEF is systemic inflammation, mostly originating from extracardiac comorbidities, which initiates and sustains the process of myocardial fibrosis, resulting in diastolic dysfunction. Recent evidence has identified specific micro ribonucleic acids (miRNAs) as key regulatory molecules in this inflammation–fibrosis cascade. Particularly, miR-21 and miR-29 play a central role in modulating these pathological processes by regulating the post-transcriptional expression of genes involved in inflammation, cardiac fibrosis, and remodeling. The inflammation-fibrosis axis in HFpEF offers multiple therapeutic opportunities ranging from direct anti-fibrotic strategies to the modulation of inflammation and fibrosis-related miRNA signatures. Such targeted approaches, especially miRNA modulation, hold potential to disrupt fundamental molecular mechanisms driving disease progression, moving beyond conventional HFpEF management. This narrative review explores the roles of miRNAs in modulating inflammation and fibrosis in HFpEF, critically assesses their potential as diagnostic and prognostic biomarkers, and evaluates their therapeutic application. Given the urgent clinical need for efficient HFpEF treatment strategies, understanding miRNA-mediated regulation of the inflammation–fibrosis axis is essential for developing personalized, mechanism-based therapies for HFpEF that could fundamentally change the HFpEF management paradigm. Full article

Cardiogenesis and heart cell composition and function constitute fundamental areas of cardiovascular medicine research, and exploring their underlying mechanisms is closely tied to the goals of precision medicine. This review comprehensively examines the composition and functions of the heart from embryonic organogenesis to maturity, and highlights the main breakthroughs of treatment strategies associated with these processes. By elaborating on the spatiotemporally specific signaling pathways and transcriptional networks that drive heart organogenesis and progenitor cell fate determination during the pivotal stages of cardiac development, and by systematically presenting the molecular biomarkers and functional characteristics of the principal cell types in mature heart, the latest advancements in related applications are summarized, with a particular emphasis on breakthroughs in gene/cell therapy, organoid development, and tissue engineering and regenerative medicine. This paper provides a theoretical foundation for precision interventions and regenerative medicine in cardiovascular disease using an axis that integrates cardiogenesis, cellular architecture, and therapeutic translation. Full article

Background: Atherosclerosis is the main cause of coronary heart disease, which frequently precedes the onset of heart failure. Lipopolysaccharide (LPS), a pro-inflammatory endotoxin produced by Gram-negative bacteria, exacerbates atherosclerotic processes and negatively impacts myocardial function, particularly in the context of activating low grade inflammation. Zonulin, a key regulator of the blood-gut barrier, modulates tight junction permeability, potentially facilitating the translocation of microbial-derived compounds, including LPS, into the circulation. Given these interactions, we investigated serum levels of lipopolysaccharide and zonulin in patients following myocardial infarction. This study aimed to assess serum levels of zonulin and lipopolysaccharide (LPS) in patients who had experienced a myocardial infarction (MI) and to evaluate the association between these biomarkers and ejection fraction (EF) across different patient groups. Methods: 78 patients (22 women and 56 men) diagnosed with MI, who underwent primary PCI (percutaneous coronary intervention), were included in the study. The blood samples were collected between 24 and 48 h after PCI. Results: Post-myocardial infarction patients with an ejection fraction ≤ 40% exhibited significantly elevated serum lipopolysaccharide levels compared to those with an ejection fraction > 40%. However, no significant differences in zonulin levels were observed between the study groups. Conclusions: Our findings suggest that elevated serum lipopolysaccharide levels may be associated with a reduction in post-infarction ejection fraction. This observation highlights a potential link between endotoxemia and impaired myocardial function following MI, warranting further investigation. Full article

The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article

Congenital heart disease (CHD), the most prevalent congenital abnormality, is becoming increasingly acknowledged as a component of a broad fetoplacental pathology. This systematic review summarizes recent imaging-based data linking CHD to quantifiable placental abnormalities. In CHD pregnancies, placenta studies consistently show patterns of altered vascularization, decreased volumetric growth, microstructural heterogeneity, and impaired placental oxygenation. We conducted a thorough literature search from January 2020 to May 2025 to identify studies on placenta function and structure in CHD-affected pregnancies. The included studies primarily utilized MRI and Doppler methods, as well as some modern modalities. Seven studies were included in this review. Placental imaging reveals consistent structural and functional abnormalities in pregnancies affected by congenital heart disease, indicating some possible contribution of the placenta in CHD pathophysiology. Placental imaging may improve outcomes in this susceptible group of pregnancies, improve risk assessment, and direct surveillance when incorporated into prenatal care for congenital heart disease. Future research should concentrate on lesion-specific analysis, longitudinal imaging, and placenta–heart axis-targeting treatment therapies. Full article

Cirrhotic cardiomyopathy (CCM) is a cardiac dysfunction in patients with cirrhosis, occurring in the absence of structural heart disease. It increases perioperative risk, especially in liver transplantation, and may contribute to hepatorenal syndrome. Despite its clinical significance, CCM remains poorly understood and lacks effective treatments. This review aims to summarize recent findings on the pathogenesis of CCM and highlight potential therapeutic targets. A focused literature review was conducted using PubMed, Scopus, and Clarivate databases, selecting studies from the last five years. Included studies investigated molecular, cellular, and receptor-mediated mechanisms involved in CCM. Results: CCM results from neurohumoral, inflammatory, and electrophysiological disturbances. Key mechanisms involve dysfunction of β-adrenergic and muscarinic receptors, altered ion channels (potassium, L-type calcium), impaired sodium–calcium exchange, and suppression of the P2X7 receptor (P2X7R). Dysregulation of the CD73 (5’-nucleotidase, ecto-5’-nucleotidase)–A2 adenosine axis, along with effects from endocannabinoids, nitric oxide (NO) inhibition by tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), carbon monoxide (CO), and elevated galectin-3 (Gal-3), further contribute to myocardial dysfunction. Conclusions: CCM is a multifactorial condition linked to systemic and myocardial effects of cirrhosis. A deeper understanding of its mechanisms is essential for developing targeted therapies. Further research is needed to improve patient outcomes. Full article

The heart–brain axis (HBA) is a dynamic system of reciprocal communication between the cardiovascular and central nervous system, incorporating neural, immunologic, molecular and hormonal pathways. The central autonomic network is described as a key regulator of cardiovascular activity and autonomic dysfunction as an important mechanism underlying various neurologic and cardiac disorders. Heart rate variability (HRV) is identified as the key biomarker of the axis reflecting autonomic nervous system balance. Increased understanding of its molecular mechanisms has led to the proposal of new therapeutic strategies focused on modulating heart–brain communication including β-blockers, vagus nerve stimulation, neurotrophin modulation, and nanoparticle-based approaches. The integration of wearables and artificial intelligence (AI) has allowed for real-time monitoring and innovative diagnostic and prognostic applications. The present narrative review summarizes current knowledge on the mechanisms comprising the heart–brain axis, their implication in neurologic and cardiac disorders, and their potential for developing novel therapies. It also highlights how advancements in wearable technology and AI systems are being integrated into clinical practice and transforming the landscape. Full article