Search Results (5,798)

Inflammatory cytokines, including interleukin 6 (IL6), are associated with ion channel remodeling and enhance the propensity to alterations in cardiac rhythm generation and propagation, in which the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role. Hence, we investigated the consequences of exposure to IL6 on HCN channels in cell models and human atrial biopsies. In murine atrial HL1 cells and in cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs), IL6 elicited STAT3 phosphorylation, a receptor-mediated downstream signaling. Downregulation of HCN1,2,4 by IL6 was observed after 24–48 h; in hiPS-CMs, this effect was reverted by 24 h of application of tocilizumab, a human IL6 receptor antagonist. In parallel, hiPS-CM action potentials (APs) showed a reduced spontaneous frequency. Moreover, we assessed IL6 and HCN expression in dilated left atrial samples from patients with mitral valve disease, an AF-prone condition. IL6 levels were increased in dilated atria compared to controls and positively correlated with echocardiographic atrial dimensions. Interestingly, the highest IL6 transcript levels and the lowest HCN4 and HCN2 expression were in these samples. In conclusion, our data uncovered a novel link between IL6 and cardiac HCN channels, potentially contributing to atrial electrical disturbances and a higher risk of dysrhythmias in conditions with elevated IL6 levels. Full article

Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review provides insight into the complex interactions between coronary artery disease and CHD in adults. We describe the peculiar features of cardiac anatomy in these patients, the possible role cardiac sequelae may play in an increased risk of myocardial ischemia, and the diagnostic challenges in this patient group. Furthermore, this review outlines the risk factors and potential mechanisms of accelerated atherosclerosis in adults with CHD by pointing out areas where current knowledge is incomplete and highlighting areas for further research. The review concludes by examining potential management strategies for this particular population, emphasizing the necessity for a multidisciplinary approach. Understanding the unique coronary risks that adults with CHD experience can enhance patient care and improve long-term results. Full article

Background and Purpose: The cerebral circulation is highly regulated to maintain brain perfusion, keeping an equilibrium between the brain tissue, cerebrospinal fluid (CSF) and blood of the arterial and venous systems. Cerebral venous drainage abnormalities have been implicated in multiple cerebrovascular diseases. The purpose of this study is to evaluate the relationship between the arterial inflow (AI) and the cerebral venous outflow (CVO) and their correlation with the cardiac outflow in healthy adults and children to understand the role of the emissary veins in normal venous drainage. Materials and Methods: A total of 31 healthy volunteers (24 adults (39.5 ± 16.0) and seven children (3.4 ± 2.2)) underwent intracranial 4D flow with full circle of Willis coverage and 2D PC-MRI at the level of the transverse sinus for measurement of the AI and CVO, respectively. The AI was calculated as the sum of the flow values in the bilateral internal carotid and basilar arteries. The CVO was calculated as the sum of the flow values in the bilateral transverse sinuses. The cardiac outflow was measured via 2D PC-MRI with retrospective ECG gating with images acquired at the proximal ascending aorta (AAo) and descending (DAo) aorta. The ratios of the AI/AAo flow and CVO/AI were calculated to characterize the fraction of cerebral arterial inflow in relation to cardiac outflow and venous blood draining through the transverse sinuses, respectively. Results: The AI and CVO were significantly correlated (r = 0.81, p < 0.001). The CVO constituted approximately 60–70% of the AI. The CVO/AI ratio was significantly lower in children versus adults (p = 0.025). In adults, the negative correlation of the AI with age remained strong (r = −0.81, p < 0.001). However, the CVO was not significantly associated with age. Conclusion: The CVO/AI ratio suggests an important role of the emissary veins, accounting for approximately 30–40% of venous drainage. The lower CVO/AI ratio in children, although partially related to decreased AI with age, suggests a greater role of the emissary veins in childhood, which strongly decreases with age. Full article

Background/Objectives: Few studies have analyzed in-hospital complications and events following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures for patients who underwent these interventions for single-vessel coronary artery disease (CAD). This study aims to compare the outcomes of PCI and CABG in such patients using a large propensity-matched real-world database based on procedural codes. Methods: Adult patients receiving PCI or CABG for single-vessel CAD were identified from the 2016–2020 National Inpatient Sample (NIS) database. Any cases targeting multi-vessel disease or employing a multi-treatment approach were excluded using appropriate procedural codes. Differences in events and complications from admission to discharge were studied between the two procedures (PCI vs. CABG) via logistic regression analysis. Results: After propensity matching with 273,380 patients in both groups, complication risks such as cardiac tamponade (aOR: 3.6 [3.27–3.96]), acute kidney injury (aOR: 1.53 [1.51–1.56]), cardiogenic shock (aOR: 1.38 [1.34–1.40]), procedural bleeding (aOR: 1.75 [1.67–1.83]), acute ischemic stroke (aOR: 1.89 [1.80–1.97]), and all-cause mortality (aOR: 1.05 [1.02–1.08]) were higher among CABG patients. No differences were observed for events of cardiac perforation (aOR: 0.92, [0.84–1.01]). Conclusions: In this large real-world propensity-matched analysis, CABG was associated with higher risks of multiple in-hospital complications and all-cause mortality compared to PCI following a single-vessel coronary intervention. Full article

Background. Phenotyping inflammation in ST-elevation myocardial infarction (STEMI) is a challenge for modern cardiology. NLRP3 inflammasome is a proven predictor of adverse outcomes in cardiovascular disease, but its specificity in stratifying inflammatory activity in patients with myocardial infarction (MI) has not been demonstrated. The aim of this paper is to describe the levels of NLRP3 protein and IL-1β concentrations and their changes in dynamics and associations with clinical, laboratory and instrumental characteristics of patients with STEMI. Methods. A total of 45 patients with STEMI were enrolled. Concentrations of NLRP3 and IL-1β were evaluated in arterial and venous EDTA blood from the infarct-related coronary and peripheral arteries and veins on days 1, 3 and 7 after MI. Results and Conclusions. The concentrations of markers were higher on the first day after MI with a maximum decrease on the third day. The levels of both markers in venous plasma correlated with those in arterial blood, allowing their routine determination in venous plasma on the first day after MI. IL-1β levels correlated directly with the wall motion index and inversely with left ventricular ejection fraction and stroke volume, which characterize the potential contribution to adverse myocardial remodeling. There were two multidirectional trends in changes in NLRP3 and IL-1β levels during hospitalization. Initially higher levels with a gradual decrease by day 7 were associated with a longer duration of myocardial ischemia and higher plasma troponin I levels. Further evaluation of the long-term outcomes of MI will allow identifying inflammatory factors that input to the development of secondary major adverse cardiac events and will provide a new step in the understanding of inflammatory phenotyping. Full article

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. Methods: We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. Results: The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in PTPN11 were most commonly associated with pulmonary valve stenosis (PVS), while RAF1 mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development (p = 0.755), even though the likelihood ratio showed significance in that regard (p = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. Conclusions: The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype–phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies. Full article

Heart failure is a complex syndrome and our understanding and therapeutic approach relies mostly on its phenotypic presentation. Notably, the heart is characterized as the most energy-consuming organ, being both a producer and consumer, in order to satisfy multiple cardiac functions: ion exchange, electromechanical coordination, excitation–contraction coupling, etc. By obtaining further knowledge of the cardiac energy field, we can probably better characterize the basic pathophysiological events occurring in heart disease patients and understand the metabolic substance changes, the relationship between the alteration of energy production/consumption, and hence energetic deficiency not only in the heart as a whole but in every single cardiac territory, which will hopefully provide us with the opportunity to uncover the beginning of the heart failure process. In this respect, using (a) newer imaging techniques, (b) biomedicine, (c) nanotechnology, and (d) artificial intelligence, we can gain a deeper understanding of this complex syndrome. This, in turn, can lead to earlier and more effective therapeutic approaches, ultimately improving human health. To date, the scientific community has not given sufficient attention to the energetic starvation model. In our view, this review aims to encourage scientists and the medical community to conduct studies for a better understanding and treatment of this syndrome. Full article

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions. Full article

Hemorrhagic stroke is the deadliest type of stroke. Cellular and molecular biomarkers are important for understanding the pathophysiology of stroke. Microglia are among the most promising biological markers. However, the morphological and physiological characteristics of microglia, as well as the structural and functional aspects of their interactions with neurons and other cells, are largely unknown. Due to the large number of different morphological phenotypes and very limited information on microglial changes in subarachnoid hemorrhage (SAH), we performed this study aimed at identifying the features of the distribution of various microglial phenotypes in the layers of the cerebral cortex in the hyperacute phase of non-traumatic SAH. We studied the distribution of various microglial phenotypes in the layers of the cerebral cortex of SAH non-survivors with a control group (coronary heart disease and sudden cardiac death were the underlying causes of death). An immunohistochemical study using antibodies to iba-1 (a marker of microglia) revealed changes in the morphological phenotypes of microglia in the cerebral cortex after subarachnoid hemorrhage. Significant differences between the groups indicate a rapid microglial response to injury. The findings indicate that there are quantitative and phenotypic changes in microglia in the cerebral cortex during early SAH in the human cortex. Full article

Background: Cardiovascular disease (CVD) is the predominant cause of mortality, with aging being a significant risk factor. Nucleotides (NTs), essential for numerous biological functions, are particularly vital under conditions like aging, starvation, and nutrient deficiency. Although the antiaging benefits of exogenous NTs have been recognized in various systems, their cardiac-specific effects are not well understood. This study, therefore, investigated the impact of exogenous NTs on cardiac aging and delved into the potential mechanisms. Methods: Senescence-accelerated mouse prone-8 (SAMP8) mice were utilized, randomly assigned to one of three groups: a control group (Control), a low-dose NTs group (NTs_L), and a high-dose NTs group (NTs_H). Meanwhile, senescence-accelerated mouse resistant 1 (SAMR1) mice were set up as the SAMR1 group. Following a 9-month intervention, cardiac tissues were subjected to analysis. Results: The results showed that NTs improved the morphological structure of the cardiac tissue, enhanced the antioxidant capacity, and mitigated inflammation. Metabolomics analysis revealed that the high-dose NT intervention improved cardiac tissue energy metabolism, potentially through activating the AMPK pathway, enhanced mitochondrial biogenesis, and increased TFAM protein expression. Conclusions: Together, these results indicate that exogenous NTs exert beneficial effects on the cardiac tissues of SAMP8 mice, potentially mitigating the cardiac aging process. Full article

Background/Objectives: Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB’s effects on the heart are unclear. Therefore, we investigated the potential cardioprotective or arrhythmogenic effects of MB in an animal model of CIR. To this end, 12–16-week-old male Wistar rats were divided into four experimental groups: (a) rats subjected to SHAM surgery with no ischemia; (b) rats subjected to CIR and treated with a vehicle (SS + CIR); and (c) rats subjected to CIR and treated with 2 mg/kg i.v. MB before ischemia (MB + ISQ) or (d) after ischemia but before reperfusion (ISQ + MB). An ECG analysis was used to evaluate the incidence of ventricular arrhythmias (VAs), atrioventricular blocks (AVBs), and lethality (LET) resulting from CIR. After CIR, rat hearts were removed for histopathological analysis and lipid hydroperoxide (LH) measurements. Results: The incidence of VA, AVB, and LET was significantly increased in the MB + ISQ group (VA = 100%; AVB = 100%; LET = 100%) but significantly reduced in the ISQ + MB group (VA = 42.8%; AVB = 28.5%; LET = 21.4%) compared with the SS + CIR group (VA = 85.7%; AVB = 71.4%; LET = 64.2%). LH concentration was significantly reduced in both MB-treated groups, but myocardial injuries were increased only in the MB + ISQ group when compared with the SS + CIR group. Conclusions: These results indicate that MB produces a biphasic effect on CIR, with cardiotoxic effects when administered before cardiac ischemia and cardioprotective effects when administered after ischemia but before cardiac reperfusion. Full article

This review discusses the pivotal role of microcirculation in maintaining tissue oxygenation and waste removal and highlights its significance in various pathological conditions. It delves into the cellular mechanisms underlying hemodynamic coherence, elucidating the roles of the endothelium, glycocalyx, and erythrocytes in sustaining microcirculatory integrity. Furthermore, the review gives comprehensive information about microcirculatory changes observed in cardiac surgery, sepsis, shock, and COVID-19 disease. Through comprehensive exploration, the review underscores the intricate relationship between microcirculation, disease states, and clinical outcomes, emphasizing the importance of understanding and monitoring microvascular dynamics in critical care settings. Full article

Background: Mitral Regurgitation (MR) is a common heart valve disease. Severe MR can lead to pulmonary hypertension, cardiac arrhythmia, and even death. Therefore, early diagnosis and assessment of MR severity are crucial. In this study, we propose a deep learning-based method for segmenting MR regions, aiming to improve the efficiency of MR severity classification and diagnosis. Methods: We enhanced the Efficient Multi-Scale Attention (EMA) module to capture multi-scale features more effectively, thereby improving its segmentation performance on MR regions, which vary widely in size. A total of 367 color Doppler echocardiography images were acquired, with 293 images used for model training and 74 images for testing. To fully validate the capability of the improved EMA module, we use ResUNet as the backbone, partially integrating the enhanced EMA module into the decoder’s upsampling process. The proposed model is then compared with classic models like Deeplabv3+ and PSPNet, as well as UNet, ResUNet, ResUNet with the original EMA module added, and UNet with the improved EMA module added. Results: The experimental results demonstrate that the model proposed in this study achieved the best performance for the segmentation of the MR region on the test dataset: Jaccard (84.37%), MPA (92.39%), Recall (90.91%), and Precision (91.9%). In addition, the classification of MR severity based on the segmentation mask generated by our proposed model also achieved acceptable performance: Accuracy (95.27%), Precision (88.52%), Recall (91.13%), and F1-score (90.30%). Conclusion: The model proposed in this study achieved accurate segmentation of MR regions, and based on its segmentation mask, automatic and accurate assessment of MR severity can be realized, potentially assisting radiologists and cardiologists in making decisions about MR. Full article

Cardiac channelopathies are inherited diseases that increase the risk of sudden cardiac death. While different genes have been associated with inherited channelopathies, there are still subtypes, e.g., catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome, where the genetic cause remains unknown. Various models, including animal models, heterologous expression systems, and the human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSCs-CMs) model, have been used to study the pathophysiological mechanisms of channelopathies. Recently, researchers have focused on using hiPSCs-CMs to understand the genotype–phenotype correlation and screen drugs. By combining innovative techniques such as Clustered Regularly Interspaced Short Palindromic Repeats/Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR/Cas9)-mediated genome editing, and three-dimensional (3D) engineered heart tissues, we can gain new insights into the pathophysiological mechanisms of channelopathies. This approach holds promise for improving personalized drug treatment. This review highlights the role of hiPSCs-CMs in understanding the pathomechanism of Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia and how these models can be utilized for drug screening. Full article

Carbon monoxide (CO) poisoning is a leading cause of poisoning-related deaths, particularly affecting organs with high oxygen demands such as the heart and brain. Cardiac complications, including non-ST elevation myocardial infarction (NSTEMI), can occur due to CO poisoning but are not frequently reported in the elderly. We present the case of an 82-year-old female with a medical history of diabetes, hypertension, dyslipidemia, and previous ischemic heart disease. She was brought to the emergency department after being found drowsy in a closed room with a burning charcoal heater. The initial assessment revealed a carboxyhemoglobin level of 33.5%, which decreased to 9.3% after high-flow oxygen therapy and hyperbaric oxygen therapy (HBOT). Laboratory tests indicated elevated troponin levels, and an ECG showed asymmetrical T-wave inversion and ST depression. Despite the improvement in carboxyhemoglobin, the patient experienced persistent chest pain and rising troponin levels. She was treated with dual antiplatelet therapy and low molecular weight heparin as per acute coronary syndrome protocol, leading to a gradual improvement and a subsequent discharge in a stable condition. This case highlights the potential for CO poisoning to induce NSTEMI in elderly patients. A prompt diagnosis and appropriate management, including the use of HBOT, were crucial for the patient’s recovery. Full article