Search Results (263)

The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg⁻¹·day⁻¹) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article

Protein S-nitrosylation is a selective post-translational modification in which a nitrosyl group is covalently attached to the reactive thiol group of cysteine, forming S-nitrosothiol. This modification plays a pivotal role in modulating physiological and pathological cardiovascular processes by altering protein conformation, activity, stability, and other post-translational modifications. It is instrumental in regulating vascular and myocardial systolic and diastolic functions, vascular endothelial cell and cardiomyocyte apoptosis, and cardiac action potential and repolarization. Aberrant S-nitrosylation levels are implicated in the pathogenesis of various cardiovascular diseases, including systemic hypertension, pulmonary arterial hypertension, atherosclerosis, heart failure, myocardial infarction, arrhythmia, and diabetic cardiomyopathy. Insufficient S-nitrosylation leads to impaired vasodilation and increased vascular resistance, while excessive S-nitrosylation contributes to cardiac hypertrophy and myocardial fibrosis, thereby accelerating ventricular remodeling. This paper reviews the S-nitrosylated proteins in the above-mentioned diseases and their impact on these conditions through various signaling pathways, with the aim of providing a theoretical foundation for the development of novel therapeutic strategies or drugs targeting S-nitrosylated proteins. Full article

Right heart failure (RHF) is a major cause of morbidity and mortality, often resulting from pulmonary arterial hypertension and characterized by impaired calcium (Ca²⁺) handling and maladaptive remodeling. Phosphodiesterase 9A (PDE9A), a cGMP-specific phosphodiesterase, has been proposed as a potential contributor to RHF pathogenesis by suppressing the cardioprotective cGMP–PKG signaling pathway—a conclusion largely extrapolated from left-sided heart failure models. This review examines existing evidence regarding PDE9A’s role in RHF, focusing on its effects on intracellular calcium cycling, fibrosis, hypertrophy, and contractile dysfunction. Data from preclinical models demonstrate that pathological stress upregulates PDE9A expression in cardiomyocytes, leading to diminished PKG activation, impaired SERCA2a function, RyR2 instability, and increased arrhythmogenic Ca²⁺ leak. Pharmacological or genetic inhibition of PDE9A restores cGMP signaling, improves calcium handling, attenuates hypertrophic and fibrotic remodeling, and enhances ventricular compliance. Early-phase clinical studies in heart failure populations suggest that PDE9A inhibitors are well tolerated and effectively augment cGMP levels, although dedicated trials in RHF are still needed. Overall, these findings indicate that targeting PDE9A may represent a promising therapeutic strategy to improve outcomes in RHF by directly addressing the molecular mechanisms underlying calcium mishandling and myocardial remodeling. Full article

Tricuspid regurgitation (TR) represents a significant, often silently progressing, valvular heart disease with historically suboptimal management due to perceived high surgical risks. Transcatheter tricuspid valve interventions (TTVI) offer a promising, less invasive therapeutic avenue. Central to the success of TTVI is Right Ventricular Reverse Remodelling (RVRR), defined as an improvement in RV structure and function, which strongly correlates with enhanced patient survival. The right ventricle (RV) undergoes complex multi-scale biomechanical maladaptations, progressing from adaptive concentric to maladaptive eccentric hypertrophy, coupled with increased stiffness and fibrosis. Molecular drivers of this pathology include early failure of antioxidant defenses, metabolic shifts towards glycolysis, and dysregulation of microRNAs. Accurate RV function assessment necessitates advanced imaging modalities like 3D echocardiography, Cardiac Magnetic Resonance Imaging (CMR), and Computed Tomography (CT), along with strain analysis. Following TTVI, RVRR typically manifests as a biphasic reduction in RV volume overload, improved myocardial strain, and enhanced RV-pulmonary arterial coupling. Emerging molecular biomarkers alongside advanced imaging-derived biomechanical markers like CT-based 3D-TAPSE and RV longitudinal strain, are proving valuable. Artificial intelligence (AI) and machine learning (ML) are transforming prognostication by integrating diverse clinical, laboratory, and multi-modal imaging data, enabling unprecedented precision in risk stratification and optimizing TTVI strategies. Full article

This article reveals the various types of complications that are associated with dialysis and kidney-associated disease, including left ventricular hypertrophy, heart failure, vascular heart disease, arrhythmias, diabetes mellitus, intradialytic hypertension, and coronary heart disease. The molecular mechanisms underlying the development of cardiovascular disease in patients with chronic kidney disease (CKD), including the role of nitric oxide (NO) signaling, have been extensively studied. Patients suffering from CKD need treatment with hemodialysis at the end stages. The kidney is considered the chief excretory organ in humans, which excretes various types of waste materials from the body and balances the acid–base ratio, due to which its role in homeostasis has been considered. When kidneys fail to function properly due to various diseases, hemodialysis plays the role of the kidneys. This procedure involves removing a patient’s blood, filtering it through a dialyzer to remove waste products, and returning the cleaned blood to the body. However, for the hemodialysis procedure, fistula formation is necessary, which is created by specific surgery in which the radial artery and superficial vein are connected in the forearm, near the wrist or elbow. This arteriovenous (AV) fistula creation fails sometimes and causes complications. The prolonged use of hemodialysis procedures and improper care also lead to many complications in chronic kidney patients, which have been discussed in detail in this review article. Full article

Background/Objectives: As aging leads to a decline in muscle mass, strength, and functional capacity, identifying effective, low-risk interventions for older adults is essential. Blood flow restriction training (BFRT) has gained recognition as a potential substitute for traditional high-load resistance training, offering comparable benefits with reduced mechanical stress. This scoping review explores current BFRT protocols—specifically cuff pressure, training frequency, and duration—and their impact on muscular strength, hypertrophy, and functional capabilities among healthy elderly individuals. Methods: Following PRISMA-ScR and Arksey and O’Malley’s framework, six databases were searched (2010–2024), yielding 13 eligible studies. Data were charted for BFRT parameters, training regimens, and outcomes related to strength, muscle size, and functionality. Risk of bias was assessed using Cochrane guidelines. Results: Low-load BFRT (20–40% 1RM), applied 2–4 times weekly for 6–12 weeks, significantly improved muscle strength, hypertrophy (e.g., quadriceps CSA), and functional performance (e.g., TUG, 6MWT). Cuff pressures ranged from 50 to 80% arterial occlusion pressure (AOP) for the lower limbs and 30–50% above systolic pressure for the upper limbs. Wider cuffs enhanced safety and comfort. BFRT demonstrated comparable or superior outcomes to conventional training in most studies, with minimal adverse effects reported. Conclusions: The existing evidence suggests that BFRT may be a promising intervention for improving muscle health and functionality in older adults; however, future research should focus on standardizing protocols, long-term outcomes, and tailored guidelines to optimize safety and efficacy. Full article

Background/Objectives: Obesity is a key driver of cardiovascular disease (CVD), with central adiposity directly involved in adverse cardiac remodeling. Body mass index (BMI) is limited in capturing fat distribution and associated cardiovascular risk. Novel anthropometric indices, including A Body Shape Index (ABSI) and Body Roundness Index (BRI), may offer greater clinical value, but their relationship with electrocardiographic markers of left ventricular hypertrophy (LVH) remains underexplored. This study aims to assess the correlation between novel adiposity indices (ABSI and BRI) and electrocardiographic evidence of LVH, as measured by the Sokolow-Lyon Index (SLI), in individuals with arterial hypertension. Methods: 274 hypertensive patients were recruited, and BMI, ABSI, and BRI were calculated. LVH was assessed via SLI on 12-lead ECG. Participants were stratified by the SLI (≤35 mm vs. >35 mm) for statistical analyses. Results: Patients with a lower SLI showed significantly higher values of ABSI and BRI compared to those in higher SLI group, without differences in BMI. In the entire population, SLI was significantly and inversely correlated with both ABSI (r = −0.296, p < 0.001) and BRI (r = −0.238, p < 0.01), but not with BMI. Multivariate regression analysis confirmed ABSI (p = 0.013) and BRI (p = 0.038) as independent predictors of SLI, even after adjusting for age, blood pressure, renal function, and metabolic parameters. Conclusions: ABSI and BRI are inversely and independently associated with ECG-derived SLI in hypertensive individuals, suggesting that central adiposity may attenuate ECG voltages and obscure LVH detection. Incorporating novel adiposity indices into ECG interpretation may enhance diagnostic accuracy and risk stratification in obese and hypertensive populations. Longitudinal studies are needed to validate these findings and refine clinical algorithms. Full article

Aortic valve stenosis (AS) is a valvular heart disease that imposes a high afterload on the left ventricle (LV) due to restricted opening of the aortic valve, resulting in LV hypertrophy. Severe AS can lead to syncope, angina pectoris, and heart failure. The number of patients with AS has been increasing due to aging populations, the growing prevalence of lifestyle-related diseases, and advances in diagnostic technologies. Therefore, accurate diagnosis and appropriate treatment of AS are essential. In recent years, transcatheter aortic valve implantation (TAVI) has become feasible, and the number of procedures has rapidly increased, particularly among elderly patients. As treatment options for AS expand and diversify, detailed pre-procedural evaluation has become increasingly important. In particular, diagnostic imaging modalities such as computed tomography (CT) have advanced significantly, with notable improvements in image quality. With recent advancements in CT technology—such as increased detector rows, faster gantry rotation speeds, new image reconstruction methods, and the introduction of dual-energy imaging—the scope of cardiac assessment has expanded beyond the coronary arteries to include valves, myocardium, and the entire heart. This includes evaluating restricted AV opening and cardiac function using four-dimensional imaging, assessing AV annulus diameter and AS severity via calcium scoring with a novel motion correction algorithm, and detecting myocardial damage through late-phase contrast imaging using new reconstruction techniques. In cases of pre-TAVI evaluation or congenital bicuspid valves, CT is also valuable for assessing extracardiac structures, such as access routes and associated congenital heart anomalies. In addition, recent advancements in CT technology have made it possible to significantly reduce radiation exposure during cardiac imaging. CT has become an extremely useful tool for comprehensive cardiac evaluation in patients with aortic stenosis, especially those being considered for surgical treatment. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic that devastated the world. While this is a respiratory virus, one feature of the SARS-CoV-2 infection was recognized to cause pathogenesis of other organs. Because the membrane fusion protein of SARS-CoV-2, the spike protein, binds to its major host cell receptor angiotensin-converting enzyme 2 (ACE2), which regulates a critical mediator of cardiovascular diseases, angiotensin II, COVID-19 is largely associated with vascular pathologies. The present study examined the pulmonary vasculature of COVID-19 patients using large sample sizes and provides mechanistic information through histological observations. We studied 56 postmortal lung samples from COVID-19 patients. The comparative group consisted of 17 postmortal lung samples from patients who died of influenza A virus subtype H1N1. The examination of 56 autopsy lung samples showed thickened vascular walls of small pulmonary arteries after 14 days of disease compared to H1N1 influenza patients who died before the COVID-19 pandemic started. Pulmonary vascular remodeling in COVID-19 patients was associated with hypertrophy of the smooth muscle layer, perivascular fibrosis, edema and lymphostasis, inflammatory infiltration, perivascular hemosiderosis, and neoangiogenesis. We found a correlation between the duration of hospital stay and the thickness of the muscular layer of the pulmonary arterial walls. These results demonstrate that COVID-19 significantly affected the pulmonary vasculature in fatal-course patients, also suggesting the need for careful follow-up in non-fatal cases, at risk of pulmonary hypertension. Full article

Pulmonary arterial hypertension (PAH) is a lethal condition marked by the proliferation and remodeling of small pulmonary arteries, ultimately leading to right ventricular hypertrophy and right heart failure. PAH secondary to connective tissue diseases (CTDs) is a progressive complication with a complex pathogenesis that results in the reduced efficacy of vasodilation-based therapies and poor clinical outcomes. Systemic sclerosis is the most commonly associated CTD with PAH in Western countries and has been most extensively investigated. Systemic lupus erythematosus and other CTDs may also be associated with PAH; however, they are less studied. In this review, we explore the general pathobiology of PAH, with a particular emphasis on recent advances in the molecular pathogenesis of CTD-PAH, including endothelial cell dysfunction, dysregulated cell proliferation and vascular remodeling, extracellular matrix remodeling, in situ thrombosis, right ventricular dysfunction, genetic aberrations, and immune dysregulation. We also conduct a thorough investigation into the potential serum biomarkers and immune dysregulation associated with CTD-PAH, summarizing the associated autoantibodies, cytokines, and chemokines. Furthermore, relevant animal models that may help unravel the pathogenesis and contribute to the development of new treatments are also reviewed. Full article

Iron deficiency is highly prevalent in patients with idiopathic pulmonary hypertension; nevertheless, its role and clinical significance in hypoxic pulmonary hypertension (HPH) remain elusive. Therefore, this study aims to clarify the role and molecular mechanisms of iron in HPH. By means of a retrospective analysis of clinical data from HPH patients and examinations of HPH animal models, we discovered that both HPH patients and animal models exhibit significant iron deficiency, characterized by reduced hepatic iron storage and elevated hepcidin expression. To further explore iron’s role in HPH, we modulated iron metabolism through pharmacological and dietary interventions in chronic hypoxic animal models. The results showed that iron deficiency exacerbated chronic hypoxia-induced pulmonary hypertension and right ventricular hypertrophy, while iron supplementation alleviated these conditions. Further investigations revealed that iron regulates HIF2α expression in pulmonary arterial endothelial cells (PAECs) under chronic hypoxia. Therefore, through in vivo and in vitro experiments, we demonstrated that HIF2α inhibition attenuates chronic hypoxia-induced pulmonary hypertension and right ventricular hypertrophy. Mechanistically, chronic hypoxia-mediated iron deficiency enhances HIF2α activation, subsequently suppressing iron/sulfur cluster assembly enzyme (ISCU) expression. This leads to decreased mitochondrial complexes I and III activity, increased reactive oxygen species (ROS) production, and inhibited oxidative phosphorylation. Consequently, metabolic reprogramming in PAECs results in a proliferation/apoptosis imbalance, ultimately exacerbating hypoxia-induced pulmonary hypertension and right ventricular hypertrophy. Collectively, our findings demonstrate that iron supplementation mitigates HPH progression by modulating HIF2α-mediated metabolic reprogramming in PAECs, revealing multiple therapeutic targets for HPH. Full article

Type 2 diabetes is a significant risk factor for cardiovascular disease, particularly coronary heart disease, heart failure, and diabetic cardiomyopathy. Diabetic cardiomyopathy, characterized by heart dysfunction in the absence of coronary artery disease or hypertension, is triggered by various mechanisms, including hyperinsulinemia, insulin resistance, and inflammation. At the cellular level, increased insulin resistance leads to an imbalance in lipid and glucose metabolism, causing oxidative stress, mitochondrial dysfunction, and excess production of reactive oxygen species (ROS). This disrupts normal heart function, leading to fibrosis, hypertrophy, and cardiac remodeling. In diabetic patients, the excessive accumulation of fatty acids, advanced glycation end products (AGEs), and other metabolic disturbances further contribute to endothelial dysfunction and inflammatory responses. This inflammatory environment promotes structural damage, apoptosis, and calcium-handling abnormalities, resulting in heart failure. Additionally, diabetes increases the risk of arrhythmias, such as atrial fibrillation, which worsens cardiac outcomes. New insights into these molecular mechanisms have led to improvements in diabetes management, focusing on mitigating complications and understanding the cellular processes involved. Recent therapeutic advances, such as SGLT-2 inhibitors, have shown promise in addressing the energy imbalance and cardiac dysfunction seen in diabetic cardiomyopathy, offering new hope for better cardiovascular outcomes. Full article

Pulmonary hypertension (PH) is a serious cardiovascular disease caused by a variety of pathogenic factors, which is characterized by increased pulmonary vascular resistance (PVR) and progressive elevation of mean pulmonary artery pressure (mPAP). This disease can lead to right ventricular hypertrophy and, in severe cases, right heart failure and even death. Vascular remodeling—a pathological modification involving aberrant vasoconstriction, cell proliferation, apoptosis resistance, and inflammation in the pulmonary vascular system—is a significant pathological hallmark of PH and a critical process in its progression. Recent studies have found that vascular remodeling involves the participation of a diversity of cellular pathological alterations, such as the dysfunction of pulmonary artery endothelial cells (PAECs), the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), the phenotypic differentiation of pulmonary artery fibroblasts, the inflammatory response of immune cells, and pericyte proliferation. This review focuses on the mechanisms and the intercellular crosstalk of these cells in the PH process, emphasizing recent advances in knowledge regarding cellular signaling pathways, inflammatory responses, apoptosis, and proliferation. To develop better treatments, a list of possible therapeutic approaches meant to slow down certain biological functions is provided, with the aim of providing new insights into the treatment of PH by simplifying the intricacies of these complex connections. In this review, comprehensive academic databases such as PubMed, Embase, Web of Science, and Google Scholar were systematically searched to discuss studies relevant to human and animal PH, with a focus on vascular remodeling in PH. Full article

Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article