Search Results (195)

Myocardial hypertrophy (MH) represents a complex and heterogeneous condition in the pediatric and young adult population. While rare in children, MH encompasses a wide spectrum of physiological and pathological entities, ranging from transient hypertrophy in the infants of diabetic mothers to progressive genetic hypertrophic cardiomyopathies (HCM) with significant morbidity and mortality. Differential diagnosis is critical, as many phenocopies—including metabolic, mitochondrial, and syndromic diseases—can mimic HCM. Echocardiography remains the first-line imaging modality, with cardiac magnetic resonance (CMR) and molecular diagnostics increasingly used for detailed characterization. Risk stratification tools, such as the HCM Risk-Kids model, support clinical decision-making but must be integrated with individualized assessment. Advances in prenatal screening and genetic testing have significantly improved outcomes, though long-term management requires multidisciplinary care. Understanding age-specific presentations and the underlying etiologies is essential for accurate diagnosis and targeted treatment. This review provides a comprehensive overview of cardiac hypertrophy from fetal life through young adulthood, with a focus on etiologies, diagnostic approaches, imaging modalities, and therapeutic strategies, and aims to guide clinicians through the evolving landscape of MH, emphasizing early recognition, comprehensive evaluation, and personalized care. 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

Hypertensive left ventricular hypertrophy (LVH) is an ominous cardiovascular sequel to chronic hypertension, marked by structural and functional alterations in the heart. Identified as a significant risk factor for adverse cardiovascular outcomes, LVH is typically detected through echocardiography and is characterized by pathological thickening of the left ventricular wall. This hypertrophy results from chronic pressure overload (increased afterload), leading to concentric remodelling, or from increased diastolic filling (preload), contributing to eccentric changes. Apoptosis, a regulated process of cell death, plays a critical role in the pathogenesis of LVH by contributing to cardiomyocyte loss and subsequent cardiac dysfunction. Given the substantial clinical implications of LVH for cardiovascular health, this review critically examines the role of cardiomyocyte apoptosis in its disease progression, evaluates the impact of pharmacological interventions, and highlights the necessity of a comprehensive, multifaceted treatment approach for the prevention and management of hypertensive LVH. Finally, we address the health disparities associated with LVH, with particular attention to the disproportionate burden faced by African Americans and other Black communities, as this remains a key priority in advancing equity in cardiovascular care. Full article

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular signal transduction cascades that translate extracellular stress into cellular responses. Among these, the mitogen-activated protein kinase (MAPK) pathways have received considerable attention due to their roles in mediating inflammation, apoptosis, hypertrophy, and adverse cardiac remodeling. The canonical MAPK cascades—including extracellular signal-regulated kinases (ERK1/2), p38 MAPK, and c-Jun N-terminal kinases (JNK)—are activated by upstream stimuli such as angiotensin II (Ang II), aldosterone, endothelin-1 (ET-1), and sustained catecholamine release. Additionally, emerging evidence highlights the role of receptor-mediated signaling, cellular stress, and myeloid cell-driven coagulation events in linking MAPK activation to fibrotic remodeling following myocardial infarction. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade plays a central role in regulating cardiomyocyte survival, hypertrophy, energy metabolism, and inflammation. Activation of the PI3K/Akt pathway has been shown to confer cardioprotective effects by enhancing anti-apoptotic and pro-survival signaling; however, aberrant or sustained activation may contribute to maladaptive remodeling and progressive cardiac dysfunction. In the context of AHF, understanding the dual role of this pathway is crucial, as it functions both as a marker of compensatory adaptation and as a potential therapeutic target. Recent reviews and preclinical studies have linked PI3K/Akt activation with reduced myocardial apoptosis and attenuation of pro-inflammatory cascades that exacerbate heart failure. Among the multiple signaling pathways involved, glycogen synthase kinase-3β (GSK-3β) has emerged as a key regulator of apoptosis, inflammation, metabolic homeostasis, and cardiac remodeling. Recent studies underscore its dual function as both a negative regulator of pathological hypertrophy and a modulator of cell survival, making it a compelling therapeutic candidate in acute cardiac settings. While earlier investigations focused primarily on chronic heart failure and long-term remodeling, growing evidence now supports a critical role for GSK-3β dysregulation in acute myocardial stress and injury. This comprehensive review discusses recent advances in our understanding of the MAPK signaling pathway, the PI3K/Akt cascade, and GSK-3β activity in AHF, with a particular emphasis on mechanistic insights, preclinical models, and emerging therapeutic targets. 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

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Heat stress has become a significant challenge in animal husbandry and human health, posing significant threats to both livestock and human health and profoundly impacting agricultural productivity. Sheng Mai San has been shown to effectively alleviate heat stress, yet the underlying mechanisms remain unclear. Therefore, this study established a heat stress model and employed Sheng Mai San as an intervention, with NAC as the positive control. Using histopathological analysis, Western blotting, ELISA, and 16S rDNA sequencing, we investigated the protective effects of Sheng Mai San against heat-stress-induced cardiac and intestinal injuries, as well as gut microbiota dysbiosis. The results demonstrated that heat stress-induced cardiac injury primarily occurred within 6–12 h of the cessation of heat stress. This injury was manifested by a significant elevation in the cardiac index, accompanied by attenuated expression of cardiac antioxidants (GSH, SOD, CAT, and T-AOC) and increased MDA content. Following Sheng Mai San intervention, the cardiac index was reduced, antioxidant indices (GSH, SOD, and CAT) were significantly elevated, and MDA and inflammatory markers (IL-1β, IL-6, and TNF-α) were markedly decreased. Additionally, Sheng Mai San was found to activate the Keap1-Nrf2 signaling pathway in the heart. Sheng Mai San demonstrated significant protective effects on small intestinal morphology, attenuating pathological alterations while promoting goblet cell proliferation. Analysis of the gut microbiota revealed that Sheng Mai San increased the Chao1, ACE, Shannon, and Simpson indices while reducing the abundance of harmful bacteria, such as g_Globicatella, g_Thermoactinomyces, g_Staphylococcus, g_Gemella, and g_Veillonella. Additionally, it promoted the expression of beneficial bacteria, including g_Lactobacillus and g_Ruminococcaceae. In summary, Sheng Mai San alleviates heat stress-induced cardiac hypertrophy and restores the oxidative stress balance in the heart. It also mitigates pathological damage in the small intestine, enhances the diversity and richness of the gut microbiota, and ameliorates gut microbiota dysbiosis. These findings highlight the significance of the heart-small intestine-gut microbiota axis in the protective effects of Sheng Mai San against heat stress injury. This study provides a potential therapeutic approach for heat-stress-related diseases and offers insights into the development of anti-heat-stress drugs. Full article

Translational regulation plays a pivotal role in cardiac gene expression, influencing protein synthesis in response to physiological and pathological stimuli. Although transcription regulates gene expression, translation ultimately determines protein levels, making it a crucial research focus. In cardiomyocytes, disruptions in this process contribute to various cardiac diseases, including hypertrophy, fibrosis, dilated cardiomyopathy, ischemic heart disease, and diabetic cardiomyopathy. Emerging evidence highlights the significance of translational regulation across multiple cardiac cell types, such as cardiomyocytes and fibroblasts, and its role in disease progression. During cardiac remodeling, transcriptomic changes are often modest, suggesting that post-transcriptional mechanisms, particularly translation, play a dominant role in cellular adaptation. This review discusses key methodologies for studying translational regulation and novel mechanisms of translational regulation related to different cardiac pathologies and highlights relevant therapeutic avenues for targeting these pathways. Full article

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During the progression of the disease, the myocardium senses surrounding mechanical cues, including extracellular matrix properties, tensile tension, shear stress, and pressure load, which significantly influence the pathological remodeling of the heart through mechanotransduction. At the molecular level, the mechanisms by which mechanical cues are sensed and transduced to mediate myocardial mechanical remodeling in DCM remain unclear. The mechanosensitive transcription factors YAP and TAZ fill this gap. This article reviews the latest findings of how YAP and TAZ perceive a wide range of mechanical cues, from shear stress to extracellular matrix stiffness. We focus on how these cues are relayed through the cytoskeleton to the nucleus, where they trigger downstream gene expression. Here, we review recent progress on the crucial role of YAP and TAZ mechanotransduction in the pathological changes observed in DCM, including myocardial fibrosis, hypertrophy, inflammation, mitochondrial dysfunction, and cell death. Full article

Background and Objectives: Aortic stenosis (AS) is a frequent valvular disease characterized by the obstruction of left ventricular outflow. The resulting hemodynamic and structural changes create an arrhythmogenic substrate, with sudden cardiac death (SCD) often caused by ventricular arrhythmias (VAs) being a feared complication. This review examines the relationship between severe AS and VA, detailing the epidemiology, pathophysiological mechanisms, risk factors, and management approaches prior to aortic valve replacement (AVR). Materials and Methods: We conducted a comprehensive narrative review of the historical and contemporary literature investigating ventricular arrhythmias in severe aortic stenosis. Literature searches were performed in PubMed, MEDLINE, and Scopus databases using keywords, including “aortic stenosis”, “ventricular arrhythmia”, “sudden cardiac death”, and “aortic valve replacement”. Both landmark historical studies and modern investigations utilizing advanced monitoring techniques were included to provide a complete evolution of the understanding. Results: The prevalence of ventricular ectopy and non-sustained ventricular tachycardia increases with AS severity and symptom onset. Left ventricular hypertrophy, myocardial fibrosis, altered electrophysiological properties, and ischemia create the arrhythmogenic substrate. Risk factors include the male sex, concomitant aortic regurgitation, elevated filling pressures, and syncope. Diagnostic approaches range from standard electrocardiography to continuous monitoring and advanced imaging. Management centers on timely valve intervention, with medical therapy serving primarily as a bridge to AVR. Conclusions: Ventricular arrhythmias represent a consequence of valvular pathology in severe AS rather than an independent entity. Their presence signals advanced disease and a heightened risk for adverse outcomes. Multidisciplinary management with vigilant monitoring and prompt surgical referral is essential. Understanding this relationship enables clinicians to better identify high-risk patients requiring urgent intervention before life-threatening arrhythmic events occur. Full article

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular condition in the world, affecting around 1 in 500 people. HCM is characterized by ventricular wall thickening, decreased ventricular chamber volume, and diastolic dysfunction. Inherited HCM is most commonly caused by sarcomere gene mutations; however, approximately 50% of patients do not present with a known mutation, highlighting the need for further research into additional pathological mutations. The alpha-B crystallin (CRYAB) mutation CRYAB^R123W was previously identified as a novel sarcomere-independent mutation causing HCM associated with pathological NFAT signaling in the setting of pressure overload. We generated stable H9C2 cell lines expressing FLAG-tagged wild-type and mutant CRYAB, which demonstrated that CRYAB^R123W increases calcineurin activity. Using AlphaFold to predict structural and interaction changes, we generated a model where CRYAB^R123W uniquely binds to the autoinhibitory domain of calcineurin. Co-immunoprecipitation using the CRYAB FLAG tag followed by mass spectrometry showed novel and distinct changes in the protein interaction patterns of CRYAB^R123W. Finally, mouse heart extracts from our wild-type CRYAB and CRYAB^R123W models with and without pressure overload caused by transverse aortic constriction (TAC) were used in global proteomic and phosphoproteomic mass spectrometry analysis, which showed dysregulation in cytoskeletal, metabolomic, cardiac, and immune function. Our data illustrate how CRYAB^R123W drives calcineurin activation and exhibits distinct changes in protein interaction and cellular pathways during the development of HCM and pathological cardiac hypertrophy. Full article

Heart failure (HF) is a prominent fatal cardiovascular disorder afflicting 3.4% of the adult population despite the advancement of treatment options. Therefore, a better understanding of the pathogenesis of HF is essential for exploring novel therapeutic strategies. Hypertrophy and fibrosis are significant characteristics of pathological cardiac remodeling, contributing to HF. The mechanisms involved in the development of cardiac remodeling and consequent HF are multifactorial, and in this review, the key underlying mechanisms are discussed. These have been divided into the following categories thusly: (i) mitochondrial dysfunction, including defective dynamics, energy production, and oxidative stress; (ii) cardiac lipotoxicity; (iii) maladaptive endoplasmic reticulum (ER) stress; (iv) impaired autophagy; (v) cardiac inflammatory responses; (vi) programmed cell death, including apoptosis, pyroptosis, and ferroptosis; (vii) endothelial dysfunction; and (viii) defective cardiac contractility. Preclinical data suggest that there is merit in targeting the identified pathways; however, their clinical implications and outcomes regarding treating HF need further investigation in the future. Herein, we introduce the molecular mechanisms pivotal in the onset and progression of HF, as well as compounds targeting the related mechanisms and their therapeutic potential in preventing or rescuing HF. This, therefore, offers an avenue for the design and discovery of novel therapies for the treatment of HF. Full article

Mental disorders (MDs) are among the major causes of morbidity and mortality worldwide. Individuals with severe MDs have a shorter life expectancy, primarily due to cardiovascular diseases. Echocardiography facilitates the evaluation of alterations in cardiac morphology and function, resulting from various cardiac pathologies. The aim of this review was to explore the current evidence base behind the myocardial deformation observed in echocardiography in patients with MDs. We primarily focused on the data regarding speckle tracking echocardiography. PubMed, using medical subject headings, was searched to identify studies on this topic. The collected data demonstrated changes in myocardial function in schizophrenia, bipolar disorder, depression, anxiety disorder, stressor-related disorder, post-traumatic stress disorder, eating disorders, sleep–wake disorders, substance-related and addictive disorders, neurocognitive disorders, and borderline personality disorder. The recurrent findings included impaired Left Ventricular Ejection Fraction and Left Ventricular Hypertrophy. Global Longitudinal Strain was significantly altered in patients with anorexia nervosa, bipolar disorder, and substance-related disorders. All reported studies support the consideration of cardiology consultations and a multidisciplinary approach in the care of patients with MDs with suspected cardiac dysfunction. Further investigation is warranted to determine the significance and prognostic value of myocardial deformation and strain measurements among individuals with MDs, focusing on the value of early detection, especially in asymptomatic cases. Full article

Background: High-intensity endurance training induces specific cardiac adaptations, often observed through electrocardiographic (ECG) changes. This study investigated the prevalence of ECG abnormalities in national-level Australian triathletes compared to sedentary controls. Methods: A cross-sectional observational study was conducted involving 22 triathletes and 7 sedentary controls. Standard 12-lead ECGs assessed resting heart rate, ECG intervals, and axis deviation. Peak oxygen consumption was evaluated in triathletes to correlate with ECG indices and left ventricular mass, derived via echocardiography. Results: Triathletes exhibited significantly lower resting heart rates (53.8 vs. 72.1 bpm, −34%, p = 0.04), shorter QRS durations (0.088 vs. 0.107 ms, −21.6%, p = 0.01), and longer QT intervals (0.429 vs. 0.358 ms, +16.6%, p = 0.01) compared to controls. Sinus bradycardia was present in 68.2% of triathletes, with varying severity. First-degree atrioventricular block was identified in 13.6% of athletes, and left ventricular hypertrophy was confirmed in 18 triathletes via echocardiography. A significant positive relationship was identified between VO₂peak and left ventricular mass (r = 0.68, p = 0.003). Conclusions: National-level triathletes exhibited ECG and structural cardiac adaptations consistent with high-intensity endurance training. Echocardiography is recommended for the accurate identification of LVH. These findings highlight the need for comprehensive cardiac evaluation in athletes to distinguish between physiological and pathological adaptations. Full article

Even if rarely detected, right atrial (RA) masses represent a diagnostic challenge due to their heterogeneous presentation. Para-physiological RA structures, such as a prominent Eustachian valve, Chiari’s network, and lipomatous atrial hypertrophy, may easily be misinterpreted as pathological RA masses, including thrombi, myxomas, and vegetations. Each pathological mass should always be correlated with adequate clinical, anamnestic, and laboratory data. However, the differential diagnosis between pathological RA masses may be challenging due to common constitutional symptoms, as in the case of vegetations and myxoma, which present with fever and analogous complications such as systemic embolism. The implementation of transthoracic echocardiography (TTE) with pulsed wave (PW) tissue Doppler imaging (TDI) may improve the visualization and differentiation of intracardiac masses through different color coding of the pathological structure compared to surrounding tissue. More remarkably, PW-TDI can provide a detailed assessment of the specific pattern of motion of each intracardiac mass, with important clinical implications. Specifically, a TDI-derived pattern of incoherent motion is typical of right-sided thrombi, myxomas, and vegetations, whereas right-sided pseudomasses are generally associated with a TDI pattern of concordant motion synchronous with the cardiac cycle. An increased TDI-derived mass peak antegrade velocity may represent an innovative marker of the embolic potential of mobile right-sided pathological masses. During the last two decades, only a few authors have used TTE implemented with PW-TDI for the characterization of intra-cardiac masses’ morphology and mobility. Herein, we report two clinical cases of totally different right-sided cardiac masses diagnosed using a multimodality imaging approach, including PW-TDI, followed at our institution. The prevalence and physiopathological characteristics of the most relevant RA masses and pseudomasses encountered in clinical practice are described in the present narrative review. In addition, we will discuss the principal clinical applications of PW-TDI and its potential value in improving the differential diagnosis of pathological and para-physiological right-sided cardiac masses. Full article