Search Results (639)

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

Heart failure (HF) and left ventricular hypertrophy (LVH) are linked to fibroblast growth factor 23 (FGF23). This study aims to analyze whether FGF23 can predict postoperative outcomes in unselected left ventricular assist device (LVAD) candidates. Methods: We conducted a prospective observational study that included 27 patients (25 HeartMate3 and 2 HeartMateII) with a median follow-up of 30 months. We measured preoperative FGF23 plasma levels and computed the HeartMateII risk score (HMRS), the HeartMate3 risk score (HM3RS) and the EuroSCOREII with respect to postoperative mortality, as well as the Michigan right heart failure risk score (MRHFS), the Euromacs RHF risk score (EURORHFS), the CRITT score with respect to RHF prediction and the kidney failure risk equation (KFRE) with respect to kidney failure. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: In the multivariate logistic regression, preoperative FGF23 level was found to be a predictor of postoperative RHF (OR: 1.37, 95-CI: 0.78–2.38; p = 0.031), mortality (OR: 1.10, 95%-CI: 0.90–1.60; p = 0.025) and the need for postoperative dialysis (OR: 1.09, 95%-CI: 0.91–1.44; p = 0.032). In the ROC analysis, FGF23 as a predictor of post-LVAD RHF had an area under the curve (AUC) of 0.81. Conclusions: FGF23 improves the prediction of clinically significant patient outcomes—such as need for dialysis, RHF and mortality—after HM3 and HMII implantation, as adding FGF23 to established risk scores increased their predictive value. Full article

Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via mineralocorticoid receptor activation, oxidative stress, inflammation, and extracellular matrix dysregulation. These changes culminate in a distinct cardiomyopathy phenotype, often underrecognized in early stages. Multimodality cardiac imaging, led primarily by conventional and speckle-tracking echocardiography, and complemented by exploratory cardiac magnetic resonance (CMR) techniques such as T1 mapping and late gadolinium enhancement, enables non-invasive assessment of structural, functional, and tissue-level changes in aldosterone-mediated myocardial damage. While numerous studies have established the diagnostic and prognostic relevance of imaging in PA, several gaps remain. Specifically, the relative sensitivity of different modalities in detecting subclinical myocardial changes, the long-term prognostic significance of imaging biomarkers, and the differential impact of adrenalectomy versus medical therapy on cardiac reverse remodeling require further clarification. Moreover, the lack of standardized imaging-based criteria for defining and monitoring PA-related cardiomyopathy hinders widespread clinical implementation. This narrative review aims to synthesize current knowledge on the pathophysiological mechanisms of aldosterone-induced cardiac remodeling, delineate the strengths and limitations of existing imaging modalities, and critically evaluate the comparative effects of surgical and pharmacologic interventions. Emphasis is placed on early detection strategies, identification of imaging biomarkers with prognostic utility, and integration of multimodal imaging into clinical decision-making pathways. By outlining current evidence and highlighting key unmet needs, this review provides a framework for future research aimed at advancing personalized care and improving cardiovascular outcomes in patients with PA. 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

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

Background: Well-designed endurance training leads to improved cardiovascular fitness and sports performance in prolonged exercise tasks, with the adaptations depending on multiple factors, including the training modality and the population in question. It is still disputable how the type of training affects myocardial remodeling, and the information on myocardial remodeling by high-intensity interval training (HIIT) is particularly scarce. Methods: The current study investigated changes in cardiac structure after volume-progressive HIIT in running mode. As part of their conditioning program, amateur athletes (mean ± SD age of 18.2 ± 1.0 years) exclusively conducted HIIT in a volume-progressive fashion over 7 weeks (a total of 21 sessions). Peak oxygen uptake as well as 200 m and 2000 m running performance were measured, and transthoracic two-dimensional echocardiography was conducted before and after the intervention. Results: Training improved running performance, increased the peak oxygen uptake and left atrium diameter (from 32.0 ± 2.5 to 33.5 ± 2.3 mm; p = 0.01), and induced ~11% thickening of the left-ventricular posterior wall (7.5 ± 0.7 to 8.2 ± 0.4 mm; p = 0.01) and interventricular septum (7.6 ± 0.7 to 8.6 ± 0.9 mm; p = 0.02), but not the dilation of left-ventricular, right-ventricular, or right atrium chambers. Conclusions: HIIT of just 127 km of running per 8.5 h during 7 weeks was sufficient to improve aerobic capacity and running performance, and induce left-ventricular wall hypertrophy and left atrium dilation, in young healthy athletes. Full article

Introduction: Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and organ dysfunction, affecting 5–8% of pregnancies globally and increasing women’s long-term risk of cardiovascular disease (CVD). This study investigates the association between prior PE and cardiovascular health in postmenopausal women. Methods: A total of 108 postmenopausal women with a history of PE and 100 controls without PE were enrolled. Clinical data, blood pressure readings, and echocardiographic assessments were obtained. Statistical analysis was conducted using SPSS version 20.0. Results: Women with prior PE showed a higher prevalence of eccentric left ventricular hypertrophy (37% vs. 23%, p < 0.02) and diastolic dysfunction (51% vs. 39%, p < 0.003). Maternal history of hypertension was also more common in the PE group (55% vs. 26%, p < 0.003). Obesity was more frequent in the PE group, but did not reach statistical significance (p < 0.09). Conclusions: Prior PE was linked to an increased risk of postmenopausal cardiac abnormalities, including left ventricular hypertrophy and diastolic dysfunction. A maternal history of hypertension was also more common among women with prior PE, suggesting a familial connection; PE should be acknowledged as a significant predictor of long-term cardiovascular risk, requiring lifelong monitoring and preventive measures. Full article

Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, with an estimated prevalence of 1:600 in the general population, and is associated with significant morbidity. HCM is characterized by left ventricular hypertrophy and interventricular septal thickening due to sarcomere protein gene mutations. The recent emergence of cardiac myosin inhibitors (CMIs), specifically mavacamten and aficamten, has introduced a paradigm shift in HCM management by directly targeting the hypercontractile state of the disease. This review comprehensively discusses the molecular mechanisms of mavacamten and aficamten, highlighting their biochemical similarities and differences from available data. It evaluates their reported efficacy in completed clinical trials, such as reducing left ventricular outflow tract (LVOT) obstruction, improving functional capacity, and enhancing quality of life in HCM. It further provides insight and updates to ongoing trials of both CMIs. Finally, it compares and elaborates on the safety profiles of mavacamten and aficamten, discussing their favorable safety profiles shown in completed studies. In current clinical practice, only mavacamten is approved for use, and clinical insights concerning both CMIs are limited, but encouraging. In summary, cardiac myosin inhibitors are a promising class of disease-modifying drugs for HCM with proven short-term safety and efficacy, but limited data are available to fully determine their long-term effects and efficacy in diverse patient populations. Ongoing research is necessary to further explore and define their role in HCM management. 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

Approximately 17,000 bears undergo bile extraction in facilities across Asia for traditional medicines despite the availability of proven alternatives. Bears are confined to cages and bile harvested from the gallbladder via needle aspiration, implanted catheters, or transabdominal fistulas. Bile-extracted bears develop numerous detrimental conditions, including abnormal repetitive behaviors, emaciation, dental disease, cholecystitis, hernias, abscesses, and neoplasia. A high prevalence of aortic dilation, commonly seen with systemic hypertension, was reported in bile-extracted bears, and aortic aneurysm rupture/dissection was the third leading cause of death in a population of 600 formerly bile-extracted bears. A high incidence of renal disease, a common cause of systemic hypertension in other species, was also identified in this population. We hypothesized that renal disease was positively correlated with lesions of systemic hypertension in bile-extracted bears. Archived medical records, imaging, and samples from 180 formerly bile-extracted bears were analyzed. Hypertensive retinopathy, left ventricular hypertrophy, and aortic dilation were used as validated correlates of systemic hypertension. The majority (76.1%) of bears exhibited at least one systemic hypertension lesion, and 62.8% had two or more lesions. Left ventricular hypertrophy was most common, followed by aortic dilation/aneurysm. Lesions of systemic hypertension were positively correlated to renal disease parameters of serum creatinine and renal histopathology. Understanding the etiology of systemic hypertension in this population is critical due to consequent comorbidities and increasing numbers of bile-extracted bears finding their way to sanctuary. 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: Fatty liver disease (FLD) is currently the most common liver disorder, affecting 25–30% of the global population. Its occurrence is strongly associated with overweight, obesity, and type 2 diabetes. In 2020, the disease definition was revised from NAFLD (non-alcoholic fatty liver disease) to MAFLD (metabolic-associated fatty liver disease), emphasizing its link to metabolic dysfunction and marking a major shift in clinical evaluation and risk stratification. We assessed the association between MAFLD and cardiovascular risk factors in a geriatric population by comparing patients with and without fatty liver disease and evaluating the influence of selected metabolic and echocardiographic parameters on MAFLD prevalence. Methods: This retrospective study was conducted using data from patients treated at the Department of Geriatrics, the University Clinical Hospital, in Wrocław. The study included 237 patients diagnosed with fatty liver disease and 148 controls without liver pathology. The groups were compared in terms of comorbidities, laboratory abnormalities, body mass index (BMI), and left ventricular hypertrophy. Statistical analysis was performed to assess the association between the severity of selected variables and the risk of MAFLD. Results: Patients with MAFLD had significantly higher body weight and BMI compared to controls. Diabetes mellitus and hypertriglyceridemia were more frequent in the MAFLD group, whereas HDL and vitamin D3 levels were lower. Echocardiographic indicators of left ventricular hypertrophy [IVSd, LVPWd, (IVSd + LVPWd)/2] were significantly elevated in MAFLD patients. Conclusions: This study confirms a strong association between MAFLD and cardiovascular risk factors in elderly patients. The inclusion of a control group allowed for more precise evaluation, supporting the role of MAFLD as an independent cardiometabolic risk indicator in geriatric care. Full article