Search Results (1,382)

Background/Objectives: Dilated cardiomyopathy (DCM), defined as dilation and contractile dysfunction of the left or both cardiac ventricles, remains the most common category of primary myocardial disease worldwide. It is the most prevalent cause of chronic heart failure and the most common indication for cardiac transplantation in young subjects. Accumulating evidence increasingly highlights the substantial genetic defects underlying DCM. Nevertheless, the genetic ingredients accountable for DCM in a major percentage of patients remain indefinite. Methods: A multigenerational pedigree suffering from DCM and a total of 276 healthy volunteers employed as controls were recruited from the Chinese Han-ethnicity population. A whole-exome sequencing (WES) assay followed by a Sanger sequencing analysis of the genomic DNAs from the available family members was implemented. Functional characterization of the identified genetic variant was completed by dual-luciferase analysis. Results: A new heterozygous variation in the ETS1 (erythroblast transformation-specific 1) gene, NM_005238.4:c.447T>G;p.(Tyr149*), was identified by WES and validated by Sanger sequencing analysis to co-segregate with DCM in the whole DCM family. This nonsense ETS1 variant was not found in 276 control subjects. Functional examination elucidated that Tyr149*-mutant ETS1 lost the ability to transactivate its downstream target genes CLDN5 (claudin 5) and ALK1 (activin receptor-like kinase 1), two genes crucial for cardiovascular embryonic development and postnatal structural remodeling. Conclusions: The present investigation reveals ETS1 as a new gene predisposed to human DCM and indicates ETS1 haploinsufficiency as an alternative molecular pathogenesis underlying DCM, providing a potential molecular target for genetic counseling and early diagnosis as well as personalized prophylaxis of DCM. Full article

Efficient mitochondrial matrix protein quality control (mPQC), regulated by the mitochondrial matrix protease LONP1, is essential for preserving cardiac bioenergetics, particularly in post-mitotic cardiomyocytes, which are highly susceptible to mitochondrial dysfunction. While cardiac mPQC defects could impair heart function, it remains unclear whether such defects can be mitigated through inter-organ crosstalk by modulating mPQC in extra-cardiac tissues, a potentially valuable strategy given the challenges of directly targeting the heart. To investigate this, we examined two mouse models of Lonp1 haploinsufficiency at young adulthood: a cardiomyocyte-specific heterozygous knockout (Lonp1^CKO-HET) and a whole-body heterozygous knockout (Lonp1^GKO-HET). Despite similar reductions in Lonp1 mRNA expression in the hearts, Lonp1^GKO-HET mice exhibited no cardiac dysfunction, whereas Lonp1^CKO-HET mice showed mild cardiac dysfunction accompanied by activation of the mitochondrial stress response, including induction of genes such as Clpx, Spg7, Hspa9, and Hspd1, increased mitochondrial dynamics (Pink1, Dnm1l), reduced mitochondrial biogenesis, and compensatory upregulation of the mtDNA transcriptional regulator Tfam, all occurring without overt structural remodeling. These alterations were absent in Lonp1^GKO-HET hearts. Our findings reveal a novel adaptive mechanism in which systemic mPQC deficiency can buffer mitochondrial dysfunction in the heart through inter-organ communication that is lost with cardiomyocyte-specific mPQC disruption. This study identifies systemic modulation of Lonp1-mediated mitochondrial stress pathways as a promising strategy to promote cardiac resilience through protective inter-organ signaling. Full article

Functional mitral regurgitation (FMR) is a common condition with significant prognostic implications, primarily driven by left atrial or ventricular remodeling secondary to ischemic or non-ischemic cardiomyopathies. While guideline-directed medical therapy (GDMT) remains the cornerstone of management, reducing mitral regurgitation severity in up to 40–45% of cases, additional interventions are often necessary. In patients where atrial fibrillation (AF) or ventricular dyssynchrony due to abnormal electrical conduction contributes to disease progression, guideline-directed AF management or cardiac resynchronization therapy plays a pivotal role. For those with persistent moderate to severe MR and unresolved symptoms despite optimal GDMT, percutaneous intervention may be warranted, provided specific clinical and echocardiographic criteria are met. This review highlights a precision-medicine approach to patient selection for transcatheter treatment of functional mitral regurgitation (FMR), emphasizing the integration of clinical characteristics with advanced multimodal imaging, including echocardiography, cardiac magnetic resonance, and computed tomography. In anatomically or clinically complex cases, complementary use of these imaging modalities is essential to ensure accurate phenotyping and procedural planning. Once a suitable candidate for percutaneous intervention has been identified, we provide a detailed overview of current transcatheter strategies, with a focus on device selection tailored to anatomical and pathophysiological features. Finally, we discuss emerging technologies and evolving therapeutic paradigms that are shaping the future of individualized FMR management. Full article

Asthma is a multifactorial respiratory disease that naturally occurs in horses, humans, and cats, presenting common clinical signs and species-specific mechanisms. This review addresses the impact of asthma on the cardiovascular and neurological systems, with a primary focus on horses. It highlights the need for new biomarkers beyond the respiratory system due to diagnostic difficulties in animals. A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on cardiovascular and neurological manifestations of asthma in humans, horses, cats, and experimental animal models. Studies were qualitatively compared, noting species-specific differences and mechanisms. Humans with asthma show an increased risk of cardiovascular disease and elevated cardiac biomarkers during exacerbations, while horses develop pulmonary hypertension and vascular remodeling. Cats exhibit significant pulmonary vascular changes. Heart rate variability analysis reveals altered autonomic function in humans and horses. Increased peripheral airway innervation and cough reflex sensitivity are noted across species. The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in asthma pathophysiology in murine models. Asthma impacts the cardiovascular and nervous systems differently across species, emphasizing the importance of comparative medicine. Future research should integrate cardiovascular, autonomic, and inflammatory pathways to develop effective therapeutic approaches in human and veterinary medicine, leveraging insights from naturally occurring asthma models. Full article

Background/Objectives: Heart failure (HF) with reduced ejection fraction (EF) has, in more than 50% of cases, an ischemic etiology and continues to be associated with increased mortality and morbidity despite all the progress registered in the field of medical therapy and interventional revascularization. Myocardial revascularization is extensively used in clinical practice based on the traditional concept that it can improve myocardial function and outcome in ischemic HF. This review is aimed at presenting current knowledge regarding revascularization in patients with chronic ischemic HF and reduced EF. Methods: The impact of revascularization on symptomatology, left ventricle reverse remodeling, major adverse cardiac events (MACEs), and the role of complete revascularization and of percutaneous interventional revascularization in chronic total occlusion (PCI-CTO) were analyzed. The best therapeutic strategies, revascularization and/or optimal medical therapy (OMT), are debated in different categories of patients, in order to identify who will benefit more from revascularization strategies. Results: Based on the long-term results of the STICH trial incorporated in the guidelines with a class I-b recommendation, coronary artery bypass graft (CABG) remains the main modality of revascularization for prognostic improvement in ischemic HF with multivessel disease. But real-life patients are usually old with multiple comorbidities and high surgical risk. In this category, the Heart Team opinion is required to evaluate the probability of complete revascularization and to choose between percutaneous coronary intervention (PCI) and CABG according to clinical status and coronary anatomy. Conclusions: However, until further studies are available, the results of the REVIVED-BCIS2 trial encourage OMT over PCI in patients with ischemic cardiomyopathy. The available randomized controlled trials (RCTs) showed improved angina and quality of life in PCI-CTO versus OMT, but the effect on MACEs was not demonstrated. Full article

Background: Alternative splicing is an important mechanism of transcriptomic and proteomic diversity and is progressively involved in cardiovascular disease (CVD) pathogenesis. Serum response factor (SRF), a critical transcription factor in cardiac development and function, may itself undergo splicing regulation, potentially altering its function in disease states. Objective: The objective of this study is to identify SRF-associated alternative splicing events in cardiac pathological conditions and examine regulatory interactions with splicing factors using RNA-seq data. Methods: Three human heart RNA-seq databases (PRJNA198165, PRJNA477855, PRJNA678360) were used, comprising various cardiac conditions like non-ischemic cardiomyopathy (NICM), ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), and heart failure with reduced ejection fraction (HFrEF), with and without left ventricular assist device (LVAD) support. Splicing events were identified using the rMATS tool, and correlation analyses were performed between SRF and predicted splicing factors. Functional enrichment of SRF-correlated genes was assessed via Gene Ontology (GO) and KEGG pathways. Results: The skipped exon (SE) events were the predominant splicing type across all datasets. SRF chr6, including (Exon 2, 43,173,847–43,174,113), (Exon 4, 43,176,548–43,176,667), and (Exon 5, 43,178,294-43,178,485), were most frequently involved in SE and mutually exclusive exon (MXE) events across multiple heart failure subtypes. Correlation analysis revealed strong positive associations between SRF and several splicing factors (HNRNPL, HNRNPD, SRSF5, and SRSF8). GO and KEGG analyses revealed enrichment of muscle development, sarcomere structure, lipid metabolism, and immune signaling pathways. Conclusions: Our study shows that SRF is subject to extensive alternative splicing in heart failure, particularly at Exon 2 and Exon 5, suggesting isoform-specific roles in cardiac remodeling. The strong co-expression with specific splicing factors delineates a regulatory axis that may explain the pathological transcriptome in cardiomyopathy. These findings provide a foundation for exploring splicing-based biomarkers and therapeutic targets in cardiac pathology for SRF. Full article

Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone matrix formation by regulating signaling pathways such as Akt and Wnt/β-catenin. It concurrently inhibits osteoclast activity to maintain the balance of bone remodeling, thereby simultaneously stimulating new bone regeneration and suppressing bone resorption. At the same time, ICA exerts potent anti-inflammatory and antioxidant effects and promotes angiogenesis, improving the local microenvironment of bone injury and significantly facilitating the regeneration of bone and cartilage tissues. Additionally, ICA exhibits notable protective effects in multiple organ systems including the cardiovascular, hepatic, renal, and nervous systems. Specifically, ICA reduces cardiomyocyte apoptosis and fibrosis to preserve cardiac function, improves hepatic metabolic function and alleviates oxidative stress, attenuates renal inflammation and fibrosis, and—through neuroprotective actions—reduces neuroinflammation and promotes neuronal survival. These multi-organ effects help optimize the systemic environment for bone healing. However, ICA faces significant pharmacokinetic challenges. It has low oral bioavailability (due to poor absorption and extensive first-pass metabolism) as well as a short half-life. Consequently, maintaining effective drug concentrations in vivo is difficult, which limits its therapeutic efficacy and impedes clinical translation. To fully realize its regenerative potential, advanced drug delivery strategies (e.g., nanocarrier-based delivery systems) are being explored to enhance ICA’s bioavailability and prolong its duration of action. Overall, ICA’s multi-modal actions on bone cells, the immune microenvironment, and systemic factors make it a promising multi-target agent for bone regeneration. Addressing its pharmacokinetic limitations through optimized delivery and conducting further clinical studies will be crucial to realize its full therapeutic potential. This review provides a comprehensive overview of recent advances and challenges in translating ICA’s benefits into orthopedic therapy. Full article

Background: Arteriovenous fistulas (AVFs) may contribute to cardiac remodeling and consequently to an increased risk of heart failure and cardiovascular mortality in patients with end-stage kidney disease (ESKD). We aimed to assess cardiac changes following AVF creation and identify potential parameters associated with cardiac remodeling. Methods: In our prospective, single-center study, ESKD patients without significant pre-existing cardiac disease underwent 2D and 3D echocardiographic evaluation before and after AVF creation, along with AVF flow measurement. Cardiac remodeling was assessed using 3D indexed left and right ventricular end-diastolic volumes (LVEDVi, RVEDVi), while systolic function was assessed using longitudinal strain and 3D ejection fraction. Results: We included 20 patients (18 men; median age 73.5 years [IQR: 67–77]) with a mean AVF flow of 1140 ± 345 mL/min. At a median of 8.2 months (IQR: 7.3–9.3) following AVF creation, significant biventricular dilatation was observed: LVEDVi increased from 89 ± 14 to 97 ± 21 mL/m² (p < 0.05) and RVEDVi from 80 ± 15 to 91 ± 18 mL/m² (p < 0.05), while the systolic function of both ventricles did not change significantly. The right ventricle showed the most pronounced remodeling and it was independently associated with volume overload (p = 0.003) and elevated left ventricular filling pressure (p = 0.030), but not with AVF flow. Conclusions: Moderate AVF flow was associated with cardiac remodeling, primarily affecting the right ventricle. Fluid overload and left ventricular filling pressure were key factors associated with right ventricular remodeling, underscoring the need for careful fluid management and vascular access planning in ESKD patients. Full article

Background: Standard room temperature housing (~22 °C) represents a stress for laboratory mice, resulting in an increased metabolic rate, calorie consumption, heart rate, and catecholamine levels compared to thermoneutral conditions (29–32 °C). Using a recently established two-hit model of heart failure with preserved ejection fraction (HFpEF) (Angiotensin II + High-fat diet for 28 days; MHS), we investigated how housing temperature modulates cardiac remodelling and function in male and female C57Bl/6J mice. Methods: Using the MHS mouse model, we investigated cardiac remodelling and function in 8-week-old C57BL/6J mice of both sexes housed at 10 °C, 22 °C, and 30 °C for four weeks. Control mice were analyzed in parallel. Before the MHS, the animals were allowed to acclimate for a week before the MHS started. Results: Mice housed at 10 °C consumed more food and had increased fat mass compared to those at 22 °C or 30 °C. This was accompanied by increased heart weight, stroke volume, heart rate, and cardiac output. Mice housed at 22 °C and 30 °C were similar for these cardiac parameters. Following MHS, mice at 10 °C and 22 °C developed marked cardiac hypertrophy, whereas thermoneutral housing attenuated this response and reduced left atrial enlargement. Cold-exposed females showed more diastolic dysfunction after MHS (increased E’ wave, E/E’, and isovolumetric relaxation time) than those at 22 °C or 30 °C. Ejection fraction and cardiac output declined significantly at 10 °C after MHS but were preserved at 22 °C and 30 °C in females. Conclusions: Cold housing exacerbates cardiac dysfunction in mice subjected to HFpEF-inducing stress, with pronounced effects in females. In contrast, thermoneutrality limits the cardiac hypertrophic response. Full article

Introduction: Congestive heart failure (CHF), a complex clinical syndrome characterized by the heart’s inability to pump blood effectively due to structural or functional impairments, is a growing public health concern, with profound implications for patients’ physical and emotional well-being. In India, the burden of CHF is rising due to aging demographics and increasing prevalence of lifestyle-related risk factors. Among the subtypes of CHF, heart failure with preserved ejection fraction (HFpEF), i.e., heart failure with left ventricular ejection fraction of ≥50% with evidence of spontaneous or provokable increased left ventricular filling pressure, and heart failure with reduced ejection fraction (HFrEF), i.e., heart failure with left ventricular ejection fraction of 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling, may present differing impacts on health-related quality of life (HRQoL), i.e., an individual’s or a group’s perceived physical and mental health over time, yet comparative data remains limited. This study assesses HRQoL among CHF patients using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), one of the most widely used health-related quality of life questionnaires for patients with heart failure based on physical and emotional dimensions and identifies sociodemographic and clinical variables influencing these outcomes. Methods: A cross-sectional analytical study was conducted among 233 CHF patients receiving inpatient and outpatient care at the Department of Cardiology at a quaternary care teaching hospital in coastal Karnataka in India. Participants were enrolled using convenience sampling. HRQoL was evaluated through the MLHFQ, while sociodemographic and clinical characteristics were recorded via a structured proforma. Statistical analyses included descriptive measures, independent t-test, Spearman’s correlation and stepwise multivariable linear regression to identify associations and predictors. Results: The mean HRQoL score was 56.5 ± 6.05, reflecting a moderate to high symptom burden. Patients with HFpEF reported significantly worse HRQoL (mean score: 61.4 ± 3.94) than those with HFrEF (52.9 ± 4.64; p < 0.001, Cohen’s d = 1.95). A significant positive correlation was observed between HRQoL scores and age (r = 0.428; p < 0.001), indicating that older individuals experienced a higher burden of symptoms. HRQoL also varied significantly across NYHA functional classes (χ² = 69.9, p < 0.001, ε² = 0.301) and employment groups (χ² = 17.0, p < 0.001), with further differences noted by education level, gender and marital status (p < 0.05). Multivariable linear regression identified age (B = 0.311, p < 0.001) and gender (B = –4.591, p < 0.001) as significant predictors of poorer HRQoL. Discussion: The findings indicate that patients with HFpEF experience significantly poorer HRQoL than those with HFrEF. Older adults and female patients reported greater symptom burden, underscoring the importance of demographic-sensitive care approaches. These results highlight the need for routine integration of HRQoL assessment into clinical practice and the development of comprehensive, personalized interventions addressing both physical and emotional health dimensions, especially for vulnerable subgroups. Conclusions: CHF patients, especially those with HFpEF, face reduced HRQoL. Key factors include age, gender, education, employment, marital status, and NYHA class, underscoring the need for patient-centered care. Full article

Clonal hematopoiesis of intermediate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell because of a mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. Interestingly, CHIP is associated with a two-fold increase in cardiovascular risk, independently of traditional risk factors. Recent studies using deep-targeted sequencing have revealed that CHIP mutations, primarily TET2 and DNMT3A, present a higher incidence in patients with AF compared to healthy controls. Moreover, the presence of the aforementioned mutations is positively correlated with the progression and the severity of the AF clinical course. Regarding the predisposition of AF, it has been proven that TET2 and ASXL1 mutations, and not DNMT3A mutation, are associated with higher interleukin-6 (IL-6) levels. IL-6 levels, being indices of cardiac remodeling, predispose to an elevated risk for AF in healthy subjects. Currently conducted research has focused on elaborating the mechanisms driving the association between AF and CHIP and on the evaluation of potential interventions to reduce the risk of AF development. The aims of our review are (i) to summarize published evidence regarding the presence of CHIP mutations as a contributor to AF severity and predisposition, and (ii) to highlight the potential benefits of investigating the correlations between CHIP and AF for AF-diagnosed patients. Full article

Cardiac devices have transformed the management of heart failure, ventricular arrhythmias, ischemic cardiomyopathy, and valvular heart disease. Technologies such as cardiac resynchronization therapy (CRT), conduction system pacing, left ventricular assist devices (LVADs), and implantable cardioverter-defibrillators have contributed to abated global cardiovascular risk through action onto pathophysiological processes such as mechanical unloading, electrical resynchronization, or hemodynamic optimization, respectively. While their clinical benefits are well established, their long-term molecular and structural effects on the myocardium remain under investigation. Cardiac devices dynamically interact with myocardial and vascular biology, inducing molecular and extracellular matrix adaptations that vary by pathology. CRT enhances calcium cycling and reduces fibrosis, but chronic pacing may lead to pacing-induced cardiomyopathy. LVADs and Impella relieve ventricular workload yet alter sarcomeric integrity and mitochondrial function. Transcatheter valve therapies influence ventricular remodeling, conduction, and coronary flow. Understanding these remodeling processes is crucial for optimizing patient selection, device programming, and therapeutic strategies. This narrative review integrates the current knowledge on the molecular and structural effects of cardiac devices, highlighting their impact across different disease settings. 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

Cardiac fibrosis following myocardial infarction plays a critical role in the formation of scar tissue and contributes to ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. Current clinical diagnostics use electrical and structural markers, but lack precision due to low spatial resolution and absence of molecular information. In this paper, we employed line scan Raman microspectroscopy to classify sheep myocardial tissue into muscle, necrotic, granulated, and fibrotic tissue types, using collagen as a molecular biomarker. Three spectral regions were evaluated: region A (600–2960 cm⁻¹), region B (600–1399 cm⁻¹ and 1751–2960 cm⁻¹), and region C (1400–1750 cm⁻¹), which includes the prominent collagen-associated peaks at 1448 cm⁻¹ and 1652 cm⁻¹. Linear and nonlinear principal component analysis (PCA) and support vector machines (SVMs) were applied for dimensionality reduction and classification, with nonlinear models specifically addressing the nonlinearity of collagen formation during fibrogenesis. Histological validation was performed using Masson’s trichrome staining. Raman bands associated with collagen in region C consistently outperformed regions A and B, achieving the highest explained variance and best class separation in both binary and multiclass PCA models for both linear and nonlinear approaches. The ratio of collagen-related peaks enabled stage-dependent tissue characterization, confirming the nonlinear nature of fibrotic remodeling. Our findings highlight the diagnostic potential of collagen-associated Raman bands for characterizing myocardial fibrosis. The proposed PCA-SVM framework demonstrates robust performance even with limited sample size and has the potential to lay the foundation for real-time intraoperative diagnostics. Full article

Captopril, a well-established angiotensin-converting enzyme (ACE) inhibitor, has garnered attention for its cardioprotective effects in preventing heart remodeling and maintaining cardiac function, significantly improving life quality. However, recent studies have revealed that in addition to known hemodynamic alterations, captopril exhibits significant antioxidant, anti-inflammatory, and immunomodulatory effects that may underlie its protective mechanisms. Although it appeared to be overlooked in clinical practice, in recent years, additional efforts have been made to uncover the mechanisms of all drug effects, as recent research studies predict a wide spectrum of diseases beyond the recommended indications. This review thoroughly examines the mechanisms by which captopril mediates its protective effects, bridging basic biochemical observations with applied clinical investigation, especially during ischemic reperfusion (I/R) injury, hypertension, and heart failure (HF). Evidence points to captopril as a promising agent for modulating oxidative and inflammatory pathways that are crucial for cardiovascular medicine. Directions for future research are defined to determine the molecular targets of captopril further and to optimize its clinical utility in the management of cardiovascular and possibly other diseases. Full article