Search Results (835)

Functionally single-ventricle (FSV) defects are complex congenital heart anomalies that require Fontan palliation, a surgical procedure redirecting systemic venous blood directly to the pulmonary arteries, bypassing the heart. Despite improvements in surgical techniques and perioperative care leading to enhanced survival rates, patients remain vulnerable to significant long-term complications, due to the unique Fontan circulation physiology. This circulation relies on low pulmonary vascular resistance and preserved single-ventricle function but predisposes patients to venous congestion and reduced cardiac output, resulting in multi-organ dysfunction. Key cardiovascular complications include systolic and diastolic dysfunction of the single ventricle, atrioventricular valve regurgitation, arrhythmias, pulmonary vascular disease, and thromboembolic events. Systemic complications encompass Fontan-associated liver disease (FALD), protein-losing enteropathy (PLE), plastic bronchitis (PB), renal impairment, and endocrine and psychosocial burdens. All the problems induce frequent hospitalizations, psychological challenges, and impaired educational and employment opportunities. Comprehensive management requires multidisciplinary approaches addressing the complex interplay of hemodynamic, organ-specific problems, and psychosocial factors inherent to Fontan physiology. Full article

Venous thromboembolism (VTE) is a clinically significant complication in patients with breast cancer (BC) and may disrupt treatment continuity while contributing to adverse outcomes. Although BC is generally regarded as a relatively low-risk malignancy for VTE compared with several other cancer types, its high incidence and the increasing use of multimodal therapies have resulted in a growing clinical burden of breast cancer-associated VTE. This review summarizes the epidemiological features, risk factors, biological mechanisms, and advances in the prevention and management of breast cancer-associated VTE. Current evidence indicates that patients with cancer have an approximately 4- to 7-fold higher risk of VTE than the general population, with the risk in BC being particularly pronounced during the first 3–6 months after diagnosis. Older age, metabolic comorbidities, advanced disease, and exposure to multiple anticancer therapies have all been associated with an increased risk of VTE. Mechanistically, tissue factor, procoagulant extracellular vesicles, neutrophil extracellular traps, and inflammatory signaling pathways may contribute to breast cancer-associated VTE by promoting coagulation activation and endothelial dysfunction, while also linking thrombosis to immune evasion and Smetastatic progression. Improved identification of high-risk patients, optimization of dynamic risk assessment, and the implementation of individualized prophylactic and anticoagulant strategies may help improve outcomes in patients with BC. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways. Full article

Clonal hematopoiesis refers to the clonal expansion of hematopoietic stem and progenitor cells, driven by somatic mutations. Major mutated genes in clonal hematopoiesis include genes involved in epigenetic regulation including DNA methylation and/or chromatin modification (e.g., DNMT3A, TET2, and ASXL1), tumor suppressors (e.g., TP53), signal transduction (e.g., JAK2), and RNA splicing (e.g., SF3B1 and SRSF2). Clonal hematopoiesis includes clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of unknown significance (CCUS), and myelodysplastic syndromes/neoplasms (MDS). CHIP occurs when the frequency of the variant allele equals or exceeds 2% (4% for X-linked genes in males) in the absence of cytopenias. CHIP is common among older persons and is associated with an increased risk of hematologic cancer. CHIP is also associated with an increased risk of atherosclerotic disease including acute myocardial infarction, stroke, cardiac failure, and abdominal aneurysm. Increasing evidence suggests that CHIP is associated with venous thromboembolic disease. Somatic mutations lead to proliferation of hematopoietic progenitor cells and their progeny, resulting in excessive activation of granulocytes and monocytes. It could be postulated that chronic inflammation caused by clonal expansion of myeloid cells carrying mutations in DNMT3A, TET2, and ASXL1 (“DTA”) genes may constitute an independent risk factor in clot formation and endothelial-cell damage. DTA mutations correlate with elevated proinflammatory cytokines such as IL-1β and IL-6 and enhanced activation of inflammasomes. Moreover, JAK2 mutations may have a direct role in the activation of platelets and coagulation. In vivo murine studies have demonstrated that activation of the JAK-STAT signaling pathway promotes neutrophil extracellular trap (NET) formation, contributing to a prothrombotic state. Insights from related clonal disorders such as paroxysmal nocturnal hemoglobinuria and the VEXAS syndrome support the concept that mutation-driven innate immune activation can directly perturb hemostatic balance. This review aims to summarize the association between clonal expansion of hematopoietic cells and thrombotic disease, and highlight how somatic mutations in hematopoietic cells may contribute to vascular disease and thrombogenesis. Full article

Vascular diseases (VD) remain a leading global cause of morbidity and mortality, often developing silently before manifesting as severe complications like stroke or ischemia. Traditional diagnostic imaging provides essential anatomical data but frequently fails to capture the dynamic molecular processes underlying vascular pathology. This narrative review summarizes current evidence regarding Extracellular Vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, as emerging biomarkers and mediators in vascular conditions. The review evaluates the biological mechanisms of EVs across several disorders, including arterial aneurysms, peripheral artery disease, carotid stenosis, and venous thromboembolism. Findings indicate that EVs concentration and molecular cargo, particularly microRNAs and proteins, reflect the physiological state of parent cells, offering a “liquid biopsy” for vascular inflammation, endothelial dysfunction, and plaque vulnerability. Furthermore, the review explores the therapeutic potential of stem cell-derived EVs in promoting angiogenesis and tissue repair in chronic vascular ulcers. Despite these advances, the review concludes that the clinical implementation of EV-based diagnostics faces significant hurdles, primarily due to the lack of standardized isolation and characterization methods. Addressing these methodological challenges is crucial for translating EV research into routine clinical practice. Full article

Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1–7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4–10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies). Full article

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs of acute management and long-term complications. This systematic review aimed to assess patient satisfaction with anticoagulation therapy for VTE and to highlight potential differences according to the type of anticoagulant. The review focused on factors influencing the patient experience, such as perceived efficacy, ease of use, adverse effects, and health-related quality of life. Materials and Methods: A systematic review, without quantitative meta-analysis, was conducted in accordance with PRISMA 2020 guidelines. Articles were identified through searches in major databases (PubMed, Scopus, Cochrane Library and others) using keywords including “patient satisfaction”, “anticoagulation”, “venous thromboembolic disease”, and “quality of life”. In total, 21 studies published between 2009 and 2025 met the inclusion criteria. The studies assessed patient satisfaction with different types of anticoagulation, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) injections. Results: Across the included studies, patients generally reported higher levels of treatment satisfaction with DOACs compared with VKAs, mainly due to the absence of routine laboratory monitoring and fewer dietary restrictions. However, satisfaction varied according to age, sex, and clinical status. In specific patient populations, such as those with cancer-associated thrombosis, factors including fewer drug–drug interactions and perceptions of safety with LMWH appeared to influence treatment choice and satisfaction. Adverse effects, particularly bleeding, were identified as major drivers of dissatisfaction. Several studies suggested that higher treatment satisfaction was associated with better adherence, while quality of life appeared to improve in patients treated with DOACs in comparison with VKAs. Conclusions: Patient satisfaction is a critical component of successful VTE management. Overall, DOACs appear to be associated with higher treatment satisfaction than traditional therapies such as VKAs, although further high-quality research is needed to individualise anticoagulation strategies. Systematic incorporation of patient-reported satisfaction into clinical decision-making and into international guidelines may improve adherence, enhance quality of life, and ultimately increase the effectiveness of anticoagulation therapy. Full article

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease in the general population, with a variable phenotypic expression and symptomatology. Atrial fibrillation (AF) is the most common arrhythmia identified among patients diagnosed with HCM. Treatment of both AF and HCM has continuously evolved over time, leading to a significant improvement in the prognosis and life expectancy of symptomatic patients. Numerous studies have demonstrated that the risk of developing this arrhythmia correlates with atrial morphological, functional and electrical remodeling, a process known as atrial myopathy. Once a first episode of AF is diagnosed, permanent anticoagulation is required among patients diagnosed with HCM, regardless of the CHA₂ DS₂-VA score. Additionally, atrial cardiomyopathy is associated with an increased thromboembolic risk, independent of AF presence, in patients with stable sinus rhythm, in the context of atrial mechanical and endothelial dysfunction. This article aims to evaluate the current scientific evidence and treatment approaches in patients diagnosed with HCM. Full article

Advances in implantable and wearable cardiac monitoring technologies have led to widespread detection of brief, often asymptomatic atrial high-rate episodes, frequently labelled as device-detected atrial fibrillation (AF). While detection has increased substantially, the clinical interpretation of these findings remains uncertain. Observational studies demonstrate associations between AF burden and stroke risk but reveal marked inter-individual heterogeneity and no consistent temporal threshold below which risk is eliminated. Recent randomised controlled trials show that anticoagulation guided solely by arrhythmia duration confers limited net clinical benefit, with modest reductions in ischaemic stroke offset by increased bleeding. These findings challenge the biological and clinical validity of rigid time-based thresholds for intervention. Increasing evidence suggests that AF may act primarily as a marker of underlying atrial disease rather than the sole mechanistic cause of thromboembolism. This article provides an evidence-informed perspective on the interpretation of device-detected AF in contemporary clinical practice and argues for a shift away from duration-based triggers toward a longitudinal, risk-adapted approach that integrates AF trajectory, atrial substrate, and clinical context. Emerging tools such as artificial intelligence-enhanced electrocardiography may help identify occult atrial pathology but must augment rather than replace clinical judgement. Proportionate, individualised care should supersede reflexive treatment strategies in the management of device-detected AF. Full article

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is an important but under-recognised complication in neuromuscular diseases. In adults, emerging epidemiological data suggests increased VTE occurrence in conditions such as Amyotrophic Lateral Sclerosis, myotonic dystrophy, myasthenia gravis, inflammatory neuropathies, inflammatory myopathies, and POEMS syndrome. This heightened risk reflects not only disease-related immobility but also disorder-specific biological mechanisms, including inflammation, endothelial dysfunction and cardiomyopathy-related stasis. Therapies such as corticosteroids, IVIG-related hyperviscosity, long-term central venous access, perioperative immobility, critical illness, and complex orthopaedic procedures have prothrombotic effects. Despite this multifactorial risk profile, disease-specific guidance for thromboprophylaxis is lacking, and current practice relies heavily on extrapolation from general medical and surgical recommendations rather than data derived from neuromuscular cohorts. In children and adolescents, the VTE burden is less well-characterised, but events have been reported in Duchenne and Becker muscular dystrophy, congenital myopathies, and spinal muscular atrophy particularly with advanced motor impairment, severe cardiomyopathy, ventilatory insufficiency, and prolonged hospitalisation. Beyond venous events, selected neuromuscular disorders also exhibit increased arterial thrombosis risk. Myotonic dystrophy and dystrophinopathies are associated with cardiomyopathy and arrhythmia that predispose to systemic embolism and stroke, while inflammatory myopathies may demonstrate arterial events related to vasculitic or endothelial processes, although overall evidence remains limited. This review summarises available empirical and epidemiological evidence on venous and arterial thrombosis across adult and paediatric neuromuscular disorders, outlines disease-specific mechanistic pathways, examines treatment-related contributors, and highlights key evidence gaps that must be addressed to guide rational and targeted prophylaxis strategies in this complex, heterogeneous population. Full article

Factor XII (FXII) is a central mediator at the intersection of coagulation, fibrinolysis, inflammation, and immunity. It is activated upon contact with negatively charged surfaces, triggering the intrinsic coagulation pathway and driving thrombus formation and stabilization. Beyond clotting, FXII contributes to activation of the kallikrein–kinin system, generation of bradykinin, and modulation of inflammatory and immune responses. Congenital FXII deficiency does not increase bleeding risk, highlighting its unique role and making FXII inhibition an attractive strategy for anticoagulation and immune modulation with a potentially superior safety profile. Preclinical studies provide compelling evidence for this concept. In models of ischemic stroke and traumatic brain injury, FXII blockade significantly reduced infarct volume, improved neurological outcomes, and attenuated neuroinflammation without increasing hemorrhage. Similarly, in extracorporeal circulation and vascular stent implantation, FXII inhibition prevented thrombus formation and reduced fibrin deposition, achieving effects comparable to heparin but with markedly lower bleeding risk. Several classes of FXII inhibitors are currently in development, including antisense oligonucleotides, peptides, recombinant proteins, and monoclonal antibodies. Among them, Ixodes ricinus contact phase inhibitor (Ir-CPI) and recombinant human albumin-fused Infestin-4 (rHA-Infestin-4) have demonstrated strong antithrombotic efficacy in animal models. Most notably, garadacimab, a monoclonal anti-FXIIa antibody, has completed phase 3 trials and received regulatory approval for hereditary angioedema (HAE) prophylaxis, where it markedly reduces attack frequency with a favorable safety profile. This review summarizes current knowledge on FXII biology and evaluates its translational potential as a novel target for anticoagulant and anti-inflammatory therapies. Full article

Background: Atrial fibrillation (AF) and end-stage renal disease (ESRD) are closely related conditions that increase the risk of disability, stroke, and mortality. Anticoagulation management in patients with ESRD and AF is challenging due to the high risk of bleeding. Percutaneous left atrial appendage closure (LAAC) has emerged as an alternative to reduce thromboembolic events; however, evidence in this specific population remains limited. Therefore, we aimed to evaluate the frequency of thromboembolic events, bleeding complications and mortality in patients with AF and ESRD undergoing LAAC through a systematic review and meta-analysis. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420250640241). A structured search was performed in Medline, EMBASE, Web of Science, SCOPUS, LILACs and institutional repositories through September 2024, with no language restrictions. We included original studies reporting frequencies of thromboembolic events, bleeding and mortality in patients with AF and ESRD undergoing LAAC. A random-effects model was used and heterogeneity was assessed using the I² statistic. Results: Fourteen studies were included in the qualitative analysis and seven in the quantitative synthesis, comprising a total of 2433 patients with AF and ESRD undergoing LAAC. In the qualitative analysis, the mean age was 74 ± 7.6 years; the most common comorbidities were hypertension (74%), diabetes mellitus (47%), and dyslipidemia (53%). Watchman™ devices predominated in North America, whereas Amulet™ devices were more frequently used in Europe and Latin America. Procedural success was 98.4%, with infrequent periprocedural complications: major bleeding in 1.6% and device embolization in 0.5%. In the quantitative analysis, the pooled frequency of thromboembolic events was 3% (95% CI: 1–7%; I² = 81.1%), pooled bleeding frequency was 6% (95% CI: 4–10%; I² = 76.9%), and pooled mortality was 5% (95% CI: 1–22%; I² = 97.8%). After excluding studies with extreme values, adjusted mortality was 2% (95% CI: 1–5%; I² = 76.6%). Despite high heterogeneity, the findings suggest that LAAC may offer protection against embolic events with an acceptable bleeding risk. Conclusions: LAAC in patients with AF and ESRD is associated with a low frequency of thromboembolic events and bleeding when compared with standard anticoagulation therapy and no treatment. Overall mortality is moderate and appears to be primarily attributable to underlying comorbidity rather than the procedure itself. This meta-analysis provides evidence that LAAC may be a safe and effective therapeutic strategy in patients with contraindications or high risk for chronic anticoagulation. However, prospective and comparative clinical trials are needed to confirm these findings and inform future clinical practice guidelines. Full article

Background/Objectives: Cardiovascular diseases (CVDs) frequently limit the feasibility and effectiveness of cancer treatment. However, CVD burden has not been comprehensively described in pancreatic cancer. In our systematic review and meta-analysis, we evaluated the prevalence and incidence of CVDs in pancreatic ductal adenocarcinoma (PDAC). Methods: We conducted the systematic search in PubMed, EMBASE, and CENTRAL on 5 February 2024. Studies reporting the prevalence or incidence of CVDs in PDAC were included. Subgroup analyses were performed based on cancer stage and treatment type. Pooled proportions with the 95% confidence interval (CI) were calculated using a random-effects model. (PROSPERO: CRD42023482295). Results: We included 197 articles. At PDAC diagnosis, non-thrombotic cardiovascular diseases (NT-CVDs) were as prevalent as in the general population: hypertension in 33% (CI: 27–40%), ischemic heart disease in 6% (CI: 3–12%), and heart failure, arrhythmia, and stroke each in 2–3%. Their incidence during treatment remained low (1–10%). Thrombotic events, excluding pulmonary embolism, were present in 11% (CI: 7–15%) at diagnosis, with an incidence of 8–10% regardless of stage or treatment. Pulmonary embolism affected 3% at diagnosis and occurred at a similar rate during treatment. Conclusions: Thromboembolic events are common in PDAC and occur both at diagnosis and during follow-up. Their incidence remains stable across treatment modalities and disease stages, suggesting that the tumor itself is the primary driver of thrombotic risk. The prevalence of NT-CVDs in PDAC is comparable to that in the general population and shows minimal variation across cancer stages or treatment modalities. Full article

Atrial fibrillation (AF) frequently coexists with chronic kidney disease (CKD), and their combination confers a disproportionate risk of both thromboembolic and bleeding events. Conventional anticoagulation strategies rely primarily on creatinine clearance-based dosing, which reflects pharmacokinetic safety but does not fully capture the biological processes underlying thrombohemorrhagic instability. This narrative review synthesizes recent mechanistic and translational evidence regarding the bidirectional cardio–renal axis in AF and CKD, focusing on systemic inflammation, endothelial dysfunction, platelet dysregulation, and altered coagulation. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science (2018–2026) was performed, complemented by manual review of key references and guidelines. The evidence indicates that inflammatory cytokine activation, oxidative stress, glycocalyx degradation, von Willebrand factor dysregulation, uremic platelet dysfunction, and enhanced thrombin generation converge to create a disrupted vascular interface in which stroke and bleeding arise from shared pathophysiological mechanisms. Renal trajectory and selected circulating biomarkers further highlight the dynamic and heterogeneous nature of risk in advanced CKD. These findings support reframing anticoagulation decision-making in AF with CKD from a static filtration-based model toward a biology-informed approach that integrates renal dynamics, endothelial and platelet phenotype, and clinical context to better align thromboembolic protection with hemorrhagic safety. Full article