ß-Blockers and Erectile Dysfunction in Heart Failure. Between Myth and Reality.

Erectile dysfunction (ED) is a major concern in heart failure (HF) due its high prevalence as well as its negative impact on the quality of life, this condition being usually unrecognized and thus untreated. A number of possible causes might contribute to the above mentioned tight association, i.e., shared risk factors, comorbidities and several physiologic HF abnormalities such as impaired exercise tolerance, psychogenic factors and neurohumoral, metabolic and vascular changes. Medications have been blamed for playing also a pivotal role in the ED occurrence and, particularly, the ß -blockers. Remarkably, the underlying mechanisms have not been fully identified. All the available scientific literature dealing with this topic derives from studies not addressing this issue in HF, but in other settings, (e.g., arterial hypertension) and are also characterized by important methodological flaws. Thus, given the solid evidences arguing in favor of ß -blockers in HF in terms of morbidity, mortality and quality of life, ß -blockers at the maximal tolerated dosage in this patients' category should be recommended, regardless of ED. However, the ED-related issues should not be neglected, and adequate psychological counseling and management should be provided, pursuing the correction of risk factors, the choice of more suitable medications and, in selected cases, adopting specific drugs or devices. The purpose of this narrative review is to highlight the close relationship between ED and HF and, specifically, to focus on a possible ß -blockers' role in determining or, at least, worsening this condition.

An aggressive solution for patients with heart failure and atrial fibrillation: nodal ablation and cardiac resynchronization therapy.

Heart failure and atrial fibrillation are two diseases that often coexist and contribute to worsening the prognosis and quality of life of patients. Managing this situation is still a challenge today. The ablation of the atrioventricular node associated with cardiac resynchronization therapy (CRT) fits into this context as a definitive but effective solution. Indeed, long-term positive results have been demonstrated in patients with atrial fibrillation ineligible for ablation and refractory to medical therapy in terms of symptom reduction and, more recently, also mortality. Furthermore, the role of this strategy in obtaining adequate biventricular pacing in patients who may benefit from CRT but are ineligible due to the presence of atrial fibrillation is being highlighted.

Future of left atrial appendage interventions.

Percutaneous left atrial appendage occlusion (LAAO), currently recognized as a procedure with relatively low risk, is increasingly being adopted in clinical practice. However, due to the preventive nature of the procedure and the necessity to compare it with newer and safer oral anticoagulants, further optimization is required to address remaining challenges. These latter include acquiring comprehensive data on safety and efficacy, establishing standardized pre-procedural planning, and simplifying procedural process. Consequently, we have provided an overview that encompasses future opportunities for enhancing procedural safety and efficacy, thereby establishing LAAO as the mainstream strategy for stroke and systemic embolism prevention in patients with atrial fibrillation and absolute contraindications to anticoagulant drugs.

Cardiomyopathy and Sudden Cardiac Death: Bridging Clinical Practice with Cutting-Edge Research.

Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies.

Local inhomogeneous conduction and non-uniform anisotropism in a normal voltage atrial map.

A patient with symptomatic persistent atrial fibrillation and recurrences after pulmonary vein isolation (PVI) underwent a second ablation procedure. The PVs were found isolated and the left atrial substrate tissue was mapped. During sinus rhythm, the voltage map resulted in a normal range (>0,5mV) while a map of EGMs durations revealed an area presenting prolonged EGMs (>45 ms) in the anterior region. The activation map of this area demonstrated abnormal conduction and a non-uniform anisotropism when compared with areas in which EGM's normal durations were recorded. The EGMs duration map may offer additional clinical information on the areas presenting abnormal conduction predisposing arrhythmias maintenance in patients suffering from persistent atrial fibrillation.

Platelet Phagocytosis via P-selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis.

OBJECTIVE: It is unclear why activated platelets and platelet-derived microparticles (MPs) accumulate in the blood of patients with systemic sclerosis (SSc). This study was undertaken to investigate whether defective phagocytosis might contribute to MP accumulation in the blood of patients with SSc. METHODS: Blood samples were obtained from a total of 81 subjects, including 25 patients with SSc and 26 patients with stable coronary artery disease (CAD). Thirty sex- and age-matched healthy volunteers served as controls. Studies were also conducted in NSG mice, in which the tail vein of the mice was injected with MPs, and samples of the lung parenchyma were obtained for analysis of the pulmonary microvasculature. Tissue samples from human subjects and from mice were assessed by flow cytometry and immunochemical analyses for determination of platelet-neutrophil interactions, phagocytosis, levels and distribution of P-selectin, P-selectin glycoprotein ligand 1 (PSGL-1), and HMGB1 on platelets and MPs, and concentration of byproducts of neutrophil extracellular trap (NET) generation/catabolism. RESULTS: Activated P-selectin+ platelets and platelet-derived HMGB1+ MPs accumulated in the blood of SSc patients but not in the blood of healthy controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had fewer P-selectin+ platelets and a negligible number of MPs. The expression of the receptor for P-selectin, PSGL-1, in neutrophils from SSc patients was significantly decreased, raising the possibility that phagocytes in SSc do not recognize activated platelets, leading to a failure of phagocytosis and continued neutrophil release of MPs. As evidence of this process, activated platelets were not detected in the neutrophils from SSc patients, whereas they were consistently present in the neutrophils from patients with CAD. HMGB1+ MPs elicited generation of NETs, which were only detected in the plasma of SSc patients. In mice, P-selectin-PSGL-1 interaction resulted in platelet phagocytosis in vitro and influenced the ability of MPs to elicit NETs, endothelial activation, and migration of leukocytes through the pulmonary microvasculature. CONCLUSION: The clearance of activated platelets via PSGL-1 limits the undesirable effects of MP-elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis.

Increased plasmatic NETs by-products in patients in severe obesity.

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.