Risultati per: Come stress e attacchi di cuore sono collegati

I risultati del progetto Iss “Veterani in Sella”

Introduction
The use and value of artificial intelligence (AI)-driven tools and techniques are under investigation in detecting coronary artery disease (CAD). EchoGo Pro is a patented AI-driven stress echocardiography analysis system produced by Ultromics Ltd. (henceforth Ultromics) to support clinicians in detecting cardiac ischaemia and potential CAD. This manuscript presents the research protocol for a field study to independently evaluate the accuracy, acceptability, implementation barriers, users’ experience and willingness to pay, cost-effectiveness and value of EchoGo Pro.

Methods and analysis
The ‘Evaluating AI-driven stress echocardiography analysis system’ (EASE) study is a mixed-method evaluation, which will be conducted in five work packages (WPs). In WP1, we will examine the diagnostic accuracy by comparing test reports generated by EchoGo Pro and three manual raters. In WP2, we will focus on interviewing clinicians, innovation/transformation staff, and patients within the National Health Service (NHS), and staff within Ultromics, to assess the acceptability of this technology. In this WP, we will determine convergence and divergence between EchoGo Pro recommendations and cardiologists’ interpretations and will assess what profile of cases is linked with convergence and divergence between EchoGo Pro recommendations and cardiologists’ interpretations and how these link to outcomes. In WP4, we will conduct a quantitative cross-sectional survey of trust in AI tools applied to cardiac care settings among clinicians, healthcare commissioners and the general public. Lastly, in WP5, we will estimate the cost of deploying the EchoGo Pro technology, cost-effectiveness and willingness to pay cardiologists, healthcare commissioners and the general public. The results of this evaluation will support evidence-informed decision-making around the widespread adoption of EchoGo Pro and similar technologies in the NHS and other health systems.

Ethics approval and dissemination
This research has been approved by the NHS Health Research Authority (IRAS No: 315284) and the London South Bank University Ethics Panel (ETH2223-0164). Alongside journal publications, we will disseminate study methods and findings in conferences, seminars and social media. We will produce additional outputs in appropriate forms, for example, research summaries and policy briefs, for diverse audiences in NHS.

Intervento alle Molinette di Torino su una paziente di 38 anni

Intervento alle Molinette di Torino su una paziente di 38 anni

Intervento alle Molinette di Torino su una paziente di 38 anni

I genitori di Nicholas Green presenti al NiguarDAY

Con stile di vita sano evitabile l’80% degli infarti e ictus

Per conoscere patologia che interessa 11.000 persone in Italia

Agenzia cyber, ‘c’è scarsa attenzione alla sicurezza’

Circulation, Ahead of Print. BACKGROUND:Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca2+homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca2+homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo.METHODS:Calpain-resistant JP2 knock-in mice (JP2CR) were generated by deleting the primary JP2 calpain cleavage site. Stress-dependent JP2 cleavage was assessed through in vitro cleavage assays and in isolated cardiomyocytes treated with 1 μmol/L isoproterenol by immunofluorescence. Cardiac outcomes were assessed in wild-type and JP2CRmice 5 weeks after transverse aortic constriction compared with sham surgery using echocardiography, histology, and RNA-sequencing methods. E-C coupling efficiency was measured by in situ confocal microscopy. E-C coupling proteins were evaluated by calpain assays and Western blotting. The effectiveness of adeno-associated virus gene therapy with JP2CR, JP2, or green fluorescent protein to slow HF progression was evaluated in mice with established cardiac dysfunction.RESULTS:JP2 proteolysis by calpain and in response to transverse aortic constriction and isoproterenol was blocked in JP2CRcardiomyocytes. JP2CRhearts are more resistant to pressure-overload stress, having significantly improved Ca2+homeostasis and transverse tubule organization with significantly attenuated cardiac dysfunction, hypertrophy, lung edema, fibrosis, and gene expression changes relative to wild-type mice. JP2CRpreserves the integrity of calpain-sensitive E-C coupling–related proteins, including ryanodine receptor 2, CaV1.2, and sarcoplasmic reticulum calcium ATPase 2a, by attenuating transverse aortic constriction–induced increases in calpain activity. Furthermore, JP2CRgene therapy after the onset of cardiac dysfunction was found to be effective at slowing the progression of HF and superior to wild-type JP2.CONCLUSIONS:The data presented here demonstrate that preserving JP2-dependent E-C coupling by prohibiting the site-specific calpain cleavage of JP2 offers multifaceted beneficial effects, conferring cardiac protection against stress-induced proteolysis, hypertrophy, and HF. Our data also indicate that specifically targeting the primary calpain cleavage site of JP2 by gene therapy approaches holds great therapeutic potential as a novel precision medicine for treating HF.

Ha effetti positivi sui grassi e gli zuccheri nel sangue

Circulation, Ahead of Print. BACKGROUND:The docking protein IRS2 (insulin receptor substrate protein-2) is an important mediator of insulin signaling and may also regulate other signaling pathways. Murine hearts with cardiomyocyte-restricted deletion ofIRS2(cIRS2-KO) are more susceptible to pressure overload–induced cardiac dysfunction, implying a critical protective role of IRS2 in cardiac adaptation to stress through mechanisms that are not fully understood. There is limited evidence regarding the function of IRS2 beyond metabolic homeostasis regulation, particularly in the context of cardiac disease.METHODS:A retrospective analysis of an electronic medical record database was conducted to identify patients withIRS2variants and assess their risk of cardiac arrhythmias. Arrhythmia susceptibility was examined in cIRS2-KO mice. The underlying mechanisms were investigated using confocal calcium imaging of ex vivo whole hearts and isolated cardiomyocytes to assess calcium handling, Western blotting to analyze the involved signaling pathways, and pharmacological and genetic interventions to rescue arrhythmias in cIRS2-KO mice.RESULTS:The retrospective analysis identified patients withIRS2variants of uncertain significance with a potential association to an increased risk of cardiac arrhythmias compared with matched controls. cIRS2-KO hearts were found to be prone to catecholamine-sensitive ventricular tachycardia and reperfusion ventricular tachycardia. Confocal calcium imaging of ex vivo whole hearts and single isolated cardiomyocytes from cIRS2-KO hearts revealed decreased Ca²+transient amplitudes, increased spontaneous Ca²+sparks, and reduced sarcoplasmic reticulum Ca²+content during sympathetic stress, indicating sarcoplasmic reticulum dysfunction. We identified that overactivation of the AKT1/NOS3 (nitric oxide synthase 3)/CaMKII (Ca2+/calmodulin-dependent protein kinase II)/RyR2 (type 2 ryanodine receptor) signaling pathway led to calcium mishandling and catecholamine-sensitive ventricular tachycardia in cIRS2-KO hearts. Pharmacological AKT inhibition or genetic stabilization of RyR2 rescued catecholamine-sensitive ventricular tachycardia in cIRS2-KO mice.CONCLUSIONS:Cardiac IRS2 inhibits sympathetic stress-induced AKT/NOS3/CaMKII/RyR2 overactivation and calcium-dependent arrhythmogenesis. This novel IRS2 signaling axis, essential for maintaining cardiac calcium homeostasis under stress, presents a promising target for developing new antiarrhythmic therapies.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.