Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

Background: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF).

Objective: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF.

Methods: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration.

Staff acceptability and patient usability of a self-screening kiosk for atrial fibrillation in general practice waiting rooms.

Background: Current Australian and European guidelines recommend opportunistic screening for atrial fibrillation (AF) among patients ≥65 years, but general practitioners (GPs) report time constraints as a major barrier to achieving this. Patient self-screening stations in GP waiting rooms may increase screening rates and case detection of AF, but the acceptability of patient self-screening from the practice staff perspective, and the usability by patients, is unknown.

Objective: To determine staff perspectives on AF self-screening stations and factors impacting acceptability, usability by patients, and sustainability.

Z-REX uncovers a bifurcation in function of Keap1 paralogs.

Studying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-à-vis off-target, modifications. By combining bolus dosing, knockdown, and Z-REX-a tool investigating on-target/on-pathway electrophile signaling, we document that electrophile labeling of one zebrafish-Keap1-paralog (zKeap1b) stimulates Nrf2- driven antioxidant response (AR) signaling (like the human-ortholog). Conversely, zKeap1a is a dominant-negative regulator of electrophile-promoted Nrf2-signaling, and itself is nonpermissive for electrophile-induced Nrf2-upregulation.

Intersection of Diet and Exercise with the Gut Microbiome and Circulating Metabolites in Male Bodybuilders: A Pilot Study.

Diet, exercise and the gut microbiome are all factors recognised to be significant contributors to cardiometabolic health. However, diet and exercise interventions to modify the gut microbiota to improve health are limited by poor understanding of the interactions between them. In this pilot study, we explored diet-exercise-microbiome dynamics in bodybuilders as they represent a distinctive group that typically employ well-defined dietary strategies and exercise regimes to alter their body composition.

Mechano-covalent protection of coagulation factor VIII by von Willebrand factor.

von Willebrand factor (VWF) is the protective carrier of procoagulant factor VIII (FVIII) in the shear forces of the circulation, prolonging its half-life and delivering it to the developing thrombus. Using force spectroscopy, VWF-FVIII complex formation is characterized by catch-bond behavior in which force first decelerates then accelerates bond dissociation. Patients with mutations in VWF at the FVIII binding site phenocopies hemophilia A and the most common mutations are of cysteine residues involving multiple disulfide bonds.

Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models.

Identification and management of cancer cachexia in patients: Assessment of healthcare providers' knowledge and practice gaps.

Background: Cancer cachexia negatively impacts patient outcomes, quality of life and survival. Identification and management of cancer cachexia remains challenging to healthcare professionals (HCPs). The aim of this assessment was to identify current gaps in HCPs' knowledge and practice for identifying and managing adults with cancer-related cachexia.

Risk for Mortality with Increasingly Severe Aortic Stenosis: An International Cohort Study.

Background: Aortic stenosis (AS) is the most common valvular heart disease in high-income countries. Adjusted for clinical confounders, the risk associated with increasing AS severity across the spectrum of AS severity remains uncertain.

Methods: The authors conducted an international, multicenter, parallel-cohort study of 217,599 Australian (mean age, 76.

Ischemic Preconditioning and Postconditioning Protect the Heart by Preserving the Mitochondrial Network.

Background: Mitochondria fuse to form elongated networks which are more tolerable to stress and injury. Ischemic pre- and postconditioning (IPC and IPost, respectively) are established cardioprotective strategies in the preclinical setting. Whether IPC and IPost modulates mitochondrial morphology is unknown.

Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology.

Purpose Of Review: This study is aimed at reviewing the recent progress in Drp1 inhibition as a novel approach for reducing doxorubicin-induced cardiotoxicity and for improving cancer treatment.

Recent Findings: Anthracyclines (e.g.

Intermittent hypoxia enhances the expression of hypoxia inducible factor HIF1A through histone demethylation.

The cellular response to hypoxia is regulated through enzymatic oxygen sensors, including the prolyl hydroxylases, which control degradation of the well-known hypoxia inducible factors (HIFs). Other enzymatic oxygen sensors have been recently identified, including members of the KDM histone demethylase family. Little is known about how different oxygen-sensing pathways interact and if this varies depending on the form of hypoxia, such as chronic or intermittent.

Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome.

Background: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome.

Rapid Regeneration of a Neoartery with Elastic Lamellae.

Native arteries contain a distinctive intima-media composed of organized elastin and an adventitia containing mature collagen fibrils. In contrast, implanted biodegradable small-diameter vascular grafts do not present spatially regenerated, organized elastin. The elastin-containing structures within the intima-media region encompass the elastic lamellae (EL) and internal elastic lamina (IEL) and are crucial for normal arterial function.

Quarterly versus annual ECG screening for atrial fibrillation in older Chinese individuals (AF-CATCH): a prospective, randomised controlled trial.

Background: Screening for atrial fibrillation before onset of symptoms and the subsequent initiation of oral anticoagulants could prevent stroke and death. The most cost-effective strategy to screen for atrial fibrillation in a population at high risk aged 65 years and older is unknown. Therefore, we aimed to investigate whether more frequent electrocardiography (ECG) recordings would significantly improve the detection of atrial fibrillation compared with annual ECG screenings.

The Utility and Educational Impact of a Virtual Webinar to Deliver an International Undergraduate Cardiovascular Conference.

Introduction: Conferences are an important avenue for dissemination of knowledge, research and provide networking opportunities for career development. The COVID-19 pandemic has prompted adoption of virtual platforms for delivery of these conferences. The aim of the study was to determine the utility and educational impact of a student-led virtual webinar to deliver an undergraduate cardiovascular conference compared to a traditional in-person conference.

Mechanisms for Reduced Fibrin Clot Formation on Liquid-Infused Surfaces.

Biomedical devices are prone to blood clot formation (thrombosis), and liquid-infused surfaces (LIS) are effective in reducing the thrombotic response. However, the mechanisms that underpin this performance, and in particular the role of the lubricant, are not well understood. In this work, it is investigated whether the mechanism of LIS action is related to i) inhibition of factor XII (FXII) activation and the contact pathway; ii) reduced fibrin density of clots formed on surfaces; iii) increased mobility of proteins or cells on the surface due to the interfacial flow of the lubricant.

The health digital twin to tackle cardiovascular disease-a review of an emerging interdisciplinary field.

Potential benefits of precision medicine in cardiovascular disease (CVD) include more accurate phenotyping of individual patients with the same condition or presentation, using multiple clinical, imaging, molecular and other variables to guide diagnosis and treatment. An approach to realising this potential is the digital twin concept, whereby a virtual representation of a patient is constructed and receives real-time updates of a range of data variables in order to predict disease and optimise treatment selection for the real-life patient. We explored the term digital twin, its defining concepts, the challenges as an emerging field, and potentially important applications in CVD.

The Role of Artificial Intelligence in Predicting Outcomes by Cardiovascular Magnetic Resonance: A Comprehensive Systematic Review.

Background and Objectives: Interest in artificial intelligence (AI) for outcome prediction has grown substantially in recent years. However, the prognostic role of AI using advanced cardiac magnetic resonance imaging (CMR) remains unclear. This systematic review assesses the existing literature on AI in CMR to predict outcomes in patients with cardiovascular disease.

IL11 Stimulates IL33 Expression and Proinflammatory Fibroblast Activation across Tissues.

Interleukin 11 (IL11) is upregulated in inflammatory conditions, where it is mostly believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 promotes inflammation by activating fibroblasts. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts.

Atrioventricular septal defect in Fontan circulation: Right ventricular dominance, not valve surgery, adversely affects survival.

Objective: The effect of ventricular dominance and previous atrioventricular valve (AVV) surgery on patient outcomes after Fontan operation remains unclear. We sought to determine the effect of ventricular dominance and previous AVV surgery on transplantation-free survival and long-term AVV competency in patients with atrioventricular septal defect (AVSD) and Fontan circulation.

Methods: We conducted a retrospective study of 1703 patients in the Australia and New Zealand Fontan Registry, who survived Fontan operation between 1987 and 2021.

Comparison of the modified Singapore myocardial infarction registry risk score with GRACE 2.0 in predicting 1-year acute myocardial infarction outcomes.

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an AMI risk score from the national-level Singapore Myocardial Infarction Registry (SMIR) confined to ST-segment elevation myocardial infarction (STEMI) patients and did not include non-STEMI (NSTEMI) patients.

IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR initiating a mesenchymal program in stromal, epithelial, and cancer cells.

IL11 initiates fibroblast activation but also causes epithelial cell dysfunction. The mechanisms underlying these processes are not known. We report that IL11-stimulated ERK/P90RSK activity causes the phosphorylation of LKB1 at S325 and S428, leading to its inactivation.

Clinical characteristics, treatment and long-term outcomes of patients with right-sided cardiac thrombus.

Objective: Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation (AF) and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries.

Changes in the CHADS-VAS score as a predictor of incident atrial fibrillation in older Chinese individuals: the AF-CATCH study.

Aims: Incidence of atrial fibrillation is highly associated with age and cardiovascular co-morbidities. Given this relationship, we hypothesized that the dynamic changes resulting in an increase in the CHADS-VAS score over time would improve the efficiency of predicting incident atrial fibrillation on repeated screening after a negative test.

Methods And Results: We investigated in an analysis of the AF-CATCH trial [quarterly vs.

Improving treatment for acute ischemic stroke-Clot busting innovation in the pipeline.

Acute ischemic stroke is a consequence of disrupted blood flow to the brain, caused by thrombosis-the pathological formation of occlusive clots within blood vessels, which can embolize distally to downstream tissues and microvasculature. The highest priority of stroke treatment is the rapid removal of occlusive clots and restoration of tissue perfusion. Intravenous thrombolysis is the pharmacological standard-of-care for the dissolution of blood clots, wherein thrombolytic drugs are administered to restore vessel patency.