Mineralocorticoid receptor (MR) antagonist eplerenone and MR modulator balcinrenone prevent renal extracellular matrix remodeling and inflammation via the MR/proteoglycan/TLR4 pathway.

Excessive activation of the mineralocorticoid receptor (MR) is implicated in cardiovascular and renal disease. Decreasing MR activation with MR antagonists (MRA) is effective to slow chronic kidney disease (CKD) progression and its cardiovascular comorbidities in animal models and patients. The present study evaluates the effects of the MR modulator balcinrenone and the MRA eplerenone on kidney damage in a metabolic CKD mouse model combining nephron reduction and a 60% high-fat diet.

Time from admission to randomization and the effect of empagliflozin in acute heart failure: A post-hoc analysis from EMPULSE.

Aims: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization.

Circulating beta-hydroxybutyrate levels in advanced heart failure with reduced ejection fraction: Determinants and prognostic impact.

Aims: Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF).

Methods And Results: A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383).

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease.

Background: The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes.

Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intrapatient Comparison of 3 Diuretic Regimens (DEA-HF).

Background: Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients.

Objectives: The authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients.

Methods: A prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit.

Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Impaired Renal Function.

Background: Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy.

Objectives: This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction.

Methods: We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD.

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis.

The cerebral and cardiac effects of Norepinephrine in an experimental cardiac arrest model.

Introduction: Epinephrine has been the main drug recommended for decades during cardiopulmonary resuscitation (CPR). But epinephrine's ß-adrenergic effects might increase myocardial oxygen consumption and may cause arrythmias after ROSC. Norepinephrine has a weaker ß-adrenergic effect and could be useful during CPR.

Insulin-like growth factor binding protein-7 concentrations in chronic heart failure: Results from the EMPEROR programme.

Aims: Insulin-like growth factor binding protein-7 (IGFBP7) is a biomarker of tissue senescence with a role in cardio-renal pathophysiology. The role of IGFBP7 as a prognostic biomarker across the full ejection fraction (EF) spectrum of heart failure (HF) remains less well understood. We examined associations between IGFBP7 and risk of cardio-renal outcomes regardless of EF and the effect of empagliflozin treatment on IGFBP7 concentrations among individuals with HF.

Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR-Pooled analysis.

Aim: To assess the effect of empagliflozin on patients with comorbid heart failure (HF) and diabetes with or without baseline insulin, and to study the impact of empagliflozin on insulin requirements over time.

Materials And Methods: We performed a post-hoc analysis of pooled patient-level data from two cardiovascular outcomes trials of empagliflozin in HF (EMPEROR-Reduced and EMPEROR-Preserved trials). We undertook a subgroup analysis stratified by baseline insulin use, including all patients with diabetes.

Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort.

Aims: High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables.

Methods And Results: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m).

Empagliflozin and risk of lower respiratory tract infection in heart failure with mildly reduced and preserved ejection fraction: An EMPEROR-Preserved analysis.

Aims: Lower respiratory tract infections (LRTI) are common worldwide. Patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high risk of developing LRTI. Prior studies were able to show that sodium-glucose cotransporter 2 inhibitors may reduce the incidence of LRTI in patients with type 2 diabetes.

Carbohydrate antigen 125 concentrations across the ejection fraction spectrum in chronic heart failure: The EMPEROR programme.

Aim: Vascular congestion may lead to an increase of carbohydrate antigen 125 (CA-125). The role of CA-125 as a biomarker of congestion or for prognosis across the full ejection fraction (EF) spectrum of chronic heart failure (HF) remains unknown.

Methods And Results: Serum CA-125 was measured in 1111 study participants from the EMPEROR-Reduced and EMPEROR-Preserved trials.

Untreated Allergy Among Middle School Students: Associations with Socioeconomic Adversities and Academic, Behavior, and Health Difficulties.

Background: Many adolescents with allergy do not receive physician treatment (allergy). We explored its association with socioeconomic adversities and academic-behavior-health difficulties, which remain unaddressed.

Methods: This cross-sectional school-based-population study compared the above factors of middle-school adolescents with allergy and those with treated allergy (allergy) (mean age = 13.

Comparison of interleukin-6 and high-sensitivity C-reactive protein for cardiovascular risk assessment: Findings from the MESA study.

Background And Aims: Inflammation is a risk factor for major adverse cardiovascular events (MACE). Elevated levels of both high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL6) have been associated with MACE. However, few studies have compared IL6 to hsCRP for cardiovascular risk assessment.

Associations between excessive screen time and school and out-of-school injuries among adolescents: A population-based study.

Most adolescents spend excessive screen time (with television viewing, computer/console gaming, discussion forums/chatting online, internet surfing, doing homework, and electronic mails) which may impact the occurring of various types of school and out-of-school injuries. We assessed their associations and potential confounding factors among 1559 middle-school students from north-eastern France (mean age=13.5 ± 1.