Cardiac Magnetic Resonance Imaging in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by left ventricular diastolic dysfunction, elevated filling pressures, and normal ejection fraction (left ventricular ejection fraction ≥50%) in the absence of an underlying disease process. Its prevalence is increasing, driven by an aging population and rising comorbidities including obesity, diabetes, and hypertension. Given the benefit of emerging HFpEF therapies, such as glucagon-like peptide-1 inhibitors, early and accurate diagnosis is critical to improve outcomes.

Omadacycline exhibits anti-inflammatory properties and improves survival in a murine model of post-influenza MRSA pneumonia.

Post-influenza pneumonia, particularly methicillin-resistant (MRSA), remains a major cause of mortality, highlighting the urgent need for newer therapeutic options. Omadacycline is an aminomethylcycline antibiotic that has demonstrated efficacy against MRSA across many infection models, but its potential in post-influenza A virus (IAV)-MRSA pneumonia remains unexplored. Using a murine model of this infection, we evaluated the effects of omadacycline and a comparator antibiotic, linezolid, on survival, inflammation, bacterial load, toxin production, and lung histopathology.

A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways.

Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These interactions result in a highly interconnected network of enzymes and pathways, known as the sphingolipidome.

Sonomyography-Based Proportional Control For Isokinetic Movements: A Comparative Analysis Of Features And Algorithms.

Sonomyography is a technique that uses ultrasound imaging to measure muscle activity. Unlike traditional methods, sonomyography allows for real-time imaging of deeper muscles. Recent research has focused on developing wearable ultrasound devices to enable real-time muscle activity sensing, specifically for applications in proportional control systems.

Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography and for Heart Failure With Preserved Ejection Fraction Diagnosis: An Update From the American Society of Echocardiography.

Echocardiographic assessment of left ventricular (LV) diastolic function is an integral part of the routine evaluation of patients presenting with symptoms of dyspnea or clinical concerns for heart failure. Given the presence of diastolic dysfunction in many cardiovascular diseases, clinical reports should include comments on diastolic function and/or left atrial (LA) pressure whenever possible. Since the publication of the 2016 ASE/EACVI guidelines for assessment of LV diastolic function, new data on additional echocardiographic variables as left atrial strain and their association with LV filling pressures have emerged.

HSV1 glycoprotein D utilizes an LY6-like binding domain to inhibit alpha7 nicotinic receptors.

Herpes virus1(HSV1) is a neurotropic virus that has been linked to Alzheimer's disease. An In-silico structural homology search using α -Bgtx, identified structural homology between HSV1 gD and the nicotinic receptor neurotoxin α-Bgtx. SPR binding studies using acetylcholine binding protein from Lymnaea stagnalis, and functional two electrode voltage clamp studies of α7 nAChRs demonstrate the ability of HSV1 to interact directly with nAChRs.

Innovations in Cancer Immunotherapy Drug Delivery Technologies: A Systematic Review.

An innovative method in oncology, cancer immunotherapy uses the body's immune system to fight cancer cells. Despite its potential, nonspecific inflammation and autoimmunity provide major obstacles to the clinical implementation of immunotherapy. The goal of recent developments in medication delivery technology was to improve these treatments' effectiveness and safety.

ATP-Citrate Lyase Supports Cardiac Function and NAD/NADH Balance and Is Depressed in Human Failing Myocardium.

ATP-citrate lyase (ACLY) regulates lipogenesis and cell proliferation, and forms a cytosolic TCA-bypass circuit impacting NADH. We show that acute and chronic ACLY inhibition in cardiomyocytes depresses the NAD/NADH ratio by increasing mitochondrial NADH. Acute suppression causes dose-dependent cytotoxicity, but at low doses augments aerobic respiration without impeding myocyte function.

Understanding preservation time thresholds in the modern era of heart transplantation.

A 4-h preservation time threshold for cardiac allografts is the current standard in heart transplantation, but novel technologies are proposed to decrease the morbidity associated with prolonged allograft storage. This study examined adult heart transplant recipients from 2000-2015 and 2020-2023 in the United States, stratified into an early (2000-2015) and modern era (2020-2023), then into standard (≤ 4 h) and prolonged (≥ 5 h) preservation time groups within each era. This study reinforced the 4-h threshold in the early era, where prolonged preservation significantly increased one-year mortality (HR 1.

Reduced dosing of lenvatinib with pembrolizumab for advanced endometrial cancer.

Objective: Evaluate safety and effectiveness of reduced lenvatinib doses with pembrolizumab in patients with mismatch repair-proficient (MMRp) advanced endometrial cancer.

Methods: In this retrospective cohort study of lenvatinib-pembrolizumab combination therapy, patients were grouped based on initial lenvatinib dose: 20 mg daily (Group 1), less than 20 mg daily (Group 2), and 20 mg daily five days per week (Group 3). The primary outcome was six-month progression-free survival (PFS-6); safety outcomes included incidences of lenvatinib dose discontinuation or reduction due to adverse events (AEs).

Single cell transcriptomic analyses of human heart failure with preserved ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a poorly understood, multi-system disease with high morbidity and mortality. To improve our understanding of its underlying biology, we used single-nucleus RNA sequencing (snRNA-seq) to characterize cell-specific gene expression patterns in human HFpEF myocardium.

Methods: Septal myocardial biopsies (2-3 mg) from 30 HFpEF patients and 29 non-failing donor controls were analyzed using the 10X Genomics platform, with nuclei isolated from combined samples (6 patients/pool).

Myocardial Proteome in Human Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF but has few effective therapies. Recent human myocardial transcriptomics and metabolomics have identified major differences between HFpEF and controls. How this translates at the protein level is unknown.

Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial.

Importance: Excess body fat plays a pivotal role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss.

Objective: To assess efficacy and safety of HU6 in reducing body weight, improving peak volume of oxygen consumption (VO2) and body composition among patients with obesity-related HFpEF.

In-Hospital or Out-of-Hospital Initiation of Sacubitril/Valsartan Versus Valsartan in Patients With Mildly Reduced or Preserved Ejection Fraction After A Worsening Heart Failure Event: The PARAGLIDE-HF Trial.

Background: Efficacy and tolerability of sacubitril/valsartan (Sac/Val) is not well characterized in heart failure (HF) with ejection fraction >40% initiated in-hospital. Thus, this prespecified PARAGLIDE-HF (Prospective Comparison of ARNI With ARB Given Following Stabilization In Decompensated HFpEF) analysis assessed the effects of Sac/Val versus valsartan (Val) by location of initiation in HF with ejection fraction >40% and recent worsening HF.

Methods And Results: This analysis of the double-blind, randomized controlled trial assessed patients by in-hospital and out-of-hospital (≤30 days of worsening HF) initiation.

Optimizing Micro and Macro Nutrients: Navigating Weight Loss Success and Health Risks in Bariatric Surgery for Obesity Management.

Unhealthy weight with high body mass index is recognized as markers for chronic disease. Despite the array of multiple weight loss medications, bariatric surgery (BS) remains as a recognized efficient pathway to achieve rather quick and sustainable weight loss. Despite its effectiveness, BS comes with its own plethora of complications.

Monocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.

Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1, which functionally activates TGF-β to cause vascular disease.

Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting.

Background: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards.

Methods: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Sacubitril/valsartan versus valsartan initiation in patients naïve to renin-angiotensin system inhibitors: Insights from PARAGLIDE-HF.

Aims: Whether prior treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) modifies efficacy and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure (HF) and ejection fraction (EF) >40% is unclear, thus Sac/Val according to ACEi/ARB status at baseline was assessed.

Methods And Results: This was a pre-specified analysis of Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE-HF), a double-blind, randomized controlled trial of Sac/Val versus valsartan, categorizing patients according to baseline ACEi/ARB status. The primary endpoint was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8.

Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE-HF and PRESERVED-HF.

Aims: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).

Can we diagnose aortic arch obstruction in a fetus with an atrioventricular septal defect?

Background: Aortic arch obstruction and/or coarctation of aorta is uncommon (5-20%) in balanced atrioventricular septal defects. Although technically challenging, prenatal diagnosis of aortic arch obstruction in atrioventricular septal defect is critical for delivery planning and improves prenatal counselling regarding the timing of cardiac surgery. We sought to identify prenatal predictors of coarctation of aorta in atrioventricular septal defect.

Coronary Artery Calcium for Risk Stratification of Heart Failure Mortality: The Coronary Artery Calcium Consortium.

Background: There is increasing interest in predicting heart failure (HF), a major cause of morbidity and mortality with a significant financial burden. The role of coronary artery calcium (CAC), an accessible and inexpensive test, in predicting long-term HF mortality among asymptomatic adults remains unknown. We aimed to determine whether CAC burden is associated with HF-related mortality in the CAC Consortium.