Targeting RUNX1 in Macrophages Facilitates Cardiac Recovery.

Despite advances in disease treatment, our understanding of how damaged organs recover and the mechanisms governing this process remain poorly defined. Here, we mapped the transcriptional and regulatory landscape of human cardiac recovery using single cell multiomics. Macrophages emerged as the most reprogrammed cell type.

Glycemic therapies and the risk of gastrointestinal adverse events in veterans with type 2 diabetes.

Aims: To compare the risk of gastrointestinal adverse events in new users of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and insulin glargine.

Materials And Methods: We conducted an active comparator, new user design study in veterans with type 2 diabetes who initiated one of these drug classes between 1 January 2018 and 31 December 2021 (N = 141 080). Inverse probability weighted Cox regression models were used to relate drug class to outcomes of gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis and all-cause death.

Single cell multiomics and 3D genome architecture reveal novel pathways of human heart failure.

Heart failure is a leading cause of morbidity and mortality; yet gene regulatory mechanisms driving cell type-specific pathologic responses remain undefined. Here, we present the cell type-resolved transcriptomes, chromatin accessibility, histone modifications and chromatin organization of 36 non-failing and failing human hearts profiled from 776,479 cells spanning all cardiac chambers. Integrative analyses revealed dynamic changes in cell type composition, gene regulatory programs and chromatin organization, which expanded the annotation of cardiac -regulatory sequences by ten-fold and mapped cell type-specific enhancer-gene interactions.

Left Atrial Reverse Remodeling in Patients Supported With Durable Left Ventricular Assist Devices and Clinical Implications.

Background: The left atrium (LA) maintains a dynamic interaction with the left ventricle (LV). LA forward and reverse remodeling affect prognosis in patients with chronic heart failure. We examined LA reverse remodeling in patients supported with LV assist devices (LVADs) and investigated a potential impact on clinical outcomes.

The role of sphingolipids in heart failure.

Advanced heart failure (HF) is characterized by changes in the structure, function, and metabolism of cardiac muscle. As the disease progresses, cardiomyocytes shift their ATP production from fatty acid oxidation to glycolysis. This shift results in an accumulation of lipid metabolites, particularly sphingolipids, which can disrupt normal cellular function and contribute to cardiac dysfunction.

Application of the Updated Cardiogenic Shock Working Group SCAI Classification for Cardiogenic Shock: A Single-Centre Analysis.

Background: In 2019, the Society for Cardiovascular Angiography and Interventions (SCAI) proposed an algorithm to assess cardiogenic shock (CS) severity, known as SCAI classification. In 2022, the Cardiogenic Shock Working Group (CSWG) modified the original classification using specific parameters to better define hypotension and hypoperfusion with the goal to further refine stratification.

Methods: Consecutive patients with CS who were managed at a quaternary academic medical centre from May 2015 to December 2021 were evaluated (N = 1162).

Hospital costs associated with mechanical left ventricular mechanical unloading devices during VA ECMO for adult cardiogenic shock.

Importance: No works to-date have described the financial burden and behaviors of left ventricular mechanical unloading (LVMU) for patients on veno-arterial extracorporeal membrane oxygenation (VA ECMO). Given the uptrending use of VA ECMO, describing its associated cost is essential for its continued uptake.

Objective: We describe the inpatient costs of patients who were managed with ECMO for cardiogenic shock (CS) with and without LVMU.

Peroxisome proliferator-activated receptor gamma ( )-mediated myocardial salvage in acute myocardial infarction managed with left ventricular unloading and coronary reperfusion.

Ischemic heart disease and acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Improvements have been made in coronary interventions to restore blood flow, but ischemia/reperfusion (I/R) injury significantly impacts clinical outcomes. We previously reported that activation of percutaneous mechanical unloading of the left ventricle (LV) with a transvalvular axial-flow device simultaneously with reperfusion improves myocardial salvage.

Informing Management of Patients Developing Cardiogenic Shock at a Spoke and Being Transferred to a Hub.

Background: Multidisciplinary teams and regionalized care systems have been suggested to improve cardiogenic shock (CS) outcomes. We sought to identify clinical factors associated with successful outcomes for patients developing CS at an outside healthcare facility (spoke) and being transferred to a quaternary medical center (hub).

Methods And Results: Consecutive patients with CS were evaluated (N=1162).

Recognition of the Large Ambulatory C2D Stage of Advanced Heart Failure-A Call to Action.

Importance: The advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood.

Comparative effectiveness of insulin glargine, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in veterans with type 2 diabetes.

Aims: To compare the risk of all-cause death and cardiovascular events in new users of insulin glargine, glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR).

Materials And Methods: We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP-1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023.

Advanced Markers for Hemodynamic Monitoring in Cardiogenic Shock and End-Stage Heart Failure: A Mini Review.

Right heart catheterization (RHC) provides critical hemodynamic insights by measuring atrial, ventricular, and pulmonary artery pressures, as well as cardiac output (CO). Although the use of RHC has decreased, its application has been linked to improved outcomes. Advanced hemodynamic markers such as cardiac power output (CPO), aortic pulsatility index (API), pulmonary artery pulsatility index (PAPi), right atrial pressure to pulmonary capillary wedge pressure ratio (RAP/PCWP) and right ventricular stroke work index (RVSWI) have been introduced to enhance risk stratification in cardiogenic shock (CS) and end-stage heart failure (HF) patients.

Cardiac Recovery: Webcast September 24 2024.

This 61-minute webcast features a conversation about "Cardiac Recovery"-the focus of Issue 20.4. Led by the issue's editors, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs.

Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice. Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter.

Amyloid-beta metabolism in age-related neurocardiovascular diseases.

Epidemiological evidence suggests the presence of common risk factors for the development and prognosis of both cardio- and cerebrovascular diseases, including stroke, Alzheimer's disease, vascular dementia, heart, and peripheral vascular diseases. Accumulation of harmful blood signals may induce organotypic endothelial dysfunction affecting blood-brain barrier function and vascular health in age-related diseases. Genetic-, age-, lifestyle- or cardiovascular therapy-associated imbalance of amyloid-beta (Aβ) peptide metabolism in the brain and periphery may be the missing link between age-related neurocardiovascular diseases.

Direct procurement with machine perfusion and normothermic regional perfusion in donation after circulatory death heart transplantation.

Background: Donation after circulatory death (DCD) heart transplants have increased in the United States with direct procurement with machine perfusion (DPP) and thoracoabdominal normothermic regional perfusion (TA-NRP) techniques. There remains a paucity of data examining DPP and TA-NRP outcomes. The purpose of this study was to investigate the impact of the DCD technique on post-transplant outcomes compared to donation after brain death (DBD) donors.

Cost-Effectiveness of a Shock Team Approach in Refractory Cardiogenic Shock.

Background: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care.

Methods: We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018.

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.

Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC).