Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Preserved.

Aims: Renal function (estimated glomerular filtration rate [eGFR]) changes early after the introduction of empagliflozin have not been described in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to describe early eGFR changes, assess its determinants and its clinical impact on cardiovascular and renal outcomes in patients with HFpEF enrolled in EMPEROR-Preserved.

Methods And Results: Estimated glomerular filtration rate changes (absolute and relative) from randomization to week 4 were calculated and landmark analyses performed.

Determinants and reference values of the 6-min walk distance in the general population-results of the population-based STAAB cohort study.

Aims: The 6-min walk test is an inexpensive, safe, and easy tool to assess functional capacity in patients with cardiopulmonary diseases including heart failure (HF). There is a lack of reference values, which are a prerequisite for the interpretation of test results in patients. Furthermore, determinants independent of the respective disease need to be considered when interpreting the 6-min walk distance (6MWD).

Extracellular Matrix Protein-1 as a Mediator of Inflammation-Induced Fibrosis After Myocardial Infarction.

Irreversible fibrosis is a hallmark of myocardial infarction (MI) and heart failure. Extracellular matrix protein-1 (ECM-1) is up-regulated in these hearts, localized to fibrotic, inflammatory, and perivascular areas. ECM-1 originates predominantly from fibroblasts, macrophages, and pericytes/vascular cells in uninjured human and mouse hearts, and from M1 and M2 macrophages and myofibroblasts after MI.

Safety and Tolerability of SGLT2 Inhibitors in Cardiac Amyloidosis-A Clinical Feasibility Study.

Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis.

Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies.

Background: Fibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking.

Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes.

Background: Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy.

Generation of an RBM20-mutation-associated left-ventricular non-compaction cardiomyopathy iPSC line (UMGi255-A) into a DCM genetic background to investigate monogenetic cardiomyopathies.

RBM20 mutations account for 3 % of genetic cardiomypathies and manifest with high penetrance and arrhythmogenic effects. Numerous mutations in the conserved RS domain have been described as causing dilated cardiomyopathy (DCM), whereas a particular mutation (p.R634L) drives development of a different cardiac phenotype: left-ventricular non-compaction cardiomyopathy.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression.

Background And Objective: Major depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD.

Sex- and age-related differences in the inflammatory properties of cardiac fibroblasts: impact on the cardiosplenic axis and cardiac fibrosis.

Background: Age and sex are prominent risk factors for heart failure and determinants of structural and functional changes of the heart. Cardiac fibroblasts (cFB) are beyond their task as extracellular matrix-producing cells further recognized as inflammation-supporting cells. The present study aimed to evaluate the impact of sex and age on the inflammatory potential of cFB and its impact on the cardiosplenic axis and cardiac fibrosis.

Impact of the COVID-19 pandemic on implementation of novel guideline-directed medical therapies for heart failure in Germany: a nationwide retrospective analysis.

Background: Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period.

Methods: The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance.

Vasoregulatory Autoantibodies and Clinical Outcome After Ischemic Stroke-PROSCIS-B.

Background: Vasoregulatory autoantibodies including autoantibodies targeting G-protein-coupled receptors might play a functional role in vascular diseases. We investigated the impact of vasoregulatory autoantibodies on clinical outcome after ischemic stroke.

Methods And Results: Data were used from the PROSCIS-B (Prospective Cohort With Incident Stroke-Berlin).

Generation of a CRISPR/Cas9-edited Plakoglobin (JUP) knock-out (JMUi001-A-4) iPSC line to model the cardiac phenotype of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) represents the cardiac phenotype of Naxos disease, an autosomal recessive disease with an additional cutaneous phenotype. ACM is mainly caused by mutated desmosomal proteins, which are part of cardiac adherens junctions and provide mechanical and electrical stability. Here, we generated a knock-out (KO) of the junctional protein Plakoglobin (JUP-KO; JMUi001-A-4) using the CRISPR/Cas9 system in healthy control induced pluripotent stem cells (iPSCs, (JMUi001-A).

Multimorbidity in patients with acute heart failure across world regions and country income levels (REPORT-HF): a prospective, multicentre, global cohort study.

Background: Multimorbidity (two or more comorbidities) is common among patients with acute heart failure, but comprehensive global information on its prevalence and clinical consequences across different world regions and income levels is scarce. This study aimed to investigate the prevalence of multimorbidity and its effect on pharmacotherapy and prognosis in participants of the REPORT-HF study.

Methods: REPORT-HF was a prospective, multicentre, global cohort study that enrolled adults (aged ≥18 years) admitted to hospital with a primary diagnosis of acute heart failure from 358 hospitals in 44 countries on six continents.

Effect of Dialysate and Plasma Sodium on Mortality in a Global Historical Hemodialysis Cohort.

Significance Statement: This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance hemodialysis patients. Using a large multinational cohort of 68,196 patients, we found that lower dialysate sodium concentrations (≤138 mmol/L) were independently associated with higher mortality compared with higher dialysate sodium concentrations (>138 mmol/L). The risk of death was lower among patients exposed to higher dialysate sodium concentrations, regardless of plasma sodium levels.

Activation of the integrated stress response rewires cardiac metabolism in Barth syndrome.

Barth Syndrome (BTHS) is an inherited cardiomyopathy caused by defects in the mitochondrial transacylase TAFAZZIN (Taz), required for the synthesis of the phospholipid cardiolipin. BTHS is characterized by heart failure, increased propensity for arrhythmias and a blunted inotropic reserve. Defects in Ca-induced Krebs cycle activation contribute to these functional defects, but despite oxidation of pyridine nucleotides, no oxidative stress developed in the heart.

Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming.

T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells.

Obesity and its comorbidities, current treatment options and future perspectives: Challenging bariatric surgery?

Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy and safety. This article provides a comprehensive overview of obesity and its comorbidities, with a special focus on organ-specific pathomechanisms.

Circulating miR-133a-3p defines a low-risk subphenotype in patients with heart failure and central sleep apnea: a decision tree machine learning approach.

Background: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes.

Objective: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA.

Methods: The study included patients with HFrEF and CSA from the SERVE-HF trial.

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized.