Right ventricular coupling predicts cardiopulmonary fitness in cardiac transthyretin amyloidosis.

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative disease leading to restrictive cardiomyopathy. We aimed to characterise exercise capacity in ATTRwt and to identify predictors of cardiopulmonary fitness, focusing on echocardiographic and clinical parameters.

Methods: We studied 110 ATTRwt patients from a prospective single-centre registry (2020-2024) by cardiopulmonary exercise testing (CPET).

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

Background: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice.

A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts.

Unlabelled: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings.

Spinal Stroke: Outcome Attenuation by Erythropoietin and Carbamylated Erythropoietin and Its Prediction by Sphingosine-1-Phosphate Serum Levels in Mice.

Spinal strokes may be associated with tremendous spinal cord injury. Erythropoietin (EPO) improves the neurological outcome of animals after spinal cord ischemia (SCI) and its effects on ischemia-induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are considered possible molecular mechanisms. Furthermore, sphingosin-1-phosphate (S1P) is suggested to correlate with SCI.

Protein Tyrosine Phosphatase 1B Deficiency in Vascular Smooth Muscle Cells Promotes Perivascular Fibrosis following Arterial Injury.

Background:  Smooth muscle cell (SMC) phenotype switching plays a central role during vascular remodeling. Growth factor receptors are negatively regulated by protein tyrosine phosphatases (PTPs), including its prototype PTP1B. Here, we examine how reduction of PTP1B in SMCs affects the vascular remodeling response to injury.

Enhancing Cardiomyocyte Transcription Using In Vivo CRISPR/Cas9 Systems.

Endogenous gene activation by programmable transcription factors offers gene-dose-dependent phenotyping of target cells embedded in their in vivo natural tissue environment. Modified CRISPR/Cas9 systems were developed to be used as guide (g) RNA programmable transcriptional activation platforms (CRISPRa) in vitro and in vivo allowing targeted or multiplexed gene activation studies. We specifically developed these tools to be applied in cardiomyocytes providing dCas9VPR expressing mice under the control of the Myosin heavy chain 6 (Myh6) promoter.

Real-Time Optical Mapping of Contracting Cardiac Tissues With GPU-Accelerated Numerical Motion Tracking.

Optical mapping of action potentials or calcium transients in contracting cardiac tissues are challenging because of the severe sensitivity of the measurements to motion. The measurements rely on the accurate numerical tracking and analysis of fluorescence changes emitted by the tissue as it moves, and inaccurate or no tracking can produce motion artifacts and lead to imprecise measurements that can prohibit the analysis of the data. Recently, it was demonstrated that numerical motion-tracking and -stabilization can effectively inhibit motion artifacts, allowing highly detailed simultaneous measurements of electrophysiological phenomena and tissue mechanics.

Effects of Apolipoprotein E polymorphism on carotid intima-media thickness, incident myocardial infarction and incident stroke.

The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20-79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.

Longitudinal association of Apolipoprotein E polymorphism with lipid profile, type 2 diabetes and metabolic syndrome: Results from a 15 year follow-up study.

Aims: To examine the association of different APOE alleles with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) as well as the influence of high-sensitive C-reactive protein (hs-CRP) on these associations.

Methods: We analyzed data from 3917 participants aged 20-81 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 10.8 years.

Patterned Illumination Techniques in Optogenetics: An Insight Into Decelerating Murine Hearts.

Much has been reported about optogenetic based cardiac arrhythmia treatment and the corresponding characterization of photostimulation parameters, but still, our capacity to interact with the underlying spatiotemporal excitation patterns relies mainly on electrical and/or pharmacological approaches. However, these well-established treatments have always been an object of somehow heated discussions. Though being acutely life-saving, they often come with potential side-effects leading to a decreased functionality of the complex cardiac system.

Chronic kidney disease and risk of atrial fibrillation and heart failure in general population-based cohorts: the BiomarCaRE project.

Aims: Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. The aim of this study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. We also included an assessment of baseline biomarkers of inflammation, myocardial injury, and left ventricular dysfunction with risk of AF and HF, respectively, to shed light on the potential underlying pathophysiology.

Periodontitis, dental plaque, and atrial fibrillation in the Hamburg City Health Study.

Background/aim: Atrial fibrillation (AF) is a major health problem and causes heart failure and stroke. Pathophysiological mechanisms indicate a link with oral health including periodontitis (PD), but supporting data are scarce. The aim was to investigate the link between features of oral health and the prevalence of AF.

Target Populations and Treatment Cost for Bempedoic Acid and PCSK9 Inhibitors: A Simulation Study in a Contemporary CAD Cohort.

Purpose: The lowered LDL-C treatment goal of the 2019 European Society of Cardiology dyslipidemia guidelines results in a significant increase in the projected need for cost-intensive proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Addition of bempedoic acid (BA) to established oral lipid-lowering medication (LLM) has the potential to enable affordable LDL-C goal attainment, particularly in patients with statin intolerance (SI). The goal of this study was to quantify the target populations for BA and PCSK9 inhibitors as well as the related treatment costs to achieve the LDL-C goal of <55 mg/dL and a ≥50% reduction assuming the addition of BA to LLM.

Research('s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy.

Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches.

A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression.

Depression constitutes a leading cause of disability worldwide. Despite extensive research on its interaction with psychobiological factors, associated pathways are far from being elucidated. Metabolomics, assessing the final products of complex biochemical reactions, has emerged as a valuable tool for exploring molecular pathways.

Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease.

New technologies have greatly shaped the scientific and medical landscape within the last years. The unprecedented expansion of data and information on RNA biology has led to the discovery of new RNA classes with unique functions and unexpected modifications. Today, the biggest challenge is to transfer the large number of findings in basic RNA biology into corresponding clinical RNA-based therapeutics.

Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population.

Background: Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) are associated with increased inflammation represented by elevated C-reactive protein (CRP) levels. Lifestyle changes may influence the inflammatory burden in patients with CAD, relevantly modifying the target population for emerging anti-inflammatory compounds.

Aims: The aims of this study were to analyse the association of modRF and CRP levels in CAD patients, and to define a potential target population for anti-inflammatory treatment with and without the optimisation of modRF.

MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening.

Patients with type 2 diabetes (T2D) are threatened by excessive cardiovascular morbidity and mortality. While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in T2D, specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The present translational study investigates the role of microRNA-29b (miR-29b) as a driver and therapeutic target of diabetic aortic remodeling and stiffening.

Hepatic steatosis and hepatic iron overload modify the association of iron markers with glucose metabolism disorders and metabolic syndrome.

Background: Iron status has been linked with impaired glucose metabolism (IGM), type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MetS), but the role of hepatic steatosis or iron overload on these associations remains uncertain.

Methods: We analysed data from 2310 participants without known T2DM of the population-based Study of Health in Pomerania (SHIP-TREND, Germany) through logistic regression models. We tested additive and multiplicative interactions between ferritin and hepatic steatosis or iron overload.

The need for PCSK9 inhibitors and associated treatment costs according to the 2019 ESC dyslipidaemia guidelines vs. the risk-based allocation algorithm of the 2017 ESC consensus statement: a simulation study in a contemporary CAD cohort.

Background: The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL for patients with atherosclerotic cardiovascular disease (ASCVD), with a concomitant Class IA upgrade for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients not reaching their LDL-C goal under conventional lipid-lowering therapy.

Aims: We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update.

Methods And Results: We included patients with ASCVD from an observational cohort study ongoing since 2015.

Cardiovascular risks of climate change.

Extreme heat events are now more frequent in many parts of the world as a result of climate change. The combined effects of heat, air pollution, individual age, and socioeconomic and health status are responsible for avoidable acute events of cardiovascular disease and need to be considered in order to prevent and treat cardiovascular diseases effectively.

Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project.

Background: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts.

MRI-Derived Radiomics Features of Hepatic Fat Predict Metabolic States in Individuals without Cardiovascular Disease.

Rationale And Objectives: To investigate radiomics features of hepatic fat as potential biomarkers of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) in individuals without overt cardiovascular disease, and benchmarking against hepatic proton density fat fraction (PDFF) and the body mass index (BMI).

Materials And Methods: This study collected liver radiomics features of 310 individuals that were part of a case-controlled imaging substudy embedded in a prospective cohort. Individuals had known T2DM (n = 39; 12.

High-Resolution Optical Measurement of Cardiac Restitution, Contraction, and Fibrillation Dynamics in Beating vs. Blebbistatin-Uncoupled Isolated Rabbit Hearts.

Optical mapping is a high-resolution fluorescence imaging technique, that uses voltage- or calcium-sensitive dyes to visualize electrical excitation waves on the heart surface. However, optical mapping is very susceptible to the motion of cardiac tissue, which results in so-called in the fluorescence signal. To avoid motion artifacts, contractions of the heart muscle are typically suppressed using pharmacological excitation-contraction uncoupling agents, such as Blebbistatin.