433 Regression analysis of mortality data from the EPHESUS trial reveals significantly higher risk of death for patients with non‐ST segment elevation myocardial infarction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106689/1/ehfs60288-x.pd

MicroRNA-24 regulates vascularity after myocardial infarction

BACKGROUND: Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. METHODS AND RESULTS: Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2-associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. CONCLUSIONS: Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease. [KEYWORDS: Animals, Apoptosis/drug effects, Arterioles/pathology, Capillaries/pathology, Cell Hypoxia, Cells, Cultured/drug effects/metabolism, Collagen, Drug Combinations, Drug Evaluation, Preclinical, Endothelial Cells/ metabolism/pathology, GATA2 Transcription Factor/biosynthesis/genetics, Gene Expression Profiling, Heart Failure/etiology, Heme Oxygenase-1/biosynthesis/genetics, Laminin, Male, Mice, Mice, Inbred C57BL, MicroRNAs/antagonists & inhibitors/genetics/ physiology, Myocardial Infarc

Energy efficient plasma processing of industrial wastes

The paper presents the results of thermodynamic modeling of the process of joint plasma treatment of non-combustible and combustible industrial wastes. The compositions of water-salt-organic compositions based on these wastes and regimes providing their energy-efficient joint treatment in air plasma have been determined

Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies

Most patients survive acute myocardial infarction (MI). Yet this encouraging development has certain drawbacks: heart failure (HF) prevalence is increasing and patients affected tend to have more comorbidities worsening economic strain on healthcare systems and impeding effective medical management. The heart's pathological changes in structure and/or function, termed myocardial remodelling, significantly impact on patient outcomes. Risk factors like diabetes, chronic obstructive pulmonary disease, female sex, and others distinctly shape disease progression on the 'road to HF'. Despite the availability of HF drugs that interact with general pathways involved in myocardial remodelling, targeted drugs remain absent, and patient risk stratification is poor. Hence, in this review, we highlight the pathophysiological basis, current diagnostic methods and available treatments for cardiac remodelling following MI. We further aim to provide a roadmap for developing improved risk stratification and novel medical and interventional therapies

Deep vein thrombosis in Europe—health-related quality of life and mortality

Objectives: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. Methods: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL—as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)—was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. Results: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). Conclusions: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT

Monitoring cardiac fibrosis: a technical challenge

The heart contains a collagen network that contributes to the contractility of the heart and provides cardiac strength. In cardiac diseases, an increase in collagen deposition is often observed. This fibrosis formation causes systolic and diastolic dysfunction, and plays a major role in the arrythmogenic substrate. Therefore, accurate detection of cardiac fibrosis and its progression is of clinical importance with regard to diagnostics and therapy for patients with cardiac disease. To evaluate cardiac collagen deposition, both invasive and non-invasive techniques are used. In this review the different techniques that are currently used in clinical and experimental setting are summarised, and the advantages and disadvantages of these techniques are discussed

ESC core curriculum for the general cardiologist (2013)

[No abstract available

Sex-Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD.

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex-based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low-dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74-1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00-1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P-interaction=0.22), unplanned index limb revascularization (P-interaction=0.64), and bleeding (P-interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03-1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex-based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216

Influence of palaeoweathering on trace metal concentrations and environmental proxies in black shales

The mineralogical and chemical compositions of Lower Carboniferous (Tournaisian) marine black shale from the Kowala quarry, the Holy Cross Mountains, Poland, were investigated. This study focuses on disturbances in palaeoenvironmental proxies caused by palaeoweathering, which progressively changed the major and trace element abundances. Palaeomagnetic investigations reveal that the Devonian – Carboniferous succession was weathered during the Permian-Triassic by the infiltration of oxidizing fluids related to karstification following post-Variscan exhumation. The weathering process led to vermiculitization of chlorite, partial dissolution of calcite and replacement of pyrite by hematite and goethite. Moreover, the concentrations of some trace metals, including Co, Cu, Pb, Mo, Ni, As and U, significantly decreased. Consequently, some elemental abundance ratios that are used as environmental proxies, including U/Th, Ni/Co and V/Cr, were altered. Elements that are bound to iron sulphides (e.g., Mo) appear to be especially prone to mobilization by even a lightly weathered black shale. The documented weathering, including changes in elemental concentrations, can potentially create misinterpretations of the original palaeoenvironmental conditions. In addition, the palaeoweathering of the studied samples appears to have substantially changed the carbon, oxygen, nitrogen and molybdenum stable isotope values. The nitrogen and molybdenum stable isotope ratios, in particular, appear to be most sensitive to the effects of weathering and therefore are good indicators of (palaeo)weathering processes. The major cause of these changes is the decay of organic matter and pyrite. For the organic carbon stable isotopes ratios, the main factor that controlls this process appears to be the preferential degradation of labile organic matter. A combination of the total organic carbon (TOC), total sulphur (TS) content, Mo concentration and stable isotope compositions seems to be the most useful for identify (palaeo)weathering. Our results suggest that reductions in TS and Mo in tandem with diminished Mo stable isotope values in the absence of obvious changes to the TOC content provide the most compelling evidence of (palaeo)weathering