Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Assessing the relationship between microwave vegetation optical depth and gross primary production

At the global scale, the uptake of atmospheric carbon dioxide by terrestrial ecosystems through photosynthesis is commonly estimated through vegetation indices or biophysical properties derived from optical remote sensing data. Microwave observations of vegetated areas are sensitive to different components of the vegetation layer than observations in the optical domain and may therefore provide complementary information on the vegetation state, which may be used in the estimation of Gross Primary Production (GPP). However, the relation between GPP and Vegetation Optical Depth (VOD), a biophysical quantity derived from microwave observations, is not yet known. This study aims to explore the relationship between VOD and GPP. VOD data were taken from different frequencies (L-, C-, and X-band) and from both active and passive microwave sensors, including the Advanced Scatterometer (ASCAT), the Soil Moisture Ocean Salinity (SMOS) mission, the Advanced Microwave Scanning Radiometer for Earth Observation System (AMSR-E) and a merged VOD data set from various passive microwave sensors. VOD data were compared against FLUXCOM GPP and Solar-Induced chlorophyll Fluorescence (SIF) from the Global Ozone Monitoring Experiment-2 (GOME-2). FLUXCOM GPP estimates are based on the upscaling of flux tower GPP observations using optical satellite data, while SIF observations present a measure of photosynthetic activity and are often used as a proxy for GPP. For relating VOD to GPP, three variables were analyzed: original VOD time series, temporal changes in VOD (ΔVOD), and positive changes in VOD (ΔVOD≥0). Results show widespread positive correlations between VOD and GPP with some negative correlations mainly occurring in dry and wet regions for active and passive VOD, respectively. Correlations between VOD and GPP were similar or higher than between VOD and SIF. When comparing the three variables for relating VOD to GPP, correlations with GPP were higher for the original VOD time series than for ΔVOD or ΔVOD≥0 in case of sparsely to moderately vegetated areas and evergreen forests, while the opposite was true for deciduous forests. Results suggest that original VOD time series should be used jointly with changes in VOD for the estimation of GPP across biomes, which may further benefit from combining active and passive VOD data

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Vztah vybranych klinickych a laboratornich rizikovych faktoru aterosklerozy k ultrazvukovym markerum casnych stadii aterosklerozy u dyslipidemickych jedincu.

The aims of this study were: the evaluation of relation between investigated risk factors and markers of atherosclerosis; laboratory, clinical and ultrasonographical markers of early atherosclerosis in two age and sex-adjusted middle-aged groups of healthy controls and group of hyperlipidemic patients and their comparison; association of particular laboratory and clinical factors with ultrasonographical parameters - right brachial artery flow mediated dilatation (FMD) and carotid artery intima-media thickness (IMT); reciprocal association of ultrasonographical markers or early atherosclerosis (FMD and IMT). In the study were enrolled 165 subjects - hyperlipidemic patients and healthy controls. We measured ultrasonographical markers of early atherosclerosis FMD and IMT, lipid risk factors of atherosclerosis, prothrombotic parameters, markers of oxidative stress, chronic systemic inflammation and insuline resistance syndrome. Significant correlations between the investigated laboratory and clinical parameters have been found suggesting their reciprocal association and pathogenic role.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Risk stratification using growth differentiation factor 15 in patients undergoing transcatheter aortic valve implantation

Aims. Growth differentiation factor 15 (GDF15) shows potential predictive value in various cardiac conditions. We investigated relationships between GDF15 and clinical or procedural outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) in order to propose clinically useful predictive risk stratification model. Methods. This prospective single-center registry enrolled 88 consecutive patients with severe symptomatic aortic stenosis treated with TAVI. Clinical parameters were collected and biomarkers including GDF-15 were measured within 24 h before TAVI. All relevant clinical outcomes according to the Valve Academic Research Consortium-2 were collected over the follow-up period. Results. The cohort included 52.3% of females. The mean age of study participants was 81 years; the mean Society of Thoracic Surgeons (STS) score and logistic EuroSCORE were 3.6% and 15.4%, respectively. The mortality over the entire follow-up period was 10.2%; no death was observed within the first 30 days following TAVI. Univariate analysis showed significant associations between GDF15 and mortality (P=0.0006), bleeding (P=0.0416) and acute kidney injury (P=0.0399). A standard multivariate logistic regression model showed GDF-15 as the only significant predictor of mortality (P=0.003); the odds ratio corresponding to an increase in GDF15 of 1000 pg/mL was 1.22. However, incremental predictive value was not observed when the STS score was combined with GDF15 in this predictive model. Conclusions. Based on our observations, preprocedural elevated GDF15 levels are associated with increased mortality and demonstrate their additional value in predicting adverse clinical outcomes in a TAVI population

Macitentan in pulmonary hypertension due to left ventricular dysfunction

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12, versus placebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1-0.7) L·min-1·m-2) and decrease in NT-proBNP (0.77 (0.55-1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentan versus placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo. Macitentan resulted in no significant changes in any exploratory end-points.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identifying potential sources of variability between vegetation carbon storage estimates for urban areas

understudied ecosystems. Research into urban ecosystem service provision is still an emerging field, yet evidence is accumulating rapidly to suggest that the biological carbon stores in cities are more substantial than previously assumed. However, as more vegetation carbon densities are derived, substantial variability between these estimates is becoming apparent. Here, we review procedural differences evident in the literature, which may be drivers of variation in carbon storage assessments. Additionally, we quantify the impact that some of these different approaches may have when extrapolating carbon figures derived from surveys up to a city-wide scale. To understand how/why carbon stocks vary within and between cities, researchers need to use more uniform methods to estimate stores and relate this quantitatively to standardised ‘urbanisation’ metrics, in order to facilitate comparisons

Macitentan in pulmonary hypertension due to left ventricular dysfunction

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12, versus placebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1-0.7) L·min-1·m-2) and decrease in NT-proBNP (0.77 (0.55-1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentan versus placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo. Macitentan resulted in no significant changes in any exploratory end-points.status: publishe

Ventricular septal rupture with hemodynamically important left-to-right shunt, right ventricular myocardial infarction, transient type III atrioventricular block and the development of left ventricular aneurysm as a complication of sub-acute myocardial infarction of the bottom wall accompanied by post-infarction unstable angina pectoris

AbstractVentricular septal rupture is a serious mechanical complication of myocardial infarction with important hemodynamic consequences. Without a rapid diagnosis and correction by surgical intervention, the short-term mortality of these patients is higher than 90%. We report the case of a patient with acute inferior myocardial infarction and a ventricular septal rupture with early diagnosis based on clinical examination and transthoracic echocardiography and postponed successful surgical correction