Dopamine is associated with the worst outcome among inotropes used in acute heart failure: observations from the ESC-HF-LT registry

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Discovery of a Giant Lyα Emitter Near the Reionization Epoch

‘In these times, during the rise in the popularity of institutional repositories, the Society does not forbid authors from depositing their work in such repositories. However, the AAS regards the deposit of scholarly work in such repositories to be a decision of the individual scholar, as long as the individual's actions respect the diligence of the journals and their reviewers.’ Original article can be found at : http://iopscience.iop.org/ Copyright American Astronomical SocietyWe report the discovery of a giant Lyα emitter (LAE) with a Spitzer/Infrared Array Camera (IRAC) counterpart near the reionization epoch at z = 6.595. The giant LAE is found from the extensive 1 deg2 Subaru narrowband survey for z = 6.6 LAEs in the Subaru/XMM-Newton Deep Survey (SXDS) field, and subsequently identified by deep spectroscopy of Keck/DEIMOS and Magellan/IMACS. Among our 207 LAE candidates, this LAE is not only the brightest narrowband object with L(Lyα) = 3.9 ± 0.2 × 1043 erg s–1 in our survey volume of 106 Mpc3, but also a spatially extended Lyα nebula with the largest isophotal area whose major axis is at least 3''. This object is more likely to be a large Lyα nebula with a size of 17 kpc than to be a strongly lensed galaxy by a foreground object. Our Keck spectrum with medium-high spectral and spatial resolutions suggests that the velocity width is v FWHM = 251 ± 21 km s–1, and that the line-center velocity changes by 60 km s–1 in a 10 kpc range. The stellar mass and star formation rate are estimated to be 0.9-5.0 × 1010 M and >34 M yr–1, respectively, from the combination of deep optical to infrared images of Subaru, UKIDSS-Ultra Deep Survey, and Spitzer/IRAC. Although the nature of this object is not yet clearly understood, this could be an important object for studying cooling clouds accreting onto a massive halo, or forming-massive galaxies with significant outflows contributing to cosmic reionization and metal enrichment of intergalactic medium.Peer reviewe

Long‐term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long‐Term Registry

[Abstract] Aims. The aim of this study was to assess long‐term safety of intravenous cardiovascular agents—vasodilators, inotropes and/or vasopressors—in acute heart failure (AHF). Methods and results. The European Society of Cardiology Heart Failure Long‐Term (ESC‐HF‐LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long‐term all‐cause mortality. Main secondary endpoints were in‐hospital and post‐discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long‐term mortality [HR 0.784, 95% confidence interval (CI) 0.596–1.032] nor in‐hospital mortality (HR 1.049, 95% CI 0.592–1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long‐term all‐cause mortality (HR 1.434, 95% CI 1.128–1.823), as well as in‐hospital mortality (HR 1.873, 95% CI 1.151–3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long‐term mortality in patients discharged alive (HR 1.078, 95% CI 0.769–1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031–2.572 vs. no inotropes). Conclusions. Vasodilators did not demonstrate any association with long‐term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all‐cause death, mostly related to excess of in‐hospital mortality in AHF

A Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Improves Endothelial Function and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E–Deficient Mice

ObjectivesThe aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS).BackgroundThe new class of anti–type 2 diabetes drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1.MethodsEndothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic rings and atherosclerotic lesion development in the entire aorta in apolipoprotein E–deficient mice fed a high-fat diet with or without DFS, and the antiatherogenic effects of DFS were investigated in cultured human macrophages and endothelial cells. Plasma levels of active GLP-1 were measured in patients with or without coronary artery disease.ResultsDFS significantly improved endothelial dysfunction (89.9 ± 3.9% vs. 79.2 ± 4.3% relaxation at 10−4 mol/l acetylcholine, p < 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% [15.6% to 25.8%] vs. 24.6% [19.3% to 34.6%], p < 0.01) compared with vehicle treatment. In cultured human macrophages, DFS significantly increased GLP-1-induced cytosolic levels of cyclic adenosine monophosphate compared with GLP-1 alone, resulted in inhibiting phosphorylation of c-jun N-terminal kinase and extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B p65 nuclear translocation through the cyclic adenosine monophosphate/protein kinase A pathway, and suppressed proinflammatory cytokines (i.e., interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha) and monocyte chemoattractant protein-1 production in response to lipopolysaccharide. DFS-enhanced GLP-1 activity sustained endothelial nitric oxide synthase phosphorylation and decreased endothelial senescence and apoptosis compared with GLP-1 alone. In the human study, fasting levels of active GLP-1 were significantly lower in patients with coronary artery disease than those without (3.10 pmol/l [2.40 to 3.62 pmol/l] vs. 4.00 pmol/l [3.10 to 5.90 pmol/l], p < 0.001).ConclusionsA DPP-4 inhibitor, DFS, exhibited antiatherogenic effects through augmenting GLP-1 activity in macrophages and endothelium

The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions

Aims: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. Methods and results: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). Conclusion: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF

Very Early Diuretic Response After Admission for Acute Heart Failure

BACKGROUND: In hospitalized heart failure patients, a poor diuretic response (DR) during the first days of hospital admission is associated with worse outcomes. However, it remains unknown whether diuretic response in the first hours has similar prognostic value. Moreover, data on the sequential change in DR during hospital admission are lacking. METHODS AND RESULTS: DR (urine output per 40 mg furosemide-equivalent diuretics dose) was measured from 0 to 6 hours (DR6), 6 to 48 hours (DR6-48), and 0 to 48 hours (DR48) of the patient's arrival to the emergency department (ED) in 1551 patients with AHF (mean age 78 years old; 56% were male; and 48% were de-novo patients with heart failure). Patients with a poor DR within the first 6 hours were older age, had worse renal function and were already on diuretic treatment before admission. DR6 was only weakly correlated with DR6-48 (Spearman's rho=0.273; p<0.001). DR6, DR6-48 and DR48 were all significantly associated with 60-day mortality independent of other prognostic factors. DR6 and DR48 showed comparable prognostic ability. However, the model combining DR6 with DR6-48 significantly exceeded both DR6 (NRI: 0.249, p=0.032) and DR48 (NRI: 0.287, p=0.025) with regard to 60-day mortality prediction. CONCLUSION: Both DR measured within the first 6 hours of ED arrival and DR measured during the first 48 hours in patients with AHF have similar prognostic value, although they were moderately correlated. Changes in DR over time provide additional prognostic information

Impact of early treatment with intravenous vasodilators and blood pressure reduction in acute heart failure

Objective Although vasodilators are used in acute heart failure (AHF) management, there have been no clear supportive evidence regarding their routine use. Recent European guidelines recommend systolic blood pressure (SBP) reduction in the range of 25% during the first few hours after diagnosis. This study aimed to examine clinical and prognostic significance of early treatment with intravenous vasodilators in relation to their subsequent SBP reduction in hospitalised AHF. Methods We performed post hoc analysis of 1670 consecutive patients enrolled in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure. Intravenous vasodilator use within 6 hours of hospital arrival and subsequent SBP changes were analysed. Outcomes were gauged by 1-year mortality and diuretic response (DR), defined as total urine output 6 hours posthospital arrival per 40 mg furosemide-equivalent diuretic use. Results Over half of the patients (56.0%) were treated with intravenous vasodilators within the first 6 hours. In this vasodilator-treated cohort, 554 (59.3%) experienced SBP reduction 25%. In patients experiencing Conclusions Intravenous vasodilator therapy was associated with greater DR and lower mortality, provided SBP reduction was less than 25%. Our results highlight the importance in early administration of intravenous vasodilators without causing excess SBP reduction in AHF management

Discovery of a Giant Lya Emitter Near the Reionization Epoch

We report the discovery of a giant Ly{alpha} emitter (LAE) with a Spitzer/IRAC counterpart near the reionization epoch at z = 6.595. The giant LAE is found from the extensive 1 deg{sup 2} Subaru narrow-band survey for z = 6.6 LAEs in the Subaru/XMM-Newton Deep Survey (SXDS) field, and subsequently identified by deep spectroscopy of Keck/DEIMOS and Magellan/IMACS. Among our 207 LAE candidates, this LAE is not only the brightest narrow-band object with L(Ly{alpha}) = 3.9 {+-} 0.2 x 10{sup 43} erg s{sup -1} in our survey volume of 10{sup 6} Mpc{sup 3}, but also a spatially extended Ly{alpha} nebula with the largest isophotal area whose major axis is at least {approx_equal} 3-inches. This object is more likely to be a large Ly{alpha} nebula with a size of {approx}&gt; 17-kpc than to be a strongly-lensed galaxy by a foreground object. Our Keck spectrum with medium-high spectral and spatial resolutions suggests that the velocity width is v{sub FWHM} = 251 {+-} 21 km s{sup -1}, and that the line-center velocity changes by {approx_equal} 60 km s{sup -1} in a 10-kpc range. The stellar mass and star-formation rate are estimated to be 0.9-5.0 x 10{sup 10}M{sub {circle_dot}} and &gt; 34 M{sub {circle_dot}}yr{sup -1}, respectively, from the combination of deep optical to infrared images of Subaru, UKIDSS-Ultra Deep Survey, and Spitzer/IRAC. Although the nature of this object is not yet clearly understood, this could be an important object for studying cooling clouds accreting onto a massive halo, or forming-massive galaxies with significant outflows contributing to cosmic reionization and metal enrichment of inter-galactic medium