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

The structure of Fe(III) ions in strongly alkaline aqueous solutions from EXAFS and Mossbauer spectroscopy

To establish the structure of ferric ions in strongly alkaline (pH > 13) environments, aqueous NaOH solutions supersaturated with respect to Fe(III) and the solid ferric-hydroxo complex salts precipitating from them have been characterized with a variety of experimental techniques. From UV measurements, in solutions of pH > 13, only one kind of Fe(III)-hydroxo complex species was found to be present. The micro crystals obtained from such solutions were proven to be a new, so far unidentified solid phase. Mossbauer spectra of the quick-frozen solution and that of the complex salt indicated a highly symmetrical ferric environment in both systems From the EXAFS and XANES spectra, the environment of the ferric ion in these solutions (both native and quick-frozen) and in the complex salt was found to be different. In the complex salt, the bond lengths are consistent with an octahedral coordination around the ferric centres. In solution, the coordination geometry of Fe(III) is most probably tetrahedral. Our results demonstrate that in strongly alkaline aqueous solutions, ferric ions behave very similarly to other structurally related tervalent ions, like Al(III) or Ga(III)

Synthesis, magnetochemistry, and spectroscopy of heterometallic trinuclear basic trifluoroacetates [Fe2M(μ3-O)(CF3COO)6(H2O)3]·H2O (M = Mn, Co, Ni)

Three new mu(3)-oxo(trifluoroacetato) complexes [(Fe2MII)-M- III(mu(3)-O)(CF3COO)(6)(H2O)(3)].H2O [M = Mn (1), Co (2), Ni (3)] have been prepared. Compounds 1 and 2 crystallize in the monoclinic space groups C2/c [a = 22.002(5), b = 13.647(3), c = 24.767(4) Angstrom, beta = 98.23(3)degrees] and C2/m [a = 21.426(4), b = 15.100(2), c = 14.815(3) Angstrom, beta = 117.99(2)degrees], respectively. The coordination spheres of the metal ions are essentially octahedral, with the Fe-O distances [1.870(5) Angstrom] falling in the usual range for these systems. Magnetochemical studies reveal the presence of antiferromagnetic exchange in the isosceles triangular skeletons of the polynuclear species. Application of the isotropic spin Hamiltonian H = -2J(FeM)[SFe1SM + SMSFe2] - 2J(FeFe)[SFe1SFe2] gives the fitting parameters: g(Fe) = g(Mn) = 2.00, J(Fe-Fe) = -56.50(7) and J(Fe-Mn) = -16.23(4) cm(-1) (1), g(mol) = 2.09(1), J(Fe-Fe) = -42.8(3.5) cm(-1), J(Fe-Co) = -17.8(1.4) cm(-1) (2) and g(Fe) = 2.00, g(Ni) = 2.215(2), J(Fe- Fe) = -45.60(1) and J(Fe-Ni) = -16.96(2) cm(-1) (3). A Mossbauer investigation confirms that no electron transfer from Mn-II or Co-II to Fe-III occurs during the syntheses of these complexes. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

Hydrothermal nontronite formation at Eolo Seamount (Aeolian volcanic arc, Tyrrhenian Sea).

International audienceA sediment core containing a yellowish-green clay bed was recovered from an area of extensive hydrothermal deposition at the SE slope of the Eolo Seamount, Tyrrhenian Sea. The clay bed is composed of pure nontronite (described for the first time in the Tyrrhenian Sea), which appears to be the most aluminous nontronite ever found among the seafloor hydrothermal deposits. The high Al content suggests precipitation from Al-containing hydrothermal solutions. The REE distribution of the Eolo nontronite has a V-shape pattern. The heavy REE enrichment is in part due to their preferential partitioning in the nontronite structure. This enrichment was possibly further enhanced by the HREE preferential sorption on bacterial cell walls. The light REE enrichment is the result of scavenging uptake by one of the nontronite precursors, i.e., poorly-ordered Fe-oxyhydroxides, from the hydrothermal fluids. Oxygen isotopic composition of the nontronite yields a formation temperature of 30 °C, consistent with a low-temperature hydrothermal origin. The relatively radiogenicNd isotopic signature of the nontronite compared to the present-dayMediterranean seawater indicates that approximately half of Nd, and presumably the rest of the LREE, are derived from local volcanic sources. On the other hand, 87Sr/86Sr is dominated by present-day seawater Sr. Scanning electron microscopy investigation revealed that the nontronite is composed of aggregates of lepispheres and tube-like filaments, which are indicative of bacteria assisted precipitation. Bacteria inhabiting this hydrothermal site likely acted as reactive geochemical surfaces on which poorly-ordered hydrothermal Fe-oxyhydroxides and silica precipitated. Upon aging, the interactions of these primary hydrothermal precipitates coating bacterial filaments and cell walls likely led to the formation of nontronite. Finally, the well-balanced interlayer and layer charges of the crystal lattice of seafloor hydrothermal nontronite decrease its sorption capacity to zero

Metalliferous sediments from Eolo Seamount (Tyrrhenian Sea): Hydrothermal deposition and re-deposition in a zone of oxygen depletion

International audienceA sediment core taken from the south-east slope of the Eolo Seamount is composed of alternating red-brown and light-brown to bluish-grey layers with signs of re-deposition in the middle-upper section. The red-brown layers are Fe-rich metalliferous sediments formed as a result of low-temperature (~ 77 °C) hydrothermal discharge, whereas the bluish-grey layers most probably originated from background sedimentation of Al-rich detrital material. The metalliferous layers are composed mainly of Si-rich goethite containing some Al. Co-precipitation of hydrothermally released SiO44- and Fe2+ as amorphous or poorly crystalline Fe-Si-oxyhydroxides explains the high Si concentration in goethite. The elevated Al content of the goethite is fairly unusual, but reflects the extremely high background Al content of the Tyrrhenian seawater due to the high eolian terrigenous flux from the Sahara desert. The Sr and Nd isotope data suggest that the Eolo metalliferous sediments are the product of a 3-component mixture: hydrothermal fluid, seawater, and detrital material (Saharan dust and Aeolian Arc material). The enrichment in Fe, P, As, Mo, Cd, Be, Sb, W, Y, V, depletion in REE and transition elements (Cu, Co, Ni, Zn) and the REE distribution patterns support the low-temperature hydrothermal deposition of the metalliferous layers. The hydrothermal field is located in a seawater layer of relative O2 depletion, which led to a significant fractionation of the hydrothermally emitted Fe and Mn. Fe-oxyhydroxides precipitated immediately around the vents whereas Mn stayed in solution longer and the Mn-oxides precipitated higher up on the seamount slope in seawater with relatively higher O2 levels. High seismic activity led to sediment re-deposition and slumping of the Mn-rich layers down slope and mixing with the Fe-rich layer

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes