The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
The newly defined gadolinite supergroup approved by the IMA CNMNC (vote 16-A) includes mineral species that have the general chemical formula A 2 MQ 2 T 2 O 8 ' 2 and belong to silicates, phosphates and arsenates. Each site is occupied by: A À Ca, REE (Y and lanthanoids), actinoids, Pb, Mn 2þ , Bi; M À Fe, □ (vacancy), Mg, Mn, Zn, Cu, Al; Q À B, Be, Li; T À Si, P, As, B, Be, S; and ' À O, OH, F. The classification of the gadolinite supergroup is based on the occupancy of A, M, Q, T and ' sites and application of the dominant-valency and dominant-constituent rules. The gadolinite supergroup is divided into two groups defined by prevailing charge occupancy at the T site À Si 4þ in gadolinite group and P 5þ or As 5þ in herderite group. The gadolinite group is divided into the gadolinite and datolite subgroups. The A site is dominantly occupied by divalent cations in the datolite subgroup and by trivalent cations in the gadolinite subgroup. Accordingly, the Q site is dominantly occupied by B 3þ in the datolite subgroup and by Be 2þ in the gadolinite subgroup. The herderite group is divided into two subgroups. The herderite subgroup is defined by the dominant divalent cation (usually Ca 2þ ) in the A site and Be 2þ in the Q site, while the M site is vacant. The drugmanite subgroup is defined by the dominance of divalent cations (usually Pb 2þ ) in the A site, vacancy in the Q site and the occupation of the M site. Moreover, "bakerite" is discredited as mineral species because it does not meet the conditions of the dominant-constituent rule.
The site preference for each cation and site in beryl based on bond-length calculations was determined and compared with analytical data. Tetrahedral SiO4 six-membered rings normally have no substitutions which results from very compact Si4+–O bonds in tetrahedra. Any substitution except Be would require significant tetrahedral ring distortion. The Be tetrahedron should also be negligibly substituted based on the bond-valence calculation; the tetrahedral Li–O bond length is almost 20% larger than Be2+–O. Similar or smaller bond lengths were calculated for Cr3+, V3+, Fe3+, Fe2+, Mn3+, Mg2+, and Al3+, which can substitute for Be but also can occupy a neighboring tetrahedrally coordinated site which is completely vacant in the full Be occupancy. The octahedral site is also very compressed due to dominant Al with short bond lengths; any substitution results in octahedron expansion. There are two channel sites in beryl: the smaller 2b site can be occupied by Na+, Ca2+, Li+, and REE3+ (Rare Earth Elements); Fe2+ and Fe3+ are too small; K+, Cs+, Rb+, and Ba2+ are too large. The channel 2a-site average bond length is 3.38 Å which allows the presence of simple molecules such as H2O, CO2, or NH4 and the large-sized cations-preferring Cs+.
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