Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Metallogenic Model and Prospecting Progress of the Qiandongshan–Dongtangzi Large Pb-Zn Deposit, Fengtai Orefield, West Qinling Orogeny

The Qiandongshan–Dongtangzi large Pb-Zn deposit is located in the Fengxian–Taibai (abbr. Fengtai) polymetallic orefield. The ore bodies primarily occur within and around the contact surface between the limestone of the Gudaoling Formation and the phyllite of the Xinghongpu Formation, which are clearly controlled by anticline and specific lithohorizon. Magmatic rocks are well developed in the mining area, consisting mainly of granitoid plutons and mafic–felsic dikes. Previous metallogenic geochronology studies have yielded a narrow range of ages between 226 and 211 Ma, overlapped by the extensive magmatism during the Late Triassic period in this region. The ω(Co)/ω(Ni) ratio of pyrite in lead–zinc ore ranges from 4.44 to 15.57 (avg. 8.56), implying that its genesis is probably related to volcanic and magmatic-hydrothermal fluids. The δD and δ18O values (ranging from −94.2‰ to −82‰, and 18.89‰ to 20.72‰, respectively,) of the ore-bearing quartz indicate that the fluids were perhaps derived from a magmatic source. The δ34S values of ore-related sulfides display a relatively narrow range of 4.29‰ to 9.63‰ and less than 10‰, resembling those of magmatic-hydrothermal origin Pb-Zn deposits. The Pb isotopic composition of the sulfides from the Qiandongshan–Dongtangzi Pb-Zn deposit (with 206Pb/204Pb ratios of 18.06 to 18.14, the 207Pb/204Pb ratios of 15.61 to 15.71, and 208Pb/204Pb ratios of 38.15 to 38.50) is similar to that of the Late Triassic Xiba granite pluton, suggesting that they share the same Pb source. The contents of W, Mo, As, Sb, Hg, Bi, Cd, and other elements associated with magmatic-hydrothermal fluids are high in lead–zinc ores, and the contents of Sn, W, Co, and Ni are also enriched in sphalerite. The contents of trace elements and rare earth elements in the ore are similar to those in the Xiba granite pluton, and they maybe propose a magmatic-hydrothermal origin as well. As a result of this information, the Qiandongshan–Dongtangzi large Pb-Zn deposit may be classified as a magmatic hydrothermal stratabound type, with the Si/Ca contact area being the ore-forming structural plane. Thus, a mineralization model has been proposed based on a comparative analysis of the geological and geochemical properties of the lead–zinc deposit in the Fengtai orefield. It is considered that the secondary anticlines developed on both wings of the Qiandongshan–Dongtangzi composite anticline are the favorable sites for Pb-Zn deposition. Accordingly, the Si/Ca plane and secondary anticline are the major ore-controlling factors and prospecting targets. The verification project was first set up on the north wing of the composite anticline, and thick lead–zinc ore bodies were found in all verification boreholes, accumulating successful experience for deep exploration of lead–zinc deposits in this region