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

MODELING OF UNDERGROUND MINE WORKINGS IN CONSOLIDATING THE SOIL-ARRAY

The article deals with the analysis of computer modeling of stability of underground workings in the ground array strengthen cement mixtures. Based criteria by which the results of the computer simulation, the optimum strength of reinforced soil-array. It is shown that this technology can be used to strengthen in the sinking of underground mine workings in the loose soil

Experience of using the NALCO 1392 scale inhibitor in the circulating water supply system of the Novovoronezh NPP

Power facilities use large amounts of water to cool steam in the steam turbine condensers, and lubricating oils, gas and air in turbine sets. The key requirement for the quality of cooling water is to ensure normal vacuum in condensers. Cooling water must not form mineral and biological deposits and corrosion products in the system. Deposits of mineral salts in the condenser tube system, as well as in auxiliary cooling systems, lead to deterioration in heat exchange and a major decrease in the cost effectiveness of the power equipment operation, and require the heat-exchange equipment to be periodically cleaned. The source water used for cooling is normally taken from nearby water bodies (large rivers or lakes). Circulating water supply systems are used most commonly: these systems use repeatedly the same water inventory for cooling, and require only small amounts of water added to make up for evaporation losses. Coolers, in this case, are cooling towers, spray pools and evaporation ponds. The water chemistry should ensure the operation of equipment without any damage to its components or the loss of efficiency caused by the corrosion of the internal surfaces as well as without scale and sludge formation. It is exactly when using circulating water supply that a stabilizing treatment program is the most practicable way to ensure a cost-effective and environmentally friendly mode of operation. To inhibit scaling processes on the heat-exchange surfaces of the turbine condenser tubes at the Novovoronezh NPP’s unit 5, the cooling water was treated with the NALCO 1392 inhibitor. The results of the NALCO 1392 inhibitor pilot tests in the circulating water supply system (with a cooling pool) are presented

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)