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

TURBULENT FLOW IN A MICRO-CHANNEL

Turbulent flow of water in a narrow gap of an emulsifier is investigated experimentally using micro-PIV (micro Particle Image Velocimetry) technique and compared with numerical predictions performed using the commercial code Fluent. The purpose of the investigations is to develop a procedure for wellcontrolled generation of mono-disperse suspension of micro droplets. These droplets will form a matrix for collection of nano-particles into well-structured configuration [1]. The micro-flow measurements are based on epi-fluorescence illumination and high-speed imaging. The experimental data are compared with the numerical results obtained using both turbulent and laminar flow models. It was found that, due to small channel dimensions and very small flow development length, the turbulent energy dissipation takes place mainly in the gap and shortly behind it. Very low amount of oil-phase fraction in investigated emulsions justifies us to use mean energy dissipation estimated for pure water to predict mean diameter of oil droplets. These predictions are validated using experimental data for the emulsion

Continuous Recirculation of Microdroplets in a Closed Loop Tailored for Screening of Bacteria Cultures

Emerging microfluidic technology has introduced new precision controls over reaction conditions. Owing to the small amount of reagents, microfluidics significantly lowers the cost of carrying a single reaction. Moreover, in two-phase systems, each part of a dispersed fluid can be treated as an independent chemical reactor with a volume from femtoliters to microliters, increasing the throughput. In this work, we propose a microfluidic device that provides continuous recirculation of droplets in a closed loop, maintaining low consumption of oil phase, no cross-contamination, stabilized temperature, a constant condition of gas exchange, dynamic feedback control on droplet volume, and a real-time optical characterization of bacterial growth in a droplet. The channels (tubing) and junction cubes are made of Teflon fluorinated ethylene propylene (FEP) to ensure non-wetting conditions and to prevent the formation of biofilm, which is particularly crucial for biological experiments. We show the design and operation of a novel microfluidic loop with the circular motion of microdroplet reactors monitored with optical sensors and precision temperature controls. We have employed the proposed system for long term monitoring of bacterial growth during the antibiotic chloramphenicol treatment. The proposed system can find applications in a broad field of biomedical diagnostics and therapy