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

El Desarrollo Psicomotriz y su relación con la Actividad Físico-Deportiva en las Edades Tempranas.

Introduction. The psychomotor development of the child is essential for their progress in the practice of physical-sports activities, however, in order to achieve favorable results, different aspects must be considered. Objective. Reflect on the relationship between psychomotor development and the practice of sports physical activities at an early age. Methodology. The methodology followed was descriptive, documentary, based on the RSL (Systematic Literature Review). The use of theoretical methods favored the inquiry, review and analysis of the preceding documentary information, located in 37 sources from different databases; all related to the subject under study. Results. 1. The relationship that exists between psychomotor development and potential reached for the practice of sports physical activities is evident. The greater the psychomotor stimulation received at an early age, the better the child's performance in physical sports activities. 2 Psychomotor development goes through several stages, which must be respected and stimulated through playful activities to promote full child development. 3. All physical-sports program at this stage must consider the dosage, loads, intensity, sex, age and type of activities to be carried out 4. There is no single criterion in the scientific community regarding the advantages or disadvantages of early initiation to   The   practice of physical sports activities, regardless of this, the close relationship between optimal psychomotor development and perceptible improvements in the practice of physical sports activities at an early age is established. Conclusions. Coinciding with the preliminary theoretical and scientific position, the close relationship between the child's psychomotor development and the favorable potential for the practice of physical-sports activities is supported. Optimal psychomotor development encourages perceptible improvements for the practice of sports physical activities at an early age, making it necessary to respect the evolutionary stages of child development to enhance their maximum performance.Introducción. El desarrollo psicomotriz del niño resulta esencial para su progreso en la práctica de las actividades físico-deportivas, sin embargo, para concretar resultados favorables se deben considerar diferentes aspectos. Objetivo. Reflexionar en torno a la relación entre desarrollo psicomotriz y la práctica de actividades físicas deportivas en edades tempranas. Metodología. La metodología seguida fue descriptiva, documental, basada en la RSL (Revisión Sistemática de Literatura). La utilización de métodos teóricos favoreció la indagación, revisión y análisis de la información documental precedente, ubicada en 37 fuentes de diferentes bases de datos; todas relacionadas con el tema objeto de estudio. Resultados. 1. La relación que se da entre desarrollo psicomotriz y potencial alcanzado para la práctica de actividades físicas deportivas resulta evidente. Mientras mayor sea la estimulación psicomotriz recibida en las edades tempranas mejor será el desempeño del niño en las actividades físicas deportivas. 2. El desarrollo psicomotriz transita por varias etapas, las cuales deben ser respetadas y estimuladas mediante actividades lúdicas para potenciar el pleno desarrollo infantil. 3. Todo programa físico- deportivo en esta etapa debe considerar la dosificación, cargas, intensidad, sexo, edad y tipo de actividades a realizar 4. No existe un criterio único en la comunidad científica respecto a las ventajas o perjuicios de la iniciación temprana a la práctica de actividades físicas deportivas, independientemente a esto sí se establece la estrecha relación entre desarrollo psicomotriz óptimo y mejoras perceptibles en la práctica de actividades físicas deportivas en edades tempranas. Conclusiones. Coincidiéndose con el posicionamiento teórico y científico preliminar queda sustentada la estrecha relación entre desarrollo psicomotriz del niño y el potencial favorable para la práctica de actividades físicas-deportivas.  Un desarrollo psicomotriz óptimo, propicia mejoras perceptibles para la práctica de actividades físicas deportivas en edades tempranas, resultando necesario respetar las etapas evolutivas del desarrollo infantil para potenciar su máximo desempeño

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.)