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

Professional activity of Polish peri- and postmenopausal women

Introduction: The menopausal transition as one of the stages in women’s life can bring many ailments which complicate the accomplishment of professional duties. The situation of women on the Polish job market is determined by many barriers and stereotypes which impede women’s access to jobs and professional promotions. Material and methods : The aim of the study was to estimate the professional status and job satisfaction of women aged 40-65. The research was carried out by a survey method, a poll technique in the period from January to March 2016. An original questionnaire consisting of 35 questions was used as a research tool. Results: The analysis of obtained results shows that the arithmetic mean of the age of women in full-time employment was 51.84 years whereas the arithmetic mean of the age of women in part-time or seasonal employment was 52.64. Women aged 45-60 were characterised by a significantly lower job satisfaction than women over 60 years of age. The highest percentage of women in full-time employment lived in large cities. The financial situation of working women determined their job satisfaction. Well-off respondents were more pleased with their jobs than women in a worse financial situation. Conclusions : There is a strong need of education about counteraction of gender and age discrimination on the Polish labour market. The struggle against discrimination requires support on each level of the state administration through the implementation of numerous regulations facilitating the final period and resumption of women’s professional activity

Neuron-specific enolase concentrations for the prediction of poor prognosis of comatose patients after out-of-hospital cardiac arrest: an observational cohort study

Background: Neuron-specific enolase (NSE) is a biomarker for neurological outcomes after cardiac arrest with the most evidence collected thus far; however, recommended prognostic cutoff values are lacking owing to the discrepancies in the published data.Aims: The aim of the study was to establish NSE cutoff values for prognostication in the environment of a cardiac intensive care unit following out-of-hospital cardiac arrest (OHCA).Methods: A consecutive series of 82 patients admitted after OHCA were enrolled. Blood samples for the measurement of NSE levels were collected at admission and after 1 hour, 3, 12, 24, 48, and 72 hours. Neurological outcomes were quantified using the cerebral performance category (CPC) index. Each patient was classified into either the good (CPC ≤2) or poor prognosis (CPC ≥3) group.Results: Median NSE concentrations were higher in the poor prognosis group, and the difference reached statistical significance at 48 and 74 hours (84.4 ng/ml vs 22.9 ng/ml at 48 hours and 152.1 ng/ml vs 18.7 ng/ml at 72 hours; P <0.001, respectively). Moreover, in the poor prognosis group, NSE increased significantly between 24 and 72 hours (P <0.001). NSE cutoffs for the prediction of poor prognosis after OHCA were 39.8 ng/ml, 78.7 ng/ml, and 46.2 ng/ml for 24, 48, and 72 hours, respectively. The areas under the curve were significant at each time point, with the highest values at 48 and 72 hours after admission (0.849 and 0.964, respectively).Conclusions: Elevated NSE concentrations with a rise in levels in serial measurements may be utilized in the prognostication algorithm after OHCA

Neuron-Specific Enolase and S100B: The Earliest Predictors of Poor Outcome in Cardiac Arrest

Background: Proper prognostication is critical in clinical decision-making following out-of-hospital cardiac arrest (OHCA). However, only a few prognostic tools with reliable accuracy are available within the first 24 h after admission. Aim: To test the value of neuron-specific enolase (NSE) and S100B protein measurements at admission as early biomarkers of poor prognosis after OHCA. Methods: We enrolled 82 consecutive patients with OHCA who were unconscious when admitted. NSE and S100B levels were measured at admission, and routine blood tests were performed. Death and poor neurological status at discharge were considered as poor clinical outcomes. We evaluated the optimal cut-off levels for NSE and S100B using logistic regression and receiver operating characteristic (ROC) analyses. Results: High concentrations of both biomarkers at admission were significantly associated with an increased risk of poor clinical outcome (NSE: odds ratio [OR] 1.042 per 1 ng/dL, [1.007–1.079; p = 0.004]; S100B: OR 1.046 per 50 pg/mL [1.004–1.090; p < 0.001]). The dual-marker approach with cut-off values of ≥27.6 ng/mL and ≥696 ng/mL for NSE and S100B, respectively, identified patients with poor clinical outcomes with 100% specificity. Conclusions: The NSE and S100B-based dual-marker approach allowed for early discrimination of patients with poor clinical outcomes with 100% specificity. The proposed algorithm may shorten the time required to establish a poor prognosis and limit the volume of futile procedures performed

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.)