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

Beyond epidemiology: field studies and the physiology laboratory as the whole world

There is no exercise training regimen broadly available in the field to increase physical fitness and prevent lifestyle-related diseases in middle-aged and older people. We have developed interval walking training (IWT) repeating five or more sets of 3 min fast walking at ≥70% peak aerobic capacity for walking (w) per day with intervening 3 min slow walking at 40% w, for ≥4 days week−1, for ≥5 months. Moreover, to determine w in individuals and also to measure their energy expenditure even while incline walking, we have developed a portable calorimeter. Further, to instruct subjects on IWT even if they live remotely from the trainers, we have developed e-Health Promotion System. This transfers individual energy expenditure during IWT stored on the meter to a central server through the internet; it sends back the achievement to individuals along with advice generated automatically by the sever according to a database on ≥4000 subjects. Where we found that 5 months of IWT increased physical fitness and improved the indices of lifestyle-related diseases by 10–20% on average. Since our system is run at low cost with fewer staff for more subjects, it enables us to develop exercise prescriptions appropriate for individuals

Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients

SummaryBackgroundRecently, serum beta2-microglobulin, an endogenous marker for renal function, has been shown to be an independent predictor of mortality in older adults. However, the prognostic role of beta2-microglobulin in heart failure has not been elucidated.MethodsWe prospectively evaluated serum beta2-microglobulin and creatinine concentrations, creatinine-based renal parameters (estimated glomerular filtration rate and creatinine clearance), and echocardiographic data in 131 patients with acute heart failure and creatinine concentrations ≤3.0mg/dL admitted to our hospitals.ResultsDuring 2.3±1.3 years, 42 patients died of cardiovascular causes and 12 died of noncardiac causes. Cardiovascular events were observed in 63 patients: 53 were readmitted due to worsening heart failure, 5 readmitted for cerebral embolism, and 5 died from sudden cardiac death. According to multivariate stepwise Cox proportional hazard analysis, higher baseline serum beta2-microglobulin concentrations (X2=16, p<0.0001), previous congestive heart failure (X2=11, p<0.001), presence of chronic obstructive pulmonary disease (X2=8, p<0.01), and lower diastolic blood pressure (X2=6, p<0.05) were independent predictors of increased cardiovascular events. Also, higher baseline serum beta2-microglobulin (X2=20, p<0.0001), lower systolic blood pressure (X2=11, p<0.001), higher relative left ventricular wall thickness (X2=6, p<0.05), and lower body mass index (X2=5, p<0.05) were independent predictors of increased cardiac mortality. The adjusted hazard ratio for cardiovascular events increased with baseline serum beta2-microglobulin above 2.1mg/L: 2.9 with beta2-microglobulin of 2.2–2.6mg/L (95%CI 1.2–6.9, p<0.05), 2.9 with beta2-microglobulin of 2.7–3.9mg/L (95%CI 1.2–7.2, p<0.05), and 4.7 with beta2-microglobulin of ≥4.0mg/L (95%CI 2.0–11, p<0.001).ConclusionsHigher baseline serum beta2-microglobulin concentration could be a promising risk marker in acute heart failure patients with creatinine ≤3.0mg/dL