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

1024-76 Beta-Adrenergic Blockade in Patients with Moderate Mitral Stenosis

β-blocker therapy remains controversial in patients with mitral stenosis. In this randomized, double-blinded, crossover, placebo-controlled study, the effects of atenolol (50 and 100 mg/day) were assessed in 15 patients (age=46±11 yrs) with moderate mitral stenosis (mitral valve area=1.0±0.4cm2; NYHA class II-III) at rest (R) and during upright bicycle ergometry (E). Doppler-echocardiography was employed to compare heart rate (HR), cardiac (CI) and stroke volume (SVI) indices, diastolic filling period (DFP), and peak and mean (Mn Grad) transmitral gradients; a metabolic cart was used to obtain maximum VO2, VCO2 and anaerobic threshold (AT). β-blockade therapy did not improve exercise time, extemal work, max VO2 or AT. During exercise, max V02 and CI decreased (p<0.05)>11% and>20%, respectively, with atenolol. Thefollowing hemodynamic data are presented as mean±sd:PlaceboAtenolol50mg100mgHRR76±1360±11*58±13*(bpm)E144±15112± 23*103±21*DFPR431±97604±148*629±175*(msec)E208±35277±90*300±95*SVIR22±722±626±8(ml/m2)E21±1022±1026±9Mn GradR5±44±34±2(mmHg)E20±817±815±8**p<0.05 Placebo vs AtenololAlthough HR and Mn Grad decreased and DFP increased with atenolol, SVI changed little compared with placebo. The data suggest that in spite of lower transvalvular pressure gradients little benefit in exercise performance is achieved with β-blocker therapy in patients with moderately severe mitral stenosis