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BACKGROUNDThe 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. METHODSWe 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. RESULTSDuring 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. CONCLUSIONSAmong 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.

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Background-In patients with chronic heart failure (CHF), the presence of sleep-disordered breathing, including either obstructive sleep apnea or Cheyne-Stokes respiration-central sleep apnea, is associated with a poor prognosis. A large-scale clinical trial showed that continuous positive airway pressure (CPAP) did not improve the prognosis of such patients with CHF, probably because of insufficient sleep-disordered breathing suppression. Recently, it was reported that adaptive servo-ventilation (ASV) can effectively treat sleep-disordered breathing. However, there are no specific data about the efficacy of flow-triggered ASV for cardiac function in patients with CHF with sleep-disordered breathing. The aim of this study was to compare the efficacy of flow-triggered ASV to CPAP in patients with CHF with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea. Methods and Results-Thirty-one patients with CHF, defined as left ventricular ejection fraction Ͻ50% and New York Heart Association class ՆII, with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea, were randomly assigned to either CPAP or flow-triggered ASV. The suppression of respiratory events, changes in cardiac function, and compliance with the devices during the 3-month study period were compared. Although both devices decreased respiratory events, ASV more effectively suppressed respiratory events (