Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Atrial Structure and Function in Chronic Heart Failure (COSMIC-HF)

Introduction: Left atrial (LA) size is generally increased and LA function reduced in patients with chronic heart failure (CHF). Omecamtiv mecarbil (OM) is a selective cardiac myosin activator which recently was shown to improve measures of left ventricular structure and function. Hypothesis: We hypothesized that chronic therapy with OM improves LA structure and function in patients with CHF. Methods: In the double-blinded COSMIC-HF trial, 448 patients with stable, symptomatic CHF and left ventricular ejection fraction (LVEF) ≤40% were randomly assigned to oral OM [25 mg twice daily; or 25 mg twice daily with pharmacokinetic-guided uptitration to 50 mg twice daily (PK group)] or placebo for 20 weeks. We assessed changes in measures of LA structure (maximal and minimal LA volume indexed by body surface area) and function (LA emptying fraction, or LA EF) by echocardiography between the placebo (n=149) and PK groups (n=149) at weeks 12 and 20. LS means were calculated from repeated measure models which assessed the treatment differences vs placebo and included the stratification factor of presence or absence of atrial fibrillation/flutter at randomization, baseline value, visit, and the treatment group by visit interaction as covariates. Results: Patients were 63±11 years old, predominantly (82%) male, with LVEF of 29.1±7.3%, maximal LA volume of 41.0±15.4 mL/m 2 , minimal LA volume of 28.2± 14.7 mL/m 2 and LA EF of 34.2±13.3%; there were no differences between the placebo and PK group at baseline. Both minimal LA volume and LA EF improved significantly in patients receiving OM ( Figure ). Conclusion: In patients with chronic heart failure and reduced systolic function, OM improved measures of LA structure and function. Given the absence of any direct effect on preload or afterload by OM, further analyses will be performed to attempt to assess the relative contributions of intrinsic increases in atrial contractility and improvements in atrial remodeling and loading conditions.