University of Kansas Medical Center

Adult patients who meet all the following criteria at screening may be included in the study: - Are between ≥ 18 years and ≤ 85 years at the signing of informed consent - Have a history of chronic HFrEF, defined as requiring treatment for HF for a minimum of 3 months prior to screening - Are receiving oral loop diuretics - Patients without AFF on screening ECG: - LVEF < 30% within 6 months of screening - Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 1000 pg/mL (BNP ≥ 300 pg/mL) - Patients with AFF on screening ECG: - LVEF < 25% within 6 months of screening - Elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) ≥ 3000 pg/mL (BNP ≥ 900 pg/mL) - Not currently taking digoxin - Are currently hospitalized with the primary reason of HF, or had an HF event within 6 months prior to screening - Are established on regional standard-of-care HF therapies for at least 30 days prior to screening - Systolic blood pressure ≤ 130 mmHg and diastolic blood pressure ≤ 90 mmHg

Any of the following criteria will exclude potential patients from the study: - Have AFF on the screening ECG and are currently taking digoxin - Have had acute coronary syndrome, cardiac surgery, valve surgery, any coronary revascularization, and/or cardiac resynchronization therapy within 3 months of screening - Are admitted to a long-term care facility or hospice - Have a projected survival of < 12 months due to non-cardiovascular causes based on clinical judgment - Are receiving intravenous inotropes or intravenous vasopressors ≤ 3 days prior to screening - Are receiving mechanical hemodynamic support or mechanical ventilation ≤ 7 days prior to screening - Are receiving intravenous diuretics, intravenous vasodilators, or supplemental oxygen therapy ≤ 12 hours prior to screening - Have an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 or receiving dialysis at screening - Have previously had a solid organ transplant - Are receiving treatment in another investigational device or drug study or are within 30 days of ending such investigational treatment at screening - Have previously received omecamtiv mecarbil - Are pregnant or planning pregnancy during the study period, or planning to breastfeed during treatment with IP or within 5 days after the end of treatment with IP