Inclusion
Participants with New York Heart Association (NYHA) Class II-III.
Cohort 1 - Left Ventricular Ejection Fraction (LVEF) ≤ 40%.
Cohort 2 - Left Ventricular Ejection Fraction (LVEF) \>40% and ≤ 65%, elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥ 600pg/mL and atrial fibrillation/flutter.
Stable heart failure and on optimal medical therapy.
Screening hemoglobin ≥ 9.0 g/dL.
Exclusion
Uncontrolled hypertension.
Sustained systolic Blood Pressure (BP) \< 90 mmHg and/or diastolic BP \< 50 mmHg on 2 consecutive (duplicate seated) readings at screening.
Heart failure due to hypertrophic cardiomyopathy, restrictive and/or infiltrative cardiomyopathy, arrhythmogenic right ventricular dysplasia, Fabry disease, or Noonan syndrome with LV hypertrophy or a positive serum immunofixation result.
Diagnosis of stress-induced (Takotsubo) cardiomyopathy, myocarditis, or peripartum cardiomyopathy.
Diagnosis of chemotherapy- or radiation-induced cardiomyopathy.
Diagnosed with stroke or Transient Ischemic Attack (TIA) within 12 weeks of screening.
History of syncope within the last 12 weeks prior to screening or sustained ventricular tachycardia without an implantable cardioverter-defibrillator.
Moderate or severe aortic and/or mitral valve stenosis.
Medically documented unstable angina, acute coronary syndrome (e.g., myocardial infarction, troponin-positive with symptoms of angina or unstable angina) within the last 8 weeks prior to start of screening.
Medically documented ST-elevation myocardial infarction within 12 weeks of screening.
Any tachycardia (inclusive of Atrial Fibrillation (AF) or atrial flutter) with a resting ventricular rate \> 110 beats per minute at screening.
For participants with a history of AF or atrial flutter, not on adequate anticoagulant therapy via non-vitamin K oral anticoagulants or warfarin if the CHA2DS2-VASc score is ≥ 2 in men or ≥ 3 in women or per local guidelines. Percutaneous occlusion of the left atrial appendage alone is not adequate.
AF ablation within the last 12 weeks prior to screening or planned during the study duration.
Symptomatic bradycardia or second (Mobitz Type II)- or third-degree heart block without a pacemaker.
Cardiac surgery, coronary artery revascularization or indication for coronary artery revascularization, percutaneous coronary intervention, valve repair/replacement or valvuloplasty within 12 weeks prior to screening.
Implantation of a Cardiac Resynchronization Therapy (CRT) device within 12 weeks prior to screening, or intent to implant a CRT device during the course of the study.
Previous cardiac transplantation, or any use of mechanical circulatory support or similar device, or implantation expected after randomization.
Receiving mechanical hemodynamic support or invasive mechanical ventilation within the last 8 weeks prior to screening.
Receiving Intravenous (IV) inotropes or IV vasopressors within the last 8 weeks prior to screening.
Receiving IV vasodilators within the last 4 weeks prior to screening.
Receiving noninvasive mechanical ventilation within the last 4 weeks prior to screening. The use of noninvasive ventilation for sleep disordered breathing is permitted.