A Study to Evaluate the Safety and Efficacy of AC01 Compared to Placebo in Participants With Chronic Heart Failure

The primary purpose of the study is to evaluate the safety and efficacy of 2 doses of AC01 compared to placebo over 12 weeks in participants with chronic advanced HFrEF.

Key Inclusion Criteria: * History of Chronic Heart Failure (CHF) diagnosed greater than or equal to (\>=6) months before screening, and in NYHA Class II to IV at screening. * Chronic advanced HFrEF defined as: * LVEF less than or equal to (\=6 months before screening or a record of LVEF qualitatively described as severely reduced or moderately-severely reduced \>=6 months before screening, and * LVEF \) 35% (or qualitatively described as less than moderately-severely reduced) between the 2 readings. * Sinus rhythm or permanent, persistent, or paroxysmal atrial fibrillation flutter (AFF) (AFF at screening is capped at maximum 15% of participants enrolled) with mean resting heart rate of \>=55 and \=50 and \=400 picograms per milliliter (pg/mL) in sinus rhythm and \>=800 pg/mL in AFF at screening (confirmed by central laboratory). * Transvenous implantable cardioverter-defibrillator (ICD) for primary prevention with back-up pacing set at 40 bpm. * Treated with optimal, stable, medical therapy for HF consistent with prevailing local and international guidelines unless contraindicated or not tolerated, as judged and documented by the investigator. Key Exclusion Criteria: * Any acute or serious co-morbid condition that could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study. * Admitted to hospital with the primary reason of HF within 24 hours before randomization or currently hospitalized with the primary reason of HF for more than 10 days. Current hospitalization (\>24 hours and \130 or ˂90 millimeters of mercury (mmHg) at screening, or \>140 or ˂85 mmHg at randomization. * Uncontrolled diabetes mellitus, defined as Hemoglobin A1c (HbA1c) \>=9.0% (\>=75 millimoles per mole \[mmol/mol\]) at screening, or severe complications of diabetes. * Body weight \