AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF

Inclusion Criteria: * Males and females ≥ 40 years and ≤ 85 years of age at screening. * Diagnosed with HF with NYHA functional class II or III. * Screening echocardiography with LVEF ≥ 60%. * Screening NT-proBNP ≥ 300 pg/mL for participants in sinus rhythm and ≥ 900 pg/mL for participants with comorbid atrial fibrillation or flutter. * Body mass index \< 40 kg/m2. * Participants on beta-blockers, angiotensin-converting enzyme (ACE)/angiotensin II receptor blocker (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI), must be on stable doses for more than 30 days prior to screening. * Participants on a glucagon-like peptide-1 (GLP-1) agonist must be on a stable dose for more than 24 weeks prior to screening with no anticipated plans to change dose during this study. Exclusion Criteria: * History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion. * Other protocol-defined Inclusion/Exclusion criteria apply.