A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Heart Failure and Inflammation

Inclusion Criteria:

• Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular

• At least one of the following:

1. N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300picograms per milliliter (pg/mL) at screening (Visit 1) for patients withoutongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter atscreening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Notethat the screening electrocardiogram (ECG) must be obtained the same day assampling for NT-proBNP.

2. Hospitalisation or urgent/unplanned visit with a primary diagnosis ofdecompensated heart failure which required intravenous loop diuretic treatment,within the last 9 months prior to screening (visit 1) in combination withNT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patientswithout ongoing atrial fibrillation/flutter. If ongoing atrialfibrillation/flutter at screening (visit 1), NT-proBNP must be greater thanequal to 600 pg/mL.

• Diagnosis of heart failure (New York Heart Association [classification] [NYHA] ClassII-IV).

• Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documentedby echocardiography within 12 months prior to or at screening (visit 1). The LVEFmust be documented in medical records and the most recent measurement must be usedto determine eligibility with no interim event signalling potential deterioration inejection fraction (e.g., myocardial infarction [MI] or heart failure [HF]hospitalisation).

• Structural heart disease and/or functional heart disease documented byechocardiography within 12 months prior to or at screening (visit 1) showing atleast one of the following:

• Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m^2).

• LA diameter greater than equal to 3.8 centimeter (cm).

• LA length greater than equal to 5.0 cm.

• LA area greater than equal to 20 cm square.

• LA volume greater than equal to 55 milliters (mL).

• Intraventricular septal thickness greater than equal to 1.1 cm.

• Posterior wall thickness greater than equal to 1.1 cm.

• Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m^2 ) in men or greater than equal to 95 g⁄m^2 in women.

• E/e' (mean septal and lateral) greater than equal to 10.

• e' (mean septal and lateral) less than 9 centimeter per second (cm/s).

• No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).

Exclusion Criteria:

Medical conditions - cardiovascular

• Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack,or heart failure hospitalisation, within 30 days prior to screening (visit 1).

• Systolic blood pressure greater than equal to 180 millimeters of mercury (mmHg) atscreening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patientshould be receiving greater than equal to 3 antihypertensive drugs. (Note: Potentialparticipants may be retested for this criterion within the visit window and withoutrescreening, at the discretion of the investigator).

• Heart rate above 110 or below 40 beats per minute as evaluated on theelectrocardiogram (ECG) performed at screening (visit 1) (Note: Potentialparticipants may be retested for this criterion within the visit window and withoutrescreening, at the discretion of the investigator).

• Planned coronary, carotid or peripheral artery revascularisation known during thescreening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).

• Planned cardiac device or atrial flutter/atrial fibrillation ablation procedureknown during the screening period (visit 1).

• Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).

• Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid),arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetichypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis,constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primaryvalve disease.

• Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary diseaseincluding COPD.

• Any other condition judged by the investigator that could account for heart failuresymptoms and signs (e.g., anaemia, hypothyroidism).

Medical conditions - infections/immunosuppression

• Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.