A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation

Inclusion Criteria:

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

• Disease specific - cardiovascular:

• N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than or equal to 225picograms per milliliter (pg/mL) (375 pg/mL for participants with atrialfibrillation/flutter) at screening

• Diagnosis of heart failure (New York heart association (NYHA) Class II-III)

• Left ventricular ejection fraction (LVEF) greater than 40 percent documented byechocardiography within 12 months prior to or at screening (visit 1). The LVEF mustbe documented in medical records and the most recent measurement must be used todetermine eligibility with no interim event signalling potential deterioration inejection fraction (example 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:

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

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

3. LA length greater than or equal to 5.0 cm

4. LA area greater than or equal to 20 square centimeter (cm^2)

5. LA volume greater than or equal to 55 milliliter (mL)

6. Intraventricular septal thickness greater than or equal to 1.1 cm

7. Posterior wall thickness greater than or equal to 1.1 cm

8. LV mass index greater than or equal to 115 gram per square meter (g/m^2) in menor greater than or equal to 95 g/m^2 in women h) E/e' (mean septal and lateral) greater than or equal to 10 i) e' (mean septal andlateral) less than 9 centimeter per second (cm/s)

• No heart failure hospitalisations or urgent heart failure visits between screeningand randomisation

• Able to perform the 6-minute walk test (6MWT) at screening with a minimum distanceof 100 metres

• Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score lesser than 80 at screening

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 or equal to 180 millimeters of mercury (mmHg)at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patientshould be receiving greater than or equal to 3 antihypertensive drugs

• Heart rate above 110 or below 40 beats per minute as evaluated on theElectrocardiogram (ECG) performed at screening (visit 1)

• Planned coronary, carotid or peripheral artery revascularisation known during thescreening period (visit 1)

• 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 chronic obstructive pulmonary disease (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 theinvestigator