A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2

Inclusion criteria:

1. Participant must be ≥ 18 years of age inclusive.

2. Participants must have a pre-existing diagnosis of HF, NYHA function class (FC) II to IV, and a pre-existing diagnosis of PH-LHD or likely or intermediate probability of Pulmonary hypertension due to left heart disease (PH-LHD) as per 2022 Pulmonary hypertension due to left heart disease European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. Participants must be on stable HF standard of care medication, including diuretics.

3. Participants must have a combination of echocardiographic parameters that show intermediate or high probability of PH as per 2022 ESC/ERS guidelines.

4. Participants must have an on-study elevated pulmonary artery pressure from RHC performed as per RHC manual provided by the Sponsor, at Screening Visit 2:

5. PAWP ≥ 15 mmHg

6. mPAP ≥ 20 mmHg

7. Minimum body weight of 45 kg (inclusive).

8. Capable and willing of giving signed informed consent.

Exclusion Criteria

1. Diagnosis of PH in World Health Organization (WHO) Group 1, WHO Group 3, WHO Group 4, or WHO Group 5.

2. Historical or current evidence of a clinically significant disease or disorder.

3. Decompensated HF or hospitalisation due to decompensated HF.

4. Any contraindications to RHC.

5. History of hypersensitivity to SC injections or devices.

6. History of hypersensitivity to drugs with a similar chemical structure or class to AZD3427 or any component of AZD3427 drug product, or ongoing clinically important allergy/hypersensitivity.

7. Known lung disease with Forced expiratory volume in the first second (FEV1) < 30% of predicted.

8. Congenital long QT syndrome.

9. Cardiac ventricular arrhythmia which requires treatment. Participants with atrial fibrillation or flutter and controlled ventricular rate are permitted.

10. History of or anticipated heart transplant or ventricular assist device implantation.

11. Any known planned (scheduled) highly invasive Cardiovascular (CV) procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).

12. Participants who have previously received AZD3427.