Table 1 Inclusive and exclusive criteria

Inclusion criteria

1) Provision of signed informed consent prior to any study specific procedures

2) Male or female, aged ≥ 18 years at the time of consent

3) Established documented diagnosis of heart failure for at least three months ago according to “Chinese Heart Failure Diagnosis and Treatment Guideline” issued by the Chinese Medical Association Cardiovascular Branch

4) Left ventricular ejection fraction (LVEF) ≤ 40% (echocardiogram, radionuclide, ventriculogram, contrast angiography or cardiac MRI)

5) NYHA cardiac functional grading II to III, with stable clinical symptoms; including those diagnosed as grade IV within 2 weeks before enrollment

6) Serum NT-proBNP ≥ 450 pg/ml

7) Those who have received standardized baseline treatment regimens without doses adjusted and given intravenously for at least two weeks prior to enrollment; standardized drug treatment includes: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor (ARNI), beta blocker, and aldosterone receptor antagonist (the optimal therapeutic dose should be achieved, except for contraindications or intolerance)

Exclusion criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled

1) Heart failure caused by valvular disease, congenital heart disease, pericardial disease, arrhythmia or non-cardiogenic disease, or caused by vital organ failure (such as renal, hepatic failure, etc.); and right heart failure caused by pulmonary or other definite causes; and acute heart failure

2) Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or cardiac synchronization therapy planned to undergo after randomization, or had received cardiac resynchronization therapy prior to enrolment

3) Any condition outside the CV diseases such as but not limited to malignant tumor, severe mental illness, hematopoietic diseases, neuroendocrine system disease, liver transaminase and alkaline phosphatase ≥ 3 × upper limit of normal (ULN), abnormal renal function serum creatinine > 2 mg/dl (176.82 umol/L), potassium > 5.5 mmol/L

4) Patient with left ventricular outflow tract obstruction, myocarditis, aortic aneurysm, aortic dissection, or obvious hemodynamic changes caused by unrepaired valve

5) Cardiogenic shock, uncontrollable malignant arrhythmia, sinus or atrioventricular block at second degree type II or above without pacemaker treatment, progressive unstable angina pectoris or acute myocardial infarction

6) Uncontrolled hypertension systolic blood pressure (SBP) ≥ 180 mmHg and/or diastolic blood pressure (DBP) ≥ 110 mmHg; or SBP < 90 mmHg and/or DBP < 60 mmHg

7) Participation in another clinical study with an IP during the last month prior to enrolment

8) Women of child-bearing potential (i.e., those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator, from the time of signing the informed consent throughout the study and 4 weeks thereafter, OR women who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding

9) Allergic constitution; known to be allergic to research drug

10) Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures or any conditions may render the patient unable to complete the study