The purpose of this study is to evaluate efficacy of rhNRG-1 in reducing the death rate of heart failure subjects with baseline NT-proBNP level between 600 pg/ml and 1700 pg/mL and NYHA class II to III.

The mortality of chronic heart failure patients remains high, in spite of current treatment. RhNRG-1(recombinant human neuregulin-1)directly work on the cardiomyocyte and restored the normal structure and function of it. Both the preclinical trials, phase II clinical trials and already completed phase III clinical trails have confirmed that rhNRG-1 effectively enhance the heart function, reverse the remodeling of left ventricular, and reduce all-cause mortality in heart failure animals and humans. More importantly, rhNRG-1 can significantly reduce the mortality of heart failure subjects with baseline NT-proBNP level ≤1600 fmol/mL and NYHA class II to III. In this phase III study, the investigators will further confirm the efficacy of rhNRG-1 in reducing the death rate of heart failure subjects with baseline NT-proBNP level between 600 pg/ml and 1700 pg/mL and NYHA class II to III.

Inclusion Criteria:

• 1. Age between 18 and 75, gender balance (no more than 960 subjects of either gender in total 1600 subjects).
• 2. Left ventricular ejection fraction (LVEF)≤40% (ECHO).
• 3. Subjects with chronic heart failure (NYHA class II OR III ).
• 4. 600 pg/ml ≤NT-proBNP≤1700 pg/ml ( by Roche assay Kit in central lab).
• 5. Diagnosed as chronic systolic heart failure (history, symptoms, signs), and in stable condition in the last one month.
• 6. Receiving standard therapy for chronic heart failure, reach target dose or max tolerable dose for one month, or has not changed the dose for one month before randomization.
• 7. Capable of signing the informed consent form.

Exclusion Criteria:

• 1. New chronic heart failure patients, or patients receiving standard therapy on chronic heart failure for less than 3 months.
• 2. NYHA functional class I OR IV.
• 3. NT-proBNP < 600 pg/ml OR NT-proBNP>1700 pg/ml (by Roche assay Kit in central lab).
• 4. Patients with hypertrophic cardiomyopathy, rheumatic heart disease, constrictive pericarditis, significant valvular pathological change or congenital heart diseases, primary or secondary severe pulmonary artery hypertension.
• 5. Ischemic heart failure without recanalization or with recanalization in recent six months.
• 6. Acute MI in the last 3 months.
• 7. Unstable angina.
• 8. Patients with acute pulmonary edema or acute hemodynamic disorder.
• 9. Chronic heart failure patients with acute hemodynamic disorder or acute decompensation in the last 1 month (symptoms and signs suggest worsening chronic heart failure and may require intravenous drug therapy).
• 10. Patients with right heart failure caused by pulmonary disease.
• 11. Patients diagnosed with pericardial effusion (>50 ml) or pleural effusion(>200 ml), or evidenced by Echocardiogram.
• 12. Cardiac surgery or cerebrovascular accident within recent six months.
• 13. Preparing for heart transplantation or CRT, or has received CRT.
• 14. Serious ventricular arrhythmia (sustained ventricular tachycardia or frequent paroxysmal ventricular tachycardia).
• 15.Diagnosis of perinatal or chemotherapy-induced cardiomyopathy in last 12 months.
• 16. Serious hepatic or renal dysfunction (bilirubin 1.5 times above the normal upper limit, AST or ALT 2 times above the normal upper limit, serum creatinine>2.0mg/dL, HBV or HCV positive).
• 17. Serum potassium <3.2 mmol/L or >5.5 mmol/L.
• 18. Systolic blood pressure <90mmHg or >160mmHg.
• 19. Women of childbearing age who have a pregnancy plan within 2 years (women of childbearing age are defined as women who have a pregnancy physiology).
• 20. Pregnant or lactating women.
• 21. Patients who participated in any clinical trial in the recent three months.
• 22. Subject with a life expectancy less than 6 months as assessed by the investigator.
• 23. Serious nervous system diseases (Alzheimer's disease, advanced Parkinsonism),lower limb defects, or deaf-mute.
• 24. History of any malignancy or suffering from cancer, or biopsy proven pre-malignant condition (e.g., DICS or cervical atypia).
• 25. Evidence (physical examination, chest X-ray (CXR), ECHO or other tests) shows some active malignancy or adenoidal hypertrophy or neoplasm that has an effect on heart function or the endocrine system, e.g., pheochromocytoma or hyperthyroidism (Thyroid nodules with normal thyroid function do not need to be excluded).
• 26. As judged by the investigator that the subject cannot complete the study or adhere to the study requirements (due to the management reasons or others).