Heart failure (HF) is a complex syndrome with increasing incidence and high rates of mortality and hospitalization. Although inhibitors of angiotensin converting enzyme (ACE), β-blockers and aldosterone-receptor blockers have improved the treatment of heart failure, mortality of HF remains unacceptably high.

Recently, we identified a key metabolite N-acetylneuraminic acid (Neu5Ac) increased in the plasma of patients with heart failure. Also, elevated plasma Neu5Ac, independent of other traditional risk factors, is associated with poor prognosis in patients with HF in long-term follow up. Neu5Ac levels, the most common sialic acid in mammals, generated from sialylated glycoconjugates by neuraminidase. Neu5Ac and its regulatory enzyme neuraminidase play a key role in heart failure. We found neuraminidase inhibitor could reduce Neu5Ac levels and improve heart failure in mice model, providing opportunity for a novel therapeutic strategy in HF. Neuraminidase inhibitor oseltamivir is also an old anti-influenza drug. Using oseltamivir may be a new therapeutic strategy in heart failure.

Based on above information, we designed the randomized, open-label, blank-controlled study in patients with chronic HF to receive either oseltamivir or placebo, in addition to standard HF therapy to Identify the effect of oseltamivir on serum Neu5Ac level in patients with heart failure and assess the clinic outcomes of level in patients with heart failure using oseltamivir.

Inclusion Criteria:

1. 18 of age or older, regardless of gender;
2. Patients with NYHA II-IV, LVEF less than 40%;
3. Levels of NT-proBNP more than 450 pg/ml
4. Willing to participate in this study and sign an informed consent, and receive follow-up contact for at least 6 months.

Exclusion Criteria:

1. Onset of acute myocardial infarction within the last 1 month;
2. Had cardiac surgery or onset of cerebrovascular accident within the last 6 months;
3. Plan to have cardiac transplantation or CRT, or already having CRT therapy;
4. Females with pregnancy or plan to have pregnancy;
5. Have participate in any other clinical trial within the last 3 months;
6. Severe neurological disorders (Alzheimer's disease, progressive stage of Parkinson's syndrome), disabilities of lower limbs or deaf-mute;
7. had a history of tumour, or precancerous lesions confirmed by pathological tests (ductal carcinoma in situ, cervical dysplasia, etc.);
8. had malignant tumours (by physical examinations, X-ray, type-B ultrasonic imaging or other methods), or had hyperplastic glands or adenoma which possess endocrine activity and affect cardiac or endocrine functions (pheochromocytoma, goitre, etc.);
9. The subjects who refuse to comply with the items of the research protocol;
10. The subjects who are not available to fulfil the follow-up plan (due to project management or other reasons), according to the judgement of researchers.