In the United Kingdom, heart failure (HF) affects about 900,000 people with 60,000 new cases annually. Up to 60% of people living with HF also experience sarcopenia, known as loss of muscle mass and strength. Sarcopenia contributes significantly to low physical capacity and exercise intolerance and worsens the prognosis of the disease and quality of life.

In comparison to primary sarcopenia (age-related sarcopenia), secondary sarcopenia occurs if other factors, including malignancy or organ failure, are evident in addition to aging. Secondary sarcopenia is highly common in patients with heart failure (Sarc-HF) (prevalence is 35%-69%), and has a significantly negative impact on exercise capacity, weight-adjusted peak maximal oxygen consumption, left ventricular function, and re-hospitalization rates and mortality.

In this integrated study of NHS patients with HF, the investigators aim is to identify the underlying mechanisms of muscle weakness in HF utilizing including body composition, circulating metabolites (metabolic profile), and functional tests for (1) early detection of otherwise subclinical HF, (2) diagnostic assessment of clinically manifest HF-sarcopenia, (3) the risk stratification of subjects with a suspected or confirmed diagnosis, and (4) selection of an appropriate therapeutic intervention.

Investigators aim to understanding the underlying physiological links for secondary sarcopenia in older age and particularly those with heart failure. This links partly can be explained by impaired energy metabolism of amino acids and fatty acid oxidation. This can lead to lower ATP production and deprivation of both skeletal muscle and heart from energy sources, which worsens the sarcopenia in HF.

RESEARCH QUESTION/AIM(S)

• Faecal and plasma metabolite content will be correlated with matrix of global muscle function to assess if there are differences according to sarcopenia status in heart failure.
• Utilizing metabolomic data to disclose dysregulation of pathways linked to energy production (Krebs cycle, Warburg effect), amino acid catabolism and free fatty acids and Bile acids. I will investigate these relationships with gut microbiome composition.

Outcomes Descriptive and bioinformatic analysis on associations of multivariate biomarkers including muscle mass and muscle strength from lower and upper body and functional tests, and plasma metabolome and proteome items according to cardiac function and HF status.

Inclusion criteria for HF:

1. Clinically diagnosed HF regardless of ejection fraction rate (both HFrEF and HFpEF).
2. Age 50 years and older.
3. BMI more than 18 and less than 30 kg/m^2.
4. Must be on optimal medical treatment for three months prior to inclusion.
5. Do not have contraindications to providing a blood sample.
6. Sufficient mental capacity to consent as determined by the researchers.
7. Able to walk with or without a walker for at least 16 m.
8. No objection to the researchers contacting their general practitioner and neurologist.

Exclusion criteria for HF:

1. Receiving treatment with antibiotics, probiotics, or fish oil during the last 3 months prior to inclusion.
2. Major comorbidities (i.e., cancer, Alzheimer's, type 2 diabetes, chronic kidney disease).
3. Treatment with immunosuppressive drugs.
4. Concurrent infections, or bowel disease.
5. Patients who had received cardiac resynchronization therapy during the past 6 months will not be included.
6. Participants must also not be on any other clinical trial during the study.

Inclusion criteria for Healthy controls:

1. No history of chronic disease and will be screened for hypertension.
2. BMI more than 18 and less than 30 kg/m^2.
3. Although other cardiovascular conditions will be exclusionary, treated hypercholesterolemia and controlled hypertension will be allowed in the healthy group to allow the representation of elderly subjects within this cohort.

both men and women

Older men and women with and without HF are targeted following a screening of medical records from the Liverpool Hospital Foundation NHS Trust HF clinic. Our usual practice is to recruit the non-HF controls by community approach.