The goal of this cross-sectional study is to investigate the prevalence of sarcopenia in patients with Heart Failure. The main question it aims to answer is:

Whether there is a difference in the prevalence of sarcopenia across the spectrum of HFpEF (Heart failure with preserved ejection fraction) and HFrEF (heart failure with reduced ejection fraction).

This is an observational study. The participant population involves patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Healthy volunteers will be recruited as controls in addition to adults with asymptomatic Type 2 Diabetes.

Participants will undergo the following:

1. Skeletal muscle mass, quality and body composition assessments using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA)
2. Skeletal muscle strength assessments (Dynamometer, FysioMeter, handgrip strength)
3. Skeletal muscle energetics assessment (31p-Spectroscopy pre/post-exercise recovery)

Researchers will compare Heart failure groups with healthy controls and adults with asymptomatic type 2 Diabetes to see if there are significant differences in the strength, mass and quality of skeletal muscle.

Heart failure is a complex condition which affects the hearts' ability to pump blood around the body properly. Due to this complexity, it often affects multiple systems in the body and can impact the quality of life. A proportion of heart failure patients also have muscle weakness, where one can feel fatigued, and weak, and may have trouble balancing and standing. To characterise muscle weakness, it is important to look at skeletal muscle mass, strength, and function. The study will focus on the prevalence of reduced muscle strength or function, using a variety of assessments within patients with heart failure. The prevalence of muscle weakness will be investigated by running assessments to look into muscle strength, a series of simple exercise tests will be run of the calf and thigh, in addition to a walking test, a balance test and a standing test to assess whole body performance. To look at the quality of skeletal muscle, a magnetic resonance imaging (MRI) and spectroscopy session will allow us to investigate the quality of the thigh muscle and the energetics in the calf. Finally, a muscle biopsy will be performed to understand differences in muscle tissue in people with different types of heart failure.

Overall, this study will provide us with unique information on skeletal muscle strength, composition and energetics within patients with heart failure, by looking at the main factors which characterise muscle weakness.

Inclusion Criteria:

Heart Failure (HF) Patients: Stage A/B HFpEF

1. Established clinical diagnosis of HFpEF (EF>50%)
2. Clinically stable for ≥ 3 months (no admissions to hospital)
3. Age ≥65
4. Willing to provide written consent for participation in the study.

HF Patients: Stage C/D HFpEF and HFrEF

1. Established clinical diagnosis of HFpEF (EF>50%) OR HFrEF (EF<40%)
2. Clinically stable for ≥ 3 months (no admissions to hospital)
3. Age ≥65
4. Willing to provide written consent for participation in the study. Healthy volunteers

1. Age >18 2. Able to provide written informed consent Asymptomatic T2D

1. Male or female, aged ≥18 and ≤75 years.
2. Diagnosis of stable T2D (determined by i) formal diagnosis in primary care physician case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

Exclusion criteria:

Heart failure

1. Absolute contraindication to MRI
2. Inability to walk/undertake the 6-Minute Walk Test (6MWT)
3. Neuromuscular disorders that may impact skeletal muscle assessment, such as motor neurone disease, multiple sclerosis, skeletal muscle myopathies and myositis
4. Regular or intermittent oral corticosteroid use
5. Untreated hyper or hypothyroidism
6. Heart failure-related hospitalisations in the last 3 months

Healthy volunteers

1. Previous or current signs of HF
2. Risk factors for the development of HF, such as hypertension, diabetes Mellitus or coronary artery disease

Asymptomatic Type 2 Diabetes Mellitus (T2D)

1. Angina pectoris or limiting dyspnoea (>NYHA II)
2. Major atherosclerotic disease: Symptomatic CAD, history of MI, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.
3. Atrial fibrillation or flutter.
4. Moderate to severe valvular heart disease.
5. History of heart failure or cardiomyopathy.
6. Type 1 diabetes mellitus (T1DM).
7. Low fasting C-peptide levels suggestive of adult-onset T1DM.
8. Stage III-V renal disease (estimated glomerular filtration rate ≤30ml/min/1.73m2).
9. Absolute contraindications to MRI.

Four groups of subjects will be recruited, subjects with HFpEF, HFrEF, asymptomatic T2D and metabolically healthy non-diabetic controls. The ongoing studies will allow the co-enrolment of participants. They will be recruited to match age, sex and ethnicity as closely as possible to the HF participants.