The mechanisms behind heart failure are largely unknown. Despite an increasing arsenal of pharmacological therapies, cardiovascular disease is still the most common cause of death in the western world, which demonstrates a pronounced need for more patient-related mechanistic research. Cachexia and limited exercise capacity are the symptoms that best match prediction of heart failure, both of which are symptoms involving a dysfunctional skeletal muscle. An increased understanding of the mechanisms and signaling pathways connects the failure heart with skeletal muscle dysfunction is likely to lead both to discoveries of prognostic factors and possible therapeutic options.

The study is a prospective, non-blinded, study. The study will consist of the assignment of patients with heart failure, New York Heart Association (NYHA) III-IV, 60-80 years old. One hundred (100) patients will be enrolled in this study.

The primary objective is to investigate how changes in the skeletal muscle coincide with changes in physical performance, cardiac function, and prognosis in patients with heart failure, and changes over time. Therefore, the investigators will investigate patients with severe heart failure at 'baseline' and on a second follow-up occasion after 12-16 months.

The secondary and tertiary objective is to investigate how changes in the metabolic signature of blood and satellite cells coincide with changes in physical performance, cardiac function, and prognosis in patients with heart failure, and changes over time. Patient recruitment is expected to occur over 36 months.

The study will be conducted in Sweden at Karolinska University Hospital, Huddinge.

Inclusion criteria:

• Signed informed consent
• 60-80 years old upon inclusion
• Chronic heart failure ≥ 45 days.
• Left ventricular ejection fraction ≤ 35%.
• NYHA III-IV
• Receiving medical management with optimal doses of betablockers, acetylcholinesterase (ACE)-inhibitors or angiotensin II receptor blockers (ARB), and mineral receptor antagonists (MRA) for at least 30 days if tolerated.

Exclusion criteria:

• Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 "crash and burn"
• On-going mechanical circulatory support.
• Severe chronic obstructive pulmonary disease (COPD) or severe restrictive lung disease.
• Psychiatric disease, cognitive dysfunction, alcohol or drug abuse, or psychosocial issues that are likely to impair study compliance
• Condition, other than heart failure, requiring end-of-life care within <6 months in time or where the risk of death within <2 years is considered to be imminent.
• Participation in studies that resulted in departure from normal treatment routine or invasive investigations within <6 months back in time.

Patients with severe heart failure