Mechanism of Sarcopenia in Heart Failure

Study Overview
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Brief Summary
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The aim of the study is to provide information on the interaction between socioeconomic factors, daily physical activity, nutrition and lifestyle on loss of muscle mass and muscle function in patients with heart failure.

Detailed Description
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A total of 200 consecutive heart failure patients will be included and 50 age and sex-matched individuals with no history of cardiovascular disease will serve as controls. Baseline variables of body composition, physical capacity, daily physical activity, nutritional status, quality of life, socioeconomic status and insulin resistance will be obtained along with a skeletal muscle tissue biopsy and blood samples for laboratory analyses. Baseline variables from heart failure patients will be compared to healthy controls. Patients and controls will be invited to follow-up visits at 12 and 36 months. Changes in baseline variables will be analyzed. Events will be identified through national registries.

Official Title
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Socioeconomic Factors and Mechanisms of Sarcopenia and Muscle Strength in Chronic Heart Failure Patients

Conditions
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Heart Failure, Sarcopenia, Cachexia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide valid informed consent. Heart failure with preserved, mid-range or reduced ejection fraction (NYHA I-IV) according to European Society of Cardiology guidelines. Exclusion Criteria: Cancer requiring treatment (e.g. prostate cancer on watchful waiting does not exclude patients). Severe musculoskeletal or neurological disability. Severe lung disease with a forced expiratory volume 1 < 40% of predicted. Treatment with anticoagulants (warfarin, apixaban, edoxaban, dabigatran and rivaroxaban) is an exclusion criterion for muscle biopsy. Patients with anticoagulant treatment will be invited to participate in the study without muscle biopsy. Other comorbidities that prevent the patient from participating in the study examinations as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic Heart Failure<br>Patients with heart failure with preserved, mid-range or reduced ejection fraction (NYHA I-IV) according to European Society of Cardiology guidelines. | |
| Controls<br>Age and sex matched control group. Individuals with no history of cardiovascular disease or severe lung, musculoskeletal or neurological disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical performance, peak VO2 | Change in peak oxygen uptake (peak VO2), measured in ml O2/kg/min | From baseline to 12 and 36 months | 
| Physical performance, walking distance | Change in walking distance (6MWT) in meters | From baseline to 12 and 36 months | 
| Physical performance, muscle strength | Change in knee extension/flexion isokinetic strength (assessed by peak torque, Nm) and isometric strength (assessed by peak torque, Nm) | From baseline to 12 and 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular events | Incidence of a composite endpoint of death, hospitalization with worsening of heart failure other cardiovascular events (myocardial infarction, unstable angina, revascularization and stroke) and non-cardiovascular hospitalizations | During follow-up of 10 years | 
| Body composition | Change in appendicular lean mass (measured in grams) and fat mass (measured in grams) | From baseline to 12 and 36 months | 
| Muscle tissue fiber types | Change in ratio between muscle fiber types (type I, IIa and IIb) assessed by immunohistochemistry | From baseline to 12 and 36 months | 
| Muscle tissue cellular composition | Change in muscle tissue cellular composition assessed by cell sorting | From baseline to 12 and 36 months | 
| Muscle tissue mitochondrial function | Change in muscle mitochondrial function assessed by high-resolution respirometry | From baseline to 12 and 36 months | 
| Daily physical activity | Change in daily physical activity assessed by 7-day accelerometry | From baseline to 12 and 36 months | 
| Insulin resistance | Changes in insulin resistance assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | From baseline to 12 and 36 months | 
| Whole body metabolism | Changes in circulating metabolic markers | From baseline to 12 and 36 months | 
| Muscle metabolism | Changes in metabolic signature of muscle tissue assessed by liquid chromatography-high-resolution mass spectrometry | From baseline to 12 and 36 months | 
| Symptoms | Changes in the Minnesota Living with Heart Failure Questionnaire score (range 0-105, from best to worst) | From baseline to 12 and 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Sarcopenia, Cachexia