Influence of Severe Heart Failure to Function and Molecular Biological Parameters of Catabolism in the Human Diaphragm and Peripheral Skeletal Muscle

Study Overview
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Brief Summary
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Project aim is to quantify the influence of a severe therapy-refractory heart failure caused by ischemic or dilative myocardiopathy on the function of the diaphragm, its molecular biological parameters and on the M. vastus lateralis. The control group consists of patients with coronary artery disease (CAD) and normal left ventricular ejection fraction indicated for coronary artery bypass graft surgery (CABG) Differences in the geneses of heart failure (ischemic vs. dilative cardiomyopathy) will be evaluated during analysis. The ubiquitin-proteasome signaling pathway is considered as a central issue for the mechanism of the analyses muscle catabolism.

Conditions
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Heart Failure, Ischemic Myocardiopathy, Dilatative Myocardiopathy

Intervention / Treatment
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* Other: Biopsy of the diaphragmatic muscle
* Other: Skeletal muscle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: inclusion criteria Group A: age 40 - 70 years Restricted left ventricular pump function left ventricular ejection fraction (LVEF) > 35% on the basis of ischemic cardiomyopathy (ICM) and restricted resting cardiac output (CI> 2.4 L / min / m²) or restricted maximal oxygen uptake (VO2max> 17 ml / min / m²) Duration of heart failure> 1 year Maximum of individual heart failure therapy Heart team decision to LVAD Implantation inclusion criteria Group B: age 40 - 70 years Restricted left ventricular pump function (LVEF) > 35% on the basis of dilatative cardiomyopathy (DCM) and restricted resting cardiac output (CI> 2.4 L / min / m²) or restricted maximal oxygen uptake (VO2max> 17 ml / min / m²) Duration of heart failure> 1 year Maximum of individual heart failure therapy Heart team decision to LVAD Implantation inclusion criteria Group C: age 40 - 70 years coronary heart disease with indication for elective, coronary artery bypass surgery normal left ventricle (LV) pumping function LVEF> 50% stable clinical situation (no cardiac decompensation within the last 6 months) Exclusion Criteria: Mechanical ventilation within the last 3 months Forced Expiratory Pressure (FEV1) <70% of the norm and / or therapy with α antagonists, β-mimetics or inhaled corticosteroids for the treatment of a lung disease Pulmonary fibrosis elevated diaphragm in the ultrasound or X-ray diagnosis or known paresis of the phrenic nerve chronic kidney disease (CKD) stage 4 and 5, i.e. glomerular filtration rate (GFR) <30ml / min / 1.73m and / or dialysis Acute renal failure Treatment with immunosuppressive agents Hepatic insufficiency Child-Pugh B and C Higher grade ventricular arrhythmias (Lown IV b) Acute myocardial infarction (less than three months) Decompensated Vitium cordis Age <40 years and> 70 years Pregnancy

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>Patients (age 40 - 70 years) with severe therapy-refractory heart failure caused by ischemic or dilatative myocardiopathy with indication for left ventricular assist device (LVAD) therapy | Other: Biopsy of the diaphragmatic muscle<br> <br> Other: Skeletal muscle biopsy<br> <br> |
| Arm 2<br>Patients (age 40-70 years) with the indication for elective bypass surgery and normal left ventricular function (EF>50%) | Other: Biopsy of the diaphragmatic muscle<br> <br> Other: Skeletal muscle biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of catabolic E3 ligase Muscle ring finger 1 (MuRF1) |  | at the time of index procedure (biopsy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| in vitro measurement of the muscle protein - poly ubiquitination of Proteins |  | at the time of index procedure (biopsy) | 
| in vitro measurement of the muscle protein - the proteasome activity |  | at the time of index procedure (biopsy) | 
| in vitro measurement of the muscle protein - fiber typing in the muscle samples |  | at the time of index procedure (biopsy) | 
| in vitro measurement of the force development of skinned muscle fibers |  | at the time of index procedure (biopsy) |