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

Completed

• Conditions: Dilatative Myocardiopathy; Heart Failure; Ischemic Myocardiopathy
• Interventions: Other: Biopsy of the diaphragmatic muscle; Other: Skeletal muscle biopsy

• Registration Number: NCT02663115
• Lead Sponsor: Norman Mangner

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-15
• Study First Submitted QC: 2016-01-21
• Study First Posted: 2016-01-26
• Primary Completion: 2018-03
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-08
• Last Update Posted: 2018-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm 2	Skeletal muscle biopsy	Patients (age 40-70 years) with the indication for elective bypass surgery and normal left ventricular function (EF\>50%)
Arm 2	Biopsy of the diaphragmatic muscle	Patients (age 40-70 years) with the indication for elective bypass surgery and normal left ventricular function (EF\>50%)
Arm 1	Biopsy of the diaphragmatic muscle	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
Arm 1	Skeletal muscle biopsy	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

Primary Outcome Measures

Name	Time	Method
Expression of catabolic E3 ligase Muscle ring finger 1 (MuRF1)	at the time of index procedure (biopsy)

Secondary Outcome Measures

Name	Time	Method
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 - 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)
in vitro measurement of the muscle protein - the proteasome activity	at the time of index procedure (biopsy)

Trial Locations

Locations (1)

Heart Center Leipzig; 🇩🇪 Leipzig, Germany