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

NCT02663115 | Completed

• 1 other identifier: U1111-1178-1176
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Ischemic Myocardiopathy; Dilatative Myocardiopathy

Outcome Measures

Primary Outcomes (1)

• Expression of catabolic E3 ligase Muscle ring finger 1 (MuRF1)

  at the time of index procedure (biopsy)

Secondary Outcomes (4)

• 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)

Study Arms (2)

Arm 1

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; Other: Skeletal muscle biopsy

Arm 2

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; Other: Skeletal muscle biopsy

Interventions

Biopsy of the diaphragmatic muscle OTHER

Arm 1; Arm 2

Skeletal muscle biopsy OTHER

Arm 1; Arm 2

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with severe therapy-refractory heart failure

You may qualify if:

• 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
• 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
• age 40 - 70 years
• coronary heart disease with indication for elective, coronary artery bypass surgery
• normal left ventricle (LV) pumping function LVEF\> 50%

You may not qualify if:

• 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

Sponsors & Collaborators

• Norman Mangner: lead

Study Sites (1)

Heart Center Leipzig

Leipzig, Germany

Location

Related Publications (1)

• Mangner N, Garbade J, Heyne E, van den Berg M, Winzer EB, Hommel J, Sandri M, Jozwiak-Nozdrzykowska J, Meyer AL, Lehmann S, Schmitz C, Malfatti E, Schwarzer M, Ottenheijm CAC, Bowen TS, Linke A, Adams V. Molecular Mechanisms of Diaphragm Myopathy in Humans With Severe Heart Failure. Circ Res. 2021 Mar 19;128(6):706-719. doi: 10.1161/CIRCRESAHA.120.318060. Epub 2021 Feb 4.

  PMID: 33535772 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med. Norman Mangner

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 26, 2016
• Study Start: January 1, 2016
• Primary Completion: March 1, 2018
• Last Updated: June 11, 2018

Record last verified: 2018-06

Locations

DE (1)