Clinical trial NCT02663115: Influence of Severe Heart Failure to Function and Molecular Biological Parameters of Catabolism in the Human Diaphragm and Peripheral Skeletal Muscle
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Ischemic Myocardiopathy
Dilatative Myocardiopathy
Lead sponsor: Heart Center Leipzig - University Hospital
Sponsor class: OTHER
First posted: 2016-01-26
Enrollment: 44
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe therapy-refractory heart failure

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.


Eligibility criteria: 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

Primary outcomes:
measure: Expression of catabolic E3 ligase Muscle ring finger 1 (MuRF1)
timeFrame: at the time of index procedure (biopsy)
Secondary outcomes:
measure: in vitro measurement of the muscle protein - poly ubiquitination of Proteins
timeFrame: at the time of index procedure (biopsy)
measure: in vitro measurement of the muscle protein - the proteasome activity
timeFrame: at the time of index procedure (biopsy)
measure: in vitro measurement of the muscle protein - fiber typing in the muscle samples
timeFrame: at the time of index procedure (biopsy)
measure: in vitro measurement of the force development of skinned muscle fibers
timeFrame: at the time of index procedure (biopsy)
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Heart Center Leipzig
Study officials:
References:
citation: 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.