Diabetes can lead to heart failure independently, but the underlying causes remain incompletely understood. The main aim of this study is to identify differential regulation of mitochondrial substrate utilization and complex activity in heart failure and type 2 diabetes mellitus (T2DM). For this, we will conduct a prospective, observational study to examine myocardial mitochondrial oxidative function and related metabolic parameters, gene expression, histological markers, and inflammation in cardiac tissue from patients with heart failure or patients after heart transplantation. We will further assess cardiac function using cardiac magnetic resonance imaging with and without stress protocols and magnetic resonance spectroscopy. Glycemic control/T2DM will be characterized by oral glucose tolerance tests. The results of this project will help to better understand the cellular mechanisms of the development of diabetic cardiomyopathy and contribute to the development of early diagnostic, as well as therapeutic approaches for the prevention and treatment of diabetic cardiomyopathy.
Age ≥ 20 and ≤ 85 years
Male and female patients with manifest heart failure (NYHA II-IV) and clinical indication for myocardial biopsy or after transplantation and clinical indication for myocardial biopsy with or without type II diabetes mellitus or terminal (NYHA IV) heart failure with or without type II diabetes mellitus.
Written informed consent
Acute infectious diseases within the last 2 weeks before the examination
Autoimmune diseases or acute immunocompromising diseases (leukocytes < 5000/μl)
Pregnancy
Use of alcohol or drugs (addiction), psychiatric diseases
Patients with heart failure with or without T2DM undergoing endomyocardial biopsy for clinical reasons (WP1), patients with terminal heart failure with or without T2DM undergoing left ventricular assist device surgery or heart transplantation (WP2), and patients after heart transplantation with and without T2DM undergoing endomyocardial biopsy for clinical reasons (post-transplant surveillance).
Cohort
Prospective
Not listed
Substrate-specific JVO2 of ventricular myocardial mitochondrial oxidative capacity
measured in (pmol/s\*mg)
Markers of cardiac function and structure
measured by cardiac magnet resonance tomography
Markers of cardiac function
measured by echocardiography
Cardiac substrate utilization
measured by cardiac magnet resonance spectroscopy (MRS)
Patterns in the myocardial transcriptome and systemic metabolome
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