Mitochondrial Substrate Utilization in the Diabetic Human Heart

Summary

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.

Eligibility

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Suspected or manifest AIDS (HIV); hepatitis B or C.
* Liver disease not attributed to the presence of nonalcoholic fatty liver hepatitis or congestive hepatopathy in heart failure
* Malignant cancer
* Lack of capacity to give informed consent or lack of consent to participate in the study
* For MRI study with drug stress: contraindications to the use of regadenoson, specifically: a) Hypersensitivity to the active ingredient or any of the other ingredients mentioned. b) Second- or third-degree atrioventricular (AV) block or sinus node dysfunction, unless these patients have a functioning pacemaker. c) Unstable angina that has not been stabilized with medication. d) Severe hypotension. e) Decompensated stages of heart failure.

Conditions7

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