Metabolic Determinants of Cardiac Function

Overview

Assessment of cardiac energy metabolism in patients with impaired glucose tolerance

Insulin resistance, hepatocellular lipids (HCL) and plasma concentrations of free fatty acids (FFA) are predictors of heart failure, the leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Epidemiological data suggest that diabetic cardiomyopathy (DC) presents as ventricular dysfunction in patients with T2DM independent of coronary artery disease. The underlying cellular mechanisms are poorly understood. Reduced mitochondrial activity and insulin resistance of skeletal muscle relates to liver steatosis, possibly due to higher substrate flux to the liver. High oxidation rates in the liver result in oxidative stress, damage of mitochondria and apoptosis. The investigators hypothesize that (i) HCL and impaired liver energy metabolism correlate with ventricular dysfunction, (ii) impaired glucose uptake and mitochondrial capacity in skeletal muscle relates to enhanced oxidative capacity, oxidative stress and lipid deposition in heart tissue (iii) reduced myocardial oxidative capacity limits recovery of myocardial function in patients with acute heart failure. The investigators aim to assess (i) liver energy metabolism and heart function, (ii) respiration and lipid metabolites in skeletal muscle and heart tissue in humans with advanced heart failure and (iii) the prognostic impact of these factors in humans with acute heart failure. This study will improve the understanding of mechanisms underlying the development of DC and the identification of patients at risk for poor outcome in heart failure.

Conditions

Eligibility

Locations (1)

Outcomes