Purpose  

We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF.

Methods  

Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [¹¹C]meta-hydroxy-ephedrine (HED) volume of distribution (V _d) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 ± 6 years, p < 0.01 vs patients) data.

Results  

MGU in patients was reduced in both normal remote (0.44 ± 0.14 μmol·min⁻¹·g⁻¹) and dysfunctional (0.49 ± 0.14 μmol·min⁻¹·g⁻¹) segments compared with controls (0.61 ± 0.7 μmol·min⁻¹·g⁻¹; p < 0.001 vs both). HED V _d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml·g⁻¹) compared with normal segments (52.2 ± 19.6 ml·g⁻¹) and compared with controls (62.7 ± 11.3 ml·g⁻¹). In patients, regional MGU was correlated with HED V _d.

Conclusion  

The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts.