Abstract 3762: Myocardial Insulin Sensitivity Correlates with Sympathetic Drive in Patients with Left Ventricular Dysfunction
Background: Patients (pts) with left ventricular (LV) dysfunction have increased cardiac sympathetic drive and their myocardium is insulin resistant. Chronic β-adrenergic stimulation leads to insulin resistance in vitro. To ascertain if sympathetic drive correlates with insulin sensitivity, we measured myocardial glucose uptake (MGU) and pre-synaptic norephinephrine (NE) reuptake-1 in pts with LV dysfunction using PET.
Methods 8 pts (67±4 years) with chronic post-ischemic LV dysfunction (EF 43±9%) were studied. LV function was assessed with cardiovascular magnetic resonance and segmental viability was defined as an MGU ≥0.25 μmol/min/g measured with 18F-fluorodeoxyglucose during euglycemic hyperinsulinemic clamp. NE reuptake-1 was measured with [11C]-meta-hydroxy-ephedrine (HED). A reduction in HED volume of distribution (Vd, neuronal influx/efflux) reflects an increased sympathetic drive. 14 healthy volunteers served as controls (C) for MGU and 11 for HED.
Results Compared to C, MGU in pts was reduced in viable and non viable segments independently of LV function. HED-Vd in normally contracting segments of pts was comparable to C whilst it was reduced in dysfunctional segments. In pts, there was a correlation between regional HED-Vd and MGU (Y=0.004x+0.261; R=0.59; p<0.0001).
Conclusions 1- MGU and HED-Vd are reduced in pts with LV dysfunction; 2- HED-Vd reduction is more marked in chronically dysfunctional, but viable myocardium (hibernating) than in normal segments; 3- There is a correlation between HED-Vd and MGU suggesting that an interplay between the sympathetic and insulin axis contributes to myocardial insulin resistance.***=p<0.001