Abstract 3883: Skeletal Muscle Metabolism in Congestive Heart Failure
Exercise intolerance and exertional fatigue are characteristic symptoms reported by patients with congestive heart failure (CHF), but exercise capacity often correlates poorly with objective measures of left ventricular performance. It is also known that some patients with CHF develop insulin resistance after onset of CHF. These seemingly disparate observations may be linked as increasing evidence suggests that skeletal myopathy and impaired mitochondrial function may contribute to exertional fatigue. Furthermore, patients with primary defects in mitochondrial function (and normal left ventricular function) accumulate excess intracellular lipids in skeletal muscle causing insulin resistance. We tested the hypothesis that the concentration of intramyocellular lipids ([IMCL]) is increased in class II – IV ambulatory subjects with CHF. High field Magnetic Resonance Spectroscopy now allows rapid acquisition (< 2 min) of in vivo metabolic data. Three groups of patients were studied (n=34 total):
patients with CHF with ejection fraction (EF) <40% and characteristic symptoms,
patients with type 2 diabetes and preserved EF, and
healthy, age-matched subjects recruited from the ambulatory clinics.
Image-guided 1H NMR spectra of the gastrocnemius and soleus muscles were obtained at 7 Tesla. Parameters for the study: voxel 10×10×10 mm, TR 2000, TE 16, TM 22, NA 80. All concentrations are reported as mmols/kg wet mass and were determined using skeletal creatine as an internal standard. [IMCL] was increased in both the gastrocnemius (G, 3.3±3.1) and soleus (S, 4.8±4.8) muscles among patients with CHF subjects when compared to diabetic (G, 2.3±1.8; S, 3.6±1.3) and control subjects (G, 1.6±1.3; S, 2.4±1.3). All subjects tolerated exposure to the 7 Tesla MRI. Patients with CHF generally have increased concentration of intramyocellular lipids. The wide distribution of [IMCL] in CHF patients maybe related to skeletal muscle heterogeneity rather than poor left ventricular performance, consistent with the poor correlation between exercise intolerance and LVEF. [IMCL] maybe a useful non-invasive biomarker of altered skeletal muscle metabolism and ultimately, of mitochondrial dysfunction and functional disability in CHF patients.