acipimox and Cardiomyopathy--Dilated

Metabolic modulators that enhance myocardial glucose metabolism by inhibiting free fatty acid (FFA) metabolism may improve cardiac function in heart failure patients. We studied the effect of acute FFA withdrawal on cardiac function in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDCM).. Eighteen fasting nondiabetic patients with IDCM (14 men, 4 women, aged 58.8+/-8.0 years, ejection fraction 33+/-8.8%) and 8 matched healthy controls underwent examination of myocardial perfusion and oxidative and FFA metabolism, before and after acute reduction of serum FFA concentrations by acipimox, an inhibitor of lipolysis. Metabolism was monitored by positron emission tomography and [15O]H2O, [11C]acetate, and [11C]palmitate. Left ventricular function and myocardial work were echocardiographically measured, and efficiency of forward work was calculated. Acipimox decreased myocardial FFA uptake by >80% in both groups. Rate-pressure product and myocardial perfusion remained unchanged, whereas stroke volume decreased similarly in both groups. In the healthy controls, reduced cardiac work was accompanied by decreased oxidative metabolism (from 0.071+/-0.019 to 0.055+/-0.016 min(-1), P<0.01). In IDCM patients, cardiac work fell, whereas oxidative metabolism remained unchanged and efficiency fell (from 35.4+/-12.6 to 31.6+/-13.3 mm Hg x L x g(-1), P<0.05).. Acutely decreased serum FFA depresses cardiac work. In healthy hearts, this is accompanied by parallel decrease in oxidative metabolism, and myocardial efficiency is preserved. In failing hearts, FFA depletion did not downregulate oxidative metabolism, and myocardial efficiency deteriorated. Thus, failing hearts are unexpectedly more dependent than healthy hearts on FFA availability. We propose that both glucose and fatty acid oxidation are required for optimal function of the failing heart.

Topics: Aged; Cardiac Output, Low; Cardiomyopathy, Dilated; Coronary Circulation; Echocardiography; Fatty Acids, Nonesterified; Female; Heart; Heart Rate; Humans; Hypolipidemic Agents; Male; Middle Aged; Myocardium; Oxidation-Reduction; Positron-Emission Tomography; Pyrazines; Ventricular Function, Left