Abstract 3166: Augmenting Myocardial Glucose Utilization Improves Ischemic Regional Wall Motion Abnormalities
Background: We have previously demonstrated a beneficial effect of the metabolic drug perhexiline on exercise tolerance in heart failure (HF). Perhexiline induces a shift in myocardial substrate utilization towards glucose which is more oxygen efficient than free fatty acid oxidation. Because of this, augmenting glucose metabolism might be expected to recruit hibernating myocardium subtended by diseased coronary arteries.
Methods: This was a double-blind randomized controlled trial. Patients with ischemic left ventricular (LV) dysfunction and optimally medicated NYHA class II–III HF with or without angina symptoms were randomized to treatment with perhexiline (n = 15) or placebo (n = 15) for 8 weeks. Baseline dobutamine stress echocardiography (DSE) was performed. Using pulsed tissue Doppler, longitudinal myocardial velocities were obtained from standard apical views. Off-line analysis was performed to determine the peak systolic velocity (PSV) of 11 myocardial segments. Following treatment with perhexiline/placebo DSE was repeated.
Results: There was no effect of treatment with placebo on regional or global myocardial function. Treatment with perhexiline increased PSV in LV walls subtended by left anterior descending (LAD) and circumflex arteries with ≥ 70% stenosis on coronary angiography. There was a non-specific trend towards improvement in diseased right coronary artery (RCA) territories. The increases in PSV during peak stress were as follows: LAD segments: 21% ANCOVA p = 0.03, circumflex: 15% p = 0.04, RCA: 19% p = NS. Treatment with perhexiline also abolished the biphasic response in 16% (Chi-squared; p = 0.01) of diseased segments, suggesting a recruitment of hibernating but ischemic myocardium. There was no significant improvement with perhexiline treatment in walls not subtended by diseased arteries.
Discussion: We have demonstrated that short-term treatment with the metabolic drug perhexiline improves contractility in ischemic myocardial segments subtended by significantly diseased coronary arteries. The recruitment of hibernating myocardium could be occurring because of increased metabolic efficiency. Metabolic modulation is therefore a promising treatment paradigm for ischemic heart disease and heart failure.