Metabolic Modulation With Perhexiline in Chronic Heart Failure

• DOI: 10.1161/circulationaha.105.551457
• Publication Date: 2005-11-21T21:29:07Z
• Authors: Leong Lee; Ross Campbell; Michaela Scheuerm...; Rachel Taylor; Prasad Gunaruwan; Lynne Williams; Houman Ashrafian; John Horowitz; Alan G. Fraser; Kieran Clarke; Michael Frenneaux
• Keywords: Dobutamine; Clinical endpoint

Background— Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires novel approach to therapy. Perhexiline an antianginal drug augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects perhexiline treatment in CHF patients. Methods Results— In double-blind fashion, we randomly assigned patients with optimally medicated either (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (V̇ o 2 max), important prognostic marker. addition, effect on myocardial function quality life assessed. Quantitative stress echocardiography tissue Doppler measurements used assess regional ischemic CHF. 31 P magnetic resonance spectroscopy skeletal energetics nonischemic Treatment led significant improvements V̇ max (16.1±0.6 18.8±1.1 mL · kg −1 min ; <0.001), (Minnesota score reduction from 45±5 34±5; =0.04), left ventricular ejection fraction (24±1% 34±2%; <0.001). also increased resting dobutamine (by 15% 24%, respectively) normalized phosphocreatine recovery after exercise. There were no adverse during period. Conclusions— CHF, modulation improved max, fraction, symptoms, function, energetics. may therefore represent for good safety profile, provided dosage adjusted according plasma levels.