title: Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy.
abstract: OBJECTIVE
  The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization.
  
  
  BACKGROUND
  Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). (31)P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio. Because improvement of HF syndrome can improve cardiac energetics secondarily, we investigated the effects of short-term perhexiline therapy.
  
  
  METHODS
  Patients with systolic HF of nonischemic etiology (n = 50, 62 ± 1.8 years of age, New York Heart Association functional class II to IV, LVEF: 27.0 ± 1.44%) were randomized to receive perhexiline 200 mg or placebo for 1 month in a double-blind fashion. Clinical assessment, echocardiography, and (31)P cardiac magnetic resonance spectroscopy were performed at baseline and after 1 month. A substudy of 22 patients also underwent cross-heart blood sampling at completion of the study to quantify metabolite utilization.
  
  
  RESULTS
  Perhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; p < 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; p = 0.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (p = 0.036). Short-term perhexiline therapy did not change LVEF. Cross-heart measures of cardiac substrate uptake and respiratory exchange ratio (which reflects the ratio of substrates used) did not differ between patients who received perhexiline versus placebo.
  
  
  CONCLUSIONS
  Perhexiline improves cardiac energetics and symptom status with no evidence of altered cardiac substrate utilization. No change in LVEF is seen at this early stage. (Metabolic Manipulation in Chronic Heart Failure; NCT00841139).
authors: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors: Roger M
authors: RM
authors: Beadle
authors: Department of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors: Lynne K
authors: LK
authors: Williams
authors: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, England.
authors: Michael
authors: M
authors: Kuehl
authors: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, England.
authors: Sarah
authors: S
authors: Bowater
authors: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, England.
authors: Khalid
authors: K
authors: Abozguia
authors: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, England.
authors: Francisco
authors: F
authors: Leyva
authors: Department of Cardiology, University Hospital of Wales, Cardiff, Wales.
authors: Zaheer
authors: Z
authors: Yousef
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, England.
authors: Anton J M
authors: AJ
authors: Wagenmakers
authors: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland.
authors: Frank
authors: F
authors: Thies
authors: Department of Cardiology and Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia.
authors: John
authors: J
authors: Horowitz
authors: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland. Electronic address: m.p.frenneaux@abdn.ac.uk.
authors: Michael P
authors: MP
authors: Frenneaux
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004452:Echocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010480:Perhexiline / Q000627:therapeutic use*; D012189:Retrospective Studies; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D002317:Cardiovascular Agents; D010480:Perhexiline
keywords: heart failure; magnetic resonance spectroscopy; myocardial metabolism; perhexiline