Document Detail


Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy.
MedLine Citation:
PMID:  20921440     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hypertrophic cardiomyopathy patients exhibit myocardial energetic impairment, but a causative role for this energy deficiency in the pathophysiology of hypertrophic cardiomyopathy remains unproven. We hypothesized that the metabolic modulator perhexiline would ameliorate myocardial energy deficiency and thereby improve diastolic function and exercise capacity.
METHODS AND RESULTS: Forty-six consecutive patients with symptomatic exercise limitation (peak Vo(2) <75% of predicted) caused by nonobstructive hypertrophic cardiomyopathy (mean age, 55±0.26 years) were randomized to perhexiline 100 mg (n=24) or placebo (n=22). Myocardial ratio of phosphocreatine to adenosine triphosphate, an established marker of cardiac energetic status, as measured by (31)P magnetic resonance spectroscopy, left ventricular diastolic filling (heart rate normalized time to peak filling) at rest and during exercise using radionuclide ventriculography, peak Vo(2), symptoms, quality of life, and serum metabolites were assessed at baseline and study end (4.6±1.8 months). Perhexiline improved myocardial ratios of phosphocreatine to adenosine triphosphate (from 1.27±0.02 to 1.73±0.02 versus 1.29±0.01 to 1.23±0.01; P=0.003) and normalized the abnormal prolongation of heart rate normalized time to peak filling between rest and exercise (0.11±0.008 to -0.01±0.005 versus 0.15±0.007 to 0.11±0.008 second; P=0.03). These changes were accompanied by an improvement in primary end point (peak Vo(2)) (22.2±0.2 to 24.3±0.2 versus 23.6±0.3 to 22.3±0.2 mL · kg(-1) · min(-1); P=0.003) and New York Heart Association class (P<0.001) (all P values ANCOVA, perhexiline versus placebo).
CONCLUSIONS: In symptomatic hypertrophic cardiomyopathy, perhexiline, a modulator of substrate metabolism, ameliorates cardiac energetic impairment, corrects diastolic dysfunction, and increases exercise capacity. This study supports the hypothesis that energy deficiency contributes to the pathophysiology and provides a rationale for further consideration of metabolic therapies in hypertrophic cardiomyopathy.
Authors:
Khalid Abozguia; Perry Elliott; William McKenna; Thanh Trung Phan; Ganesh Nallur-Shivu; Ibrar Ahmed; Abdul R Maher; Kulvinder Kaur; Jenny Taylor; Anke Henning; Houman Ashrafian; Hugh Watkins; Michael Frenneaux
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-10-04
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2010-11-05     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1562-9     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00500552
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MeSH Terms
Descriptor/Qualifier:
Blood Glucose / metabolism
Cardiomyopathy, Hypertrophic / drug therapy,  metabolism*,  physiopathology*
Double-Blind Method
Energy Metabolism / drug effects*,  physiology
Exercise Tolerance / drug effects*,  physiology
Female
Heart Rate / drug effects,  physiology
Humans
Male
Middle Aged
Myocardium / metabolism
Oxygen Consumption / drug effects,  physiology
Perhexiline / pharmacology*,  therapeutic use
Quality of Life
Vasodilator Agents / pharmacology*,  therapeutic use
Ventricular Dysfunction, Left / drug therapy,  metabolism,  physiopathology
Grant Support
ID/Acronym/Agency:
PG/05/087//British Heart Foundation; RG/07/012/24110//British Heart Foundation; //Department of Health
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Vasodilator Agents; KU65374X44/Perhexiline
Comments/Corrections
Comment In:
Circulation. 2010 Oct 19;122(16):1547-9   [PMID:  20921436 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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