Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy

Roger M Beadle; Lynne K Williams; Michael Kuehl; Sarah Bowater; Khalid Abozguia; Francisco Leyva; Zaheer Yousef; Anton J M Wagenmakers; Frank Thies; John Horowitz; Michael P Frenneaux

doi:10.1016/j.jchf.2014.09.009

Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy

Roger M Beadle, Lynne K Williams, Michael Kuehl, Sarah Bowater, Khalid Abozguia, Francisco Leyva, Zaheer Yousef, Anton J M Wagenmakers, Frank Thies, John Horowitz, Michael P Frenneaux

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVES: 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).

Original language	English
Pages (from-to)	202-211
Number of pages	10
Journal	JACC. Heart failure
Volume	3
Issue number	3
Early online date	28 Jan 2015
DOIs	https://doi.org/10.1016/j.jchf.2014.09.009
Publication status	Published - Mar 2015

Bibliographical note

Date of Acceptance: 19/09/2014

Supported by the British Heart Foundation (PG/06/105) and sponsored by the University Hospitals Birmingham NHS Foundation Trust.
Dr. Leyva has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. Dr. Frenneaux is an inventor who holds method of use patents for perhexiline in heart muscle diseases; and has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Keywords

heart failure
magnetic resonance spectroscopy
myocardial metabolism
perhexiline

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10.1016/j.jchf.2014.09.009Licence: Unspecified

Frank Thies
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Reader
Person: Academic

Cite this

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title = "Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy",

abstract = "OBJECTIVES: 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).",

keywords = "heart failure, magnetic resonance spectroscopy, myocardial metabolism, perhexiline",

author = "Beadle, {Roger M} and Williams, {Lynne K} and Michael Kuehl and Sarah Bowater and Khalid Abozguia and Francisco Leyva and Zaheer Yousef and Wagenmakers, {Anton J M} and Frank Thies and John Horowitz and Frenneaux, {Michael P}",

note = "Date of Acceptance: 19/09/2014 Supported by the British Heart Foundation (PG/06/105) and sponsored by the University Hospitals Birmingham NHS Foundation Trust. Dr. Leyva has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. Dr. Frenneaux is an inventor who holds method of use patents for perhexiline in heart muscle diseases; and has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose Copyright {\textcopyright} 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",

year = "2015",

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doi = "10.1016/j.jchf.2014.09.009",

language = "English",

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journal = "JACC. Heart failure",

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TY - JOUR

T1 - Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy

AU - Beadle, Roger M

AU - Williams, Lynne K

AU - Kuehl, Michael

AU - Bowater, Sarah

AU - Abozguia, Khalid

AU - Leyva, Francisco

AU - Yousef, Zaheer

AU - Wagenmakers, Anton J M

AU - Thies, Frank

AU - Horowitz, John

AU - Frenneaux, Michael P

N1 - Date of Acceptance: 19/09/2014 Supported by the British Heart Foundation (PG/06/105) and sponsored by the University Hospitals Birmingham NHS Foundation Trust. Dr. Leyva has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. Dr. Frenneaux is an inventor who holds method of use patents for perhexiline in heart muscle diseases; and has served as a consultant for and received research support from Medtronic, St. Jude Medical, Boston Scientific, and Sorin. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2015/3

Y1 - 2015/3

N2 - OBJECTIVES: 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).

AB - OBJECTIVES: 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).

KW - heart failure

KW - magnetic resonance spectroscopy

KW - myocardial metabolism

KW - perhexiline

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DO - 10.1016/j.jchf.2014.09.009

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C2 - 25650370

SN - 2213-1787

VL - 3

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JO - JACC. Heart failure

JF - JACC. Heart failure

IS - 3

ER -

Improvement in Cardiac Energetics by Perhexiline in Heart Failure Due to Dilated Cardiomyopathy

Abstract

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Keywords

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Frank Thies

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