Cardiac work is related to creatine kinase energy supply in human heart failure: A cardiovascular magnetic resonance spectroscopy study

Refaat E. Gabr, Abdel Monem M. El-Sharkawy, Michael Schar, Gurusher S. Panjrath, Gary Gerstenblith, Robert George Weiss, Paul A Bottomley

Research output: Contribution to journalArticle

Abstract

Background: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. Methods: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. Results: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). Conclusion: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00181259.

Original languageEnglish (US)
Article number81
JournalJournal of Cardiovascular Magnetic Resonance
Volume20
Issue number1
DOIs
StatePublished - Dec 10 2018

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Creatine Kinase
Magnetic Resonance Spectroscopy
Heart Failure
Adenosine Triphosphate
Healthy Volunteers
Cardiac Volume
Phosphorus
Spectrum Analysis
Magnetic Resonance Imaging
Pressure

Keywords

  • Cardiac metabolism
  • Cardiac work
  • Heart failure
  • Magnetic resonance
  • Translational studies

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Cardiac work is related to creatine kinase energy supply in human heart failure: A cardiovascular magnetic resonance spectroscopy study",
abstract = "Background: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. Methods: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. Results: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53{\%} ± 16 vs. 79{\%} ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). Conclusion: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00181259.",
keywords = "Cardiac metabolism, Cardiac work, Heart failure, Magnetic resonance, Translational studies",
author = "Gabr, {Refaat E.} and El-Sharkawy, {Abdel Monem M.} and Michael Schar and Panjrath, {Gurusher S.} and Gary Gerstenblith and Weiss, {Robert George} and Bottomley, {Paul A}",
year = "2018",
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doi = "10.1186/s12968-018-0491-6",
language = "English (US)",
volume = "20",
journal = "Journal of Cardiovascular Magnetic Resonance",
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T1 - Cardiac work is related to creatine kinase energy supply in human heart failure

T2 - A cardiovascular magnetic resonance spectroscopy study

AU - Gabr, Refaat E.

AU - El-Sharkawy, Abdel Monem M.

AU - Schar, Michael

AU - Panjrath, Gurusher S.

AU - Gerstenblith, Gary

AU - Weiss, Robert George

AU - Bottomley, Paul A

PY - 2018/12/10

Y1 - 2018/12/10

N2 - Background: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. Methods: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. Results: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). Conclusion: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00181259.

AB - Background: It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart's primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients. Methods: Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF. Results: In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002). Conclusion: These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00181259.

KW - Cardiac metabolism

KW - Cardiac work

KW - Heart failure

KW - Magnetic resonance

KW - Translational studies

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