Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo 31P magnetic resonance spectroscopy study

Francesco Papalia; Fadi Jouhra; George Amin-Youssef; Ajay M. Shah; Geoffrey Charles-Edwards; Darlington O. Okonko

doi:10.1002/ejhf.2454

Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo ³¹P magnetic resonance spectroscopy study

Francesco Papalia, Fadi Jouhra, George Amin-Youssef, Ajay M. Shah, Geoffrey Charles-Edwards, Darlington O. Okonko^*

^*Corresponding author for this work

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

15 Citations (Scopus)

Abstract

Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. Methods and results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83–1.38]) compared to those without ID (1.72 [1.51–2.26], p < 0.01) and healthy volunteers (1.39 [1.10–3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). Conclusion: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.

Original language	English
Pages (from-to)	716-723
Number of pages	8
Journal	EUROPEAN JOURNAL OF HEART FAILURE
Volume	24
Issue number	4
DOIs	https://doi.org/10.1002/ejhf.2454
Publication status	Published - Apr 2022

Keywords

Cardiac energetics
Heart failure
Iron
Spectroscopy

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10.1002/ejhf.2454

Cite this

@article{5399a3eb3ff54b989f589b1725a3ac09,

title = "Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo 31P magnetic resonance spectroscopy study",

abstract = "Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. Methods and results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83–1.38]) compared to those without ID (1.72 [1.51–2.26], p < 0.01) and healthy volunteers (1.39 [1.10–3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). Conclusion: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.",

keywords = "Cardiac energetics, Heart failure, Iron, Spectroscopy",

author = "Francesco Papalia and Fadi Jouhra and George Amin-Youssef and Shah, {Ajay M.} and Geoffrey Charles-Edwards and Okonko, {Darlington O.}",

note = "Funding Information: D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS‐BRC‐1215‐20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS-BRC-1215-20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Conflict of interest: D.O.O. has received speaker fees and research support from Pharmacosmos, and speakers fees from Vifor. All other authors have nothing to disclose. We thank Drs Matthew Clemence and Kieran Hollingsworth for their expert guidance that enabled D.O.O. and G.C.E. to set up the cardiac 31P-MRS protocol. We are also indebted to Dr Torben Schneider for troubleshooting the protocol and Dr Tevfik Ismail for facilitating local research governance. DOO conceived the study and supervised it with GC-E. FP recruited the patients, obtained the data and wrote the first draft of the manuscript. FP and DOO performed the statistical analyses and vouch for the veracity of the data and analyses presented. All authors were involved in the acquisition, analysis, or interpretation of the data, critical revision of the manuscript for important intellectual content, and decision to submit. D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS-BRC-1215-20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Conflict of interest: D.O.O. has received speaker fees and research support from Pharmacosmos, and speakers fees from Vifor. All other authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2022",

month = apr,

doi = "10.1002/ejhf.2454",

language = "English",

volume = "24",

pages = "716--723",

journal = "EUROPEAN JOURNAL OF HEART FAILURE",

issn = "1388-9842",

publisher = "John Wiley & Sons, Ltd",

number = "4",

}

TY - JOUR

T1 - Cardiac energetics in patients with chronic heart failure and iron deficiency

T2 - an in-vivo 31P magnetic resonance spectroscopy study

AU - Papalia, Francesco

AU - Jouhra, Fadi

AU - Amin-Youssef, George

AU - Shah, Ajay M.

AU - Charles-Edwards, Geoffrey

AU - Okonko, Darlington O.

N1 - Funding Information: D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS‐BRC‐1215‐20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS-BRC-1215-20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Conflict of interest: D.O.O. has received speaker fees and research support from Pharmacosmos, and speakers fees from Vifor. All other authors have nothing to disclose. We thank Drs Matthew Clemence and Kieran Hollingsworth for their expert guidance that enabled D.O.O. and G.C.E. to set up the cardiac 31P-MRS protocol. We are also indebted to Dr Torben Schneider for troubleshooting the protocol and Dr Tevfik Ismail for facilitating local research governance. DOO conceived the study and supervised it with GC-E. FP recruited the patients, obtained the data and wrote the first draft of the manuscript. FP and DOO performed the statistical analyses and vouch for the veracity of the data and analyses presented. All authors were involved in the acquisition, analysis, or interpretation of the data, critical revision of the manuscript for important intellectual content, and decision to submit. D.O.O. and F.P. (FS/17/77/33128), and A.M.S. (CH/1999001/11735, RE/18/2/34213) are supported by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust (IS-BRC-1215-20 006) in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Conflict of interest: D.O.O. has received speaker fees and research support from Pharmacosmos, and speakers fees from Vifor. All other authors have nothing to disclose. Publisher Copyright: © 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

PY - 2022/4

Y1 - 2022/4

N2 - Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. Methods and results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83–1.38]) compared to those without ID (1.72 [1.51–2.26], p < 0.01) and healthy volunteers (1.39 [1.10–3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). Conclusion: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.

AB - Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID. Methods and results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83–1.38]) compared to those without ID (1.72 [1.51–2.26], p < 0.01) and healthy volunteers (1.39 [1.10–3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02). Conclusion: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF.

KW - Cardiac energetics

KW - Heart failure

KW - Iron

KW - Spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=85125885694&partnerID=8YFLogxK

U2 - 10.1002/ejhf.2454

DO - 10.1002/ejhf.2454

M3 - Article

C2 - 35199406

AN - SCOPUS:85125885694

SN - 1388-9842

VL - 24

SP - 716

EP - 723

JO - EUROPEAN JOURNAL OF HEART FAILURE

JF - EUROPEAN JOURNAL OF HEART FAILURE

IS - 4

ER -