{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:39:37Z","timestamp":1791538777964,"version":"4.3.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF &amp;lt;45%, n = 14) or CONTROL (LVEF &amp;gt;45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-L-carnitine, a medium chain fatty acid (MCFA). The in situ enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P \u2264 0.05). ADP sensitivity always increased significantly (P \u2264 0.05) with the addition of creatine, after which the sensitivity was highest (P \u2264 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-L-carnitine titrations elicited \u223c40% lower respiration in LVSD compared with CONTROL (P \u2264 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfs172","type":"journal-article","created":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T21:39:44Z","timestamp":1351805984000},"page":"150-157","source":"Crossref","is-referenced-by-count":83,"title":["Decreased Mitochondrial Oxidative Phosphorylation Capacity in the Human Heart with Left Ventricular Systolic Dysfunction"],"prefix":"10.1093","volume":"15","author":[{"given":"Nis","family":"Stride","sequence":"first","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen , Blegdamsvej 3b, DK-2200, Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen","family":"Larsen","sequence":"additional","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen , Blegdamsvej 3b, DK-2200, Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hey-Mogensen","sequence":"additional","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen , Blegdamsvej 3b, DK-2200, Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e5re","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens T.","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Dela","sequence":"additional","affiliation":[{"name":"Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen , Blegdamsvej 3b, DK-2200, Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"2026011921141100100_ejhfhfs172-bib-0001","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1161\/01.CIR.96.7.2190","article-title":"Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy","volume":"96","author":"Neubauer","year":"1997","journal-title":"Circulation"},{"key":"2026011921141100100_ejhfhfs172-bib-0002","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/0002-8703(91)90527-O","article-title":"Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy","volume":"122","author":"Hardy","year":"1991","journal-title":"Am Heart J"},{"key":"2026011921141100100_ejhfhfs172-bib-0003","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart\u2014an engine out of fuel","volume":"356","author":"Neubauer","year":"2007","journal-title":"N Engl J Med"},{"key":"2026011921141100100_ejhfhfs172-bib-0004","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.yjmcc.2009.02.023","article-title":"Morphological dynamics of mitochondria\u2014a special emphasis on cardiac muscle cells","volume":"46","author":"Hom","year":"2009","journal-title":"J Mol Cell Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-0005","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1161\/CIRCULATIONAHA.107.702795","article-title":"Metabolic mechanisms in heart failure","volume":"116","author":"Ashrafian","year":"2007","journal-title":"Circulation"},{"key":"2026011921141100100_ejhfhfs172-bib-0006","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.bbamcr.2010.09.006","article-title":"Bioenergetics of the failing heart","volume":"1813","author":"Ventura-Clapier","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2026011921141100100_ejhfhfs172-bib-0007","first-page":"55","article-title":"An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in patients with congestive heart failure","volume":"42","author":"Taylor","year":"2001","journal-title":"J Nucl Med"},{"key":"2026011921141100100_ejhfhfs172-bib-0008","doi-asserted-by":"crossref","first-page":"H3270","DOI":"10.1152\/ajpheart.00887.2007","article-title":"Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy","volume":"293","author":"Neglia","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026011921141100100_ejhfhfs172-bib-0009","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0735-1097(02)01967-8","article-title":"Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy","volume":"40","author":"Davila-Roman","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00010","doi-asserted-by":"crossref","first-page":"H1538","DOI":"10.1152\/ajpheart.00281.2004","article-title":"Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation","volume":"287","author":"Chandler","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00011","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1161\/CIRCGENETICS.110.957571","article-title":"Reciprocal transcriptional regulation of metabolic and signaling pathways correlates with disease severity in heart failure","volume":"4","author":"Barth","year":"2011","journal-title":"Circ Cardiovasc Genet"},{"key":"2026011921141100100_ejhfhfs172-bib-00012","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.biocel.2011.08.008","article-title":"Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart","volume":"43","author":"Lemieux","year":"2011","journal-title":"Int J Biochem Cell Biol"},{"key":"2026011921141100100_ejhfhfs172-bib-00013","first-page":"803","volume-title":"Eur J Heart Fail 2012","author":"McMurray"},{"key":"2026011921141100100_ejhfhfs172-bib-00014","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/eurjhf\/hfr071","article-title":"Towards a re-definition of \u2018cardiac hypertrophy\u2019 through a rational characterization of left ventricular phenotypes: a position paper of the Working Group \u2018Myocardial Function\u2019 of the ESC","volume":"13","author":"Kn\u00f6ll","year":"2011","journal-title":"Eur J Heart Fail"},{"key":"2026011921141100100_ejhfhfs172-bib-00015","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s11886-008-0024-2","article-title":"Myocardial fatty acid metabolism and cardiac performance in heart failure","volume":"10","author":"Tuunanen","year":"2008","journal-title":"Curr Cardiol Rep"},{"key":"2026011921141100100_ejhfhfs172-bib-00016","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/cvr\/cvr038","article-title":"Modulating fatty acid oxidation in heart failure","volume":"90","author":"Lionetti","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.2003.055095","article-title":"Energy metabolism in heart failure","volume":"555","author":"Ventura-Clapier","year":"2004","journal-title":"J Physiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00018","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/cvr\/cvr077","article-title":"Spotlight on metabolic remodelling in heart failure","volume":"90","author":"Doenst","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00019","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1161\/01.CIR.94.11.2837","article-title":"Fatty acid oxidation enzyme gene expression is downregulated in the failing heart","volume":"94","author":"Sack","year":"1996","journal-title":"Circulation"},{"key":"2026011921141100100_ejhfhfs172-bib-00020","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s10545-009-9001-1","article-title":"Fatty acid oxidation disorders: outcome and long-term prognosis","volume":"33","author":"Wilcken","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"2026011921141100100_ejhfhfs172-bib-00021","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1006\/jmcc.2000.1266","article-title":"Abnormal mitochondrial respiration in failed human myocardium","volume":"32","author":"Sharov","year":"2000","journal-title":"J Mol Cell Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00022","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1161\/CIRCHEARTFAILURE.108.812099","article-title":"Control by circulating factors of mitochondrial function and transcription cascade in heart failure: a role for endothelin-1 and angiotensin II","volume":"2","author":"Garnier","year":"2009","journal-title":"Circ Heart Fail"},{"key":"2026011921141100100_ejhfhfs172-bib-00023","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jacc.2010.03.088","article-title":"Coenzyme Q10 and statins in heart failure: the dog that didn\u2019t bark","volume":"56","author":"Felker","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00024","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.jacc.2010.02.075","article-title":"Coenzyme Q10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (controlled rosuvastatin multinational study in heart failure)","volume":"56","author":"McMurray","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00025","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/clc.20846","article-title":"Coenzyme Q10 terclatrate and creatine in chronic heart failure: a randomized, placebo-controlled, double-blind study","volume":"34","author":"Fumagalli","year":"2011","journal-title":"Clin Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00026","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.cardfail.2006.03.007","article-title":"The impact of coenzyme Q10 on systolic function in patients with chronic heart failure","volume":"12","author":"Sander","year":"2006","journal-title":"J Card Fail"},{"issue":"4 Suppl","key":"2026011921141100100_ejhfhfs172-bib-00027","first-page":"30","article-title":"Phosphocreatine pathway for energy transport: ADP diffusion and cardiomyopathy","volume":"261","author":"Saks","year":"1991","journal-title":"Am J Physiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00028","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1006\/bbrc.1995.1422","article-title":"Correlation between degree of rupture of outer mitochondrial membrane and changes of kinetics of regulation of respiration by ADP in permeabilized heart and liver cells","volume":"208","author":"Saks","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"2026011921141100100_ejhfhfs172-bib-00029","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.bbamem.2011.12.034","article-title":"Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and MtCK within mitochondrial interactosome","volume":"1818","author":"Guzun","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"2026011921141100100_ejhfhfs172-bib-00030","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.bbabio.2011.01.010","article-title":"Mitochondria\u2013cytoskeleton interaction: distribution of beta-tubulins in cardiomyocytes and HL-1 cells","volume":"1807","author":"Guzun","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"2026011921141100100_ejhfhfs172-bib-00031","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0008-6363(99)00388-0","article-title":"Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy","volume":"45","author":"Jarreta","year":"2000","journal-title":"Cardiovasc Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00032","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/S0735-1097(02)02600-1","article-title":"Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression","volume":"40","author":"Scheubel","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2026011921141100100_ejhfhfs172-bib-00033","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1161\/CIRCRESAHA.109.212753","article-title":"Defective DNA replication impairs mitochondrial biogenesis in human failing hearts","volume":"106","author":"Karamanlidis","year":"2010","journal-title":"Circ Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00034","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/cvr\/27.7.1295","article-title":"Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy","volume":"27","author":"Sylven","year":"1993","journal-title":"Cardiovasc Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00035","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1161\/01.CIR.94.8.1894","article-title":"Creatine kinase system in failing and nonfailing human myocardium","volume":"94","author":"Nascimben","year":"1996","journal-title":"Circulation"},{"key":"2026011921141100100_ejhfhfs172-bib-00036","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/cvr\/cvr034","article-title":"AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure","volume":"90","author":"Beauloye","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2026011921141100100_ejhfhfs172-bib-00037","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1046\/j.1365-2362.1999.00468.x","article-title":"Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy","volume":"29","author":"Kalsi","year":"1999","journal-title":"Eur J Clin Invest"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfs172","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1093%2Feurjhf%2Fhfs172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1093\/eurjhf\/hfs172","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1093\/eurjhf\/hfs172","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/15\/2\/150\/66440874\/eurjhf_15_2_150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/15\/2\/150\/66440874\/eurjhf_15_2_150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:16:54Z","timestamp":1768875414000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/15\/2\/150\/8428637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,1]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,1,27]]},"published-print":{"date-parts":[[2013,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjhf\/hfs172","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,2]]},"published":{"date-parts":[[2013,2,1]]}}}