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Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure. Hunter, Wynn G Kelly, Jacob P McGarrah, Robert W Khouri, Michel G Craig, Damian Haynes, Carol Ilkayeva, Olga Stevens, Robert D Bain, James R Muehlbauer, Michael J Newgard, Christopher B Felker, G Michael Hernandez, Adrian F Velazquez, Eric J Kraus, William E Shah, Svati H
dc.coverage.spatial England 2016-11-28T15:06:00Z 2016-07-29
dc.identifier JAHA.115.003190
dc.description.abstract BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No-HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long-chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no-HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance. CONCLUSIONS: We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.
dc.language eng
dc.publisher Ovid Technologies (Wolters Kluwer Health)
dc.relation.ispartof J Am Heart Assoc
dc.relation.isversionof 10.1161/JAHA.115.003190
dc.subject fatty acid oxidation
dc.subject heart failure
dc.subject metabolism
dc.subject metabolomics
dc.subject mitochondrial dysfunction
dc.title Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.
dc.type Journal article Hunter, Wynn G|0422005 McGarrah, Robert W|0586917 Khouri, Michel G|0121842 Ilkayeva, Olga|0297296 Stevens, Robert D|0111388 Bain, James R|0288387 Newgard, Christopher B|0012593 Felker, G Michael|0083675 Hernandez, Adrian F|0265265 Velazquez, Eric J|0097236 Kraus, William E|0078469 Shah, Svati H|0278341
pubs.issue 8
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.organisational-group Staff
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 2047-9980
duke.contributor.orcid Hunter, Wynn G|0000-0003-0268-594X
duke.contributor.orcid McGarrah, Robert W|0000-0001-6693-7152
duke.contributor.orcid Ilkayeva, Olga|0000-0002-9779-0883
duke.contributor.orcid Bain, James R|0000-0002-8917-9187
duke.contributor.orcid Felker, G Michael|0000-0002-5931-1239
duke.contributor.orcid Hernandez, Adrian F|0000-0003-3387-9616
duke.contributor.orcid Velazquez, Eric J|0000-0003-2245-7477
duke.contributor.orcid Kraus, William E|0000-0003-1930-9684
duke.contributor.orcid Shah, Svati H|0000-0002-3495-2830

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