title: Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.
abstract: Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population.
authors.affiliation: Duke University School of Medicine, 300 North Duke Street, Durham, NC, 27701, USA.
authors.forename: Wynn G
authors.initials: WG
authors.lastname: Hunter
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Kelly
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: McGarrah
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Duke University School of Medicine, 300 North Duke Street, Durham, NC, 27701, USA. svati.shah@duke.edu.|Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. svati.shah@duke.edu.|Duke Clinical Research Institute, Durham, NC, USA. svati.shah@duke.edu.|Duke Molecular Physiology Institute, Durham, NC, USA. svati.shah@duke.edu.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
mesh_terms: D015415:Biomarkers / Q000032:analysis; D006333:Heart Failure / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D011379:Prognosis
chemical_list: D015415:Biomarkers
keywords: Bioenergetics; Heart failure; Metabolism; Metabolomics; Mitochondrial dysfunction