title: Expert consensus document: Mitochondrial function as a therapeutic target in heart failure.
abstract: Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, 1035 Integrated Life Sciences Building, 1981 Kraft Drive, Blacksburg, Virginia 24060, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, 1035 Integrated Life Sciences Building, 1981 Kraft Drive, Blacksburg, Virginia 24060, USA.
authors.forename: Justin B
authors.initials: JB
authors.lastname: Perry
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, 1035 Integrated Life Sciences Building, 1981 Kraft Drive, Blacksburg, Virginia 24060, USA.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Allen
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202, USA.
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, 12700 East 19th Avenue, B139, Aurora, Colorado 80045, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.affiliation: Department of Biochemistry and Molecular Biology, East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, North Carolina 27834, USA.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.affiliation: National Heart &Lung Institute, National Institute of Health Research Cardiovascular Biomedical Research Unit, Royal Brompton &Harefield Hospitals, Imperial College, London, UK.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Cardiovascular Medicine Section, Boston University School of Medicine and Boston Medical Center, 88 East Newton Street, C-8, Boston, Massachusetts 02118, USA.
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.affiliation: Division of Cardiology, Health Sciences Center, T-16 Room 080, SUNY at Stony Brook, New York 11794, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen 9713 GZ, Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen (UMG), Robert-Koch-Straße, D-37075, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: University of Michigan School of Medicine, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: Department of Cardiology, Charité University Medicine, Campus Virchow Klinikum, and German Heart Center Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.affiliation: National and Kopodistrian University of Athens, School of Medicine, Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, Rimini 1, Athens 12462, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Division of Cardiology, Duke University Medical Center, 2301 Erwin Road Suite 7400, Durham, North Carolina 27705, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 201 East Huron, Galter 3-150, Chicago, Illinois 60611, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D032921:Consensus; D055808:Drug Discovery; D004579:Electron Transport; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000378:metabolism / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D017240:Mitochondrial Myopathies / Q000378:metabolism / Q000503:physiopathology; D011379:Prognosis