title: Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction.
abstract: Heart failure patients are classified by ejection fraction (EF) into distinct groups: heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). Although patients with heart failure commonly have multiple comorbidities that complicate management and may adversely affect outcomes, their role in the HFpEF and HFrEF groups is not well-characterized. This review summarizes the role of noncardiac comorbidities in patients with HFpEF versus HFrEF, emphasizing prevalence, underlying pathophysiologic mechanisms, and outcomes. Pulmonary disease, diabetes mellitus, anemia, and obesity tend to be more prevalent in HFpEF patients, but renal disease and sleep-disordered breathing burdens are similar. These comorbidities similarly increase morbidity and mortality risk in HFpEF and HFrEF patients. Common pathophysiologic mechanisms include systemic and endomyocardial inflammation with fibrosis. We also discuss implications for clinical care and future HF clinical trial design. The basis for this review was discussions between scientists, clinical trialists, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum.
authors.affiliation: Duke University, Durham, North Carolina. Electronic address: robert.mentz@duke.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mentz
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Kelly
authors.affiliation: Oslo University Hospital Ulleval, University of Oslo, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: von Lueder
authors.affiliation: University of Groningen, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Framingham Heart Study, Framingham, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.affiliation: National Heart and Lung Institute, Imperial College and Imperial College London, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Cowie
authors.affiliation: Copenhagen University Hospital (Rigshospitalet), Copenhagen, and Aalborg University, Aalborg, Denmark.
authors.forename: Keld
authors.initials: K
authors.lastname: Kjeldsen
authors.affiliation: Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.affiliation: Oslo University Hospital Ulleval, University of Oslo, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: INSERM, Centre d'Investigations Cliniques, Université de Lorraine and CHU de Nancy, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, Michigan.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D000367:Age Factors; D000740:Anemia / Q000503:physiopathology; D001168:Arthritis / Q000503:physiopathology; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D051346:Mobility Limitation; D009765:Obesity / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D044469:Racial Groups; D012737:Sex Factors; D012891:Sleep Apnea Syndromes / Q000503:physiopathology; D013318:Stroke Volume / Q000502:physiology*
keywords: comorbidities; ejection fraction; heart failure