Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction

J Am Coll Cardiol. 2014 Dec 2;64(21):2281-93. doi: 10.1016/j.jacc.2014.08.036. Epub 2014 Nov 24.


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.

Keywords: comorbidities; ejection fraction; heart failure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Anemia / physiopathology
  • Arthritis / physiopathology
  • Comorbidity
  • Continental Population Groups
  • Diabetes Mellitus / physiopathology
  • Heart Failure / physiopathology*
  • Humans
  • Kidney Diseases / physiopathology
  • Mobility Limitation
  • Obesity / physiopathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Sex Factors
  • Sleep Apnea Syndromes / physiopathology
  • Stroke Volume / physiology*