Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review

Ambarish Pandey, Sanjiv J. Shah, Javed Butler, Dean L. Kellogg, Gregory D. Lewis, Daniel E. Forman, Robert J. Mentz, Barry A. Borlaug, Marc A. Simon, Julio A. Chirinos, Roger A. Fielding, Elena Volpi, Anthony J.A. Molina, Mark J. Haykowsky, Flora Sam, Bret H. Goodpaster, Alain G. Bertoni, Jamie N. Justice, James P. White, Jingzhone DingScott L. Hummel, Nathan K. LeBrasseur, George E. Taffet, Iraklis I. Pipinos, Dalane Kitzman

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations


Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging–sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, “gero-centric” approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.

Original languageEnglish (US)
Pages (from-to)1166-1187
Number of pages22
JournalJournal of the American College of Cardiology
Issue number11
StatePublished - Sep 14 2021


  • aging
  • exercise intolerance
  • heart failure with preserved ejection fraction
  • senescence
  • skeletal muscle
  • Aging/physiology
  • Animals
  • Humans
  • Exercise Tolerance
  • Heart Failure, Diastolic/physiopathology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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