Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction
Open accessAbstract
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.
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To date, nearly all trials that have tested a variety of medications in heart failure with preserved ejection fraction for exercise function outcomes, such as 6-minute walk distance or cardiopulmonary exercise testing, have shown neutral results.
“To date, nearly all trials that have tested a variety of medications in heart failure with preserved ejection fraction for exercise function outcomes, such as the 6-minute walk distance or cardiopulmonary exercise testing, have shown neutral results. 34”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [34]
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Experimental — accuracy not yet measuredEven when patients have well-compensated heart failure with preserved ejection fraction and are in stable condition, they have markedly impaired objectively measured physical function.
“Even when patients have well compensated heart failure with preserved ejection fraction and are in stable condition, they have markedly impaired objectively measured physical function. 34”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [34]
In ‘EI: A Key Manifestation of HFpEF’ (page unavailable), the review reports that objectively measured peak oxygen uptake is, on average, 35% lower in patients with HFpEF than in matched healthy controls. This supports marked impairment, but the passage does not establish that the patients were well-compensated and clinically stable. (LLM, conf=0.82)
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References 129 · Cited by 184
Research works printed but not linked: 2
- [58]Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW. Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol 2011; 58: 265– 74. 21737017 PMC3272542
- [101]Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153: 1194– 217. 23746838 PMC3836174
- Authors
- Pandey, A., Shah, S. J., Butler, J., Kellogg, D. L., Lewis, G. D., Forman, D. E., Mentz, R. J., Borlaug, B. A., Simon, M. A., Chirinos, J. A., Fielding, R. A., Volpi, E., Molina, A. J. A., Haykowsky, M. J., Sam, F., Goodpaster, B. H., Bertoni, A. G., Justice, J. N., White, J. P., Ding, J., Hummel, S. L., LeBrasseur, N. K., Taffet, G. E., Pipinos, I. I., & Kitzman, D.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Northwestern University (US)
- University of Mississippi Medical Center (US)
- South Texas Veterans Health Care System (US)
- Massachusetts General Hospital (US)
- University of Pittsburgh (US)
- Duke Medical Center (US)
- Mayo Clinic (US)
- University of Pennsylvania (US)
- Tufts University (US)
- The University of Texas Medical Branch at Galveston (US)
- University of California San Diego (US)
- University of Alberta (CA)
- Boston University (US)
- Wake Forest University Health Sciences (US)
- Duke University (US)
- University of Michigan (US)
- Baylor College of Medicine (US)
- University of Nebraska Medical Center (US)
- ORCID
- Pandey, Ambarish
- Shah, Sanjiv J.
- Butler, Javed
- Kellogg, Dean L.
- Lewis, Gregory D.
- Forman, Daniel E.
- Mentz, Robert J.
- Borlaug, Barry A.
- Simon, Marc A.
- Chirinos, Julio A.
- Fielding, Roger A.
- Volpi, Elena
- Molina, Anthony J.A.
- Haykowsky, Mark J.
- Sam, Flora
- Goodpaster, Bret H.
- Bertoni, Alain G.
- Justice, Jamie N.
- White, James P.
- Hummel, Scott L.
- LeBrasseur, Nathan K.
- Taffet, George E.
- Pipinos, Iraklis I.
- Kitzman, Dalane
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 78
- Issue
- 11
- Pages
- 1166-1187
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC8525886
- OpenAlex
- W3196388504
- Cited by
- 184
- References
- 129
- Citations by year
- 2026: 29 · 2025: 43 · 2024: 36 · 2023: 36 · 2022: 36 · 2021: 4
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001636)
- National Institute on Aging (R01AG062198, R01AG058883, R01AG018915, R01AG045551, R03AG067960, R01AG058659, R01AG062582, R01AG060499, K01AG059837, R21AG051077, R01AG058969, P30AG024827, K24AG070459, P30AG021332, R01AG062624, U24AG059624, P30AG044271)
- National Heart, Lung, and Blood Institute (R01HL145985, R01HL128526, R01HL127028, R01HL153646, R01HL104106, R01HL151841, R01HL139813, R03HL146874, P01HL094307, R01HL121510, R01HL107577, R56HL136730, R33HL146390, R01HL131029)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- exercise intolerance, heart failure with preserved ejection fraction, older adults, aging, geroscience, multiple organ failure, therapeutic target, phenotypic characterization
- MeSH terms
- Aging, Animals, Humans, Exercise Tolerance, Heart Failure, Diastolic
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