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Original Investigation
March 17, 2021

Metabolic Cost of Exercise Initiation in Patients With Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults

Author Affiliations
  • 1Simches Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
  • 2MIT Critical Data, Laboratory for Computational Physiology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge
  • 3Biomedical Engineering and Telemedicine Group, Biomedical Technology Centre CTB, ETSI Telecomunicación, Universidad Politécnica de Madrid, Madrid, Spain
  • 4Pulmonary Critical Care Unit, Massachusetts General Hospital, Boston
  • 5Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  • 6Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • 7Division of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
JAMA Cardiol. 2021;6(6):653-660. doi:10.1001/jamacardio.2021.0292
Key Points

Question  What is the metabolic cost of starting exercise in individuals across the spectrum of functional limitation, including heart failure with preserved ejection fraction (HFpEF)?

Findings  In this cohort study of 3047 individuals from the Framingham Heart Study (an observational cohort study) and 184 individuals with HFpEF using comprehensive cardiopulmonary exercise testing, metabolic cost (in watts) of unloaded exercise (internal work) was determined. Obesity was associated with internal work across both the Framingham Heart Study and HFpEF cohorts; in patients with HFpEF, greater internal work was associated with more significant hemodynamic alterations in unloaded exercise.

Meaning  A greater energetic cost of exercise initiation is associated with obesity and greater excursions in filling pressures early in exercise, suggesting that exercise initiation (before imposing an external load on the cardiovascular system) may represent and important locus of functional limitation in HFpEF.


Importance  Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions.

Objective  To define and quantify the metabolic cost of initiating exercise in individuals with and without HFpEF and its functional consequences.

Design, Setting, and Participants  This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020.

Exposures  Internal work (IW), a measure of work equivalents required to initiate movement.

Main Outcomes and Measures  Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures.

Results  Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW.

Conclusions and Relevance  This study found that internal work, a new body mass index–related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.

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