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Original research article
Impaired oxygen uptake kinetics in heart failure with preserved ejection fraction
  1. Christopher M Hearon Jr1,2,
  2. Satyam Sarma1,2,
  3. Katrin A Dias1,2,
  4. Michinari Hieda1,2,
  5. Benjamin D Levine1,2
  1. 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  2. 2Texas Health Presbyterian Hospital Dallas, Institute for Exercise and Environmental Medicine, Dallas, Texas, USA
  1. Correspondence to Dr. Benjamin D Levine; BenjaminLevine{at}


Objective The time needed to increase oxygen utilisation to meet metabolic demand (V̇O2 kinetics) is impaired in heart failure (HF) with reduced ejection fraction and is an independent risk factor for HF mortality. It is not known if V̇O2 kinetics are slowed in HF with preserved ejection fraction (HFpEF). We tested the hypothesis that V̇O2 kinetics are slowed during submaximal exercise in HFpEF and that slower V̇O2 kinetics are related to impaired peripheral oxygen extraction.

Methods Eighteen HFpEF patients (68±7 years, 10 women) and 18 healthy controls (69±6 years, 10 women) completed submaximal and peak exercise testing. Cardiac output (acetylene rebreathing, Q̇c), ventilatory oxygen uptake (V̇O2, Douglas bags) and arterial-venous O2 difference (a-vO2 difference) derived from Q̇c and V̇O2 were assessed during exercise. Breath-by-breath O2 uptake was measured continuously throughout submaximal exercise, and V̇O2 kinetics was quantified as mean response time (MRT).

Results HFpEF patients had markedly slowed V̇O2 kinetics during submaximal exercise (MRT: control: 40.1±14.2, HFpEF: 65.4±27.7 s; p<0.002), despite no relative impairment in submaximal cardiac output (Q̇c: control: 8.6±1.7, HFpEF: 9.7±2.2 L/min; p=0.79). When stratified by MRT, HFpEF with an MRT ≥60 s demonstrated elevated Q̇c, and impaired peripheral oxygen extraction that was apparent during submaximal exercise compared with HFpEF with a MRT <60 s (submaximal a-vO2 difference: MRT <60 s: 9.7±2.1, MRT ≥60 s: 7.9±1.1 mL/100 mL; p=0.03).

Conclusion HFpEF patients have slowed V̇O2 kinetics that are related to impaired peripheral oxygen utilisation. MRT can identify HFpEF patients with peripheral limitations to submaximal exercise capacity and may be a target for therapeutic intervention.

  • heart failure with preserved ejection fraction
  • exercise capacity
  • oxygen uptake kinetics
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  • Contributors All authors provided substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This work was supported by the National Institutes of Health (NIH R01 AG17479, NIH 1F32HL137285-0) and the American Heart Association (AHA-14SFRN20600009-02).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.

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