Impaired oxygen uptake kinetics in heart failure with preserved ejection fraction

Heart. 2019 Oct;105(20):1552-1558. doi: 10.1136/heartjnl-2019-314797. Epub 2019 Jun 17.


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.

Keywords: exercise capacity; heart failure with preserved ejection fraction; oxygen uptake kinetics.

Publication types

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

MeSH terms

  • Aged
  • Biological Transport
  • Exercise Test / methods
  • Exercise Tolerance / physiology*
  • Female
  • Heart Failure* / diagnosis
  • Heart Failure* / metabolism
  • Heart Failure* / physiopathology
  • Heart Ventricles* / metabolism
  • Heart Ventricles* / physiopathology
  • Humans
  • Male
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / physiopathology
  • Outcome Assessment, Health Care
  • Oxygen / metabolism
  • Oxygen Consumption / physiology*
  • Stroke Volume


  • Oxygen