Impaired oxygen uptake kinetics in heart failure with preserved ejection fraction

Objective The time needed to increase oxygen utilisation to meet metabolic demand (VO₂ 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 VO₂ kinetics are slowed in HF with preserved ejection fraction (HFpEF). We tested the hypothesis that VO₂ kinetics are slowed during submaximal exercise in HFpEF and that slower VO₂ 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, Q_c), ventilatory oxygen uptake (VO₂, Douglas bags) and arterial-venous O₂ difference (a-vO₂ difference) derived from Q_c and VO₂ were assessed during exercise. Breath-by-breath O₂ uptake was measured continuously throughout submaximal exercise, and VO₂ kinetics was quantified as mean response time (MRT). Results HFpEF patients had markedly slowed VO₂ 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 (Q_c: 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 Q_c, and impaired peripheral oxygen extraction that was apparent during submaximal exercise compared with HFpEF with a MRT <60s (submaximal a-vO₂ difference: MRT <60s: 9.7±2.1, MRT ≥60 s: 7.9±1.1 mL/100 mL; p=0.03). Conclusion HFpEF patients have slowed VO₂ 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.