BackgroundThe amount of time needed to increase oxygen utilization to sufficiently meet metabolic demand (V̇O2 kinetics) is impaired in heart failure (HF) with reduced ejection fraction, and is an independent predictor of HF mortality. However, it is not known if V̇O2 kinetics are slowed in heart HF patients with preserved ejection fraction (HFpEF). We tested the hypothesis that V̇O2 kinetics are slowed during submaximal exercise (equivalent to activities of daily living) in HFpEF patients, and that slower V̇O2 kinetics are related to impaired peripheral oxygen extraction.MethodsEighteen healthy controls (69±6 years, 10 females) and eighteen HFpEF patients (68±7 years, 10 females) were studied during submaximal (~30% predicted max) and peak treadmill exercise. Cardiac output (Qc, acetylene rebreathing), pulmonary oxygen uptake (V̇O2, Douglas bags), and arterial‐venous oxygen difference (a‐v O2 diff) were measured during exercise. Breath‐by‐breath V̇O2 uptake was measured continuously at the onset and throughout submaximal exercise, and V̇O2 kinetics quantified as the time needed to for V̇O2 to rise to ~63% of steady state V̇O2 (mean response time, MRT).ResultsDuring submaximal exercise, absolute oxygen demand was similar between groups (V̇O2: Control: 0.81±0.1, HFpEF: 0.85±0.2 L/min; P=0.54) however, HFpEF patients had substantially slowed V̇O2 kinetics (MRT: Control: 40.1±14.2, HFpEF: 65.4±27.7 s; P=0.002), and >50% greater accumulated oxygen deficit compared to controls (Control: 400±173, HFpEF: 693±392 mL; P=0.007). At peak exercise, HFpEF patients had lower relative V̇O2 (Control: 22.2±4.0, HFpEF: 14.6±3.1 mL/kg/min; P<0.001), preserved peak Qc (Control: 13.4±4.0, HFpEF: 13.9±3.5 L/min; P=0.68), and reduced peripheral oxygen extraction (a‐v O2 diff: Control: 12.7±2.9, HFpEF: 10.4±2.1 mL/dL; P=0.01). When stratified by MRT, HFpEF patients with a MRT >60s demonstrated impaired peripheral oxygen extraction that was apparent during submaximal exercise compared to HFpEF patients with a MRT <60s (submaximal a‐v O2 diff: MRT<60s: 9.7±2.1, MRT>60s: 7.9±1.1 mL/dL; P=0.03).ConclusionsHFpEF patients have slowed V̇O2 kinetics during exercise that are due in part to impaired peripheral oxygen utilization. This finding supports growing evidence that peripheral oxidative capacity is a primary contributor to exercise intolerance in HFpEF leading to substantial oxygen deficit even during activities of daily living. Further, MRT can lend important insight into the pathophysiology of exercise intolerance in individual HFpEF patients, and identify patients with severe peripheral limitations to exercise capacity.Support or Funding InformationNIH: AG017479, F32‐HL137285This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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