Evaluating VO2 On Kinetics In Heart Failure With Preserved Ejection Fraction Patients: Insights From Submaximal Treadmill 6 Minute Walk Test

Oxygen uptake (VO2) on-kinetics is the rate of oxygen delivery and utilization to meet the metabolic demand of active muscles during the transition from rest to steady-state exercise. Impaired VO2 on-kinetics is a common characteristic of heart failure with reduced ejection fraction and closely associated with exercise intolerance and worse prognosis. Limited research has explored VO2 on-kinetics during a 6-minute walk test (6MWT) in heart failure with preserved ejection fraction (HFpEF). PURPOSE: To assess the VO2 on-kinetics during a submaximal treadmill 6MWT in HFpEF patients. METHODS: 9 HFpEF and 9 healthy matched controls (CTL) performed a submaximal treadmill 6MWT. The protocol included a 3-minute resting phase, a 6-minute walking phase at 2 mph and 2% incline, and a 3-minute recovery phase. Breath-by-breath VO2 was measured by open-circuit spirometry and averaged over 10-second intervals. VO2 kinetics were modelled using a one-phase exponential association model in GraphPad Prism: VO2(t) = VO2rest + (VO2steady state-VO2rest) * (1-exp(-k*x) where k is the rate constant. Mean response time (MRT = time to reach~63% steady state) was quantified as the exponential time constant. Rating of perceived exertion (RPE:6-20) was recorded. RESULTS: There were no significant differences between HFpEF and CTL for age (71 ± 9 vs 67 ± 12 years) or body mass index (28 ± 5 vs 26 ± 3 kg/m2), respectively (p > 0.05). During the walking phase, absolute VO2 was not different between HFpEF and CTL (0.80 ± 0.2 vs 0.91 ± 0.1 L/min), respectively, whereas relative VO2 was lower (9.8 ± 1 vs 11.8 ± 2 mL/kg/min) and RPE higher in HFpEF (11 ± 4 vs 7 ± 2) (p < 0.05 for both). During the recovery phase, VO2 was not different, but HFpEF patients reported higher RPE (9 ± 4 vs 6 ± 0.4, p < 0.05). Importantly, HFpEF patients demonstrated significantly higher MRT (75 ± 38 vs 35 ± 12 sec, p < 0.05) compared to CTL. CONCLUSIONS: Our data demonstrate HFpEF patients have slower VO₂ on-kinetics, as evidenced by prolonged MRT as well as higher RPE for the same submaximal intensity 6MWT. These data highlight impaired O2 delivery and utilization in HFpEF which may contribute to exercise intolerance. The submaximal 6MWT may be a useful tool for assessing the severity of exercise intolerance and help guide targeted interventions to improve exercise tolerance in HFpEF.