Effect of priming exercise on oxygen uptake kinetics in heart failure with preserved ejection fraction

Abstract

The cardinal symptom of heart failure with preserved ejection fraction (HFpEF) is exercise intolerance, which is associated with fatigue and reduced quality of life. HFpEF patients exhibit skeletal muscle dysfunction related to reduced peak oxygen uptake (peak V̇O2p). Prior heavy exercise speeds pulmonary oxygen uptake (V̇O2p) kinetics in older adults and in HF patients with reduced ejection fraction (HFrEF), presumably through increased oxygen delivery to the exercising muscle. We tested the hypothesis that prior heavy exercise would not speed V̇O2p on-kinetics in patients with HFpEF, suggesting HFpEF exercise intolerance stems primarily from muscle dysfunction. Eight HFpEF patients, 4 high-fit (CTL-HF), and 5 low-fit age-matched controls (CTL-LF) underwent echocardiography and peak exercise testing (cycle ergometer). Subjects performed 3 separate repetitions of 2 exercise transitions: MOD1, transition from rest to 4-min moderate intensity cycling (work rate corresponding to 90% ventilatory threshold); and MOD2, MOD1 preceded by 2-min of heavy cycling (∆50% intensity; halfway between ventilatory threshold and peak) and 5-min of inter-transition rest. V̇O2p (breath-by-breath gas exchange), heart rate (HR, ECG), stroke volume (SV, ModelFlow), cardiac output (CO, calculated), total peripheral resistance (TPR, calculated), and tissue oxygenation of the vastus lateralis (TOI, near-infrared spectroscopy) on-kinetics were measured. V̇O2p, HR, and CO data were linearly interpolated, time-aligned, averaged into 5-s time bins, and curve-fitted using a monoexponential equation. ∆SV, ∆TPR, and ∆TOI were calculated from baseline at 15s, 30s, and end-exercise to represent time-course changes. Analysis included repeated measures ANOVA, and SNK post-hoc, break-down analyses, and non-parametric testing where appropriate. Significance was P<0.05. HFpEF V̇O2p on-kinetics were slower than CTL-HF but similar to CTL-LF, pooled across conditions (P=0.008). MOD2 V̇O2p on-kinetics were faster compared to MOD1, pooled across groups (P=0.039). CTL-HF had a greater reduction in TPR across all time points compared to HFpEF (all P<0.038) and at 30s and end-exercise compared to CTL-LF (all P<0.032), pooled across conditions. HFpEF patients and CTL-LF had decreased TOI at 15-30s (all P≤0.024) in MOD1. By visual inspection, HFpEF TOI remained depressed while CTL-LF TOI increased to baseline levels, with no group difference at end-exercise (P=0.086) in MOD1. CTL-HF TOI increased at 15-30s (all P≤0.024) and decreased toward baseline levels. All groups had slower HR on-kinetics in MOD2 compared to MOD1 (P=0.001). TOI showed a greater reduction in MOD2 than MOD1 in HFpEF at 30s (P=0.033) and CTL-HF throughout MOD2 (all P<0.05). The results of this study indicate that HFpEF patients have impaired V̇O2p on-kinetics and a speeding response of V̇O2p on-kinetics to prior exercise, suggesting O2 delivery may be an important rate-limiting factor of V̇O2p on-kinetics in HFpEF.