Abstract 4146177: Oxygen uptake kinetics are not a specific marker of peripheral limitations to exercise among adults with heart failure with preserved ejection fraction.

Introduction: Oxygen uptake (VO 2 ) and cardiac output (Q C ) kinetics describe the time required for oxygen delivery and blood flow to match metabolic demand during exercise and reflect the efficiency of peripheral oxygen utilization. Individuals with heart failure with preserved ejection fraction (HFpEF) have slow VO 2 kinetics, potentially due to peripherally limited skeletal muscle or a blunted Q C response. We characterized cardiovascular kinetics to determine whether the mechanisms of VO 2 kinetics are differentially regulated in adults with HFpEF with peripheral or non-peripheral limitations to exercise. Methods: We studied 44 adults with HFpEF (62% female, age: 70 ± 7 [55-83] years, BMI: 38 ± 7 kg/m 2 [26-50]) during submaximal and maximal exercise. The Q C response normalized to metabolic demand (Q C /VO 2 slope; Direct Fick) assessed from rest to maximal exercise was used to characterize the cardiac output response to exercise. Participants were classified as either peripherally (slope: >6 or stroke volume reserve >50%) or non-peripherally limited (slope: <6 or stroke volume reserve <50%). Kinetics were measured as the mean response time (MRT) to steady-rate exercise during a 6-minute sub-maximal (20 Watts) effort on a semi-recumbent cycle ergometer. We measured VO 2 (indirect calorimetry), heart rate (HR; electrocardiography) and Q C (Modelflow analysis of radial arterial catheter waveforms) and compared groups using unpaired t-tests. Results: The Q C /VO 2 slope was higher in peripherally (n=28, 6.3 ± 2.0) versus non-peripherally limited participants (n=16, 5.2 ± 0.6; p=0.035). There was no difference in VO 2 MRT in peripherally limited (60 ± 20 sec) and non-peripherally limited participants (55 ± 20 sec; p=0.438, Panel A). There were no differences in Q C MRT (peripheral: 48 ± 23 sec; non-peripheral: 41 ± 15 sec, p=0.374) or HR MRT (peripherally: 53 ± 21; non-peripheral: 56 ± 20 sec, p=0.708) (Panels B&C). Conclusion: There was no difference in oxygen uptake or cardiovascular kinetics between adults with HFpEF with peripheral or non-peripheral limitations to exercise. Our findings indicate that differences in VO 2 kinetics are not a specific marker of peripheral limitations to exercise in adults with HFpEF.