Effect of small muscle mass versus cycle exercise training on peripheral hemodynamics and oxygen utilization in patients with heart failure with preserved ejection fraction

RATIONALE: Patients with heart failure with preserved ejection fraction (HFpEF) have exercise intolerance that impacts quality of life. Impairments in peripheral oxygen (O 2 ) delivery and extraction (i.e., lower arterio-venous O 2 difference [a-vO 2 diff] and/or muscle O 2 diffusive conductance [DMO 2 ]) contribute prominently to exercise intolerance in patients with HFpEF. Exercise improves functional capacity in patients with HFpEF, however whole-body exercise is associated with symptoms of dyspnea and fatigue. Small muscle mass exercise that reduces cardiopulmonary limitations while maximizing peripheral adaptations has been proposed as an alternative training strategy for patients with HFpEF. The objective of this investigation was to quantify peripheral O 2 transport and utilization during single leg knee extensor exercise (SKLE) before and after 16-weeks of SLKE or cycle exercise training in patients with HFpEF. We tested the hypothesis that small muscle mass training would elicit greater peripheral adaptations compared to whole-body aerobic exercise in patients with HFpEF. METHODS: 34 patients with HFpEF (77% females; age: 71±7 y) were randomly assigned to either SLKE (n=19) or cycle training with cardiac unloading with sublingual nitroglycerin (CYCLE, n=15) for 16-weeks. The SLKE group performed one endurance (55-70% baseline peak power output [PPO]) and two interval (85-95% baseline PPO) training sessions per week, for 30 minutes per leg. CYCLE performed two endurance (1-20 bpm < maximal steady state heart rate [HR]) and two interval (≥95% peak HR) exercise training sessions per week, for 30 minutes each. Sublingual nitroglycerin (0.4mg) was taken before and during each training session to lower cardiac filling pressure during exercise in the CYCLE group. Before (PRE) and after (POST) the training intervention, participants completed an invasive incremental SLKE test to exhaustion during which time leg blood flow (LBF; Doppler ultrasound), leg a-vO 2 diff (PvO 2 , mmHg and SvO 2 , % [femoral venous catheter], SaO 2 , [pulse O 2 saturation] and venous hemoglobin concentration [spectrophotometry]), leg [Formula: see text]O 2 (direct Fick) and DMO 2 were calculated. Data were compared using two-way (Training×Type) ANOVA. RESULTS: Baseline hemodynamics were not different between SLKE and CYCLE. PPO increased after training (SLKE: 3±4 Watts, P< 0.001; CYCLE: 5±4 Watts, P=0.017). SLKE training increased peak LBF (PRE: 1877±662 vs. POST: 2115±748 mL/min, P=0009) and peak leg [Formula: see text]O 2 (PRE: 214.7±102.9 vs. POST: 256.9±121.8 mL/min, P=0.014), with no effect on peak leg a-vO 2 diff (PRE: 11.1±2.3 vs. POST: 11.3±2.5%, P=0.426). Conversely, CYCLE training did not improve peak LBF (PRE: 1935±593 vs. POST: 1976±508 mL/min, P=0.680) but did increase peak leg a-vO 2 diff (PRE: 10.5±2.2 vs. POST: 11.8±1.8%, P< 0.001) and tended to increase peak leg [Formula: see text]O 2 , though with more variability (PRE: 207.0±85.1 vs. POST: 231.5±71.4 mL/min, P=0.094). DMO 2 was improved in both SLKE (PRE: 4.9±2.7 vs. POST: 6.1±3.5 mL/min/mmHg, P=0.003) and CYCLE (PRE: 4.2±2.2 vs. POST: 5.5±2.1 mL/min/mmHg, P=0.001). CYCLE training reduced the slope of the relationship between LBF and leg [Formula: see text]O 2 (PRE: 9.2±2.1 vs. POST: 8.1±1.4, P=0.002), whereas SLKE did not (PRE: 8.7±2.2 vs. POST: 8.4±1.8, P=0.177). CONCLUSION: Both whole body and small muscle mass exercise training were effective in improving leg [Formula: see text]O 2 , though the mechanism of improvement was different. SLKE improved both LBF and DMO 2 while CYCLE exercise increased DMO 2 and leg O 2 extraction. Future studies should evaluate the combination of small muscle mass and whole-body exercise training to improve overall exercise capacity in patients with HFpEF. Funding: NIH 1P01HL137630 (BDL); 1F32HL137285 (CMH) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.