Ventilatory limitation to exercise in patients with HFpEF and obesity: No room to breathe

Respir Physiol Neurobiol. 2026 Jan 27;341:104546. doi: 10.1016/j.resp.2026.104546. Online ahead of print.

ABSTRACT

BACKGROUND: Lowering pulmonary capillary wedge pressure (PCWP) by sublingual nitroglycerin (NTG) fails to increase exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). These findings beg the question as to the origin of exercise limitation. Our objective was to determine whether exercise tolerance could be ventilatory limited in older patients with HFpEF and obesity.

METHODS: Patients with HFpEF and obesity (n = 42) underwent pulmonary artery and radial artery catheterizations. Cardiorespiratory responses, breathing mechanics, and arterial blood gases were measured at rest, 20 W, and at peak exercise before and after NTG.

RESULTS: At rest, there was a drop in cardiac output and PaO₂ (p < 0.01) with subsequent increases in HR, a-v¯O₂ difference, and A-aO₂ difference (p < 0.001) after NTG. At 20 W, there were increases in HR, a-v¯O₂ difference, V̇_E/V̇CO₂, lactate, PaO₂, and A-aO₂ difference (p < 0.05). At peak exercise, there was an increase in V̇_E/V̇CO₂ and pH (p < 0.01), and a decrease in PaCO₂ (p < 0.001). However, before and after treatment, there was a qualitative decline in V̇_E/V̇CO₂ from 20 W to peak exercise suggesting these patients could not increase V̇_E further. There were no differences in breathing mechanics at rest, 20 W, or peak exercise after NTG.

CONCLUSIONS: We conclude that mechanical ventilatory constraints coupled with increased ventilatory inefficiency impose a ventilatory limitation to exercise in patients with HFpEF and obesity.

CLINICAL TRIAL INFORMATION: Clinical Trials number: NCT04068844.

PMID:41615840 | DOI:10.1016/j.resp.2026.104546