Dyspnea On Exertion In Patients With Hfpef: Association With An Increased Oxygen Cost Of Breathing

PURPOSE: Dyspnea on exertion (DOE) is the dominant symptom of heart failure with preserved ejection fraction (HFpEF); however, the mechanism is unknown. Patients with HFpEF exhibit mechanical ventilatory limitations during exercise, which could increase the oxygen (O2) cost of breathing and contribute to DOE. To test this hypothesis, we measured gas exchange, breathing mechanics, the O2 cost of breathing, and DOE in patients with HFpEF and healthy controls. METHODS: 20 patients with HFpEF (age: 69 ± 7 y, BMI: 38.4 ± 7.3 kg/m2; sex: 15F/5M) and 20 controls (age: 70 ± 3 y, BMI: 25.8 ± 3.5 kg/m2; sex: 12F/8M) underwent gas exchange, breathing mechanics, and ratings of perceived breathlessness (RPB, Borg 0-10) measurements during submaximal cycling (HFpEF: 20 W; controls: 30 W for women and 50 W for men). The O2 cost of breathing was determined by the V̇O2 (mL/min) vs. V̇E (L/min) relationship during eucapnic voluntary hyperpnea. Respiratory muscle V̇O2 (V̇O2resp) during exercise was estimated by extrapolating the O2 cost of breathing slope back to the exercise V̇E. RESULTS: Exercise V̇E (controls: 26.5 ± 4.6; HFpEF: 26.2 ± 5.8 L/min, p = 0.85) and RPB (controls: 2.3 ± 1.7; HFpEF: 2.7 ± 2.0, p = 0.53) were similar between groups, whereas the O2 cost of breathing (controls: 2.16 ± 0.43; HFpEF: 2.63 ± 0.81 mL/L, p = 0.01) and V̇O2resp (controls: 7.5 ± 2.3; HFpEF: 9.4 ± 3.2, p = 0.03) were higher in HFpEF than controls. RPB correlated more strongly with the O2 cost of breathing and V̇O2resp in HFpEF than controls (Table). The O2 cost of breathing and V̇O2resp correlated with EELV (%TLC), EILV (%TLC), VT (%IC), and V̇E (%MVV) in HFpEF, but not controls (Table). CONCLUSIONS: DOE is strongly associated with an increased O2 cost of breathing in HFpEF, the latter of which appears largely driven by mechanical ventilatory constraint. Further investigation into how mechanical ventilatory constraint might be alleviated to potentially reduce the O2 cost of breathing and exertional symptoms in HFpEF is required. Supported by: P01HL137630, K99HL164957, King Charitable Foundation, Atwell Gift for Pulmonary Research, Cain Foundation, and Texas Health Presbyterian Hospital Dallas