OBJECTIVE: To evaluate the effects of breathing oxygen-enriched air (oxygen) on exercise performance in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). METHODS: Ten patients with PH-HFpEF (five women, age 60 +/- 9 y, mPAP 37 +/- 14 mmHg, PAWP 18 +/- 2 mmHg, PVR 3 +/- 3 WU, resting SpO2 98 +/- 2%) performed two-cycle incremental exercise tests (IET) and two constant-work-rate exercise test (CWRET) at 75% maximal work-rate (Wmax), each with ambient air (FiO2 0.21) and oxygen (FiO2 0.5) in a randomized, single-blinded, cross-over design. The main outcomes were the change in Wmax (IET) and cycling time (CWRET) with oxygen versus air. Blood gases at rest and end-exercise, dyspnea by Borg CR10 score at end-exercise; continuous SpO2, minute ventilation (VE), carbon dioxide output (VCO2), and cerebral and quadricep muscle tissue oxygenation (CTO and QMTO) were measured. RESULTS: With oxygen versus air, Wmax (IET) increased from 94 +/- 36 to 99 +/- 36 W, mean difference (95% CI) 5.4 (0.9 to 9.8) W, p = 0.025, and cycling time (CWRET) from 532 +/- 203 to 680 +/- 76 s, +148 (31.8 to 264) s, p = 0.018. At end-exercise with oxygen, Borg dyspnea score and VE/VCO2 were lower, whereas PaO2 and end-tidal PaCO2 were higher. Other parameters were unchanged. CONCLUSION: Patients with PH-HFpEF not revealing resting hypoxemia significantly improved their exercise performance while breathing oxygen-enriched air along with less subjective dyspnea sensation, a better blood oxygenation, and an enhanced ventilatory efficiency. Future studies should investigate whether prolonged training with supplemental oxygen would increase the training effect and, potentially, daily activity for PH-HFpEF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04157660.

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