Effect of Breathing Oxygen-Enriched Air on Exercise Performance in Patients With Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction: A Randomized, Placebo-Controlled, Crossover Trial

Abstract

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 (W max), 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 W max (IET) and cycling time (CWRET) with oxygen vs. air. Blood gases at rest and end-exercise, dyspnea by Borg CR10 score at end-exercise; continuous SpO2, minute ventilation (V'E), carbon dioxide output (V'CO2), and cerebral and quadricep muscle tissue oxygenation (CTO and QMTO) were measured. Results: With oxygen vs. air, W max (IET) increased from 94 ± 36 to 99 ± 36 W, mean difference (95% CI) 5.4 (0.9-9.8) W, p = 0.025, and cycling time (CWRET) from 532 ± 203 to 680 ± 76 s, +148 (31.8-264) s, p = 0.018. At end-exercise with oxygen, Borg dyspnea score and V'E/V'CO2 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].

Keywords: cardiopulmonary exercise test; exercise; external cycling work; heart failure with preserved ejection fraction; oxygen therapy; pulmonary hypertension.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Müller, Lichtblau, Saxer, Calendo, Carta, Schneider, Berlier, Furian, Bloch, Schwarz and Ulrich.

Figures

Figure 1

Patient flow of the study. N = Number of participants.

Figure 2

Improvements of the primary outcomes with oxygen. Changes of maximal work-rate [Wmax (W)] at the incremental exercise test (left, purple) and mean changes of maximal cycling time [t (s)] of the constant work-rate exercise test (right, green) with oxygen-enriched vs. ambient air are shown as mean ± standard error of mean (SEM). IET, incremental exercise test; CWRET, constant work-rate exercise test.

Figure 3

Physiological changes during the incremental exercise test. Physiological changes of the incremental exercise test comparing tests with air (blue) vs. oxygen-enriched air (red) by computing means over each 10% fraction of maximal exercise duration individually achieved with ambient air, i.e., 1–10%, 11–20%, etc., up to 91–100% of total exercise duration and end-exercise defined as the mean over the final 30 s of the test. HR, heart rate; SpO2, arterial oxygen saturation; QMTO, quadriceps muscle tissue oxygenation; CTO, cerebral tissue oxygenation; V'E, minute ventilation; V'CO2, carbon dioxide output.

Figure 4

Cycling energy delivery during incremental vs. constant work-rate exercise test (IET vs. CWRET). (A) Graphical representation of the constant work-rate exercise test (CWRET, blue) with air for a mean cycling time of 418 s and a mean work-rate of 70W. (B) Graphical representation of the incremental exercise test (IET, red) with air for a mean cycling time of 361 s and a mean work-rate of 94W, starting with 20W. (C) Graphical representation of the mean delivered external work of the patients, calculated with the integral of the work-rate over cycling time, comparing both tests [CWRET (blue); IET (red)] with air. The curves represent the estimated progress with time for both tests. (D) Graphical representation of the mean delivered external work of the patients, calculated with the integral of the work-rate over cycling time, comparing both tests [CWRET (blue); IET (red)] with oxygen. The curves represent the estimated progress with time for both tests. ∫ W dt = external work (J).