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.

Julian Müller,Luigi-Riccardo Calendo,Silvia Ulrich,Arcangelo F Carta,Esther I Schwarz,Mona Lichtblau,Michael Furian,Stéphanie Saxer,Simon R Schneider,Charlotte Berlier,Konrad E Bloch

doi:10.3389/fmed.2021.692029

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 (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 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, Wmax (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].

Highlights

In patients with heart failure with preserved ejection fraction (HFpEF), pulmonary hypertension (PH) is frequent and associated with reduced quality of life, exercise intolerance, disease progression, morbidity, and mortality [1, 2]
While long-term oxygen therapy is recommended for hypoxemic patients with PH-HFpEF [10], so far, no study has assessed the potential role of oxygen during exercise training in non-hypoxemic PH-HFpEF
Of seventy-four patients having been assessed for PH-HFpEF by right heart catheter, we were able to randomize 10 patients and these patients completed all tests according to the protocol between September 2019 and January 2020

Summary

Introduction

In patients with heart failure with preserved ejection fraction (HFpEF), pulmonary hypertension (PH) is frequent and associated with reduced quality of life, exercise intolerance, disease progression, morbidity, and mortality [1, 2]. Reduced exercise capacity in HFpEF has been associated with adverse outcome such as reduction in quality of life and increased mortality. With medical therapy a substantial improvement in exercise capacity without change in cardiac function has been reported in a meta-analysis by Holland et al [3]. Exercise intolerance in patients with heart failure has been attributed to multiple factors, including impaired cardiopulmonary reserve, a reduction of peripheral and respiratory skeletal muscle function, and mitochondrial dysfunction [1, 5, 6]

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Conclusion