Effect of Normobaric Hypoxia on Exercise Performance in Pulmonary Hypertension

Patients with pulmonary hypertension (PH) exhibited a reduced exercise capacity under hypoxic conditions, although with high inter-individual variability, according to the results of a clinical trial published in CHEST.

Investigators conducted a randomized controlled, single-blinded, crossover trial (ClinicalTrials.gov Identifier: NCT03592927) between August 2018 and April 2019 at the University Hospital Zürich in Zürich, Switzerland. They sought to explore the effect of hypoxia compared to normoxia on constant-work-rate-exercise-test (CWRET) time in patients with PH and to evaluate the physiologic mechanisms that are involved in the process. Adult patients who had been diagnosed with pulmonary arterial hypertension (PAH)/chronic thromboembolic pulmonary hypertension (CTEPH) — both summarized as PH herein — were recruited from outpatients of the PH-center Zürich.

All of the participants were randomly assigned to breathe ambient air (normoxia, fraction of inspired oxygen [FiO₂]: 21%) initially, followed by normobaric hypoxia (FiO₂: 15%), or vice versa, using a sealed facemask with a non-rebreathing 2-way valve during 20 or more minutes of rest. This was followed by use of a symptom-limited cycle-ergometer CWRET until exhaustion.

The primary study outcome was the difference in CWRET time under conditions of normobaric hypoxia compared to ambient air. Arterial blood gases, Borg-dyspnea, tricuspid regurgitation pressure gradient, and mean pulmonary artery pressure (mPAP)/cardiac output ratio by echocardiography were evaluated before and after CWRET.

A total of 28 participants were included in the study. The median patient age was 66 years; 13 of the participants were women. The mean PAP was 41 mm Hg; pulmonary vascular resistance (PVR) was 5.4 Wood Units. CWRET times were 16.9 minutes and 6.7 minutes under normoxia and hypoxia, respectively (P =.006).

At the end of exercise under conditions of normoxia and hypoxia, the median values were as follows: partial pressure of oxygen (PaO₂): 8.0 kPa vs 6.4 kPa, respectively; arterial oxygen content: 19.2 mL/dL vs 17.2 mL/dL, respectively; partial pressure of carbon dioxide (PaCO₂): 4.7 kPa vs 4.3 kPa, respectively; and lactate: 3.7 mmol/L vs

3.7 mmol/L, respectively (P <.05 for all). The following measurements remained unchanged: Borg scale: 7 vs 6, respectively; tricuspid pressure gradient: 89 mm Hg vs 77 mm Hg, respectively; and mPAP/cardiac output: 4.5 Wood Units vs 3.3 Wood Units, respectively. Per multivariable regression, baseline PVR was the sole factor that predicted hypoxia-induced change in CWRET time.

The investigators concluded that additional studies at real altitude are warranted to explore longer-term changes and adaptive mechanisms to hypoxia in patients with PH, the potential adverse effects, and their risk factors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Schneider SR, Mayer LC, Lichtblau M, et al. Effect of normobaric hypoxia on exercise performance in pulmonary hypertension – randomized trial. CHEST. Published online September 8, 2020. doi:10.1016/j.chest.2020.09.004