The effect of high altitude (2500 m) on incremental cycling exercise in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a randomised controlled crossover trial

Abstract

Background: Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3-5 h at high altitude (2500 m) and one at low altitude (470 m).

Results: In 27 patients with PAH/CTEPH (44% females, mean±sd age 62±14 years), maximal work rate was 110±64 W at 2500 m and 123±64 W at 470 m (-11%, 95% CI -16- -11%; p<0.001). Oxygen saturation measured by pulse oximetry and arterial oxygen tension at end-exercise were 83±6% versus 91±6% and 6.1±1.9 versus 8.6±1.9 kPa (-8% and -29%; both p<0.001) at 2500 versus 470 m, respectively. Maximal oxygen uptake was 17.8±7.5 L·min^-1·kg^-1 at high altitude versus 20±7.4 L·min^-1·kg^-1 at low altitude (-11%; p<0.001). At end-exercise, the ventilatory equivalent for carbon dioxide was 43±9 at 2500 m versus 39±9 at 470 m (9%, 95% CI 2-6%; p=0.002). No adverse events occurred during or after exercise.

Conclusions: Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500 m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared with 470 m.

FIGURE 1

Study flowchart. PP: per protocol; ITT: intention to treat.

FIGURE 2

Physiological secondary outcomes at rest and at end-exercise, at high versus low altitude: a) oxygen uptake (V′_O2), b) carbon dioxide production (V′_CO2), c) ventilatory equivalent for carbon dioxide (minute ventilation (V′_E)/V′_CO2), d) oxygen saturation measured by pulse oximetry (S_pO2), e) arterial carbon dioxide tension (P_aCO2) and f) arterial oxygen tension (P_aO2). Box plots represent the medians with corresponding standard deviation; the black dots represent the means with corresponding standard error of measurement. The cloud plots to the right of the box plots represent the data distribution. Statistical significance between high and low altitude: *: p<0.05; **: p<0.01; ***: p<0.001.