Stable-treated patients with pulmonary vascular disease (PVD) defined as pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) wish to participate in daily activities including travel to high altitude or by air, but may be at increased risk of adverse events at high altitude (AE_HA).^1,2 Thus, pulmonary hypertension (PH) guidelines recommend that symptomatic PVD patients should not travel >1500 m or fly without supplemental oxygen therapy (SOT),³ but evidence is scarce and ambiguous.⁴

Prediction of adverse health effects at altitude or during air travel is relevant, particularly in pre-existing cardiopulmonary disease such as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH, PH). A total of 21 stable PH-patients (64 ± 15 y, 10 female, 12/9 PAH/CTEPH) were examined by pulse oximetry, arterial blood gas analysis and echocardiography during exposure to normobaric hypoxia (NH) (F_iO₂ 15% ≈ 2500 m simulated altitude, data partly published) at low altitude and, on a separate day, at hypobaric hypoxia (HH, 2500 m) within 20–30 min after arrival. We compared changes in blood oxygenation and estimated pulmonary artery pressure in lowlanders with PH during high altitude simulation testing (HAST, NH) with changes in response to HH. During NH, 4/21 desaturated to SpO₂ < 85% corresponding to a positive HAST according to BTS-recommendations and 12 qualified for oxygen at altitude according to low SpO₂ < 92% at baseline. At HH, 3/21 received oxygen due to safety criteria (SpO₂ < 80% for >30 min), of which two were HAST-negative. During HH vs. NH, patients had a (mean ± SE) significantly lower PaCO₂ 4.4 ± 0.1 vs. 4.9 ± 0.1 kPa, mean difference (95% CI) −0.5 kPa (−0.7 to −0.3), PaO₂ 6.7 ± 0.2 vs. 8.1 ± 0.2 kPa, −1.3 kPa (−1.9 to −0.8) and higher tricuspid regurgitation pressure gradient 55 ± 4 vs. 45 ± 4 mmHg, 10 mmHg (3 to 17), all p < 0.05. No serious adverse events occurred. In patients with PH, short-term exposure to altitude of 2500 m induced more pronounced hypoxemia, hypocapnia and pulmonary hemodynamic changes compared to NH during HAST despite similar exposure times and P_iO₂. Therefore, the use of HAST to predict physiological changes at altitude remains questionable. (ClinicalTrials.gov: NCT03592927 and NCT03637153).

Objective: To investigate the effect of a daylong exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH).Methods: In a randomised controlled cross-over trial, stable patients with PAH or distal CTEPH without resting hypoxemia at low altitude performed two incremental exercise tests to exhaustion, one after 3–5 h at high (2500 m) and one at low altitude (470 m).Results: In 27 patients with PAH/CTEPH (44% women, 61±14 y), maximal work-rate was 110±64 watts at 2500 m and 123±64 watts at 470 m (−11%, 95%CI: −16 to −11, p<0.001). SpO₂and PaO₂at end-exercise were 83±6%versus91±6% and 6.1±1.9 kPaversus8.6±1.9 kPa (−8%; −29%; both p<0.001) at 2500 mversus470 m, respectively. Maximal oxygen uptake at high altitude was 17.8±7.5 L·min⁻¹·kg⁻¹versus20±7.4 L·min⁻¹·kg⁻¹at low altitude (−11%, p<0.001). At end-exercise, the ventilatory equivalent for CO₂was 43±9 at 2500 mversus39±9 at 470 m (+9%, 95%CI: 2 to 6; p=0.002). No adverse events occurred during or after exercise.Conclusion: 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 to 470 m.

Background: The aim of this study was to investigate the overall and differential effect of breathing hyperoxia (inspiratory oxygen fraction ( F IO ₂ ) 0.5) versus placebo (ambient air, F IO ₂ 0.21) to enhance exercise performance in healthy people, patients with pulmonary vascular disease (PVD) with precapillary pulmonary hypertension (PH), COPD, PH due to heart failure with preserved ejection fraction (HFpEF) and cyanotic congenital heart disease (CHD) using data from five randomised controlled trials performed with identical protocols. Methods: 91 subjects (32 healthy, 22 with PVD with pulmonary arterial or distal chronic thromboembolic PH, 20 with COPD, 10 with PH in HFpEF and seven with CHD) performed two cycle incremental (IET) and two constant work-rate exercise tests (CWRET) at 75% of maximal load (W _max ), each with ambient air and hyperoxia in single-blinded, randomised, controlled, crossover trials. The main outcomes were differences in W _max (IET) and cycling time (CWRET) with hyperoxia versus ambient air. Results: Overall, hyperoxia increased W _max by +12 W (95% CI: 9–16, p<0.001) and cycling time by +6:13 min (4:50–7:35, p<0.001), with improvements being highest in patients with PVD (W _max /min: +18%/+118% versus COPD: +8%/+60%, healthy: +5%/+44%, HFpEF: +6%/+28%, CHD: +9%/+14%). Conclusion: This large sample of healthy subjects and patients with various cardiopulmonary diseases confirms that hyperoxia significantly prolongs cycling exercise with improvements being highest in endurance CWRET and patients with PVD. These results call for studies investigating optimal oxygen levels to prolong exercise time and effects on training.

Background: The course of pulmonary arterial wedge pressure (PAWP) during exercise in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), further abbreviated as pulmonary vascular disease (PVD), is still unknown. The aim of the study was to describe PAWP during exercise in patients with PVD.Methods: In this cross-sectional study, right heart catheter (RHC) data including PAWP, recorded during semi-supine, stepwise cycle exercise in patients with PVD, were analysed retrospectively. We investigated PAWP changes during exercise until end-exercise.Results: In 121 patients (59 female, 66 CTEPH, 55 PAH, 62±17 years) resting PAWP was 10.2±4.1 mmHg. Corresponding peak changes in PAWP during exercise were +2.9 mmHg (95% CI 2.1–3.7 mmHg, p<0.001). Patients ≥50 years had a significantly higher increase in PAWP during exercise compared with those <50 years (p<0.001). The PAWP/cardiac output (CO) slopes were 3.9 WU for all patients, and 1.6 WU for patients 2 WU are common in patients with PVD aged ≥50 years without exceeding the PAWP of 25 mmHg during exercise.

Introduction: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. Methods: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. Results: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference −4 W (95% CI: −9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5–1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3–19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. Conclusion: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.