More and more people are engaging in sports in the mountains, including individuals with heart or lung diseases. At the same time, such diseases are becoming more common in Switzerland. At high altitude, less oxygen is available, which places stress on the body-particularly on the heart, which has to pump blood through the lungs. How the heart, especially the right ventricle, in people with past HAPE responds to this stress is still not well understood. Therefore, this study investigates how the heart responds to simulated altitudes of 2,500 m and 4,000 m, both at rest and during light physical activity in patients with past HAPE. The primary objective is to assess how right ventricular function changes under conditions of reduced oxygen availability. In addition, vital signs, changes in blood gases, oxygen levels in blood and tissue and shortness of breath are assessed. The "altitude" is simulated using a special gas mixture that participants inhale. Participants undergo three altitude conditions (490, 2,500, and 4,000 m above sea level). The order of the altitude conditions is assigned at random. The aim is to better understand how the right ventricle and other parameters respond to low-oxygen conditions and how affected patients can be better supported in the future.

Outdoor activities in the mountains are becoming increasingly popular. At higher altitudes, the air contains less oxygen, which puts extra strain on the body-especially on the heart. The right side of the heart plays a key role in pumping blood through the lungs and may need to work harder when oxygen levels are low. While the heart's response to long-term altitude exposure is relatively well known, much less is understood about how the heart reacts to short-term (acute) exposure to low oxygen, particularly during light physical activity and in individuals past HAPE.

Participants with past HAPE will be exposed to different oxygen levels that correspond to altitudes of 490 m (near sea level), 2,500 m, and 4,000 m, both at rest and during light cycling exercise. The main focus of the study is to measure changes in right ventricular function, assessed using a non-invasive heart ultrasound technique called speckle-tracking echocardiography. In addition, heart rate, blood pressure, oxygen saturation, and symptoms such as shortness of breath and leg fatigue will be recorded. The study is conducted at a single center and uses a randomized, double-blind, cross-over design, meaning that each participant undergoes all altitude conditions in a random order, and neither the participants nor the investigators know which altitude is being simulated at a given time.

Participants Only adults aged 18-80 years with diagnosed past HAPE will be included. Participants must live below 800 m above sea level and must not have been exposed to higher altitudes for more than 24 hours in the three weeks before participation. Individuals with significant other medical conditions, pregnancy, need for long-term oxygen therapy, or inability to follow the study procedures will be excluded.

Study procedures

Each study visit includes:

• 1 hour resting period
• Measurement of vital signs (heart rate, blood pressure, oxygen saturation)
• Heart ultrasound at rest
• A 10-minute low-intensity cycling exercise
• Repeated heart ultrasound during and symptom assessment after exercise
• Low-oxygen conditions are created using a special gas mixture that participants breathe through a mask. Each condition is separated by at least 2 hours wash-out period to ensure recovery.

Study size and duration Based on statistical calculations, 18 participants will be recruited to allow balanced allocation across all study conditions and to account for potential dropouts. Participation may take place over two to three days, depending on the preferred schedule of the participant. The days can be spread or be spread over several weeks, depending on individual availability.

Aim of the study The goal of this study is to improve understanding of how the right side of the heart responds to short-term low-oxygen exposure at rest and during light exercise. This knowledge will help interpret future findings in patients with heart or lung disease and may contribute to safer recommendations for physical activity at altitude.

Inclusion Criteria:

• Signed informed consent
• Diagnosed or suspicion of past HAPE
• 18-80 years (age group young: 18-39.99 years / age group older: 40-80 years)
• All sex and genders
• Living <800m and without altitude exposure > 2500 m and > 24h within the last three weeks

Exclusion Criteria:

• <18, >80 years old
• Any other diagnosed cardiopulmonary condition
• Other clinically significant severe concomitant disease states (e.g. renal, hepatic dysfunction, etc.)
• Inability to follow the procedures of the study due to language problems, psychological neurological disorders or orthopaedic disorders
• Participants permanently living >800m and altitude exposure > 2500 m and >24h within the last three weeks
• Pregnancy: Participants will be asked if pregnant or not, no screening for undetected pregnancy
• Lactating women
• Participation in other study with active treatment

Anonymized individual participant data (IPD) are planned to be shared via an appropriate data repository, such as Zenodo. Corresponding standard operating procedures (SOPs) for our department are currently under development.