Short-term Exposure to High Altitude in Patients With Asymptomatic Aortic Stenosis

NCT06894550 | Recruiting DMC

• 1 other identifier: 2024-00126
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Aortic stenosis is a common disease with increasing prevalence due to an aging population. Aortic valve replacement is indicated for symptomatic severe aortic stenosis. Leisure activities and tourism at high altitude destinations are popular but may impose a higher risk to patients with aortic stenosis. Pathophysiological considerations led to an expert consensus to avoid high altitude exposure, though there is no robust scientific evidence. Hence, the objective of this study is to evaluate the safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis by the measurement of surrogate markers for cardiac adverse events such as the decrease in exercise capacity, the assessment of changes in cardiac filling pressures, cardiac dimensions and function, and the evaluation of the incidence of cardiac arrhythmia.

Conditions

Aortic Stenosis; Altitude

Keywords

Aortic stenosis; High altitude

Outcome Measures

Primary Outcomes (4)

• Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Spiroergometry outcome 1

  Decrease in VO2 peak, i.e. VO2-peak @high altitude minus VO2-peak @ low altitude

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Spiroergometry outcome 2

  Increase in VE/VCO2 slope, i.e. VE/VCO2 slope @high altitude minus VE/VCO2 slope @ low altitude

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Echocardiography outcome

  Increase in left ventricular filling pressure (E/e'), i.e. E/e' @high altitude minus E/e' @ low altitude

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Rhythmologic outcome

  Occurrence of ventricular tachycardia (\> 3 beats). Evaluated as presence versus absence.

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

Secondary Outcomes (4)

• Symptoms associated with the high altitude exposure

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Laboratory values associated with the high altitude exposure

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Arrhythmia associated with the high altitude exposure

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

• Hemodynamic effect of the high altitude exposure

  At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours

Study Arms (3)

Patients with asymptomatic moderate or severe aortic stenosis

EXPERIMENTAL

Patients with asymptomatic moderate or severe aortic stenosis (moderate or severe aortic stenosis (aortic valve area (AVA) ≤1.5 cm2, NYHA class I, LVEF \> 50%, aortic stenosis staging classification Stage 0 or 1)

Behavioral: Participants will be escorted to high altitude and undergo a series of test

Patients with aortic stenosis s/p aortic valve replacement

ACTIVE COMPARATOR

Patients with aortic stenosis s/p aortic valve replacement (aortic stenosis s/p aortic valve replacement within 1 year, NYHA class I , LVEF \> 50%, aortic stenosis staging classification Stage 0 or 1)

Behavioral: Participants will be escorted to high altitude and undergo a series of test

Age- and sex-matched healthy individuals

ACTIVE COMPARATOR

Age- and sex-matched healthy individuals ( NYHA class I, LVEF \>50%, no evidence of valvular heart disease, age \> 65 years)

Behavioral: Participants will be escorted to high altitude and undergo a series of test

Interventions

Participants will be escorted to high altitude and undergo a series of test BEHAVIORAL

Participants will be escorted to high altitude and undergo the following examination both at 540 and 3545m above sea level: * 12-lead electrocardiogram * Transthoracic echocardiography with measurement of left and right ventricular dimension and function, global longitudinal strain and transvalvular gradient * Symptom-limited cardiopulmonary stress exercise test with a ramp protocol with a focused echocardiography for the assessment of cardiac output and transvalvular gradient and blood gas analysis * 24 hours wearable rhythm monitoring * Blood Work: cardiac biomarkers (Troponin T, CK, CK-MB, NT-pro-BNP), blood gas analysis, Hemoglobin, Hematocrit, Leucocytes, Thrombocytes, Creatinin, eGFR, Sodium, Potassium, ASAT, ALAT, Bilirubin)

Age- and sex-matched healthy individuals; Patients with aortic stenosis s/p aortic valve replacement; Patients with asymptomatic moderate or severe aortic stenosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1:
• Moderate or severe aortic stenosis (aortic valve area (AVA) ≤1.5 cm2)
• NYHA class I
• LVEF \> 50%
• Aortic stenosis staging classification Stage 0 or 1
• Written informed consent
• Group 2:
• Aortic stenosis s/p aortic valve replacement within 1 year
• NYHA class I
• LVEF \> 50%
• Aortic stenosis staging classification Stage 0 or 1
• Written informed consent
• Group 3:
• NYHA class I
• LVEF \>50%

You may not qualify if:

• NYHA class \> I (all groups)
• History of cardiac decompensation requiring hospitalization (all groups)
• Uncontrolled arterial hypertension (\>180/100 mmHg at rest) (all groups)
• Other Cardiomyopathies w/ normal LVEF (dilatative, hypertrophic, infiltrative CMP) (all groups)
• Signs of exercise-induced ischemia (ST-segment depression \> 2 mV), hemodynamic instability (drop in systolic blood pressure \> 20 mmHg and systolic blood pressure ≤ 100 mmHg), or ventricular arrhythmias (\> 5 beats) during cardiopulmonary stress exercise testing (CPET) at Bern (540 meters) (all groups)
• Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \<60% of the predicted (all groups)
• Known pulmonary hypertension with a pulmonary artery systolic pressure \>50 mmHg or high probability of pulmonary hypertension as assessed in TTE (all groups)
• NT-pro BNP levels \> 900 pg/ml (all groups)
• Aortic stenosis staging classification \> Stage 1 (group 1 and 2)
• History of advanced stages of acute mountain sickness defined as high altitude pulmonary (HAPE) or cerebral (HACE) edema (all groups)
• Transvalvular gradient across the aortic valve ≥60 mmHg, Vmax \>5 m/s (group 1)
• Vmax progression ≥0.3 m/s/year (group 1)
• Transvalvular gradient across the aortic valve ≥20 mmHg (group 2)
• Evidence of valvular heart disease or coronary artery disease (group 3)
• History of rhythm disturbances (other than premature ventricular contraction (PVC) (group 3)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

University Hospital Inselspital, Bern

Bern, CH-3010, Switzerland

RECRUITING

Related Publications (3)

• Rimoldi SF, Sartori C, Seiler C, Delacretaz E, Mattle HP, Scherrer U, Allemann Y. High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations. Prog Cardiovasc Dis. 2010 May-Jun;52(6):512-24. doi: 10.1016/j.pcad.2010.03.005.

  PMID: 20417345 BACKGROUND

• Schmid JP, Nobel D, Brugger N, Novak J, Palau P, Trepp A, Wilhelm M, Saner H. Short-term high altitude exposure at 3454 m is well tolerated in patients with stable heart failure. Eur J Heart Fail. 2015 Feb;17(2):182-6. doi: 10.1002/ejhf.227. Epub 2015 Jan 19.

  PMID: 25597947 BACKGROUND

• Schmid JP, Noveanu M, Gaillet R, Hellige G, Wahl A, Saner H. Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease. Heart. 2006 Jul;92(7):921-5. doi: 10.1136/hrt.2005.072520. Epub 2005 Dec 9.

  PMID: 16339809 BACKGROUND

MeSH Terms

Conditions

Aortic Valve Stenosis; Altitude Sickness

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Thomas Pilgrim, MD, MSc

  University Hospital of Bern, Bern, Switzerland

  STUDY CHAIR

Central Study Contacts

Thomas Pilgrim, MD, MSc

CONTACT

+41 31 632 50 00; thomas.pilgrim@insel.ch

Marius R Bigler, MD, PhD

CONTACT

+41 31 632 50 00; mariusreto.bigler@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, monocentric, three-arm cohort study Group 1: Patients with asymptomatic moderate or severe aortic stenosis Group 2: Patients with aortic stenosis s/p aortic valve replacement Group 3: Age- and sex-matched healthy individuals

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 25, 2025
• Study Start: April 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)