- Hemodynamic changes of high altitude exposure
Atmospheric pressure exponentially decreases with increasing altitude and results in
hypobaric hypoxia and arterial hypoxemia. Adaptive mechanisms to high altitude involve
the cardiovascular, pulmonary and metabolic system and result in important hemodynamic
changes. Acute hypoxia is associated with an increase in cardiac output, heart rate,
myocardial contractility, and blood pressure. At the same time, pulmonary
vasoconstriction increases pulmonary pressure and right ventricular afterload, while
systemic vasodilatation improves peripheral oxygen delivery to the tissues.
Hyperventilation furthermore results in respiratory alkalosis and may precipitate
premature ventricular complexes and cardiac arrhythmia.
- High altitude exposure in individuals with cardiovascular disease
A range of physiological responses to the high altitude environment challenge the
cardiovascular system and potentially increase the risk of adverse cardiovascular events.
Pre-existing heart disease can mitigate compensatory mechanisms required for
physiological adaption to high altitude. Available evidence is however scarce, which is
reflected by the vague clinical recommendations of the European Society of Cardiology and
the American Heart Association. Previous evidence suggested that short-term exposure to
3454 meters above sea level was well tolerated in patients with coronary artery disease,
stable heart failure and congenital heart disease. There is however no clinical data on
the effects of high altitude exposure in patients with valvular heart disease. Expert
consensus, based on hemodynamic and pathophysiological considerations, states that
patients with symptomatic and/or severe aortic stenosis are prohibited from high altitude
exposure/activities.
Aortic stenosis is the second most prevalent valvular heart disease in the Western World
and increases with advancing age. Moderate or severe aortic stenosis was documented in
0.7% of individuals aged ≥65 years in a large-scale community-bases echocardiographic
screening program in the United Kingdom, and accounts for more than two thirds of deaths
due to degenerative valvular heart disease. The degenerative origin of the disease
forecasts an increasing incidence of aortic stenosis in the aging population. An increase
in afterload due to aortic valve stenosis leads to an increase in left ventricular
pressure and left ventricular wall stress according to the Law of LaPlace. Concentric
hypertrophy and an increase in left ventricular mass result in an increased oxygen
consumption and a reduction in coronary flow reserve. Upstream cardiac damage may result
in mitral regurgitation, left atrial enlargement, pulmonary hypertension, tricuspid
regurgitation, and eventually right ventricular dysfunction. The natural history of
aortic stenosis is characterized by a long asymptomatic course. Aortic valve replacement
is indicated when symptoms such as exercise intolerance, shortness of breath, exertional
chest pain or dizziness with syncope develop. Timing of intervention is transitioning
from grading of disease according to transvalvular gradients to staging of disease
reflecting secondary cardiac damage as a consequence of afterload increase.
- High altitude exposure of individuals with aortic stenosis
Several mechanisms may compromise the short-term adaptation of patients with aortic
stenosis to high altitude. An increased oxygen demand of the hypertrophied left ventricle
is exacerbated by the hypobaric hypoxia at altitude and may results in myocardial
ischemia. This process may be further amplified by an increase in heart rate, and
entertain a vicious cycle of myocardial ischemia. At the same time, tachycardia with
corresponding increase in cardiac output may aggravate aortic stenosis and precipitate
cardiac decompensation. Peripheral vasodilatation may furthermore cause hypotension which
is poorly tolerated in aortic stenosis.
- Research question and rationale
Top of Europe/Jungfraujoch located at 3454 meters altitude above sea level is easily
accessible by railroad, and visited by more than 1 million tourists every year. Outside
of Europe, other tourist hot spots such as Lhasa in Tibet (3658 meters), La Paz in
Bolivia (3640 meters), or Cusco in Peru (3399 meters) attract millions of tourists every
year. In addition, more than 25 million people worldwide permanently live at an altitude
≥3000 meters. In the absence of robust scientific evidence, even patients with
asymptomatic aortic stenosis are discouraged from travelling to high altitude due to
hemodynamic considerations. However, data from the Oxvalve registry indicates, that
significant valvular heart disease is undiagnosed in 2 out of 3 patients. It can
therefore be assumed, that many patients with relevant aortic stenosis travel to high
altitude every year without being aware of potential risks.
The goal of the present study is to evaluate the hemodynamic response of patients with
asymptomatic moderate or severe aortic stenosis to high altitude, and to assess the
safety of high altitude exposure in patients with aortic stenosis. The present study
would be the first study to assess the safety of high altitude exposure in patients with
aortic stenosis.
