Short-term Exposure to High Altitude in Patients With Asymptomatic Aortic Stenosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Echocardiography outcome 1
研究概览
简要总结
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.
详细描述
- 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •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
- •NYHA class I
- •LVEF >50%
- •No evidence of valvular heart disease
- •Age > 65 years
- •Written informed consent
排除标准
- •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)
- •Right ventricular dysfunction, defined as TAPSE < 17 mm, s'DTI < 9 cm/sec (all groups)
研究组 & 干预措施
Patients with asymptomatic moderate or severe aortic stenosis
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)
干预措施: Participants will be escorted to high altitude and undergo a series of test (Behavioral)
Patients with aortic stenosis s/p aortic valve replacement
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)
干预措施: Participants will be escorted to high altitude and undergo a series of test (Behavioral)
Age- and sex-matched healthy individuals
Age- and sex-matched healthy individuals ( NYHA class I, LVEF >50%, no evidence of valvular heart disease, age > 65 years)
干预措施: Participants will be escorted to high altitude and undergo a series of test (Behavioral)
结局指标
主要结局
Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Echocardiography outcome 1
时间窗: At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours
Decrease in Cardiac output, i.e. CO @high altitude minus CO @ low altitude
Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Echocardiography outcome 2
时间窗: At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours
Increase in left ventricular filling pressure (E/e'), i.e. E/e' @high altitude minus E/e' @ low altitude
Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Spiroergometry outcome 1
时间窗: At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours
Decrease in VO2 peak, i.e. VO2-peak @high altitude minus VO2-peak @ low altitude
Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Spiroergometry outcome 2
时间窗: At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours
Increase in VE/VCO2 slope, i.e. VE/VCO2 slope @high altitude minus VE/VCO2 slope @ low altitude
Safety of high altitude exposure in patients with asymptomatic moderate or severe aortic stenosis. Rhythmologic outcome
时间窗: At end of the investigation at 3545m above sea level, expected to be on average after 3-4 hours
Occurrence of ventricular tachycardia (\> 3 beats). Evaluated as presence versus absence.
次要结局
- 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)