Approach to patients with heart disease who wish to travel by air or to high altitude

INTRODUCTION — The number of individuals exposed to high altitude through air travel and recreational activities continues to increase, with tens of millions of people traveling to high-altitude destinations each year [1]. Changes in physiologic functions during high-altitude exposure vary given an individual's physical fitness, rate of ascent, severity and/or duration of exposure, cultural habits, geographic location, and genetic variation [2]. While high altitude is well tolerated by most individuals, patients with cardiovascular disease are at risk of complications caused by tissue hypoxia and reduced oxygen delivery, sympathetic stimulation, increased myocardial demand, paradoxical vasoconstriction, and alterations in hemodynamics that occur with exposure to high altitude [3-5]. The duration of travel, ascent profile, degree of exertion, and any prior cardiovascular history can each impact the health of a patient with cardiovascular disease who is considering traveling to high altitude.

High altitude provides a unique physiologic challenge to the cardiovascular system. The cardiovascular response in both healthy individuals and in patients with cardiovascular disease will be reviewed here. Insights surrounding high-altitude disease will also be included to provide a comprehensive understanding. (See "High-altitude illness: Physiology, risk factors, and general prevention".)

Most importantly, this topic will discuss the impact of high altitude on the heart and the associated hemodynamic changes. Altitude exposure can also lead to a variety of well-described clinical syndromes including some not directly involving the cardiovascular system, such as acute mountain sickness (AMS), high-altitude pulmonary edema, high-altitude cerebral edema, and high-altitude retinal hemorrhage. These conditions are discussed separately. (See "High-altitude pulmonary edema" and "Acute mountain sickness and high-altitude cerebral edema" and "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Other altitude-related illnesses'.)

BAROMETRIC PRESSURE AND PIO2 — Four key climactic indices change when moving from sea level to high altitude; atmospheric pressure, oxygen pressure, humidity, and temperature all decrease [4]. Significant changes occur beyond a critical height of 2500 meters (8200 feet) above sea level [6]. Factors such as degree of change in elevation, degree of hypoxia, rate of ascent, level of acclimatization, exercise intensity, previous history of high-altitude illness, genetics, and age significantly affect the physiologic change that the human body will experience during ascents [7]. One study involving Chinese men aged 18 to 35 years noted that increasing age (from 26 to 35 years old) was an independent risk factor for acute mountain sickness (AMS) upon rapid ascent to high altitude (from 500 to 3700 meters) and that the prevalence of AMS was more predominant with increasing age [8]. Hypoxia induces peripheral vasodilation and a pulmonary vasoconstriction, leading to changes in systemic blood pressure and an increase in pulmonary blood pressure that can also contribute to high-altitude pulmonary edema [9].

Although altitude is the most obvious determinant of barometric pressure and its resulting physiologic stress, other factors can contribute to a reduction in barometric pressure including a decrease in temperature, deteriorating weather (ie, blizzards, hail, or extreme winds), and distance from the equator.

An understanding of barometric pressure, the primary determinant of the partial pressure of oxygen (PO₂) in inspired air (PiO₂; in mmHg), is essential when interpreting the cardiovascular stress of high altitude. The relationship between the PiO₂, fraction of oxygen in inspired air (FiO₂), and barometric pressure (in mmHg) is described by the following equation:

FiO₂ is the same at all altitudes. As the barometric pressure changes, the FiO₂ remains constant while the PO₂ is altered with the change in barometric pressure. Specifically, the partial pressure of arterial oxygen decreases with altitude (hypobaric environments) and increases with depth (hyperbaric environments). In addition, oxygen within inspired air is reduced by the presence of water vapor obtained during transport into the lungs (typically 47 mmHg). As a result, the above equation can be written as:

The approximate pressures of oxygen in the atmosphere, inspired air, alveoli, and arterial blood at a variety of altitudes are shown in the following table (table 1). At 2439 meters (8000 feet), which is the maximal allowable cabin pressure (altitude equivalent) in commercial airliners, the barometric pressure is decreased to 564 mmHg (compared with 760 mmHg at sea level). The net effect is a PiO₂ of 108 mmHg, with associated partial pressures of oxygen in the alveoli and arterial blood of normal individuals of 69 and 60 mmHg, respectively. At sea level, the oxygen saturation is 99 to 100 percent. The oxygen saturation at 2439 meters (8000 feet) should be higher than 85 percent (approximately 90 percent) for a partial pressure of oxygen in arterial blood (PaO₂) of 60 mmHg based on the oxygen saturation curve. The PiO₂ is greater than the alveolar and arterial PO₂ at any altitude. This is caused by anatomical dead space in the respiratory system in which all inspired oxygen (air in the mouth and trachea) does not take part in gas exchange.

NORMAL CARDIOVASCULAR RESPONSE TO HIGH ALTITUDE — Information on the physiologic cardiovascular consequences of altitude exposure comes from both "at-altitude" studies and those in which altitude is simulated in a hypobaric chamber.

Short-term altitude exposure — Several circulatory changes occur within minutes of exposure to high altitude. Maximal aerobic exercise capacity is decreased at high altitudes due to a decrease in arterial oxygen content from the decreased inspired partial pressure of oxygen (PO₂) [10]. This results in tissue hypoxia (hypobaric hypoxia) from inspiring oxygen-poor air and causes compensatory physiologic changes at high altitude both at rest and during exercise [11].

The initial response to hypoxia is an attempt to increase oxygen delivery. The minute ventilate rate and tidal volume are increased to allow for optimal systemic arterial tension [12]. Furthermore, the pulmonary arteries constrict in response to tissue hypoxia, a condition known as hypoxic pulmonary vasoconstriction. This physiologic phenomenon occurs to redirect blood flow to alveoli located within areas containing the highest oxygen content. The hypoxic vasoconstriction ultimately leads to pulmonary hypertension and, furthermore, an increase in the alveolar-arterial oxygen (A-a) gradient (the difference between the alveolar and arterial concentration of oxygen that is used in diagnosing the source of hypoxemia) [13]. The increased A-a gradient is caused by an unequal perfusion to the lungs from hypoxic vasoconstriction and results in the development of high-altitude pulmonary edema [14]. For instance, after 24 hours, 15 percent of subjects develop pulmonary edema without symptoms, while 75 percent have an increase in pulmonary extravascular fluid [15]. Sustained exposure to high altitude for >24 hours results in the development of pulmonary edema. (See "High-altitude pulmonary edema".)

Hyperventilation leads to a decrease in carbon dioxide and causes respiratory alkalosis. This leads to a shift of the oxygen-hemoglobin dissociation curve to the left, resulting in an increased binding of oxygen to hemoglobin and thus less oxygen delivery to the tissues. Subsequently, after a few hours, there is an increase in 2,3-diphosphoglycerate that shifts the curve back to the right to improve oxygen delivery by facilitating the unloading of oxygen to the tissues. However, this makes it more difficult for oxygen to bind to hemoglobin in the lungs during gas exchange [16].

Oxygen delivery is the product of cardiac output and oxygen content. Given the reduction in oxygen content with increased altitude, cardiac output must increase to maintain the same oxygen delivery to the tissues. This can be achieved by increasing heart rate or stroke volume, which (initially, at high altitudes) increases the cardiac output [11]. Despite this effort, there is ultimately a lower peak cardiac output at high altitudes as opposed to at sea level. Such limitations are autonomic responses to limit myocardial oxygen demand and consumption during times of reduced oxygen availability. Over one to two weeks, the stroke volume is decreased from reduced preload and a lowered plasma volume from respiratory (hyperventilation), urinary (hypoxic diuresis), and cutaneous losses. Increased urine output is a response to high-altitude hypoxia. Diuresis serves to increase bicarbonate losses in the urine to stimulate increased breathing. The increased urine output also serves to increase the hematocrit by 1 to 2 g/dL to increase the oxygen-carrying capacity of the blood-per-unit volume [17]. Within hours of exposure to altitude, the red blood cell count begins to increase in response to an increase in erythropoietin. However, the overall buildup process of the red blood cell count is slow, taking months to reach equilibrium. As expected, the degree of polycythemia is related to the level of altitude.

The increase in the rate-pressure product (heart rate × systolic blood pressure), reduction in arterial oxygen saturation, and elevation in lactate concentration illustrate the potential oxygen supply/demand mismatch observed with exercise at altitude [4]. Even though the cardiac output and rate-pressure product at a given activity level tend to be higher as altitude increases, paradoxically, the maximum attainable cardiac output, heart rate, and maximum attainable workload fall with increased altitude [18].

In addition, after rapid ascent to a high altitude, the sympathetic nervous system is activated, which stimulates the release of epinephrine [19]. This shift toward sympathetic predominance during acute exposure to hypoxia has also been manifested by reduced heart rate variability (HRV) [20] (see "Evaluation of heart rate variability"). The higher the altitude, the higher the arterial epinephrine concentration rises to enhance cardiac output, increasing bronchodilation in the lungs and furthering vasodilation in the skeletal muscles [21]. This vasodilation counterbalances the escalation in cardiac output such that blood pressure changes do not markedly occur [22,23].

Several changes are observed in the resting electrocardiogram (ECG) and echocardiographic Doppler imaging for normal individuals exposed to high altitude. During ECG recordings taken from members of an expedition who climbed Mount Everest and achieved altitudes of 5335, 6250, and 7988 meters (17,500, 20,500 and 26,200 feet, respectively), the following ECG changes were noted [24]:

●Increase in resting heart rate

●Prolongation of the QT interval

●ST-T wave flattening

●Rightward shift in the frontal QRS axis

●Increase in P-wave amplitude in lead II

The last two changes are thought to reflect evidence of right ventricular and right atrial "strain" arising from hypoxia-induced pulmonary hypertension. At the most extreme altitude, 3 of the 12 patients developed a new right bundle branch block and three others showed changes consistent with right ventricular hypertrophy. Some of the ECG changes, primarily the increased heart rate, QT lengthening, and ST-T wave abnormalities, can be blunted with beta blocker administration [25], suggesting a role for catecholamines in their development. Since virtually all ECG abnormalities abate upon descent, they are not thought to be clinically significant.

Another study of 456 subjects who performed a 20-minute hypoxia exercise test with continuous recording of ECG noted a dose-dependent, hypoxia-induced decrease in the amplitude of the P, QRS, and T waves [26].

Echocardiographic Doppler imaging studies of healthy adults at rest after rapid ascent to high altitudes have noted [10]:

●Threefold increase in mean pulmonary artery pressure

●Altered right and left ventricular diastolic function

●Prolonged isovolumic relaxation time

●Maintained right ventricular systolic function

●Improved left ventricular systolic function

Long-term altitude exposure — After three to four days, the initial sympathetic nervous system manifestations of altitude exposure resolve as early acclimatization begins. Longer-term exposure to altitude is associated with a number of other adaptive physiologic responses. These include:

●Resetting of the "hypoxic ventilatory response" to allow increased ventilation at a given hypoxic stimulus.

●Increase in red blood cell mass mediated by erythropoietin.

●Increased tissue capillary density, predominantly in highly engaged muscular tissue.

●Reduction in the A-a gradient.

●Reduced parasympathetic nervous activity as a key mechanism for the elevated heart rate in chronic hypoxia [27].

●Rightward shift of the oxygen-hemoglobin dissociation curve, facilitating oxygen unloading to tissues. The sequence of events is as follows: At high altitude, the initial hypoxia and decreased dissolved oxygen in the blood stimulate peripheral chemoreceptors, which, in turn, send signals to respiratory drives, leading to hyperventilation, leading to respiratory alkalosis and then subsequently to shifts of the oxygen-hemoglobin dissociation curve to the left so that hemoglobin can pick up oxygen easier. Next, the kidney responds to alkalosis by generating hydrogen ions to correct the pH; after two to three days, the red blood cell 2,3-diphosphoglycerate level increases, shifting the oxygen-hemoglobin dissociation curve to the right and making oxygen delivery easier to the tissues.

ALTITUDE STRESS IN HEART DISEASE — The effects of high-altitude exposure may have important implications for patients with various types of heart disease. (See "High-altitude illness: Physiology, risk factors, and general prevention".)

In addition to the baseline changes to the cardiovascular system, the possible development of high-altitude diseases (mountain sickness/pulmonary or cerebral edema) can add further stress. As a result, cardiac patients engaged in recreational activities at higher altitudes should be warned about the signs of altitude illness and, in certain circumstances, carry the appropriate prophylactic medicines such as acetazolamide [28] and dexamethasone [29]. In addition, these patients should follow basic advice about altitude illness prevention, most notably acclimatization (ideally for five days) with gradual ascent and proper hydration [30]. Patient compliance for the prescribed dosing of their current antianginal medications and treatment of their cardiovascular disease should be emphasized. Most importantly, they should be advised that the quickest and most effective treatment of altitude-related illness is descent. Supplementary oxygen may also be beneficial in some individuals [31]. (See "High-altitude illness: Physiology, risk factors, and general prevention".)

Coronary heart disease — Exercise at real or simulated altitude in patients with stable coronary heart disease (CHD) appears to be relatively safe, provided that patients take the same precautions as they would at sea level [32-36]. However, the acute hemodynamic changes associated with altitude/hypoxemia result in an earlier onset of angina symptoms or ischemic electrocardiogram (ECG) changes (essentially, a shorter time to notable symptoms) [34,37].

In a study that compared 23 patients (mean age 51 years) with stable CHD and a mean left ventricular ejection fraction (LVEF) of 39 percent with control subjects during maximal bicycle ergometer stress testing at both 1000 and 2500 meters (3280 and 8202 feet) [32]:

●Patients with CHD, who were more often receiving therapy with a beta blocker and angiotensin-converting enzyme inhibitor, had a lower peak rate-pressure product (beta blocker effect) than controls at both altitudes.

●In both patients and controls, exercise capacity was lower at high altitude compared with baseline, while the maximal heart rate was the same at both altitudes.

●Both groups maintained percent oxygen saturations in the low to mid-90s at rest and with exercise at both baseline and altitude. There were no complications such as high-grade arrhythmias or provocation of significant ischemia.

In another report that demonstrated both the effect and safety of exercise at altitude, nine patients with stable CHD were evaluated during maximal treadmill stress testing both at baseline (1750 meters [5740 feet]) and at altitude (3390 meters [11,120 feet]) [33]. Exercise at altitude was associated with the expected increase in minute ventilation and reductions in both maximal exercise duration and maximal oxygen uptake. Although the rate-pressure product at which angina or significant ST segment depression occurred was similar at both altitudes, this occurred at a lower level of exercise when at the higher altitude. Exercise was not associated with an increase in the extent or complexity of ventricular arrhythmias.

A third study of the response to and safety of exercise at altitude evaluated 22 patients with a prior myocardial infarction (MI) following revascularization with stress tests, both at rest and within one to three hours following rapid ascent to 3454 meters (11,330 feet) [35]. Patients were required to have an LVEF above 45 percent, no evidence of ischemia on a baseline stress test, and controlled blood pressure. Beta blockers were withheld from patients for five days prior to the study protocol. All patients tolerated the rapid ascent, none of the cardiopulmonary stress tests needed to be stopped prematurely, and neither evidence of ischemia nor significant arrhythmias were observed in any patients during stress testing at high altitude.

Of interest, lower mortality rates from CHD and higher levels of serum high-density lipoprotein cholesterol have been observed in populations residing at high altitude [38].

An intriguing finding is the frequency with which ischemia is provoked in subjects with no history of CHD when exercising at high altitude. This was addressed in a Holter monitor evaluation study that was performed in 149 selected skiers beginning at an altitude of 3430 meters (11,250 feet) [39]. Only 5.6 percent of the skiers over age 40 showed ECG evidence of ischemia [39]. This is similar to the 5 percent incidence of ischemia noted in screening stress tests in asymptomatic individuals at sea level [40].

It is important to note that multiple cardiovascular risk factors are affected by the combination of high altitude and increasingly cold temperatures, with an increased incidence of MI occurring [41].

These studies suggest that both ascending and exercising to higher altitudes can be safe in patients with stable CHD or a remote acute coronary event. We suggest that, when advising a patient with CHD who is planning a trip to a high-altitude destination, the health care provider needs to consider the patient's functional level, clinical status, ischemic threshold, and anticipated stress workload. A graded exercise test at sea level may be prudent for assessment of exercise tolerance and provocable ischemia for clinical assessment [30]. In addition, specific recommendations include:

●In patients with recent acute coronary syndromes who have not had revascularization, there should be no ascent to high altitudes until maximal stress testing has been performed and an absence of overt ischemia is confirmed. Patients who have had an MI within two weeks should only undergo air travel, a potential stress itself, if there is no angina, dyspnea, or hypoxemia at rest and there is no fear of flying. In addition, they should fly with a companion, carry nitroglycerin, and be able to cope with the emotional and physical demands of travel.

●Patients should be warned that anginal symptoms will probably occur more easily at lower workloads and so strenuous activities should be approached with a higher degree of caution, particularly during the first three or four days at higher altitudes [32,35]. Therefore, acclimatization for at least five days is advised [30]. Access to appropriate medicines and medical care should also be confirmed prior to high-altitude travel.

●Appropriate use of CHD medications and discussions regarding compliance of medications should be communicated prior to high-altitude exposure.

Heart failure — Patients with heart failure (HF) are especially susceptible to the physiologic changes from high-altitude exposure [42]. The increased sympathetic activity elevates systemic vascular resistance, blood pressure, and heart rate, which results in reduced exercise capacity [43]. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'High altitude physiology'.)

The pulmonary vasoconstriction and hypertension that result from high altitude (hypoxemia) impair right ventricle loading and output [44]. In addition to the hypoxic pulmonary vasoconstriction, increased erythropoiesis places an increased pressure load on the right ventricle [5]. Together, these factors reduce cardiovascular performance in patients with HF [45-47].

Additional factors that may predispose patients with chronic HF to exacerbations at high altitude include [47]:

●Chronically elevated catecholamine levels (see "Pathophysiology of heart failure: Neurohumoral adaptations", section on 'Neurohumoral adaptations')

●Increased transcapillary permeability in the lung

●Poor skeletal muscle metabolism

●High oxygen extraction in the periphery (see "Exercise capacity and VO2 in heart failure")

●Poor pulmonary function

●Concurrent CHD

The response to various simulated altitudes (from 92 to 3000 meters [302 to 9840 feet]) during bicycle ergometry was studied in 14 control patients and 38 patients with stable HF who were categorized on the basis of mild, moderate, or severe impairment in baseline functional capacity (peak rate of oxygen [VO₂]) [48]. Findings included:

●All patients and controls showed the expected decreases in maximum workload attained and peak oxygen consumption with increasing altitude, but the percentage decrease was greater in the patients with HF, particularly those with the lowest baseline functional capacity (peak VO₂ <15 mL/min per kg) (figure 1).

●None of the patients, including 12 with the lowest functional capacity, were limited at altitude by arrhythmia, angina, or ECG evidence of ischemia.

●In patients with HF, maximum work rate decreased in parallel with increased simulated altitude, with a greater reduction in maximum physical activity in proportion to their exercise capacity at sea level.

Similar considerations also apply to patients with left ventricular dysfunction. As described above, patients with stable CHD and a mean ejection fraction of at least 39 percent showed no complications with exercise during brief exposure to 2500 meters (8200 feet) [32]. (See 'Coronary heart disease' above.)

An observational study on heart transplant patients found that those living at 610 to 1220 meters (2000 to 4000 feet) had an improved survival duration compared with those living at lower levels, suggesting that chronic exposure to higher altitude may benefit this group [49].

Lastly, a study of 23 healthy subjects reported that those with significantly elevated brain natriuretic peptide levels while exercising at 5150 meters (16,896 feet) were more likely to suffer acute mountain sickness (AMS) compared with those at sea level [50].

Our approach — Only limited information and guidance from clinical studies are available concerning altitude exposure in patients with chronic HF. Prior to approving exposure to altitude, the following should be assessed for this class of patients:

●Baseline functional capacity

●Expected altitude that will be encountered

●Anticipated activity level and expected duration of time spent at high altitude

If a patient exhibits symptoms at rest or during minimal activity, or requires oxygen therapy at rest (New York Heart Association [NYHA] class IV), even the stress of air flight may be significant and should therefore be approached with caution. In such patients, oxygen therapy should be considered; for patients already receiving oxygen, increased flow rates may be considered to alleviate symptoms.

By comparison, patients with only mild functional issues at sea level will probably tolerate moderate altitudes, but they should be warned that they may become symptomatic at lesser degrees of exercise.

Patients with HF are likely to notice a reduced functional capacity at moderate to high altitude when compared with sea level [4]. It is essential that altitude be considered in the etiology of any symptoms and that the patient be advised to arrange immediate descent if decompensation occurs. Symptoms that would herald decompensation may include chest pain, palpitations, shortness of breath, dyspnea, and fatigue. Furthermore, medication dose and frequency adjustments should be considered.

This report concurs with the British Cardiovascular Society's "Fitness to fly for passenger with cardiovascular disease" report, which suggests no flying or exposure to altitude for six weeks after an acute left ventricular failure episode [51].

Valvular heart disease — Travel to high altitude can aggravate symptoms in patients with underlying valvular heart disease. For those with severe valvular heart disease or those with symptoms, altitude exposure should be avoided. In those with mild to moderate valvular heart disease, echocardiography to document their current valvular and ventricular function plus an exercise stress test to evaluate their hemodynamic changes and functional capacity at sea level are recommended. The patient should be warned to reduce their activity levels below their baseline activity level (particularly during the first five days at altitude), to be cautious with or avoid alcohol, and to be aware of possible hemodynamic alterations such as hypertension. Moreover, they should be given additional instructions on adjusting their medications as needed.

In patients with preexisting valvular disease, the acute hemodynamic changes induced by the additional hypoxic stress of altitude may result in decompensation of their condition. Acutely, exposure to hypoxia results in an increased heart rate, cardiac contractility, cardiac output, and both systemic and pulmonary artery resistance and pressures [10,52-54]. These changes have the potential to decrease pressure and create volume overload in patients, affecting their heart in the following ways:

●The increased myocardial workload and oxygen demand will mean valvular symptoms may acutely worsen (dyspnea, near-syncope).

●The increased systemic afterload may increase the regurgitant fraction in both the aortic and mitral valves, worsening symptoms.

●The increased pulmonary afterload from increased pulmonary vascular resistance may exacerbate pulmonary and tricuspid regurgitation.

●Dehydration may result in reduced preload and may worsen symptoms of valvular stenosis. Elevated heart rates may increase gradients across stenotic valves and increase symptoms.

For those with prosthetic mechanical heart valves, the hypercoagulable state induced by acute high-altitude exposure may increase the risk of valvular thrombosis, especially if the anticoagulation level is not in the desired range [55].

In addition, patients should be cautious about consuming alcohol. The combined vasodilatory and dehydrating effects of a commercial flight, alcohol, and the approximate 2730 meters (9000 feet) of altitude may result in hemodynamic changes that could exacerbate their valvular function.

It is important to remember that there is a great deal of variability between individuals with the same valvular condition with regards to their responses to high altitude; additionally, cold temperature, humidity, exercise, stress, and their functional reserve can also compound the effect [52]. One protocol used to gain significant insight into how a patient will respond to air travel is the hypoxia altitude simulation test. This procedure involves a patient breathing a gas mixture with an oxygen saturation of 15.1 percent, which simulates a cabin pressure of an airplane at 2440 meters (8000 feet) and allows the clinician to screen for hypoxia, significant symptoms, and arrhythmias. Repeating the test with supplemental oxygen will ensure that the patient will receive an acceptable benefit for its use when flying [56].

Given all of the variables that can affect a patient with valvular heart disease, patients should be treated in a highly personalized manner by their clinicians. Prior to ascent to high altitude or air travel, the following should be considered:

●For those who are asymptomatic with mild to moderate valvular disease, exercise testing and transthoracic echocardiography at rest/stress are recommended for evaluating their current status and response to exercise [52,57].

●For those with symptomatic and/or severe valvular disease, exposure to altitude is contraindicated [52,57].

●Hypoxic challenge tests such as the hypoxia altitude simulation test may be helpful to obtain more practical information about possible hemodynamic effects and symptoms during high-altitude exposure [58].

●Education about blood pressure self-monitoring and treatment titration is needed just in case uncontrolled hypertension or hypotension develops [52].

●For those on anticoagulation, instructions for self-monitoring and dose adjustment should be given [52,55].

●Alcohol consumption should be avoided or consumed with caution.

Arrhythmias — It appears that altitude can aggravate arrhythmias, particularly during acute exposure and with exercise. This is especially noteworthy in older adults and those with known arrhythmias or CHD. Air travel alone is probably of low risk, except in those with baseline (resting) ventricular and supraventricular arrhythmias in whom the added stress of mild hypoxemia might lead to decompensation. Such patients should be cautioned about air travel and/or have supplemental oxygen recommended.

Similar guidance applies to those contemplating vacationing at high altitude, and patients should be warned to reduce their activity level to below their sea level baseline capacity, particularly during the first five days at altitude. Patients with arrhythmias should also be aware of and immediately treat both cardiac and noncardiac manifestations of altitude exposure.

Caution is clearly needed in patients with poorly controlled rhythm disorders. Deaths at high altitude are often sudden, and, while ascertainment of the cause of death is often difficult, the possibility that rhythm-related causes are being underestimated needs to be kept in mind.

The incidence of arrhythmias at high altitudes is variable and depends upon the patient group under study. Heightened sympathetic activity associated with high altitude may increase the frequency and duration of supraventricular and ventricular arrhythmias in patients with underlying heart disease [59,60].

A study among young, healthy individuals without arrhythmias was conducted in a hypobaric chamber study of eight healthy men aged 21 to 31 years who were observed during exercise at simulated altitudes up to the equivalent of the summit of Mount Everest (8850 meters [29,020 feet]) [61]. No arrhythmias or conduction defects were seen [61].

Examining a more advanced age group, a Holter monitor study of healthy middle-aged men found that the incidence of both supraventricular and ventricular premature beats nearly doubled at an altitude of 1350 meters (4430 feet) as compared with 200 meters (660 feet) [62]. At a still-higher altitude (2630 meters [8630 feet]), the frequency of ectopy was increased six- to sevenfold [63]. It was hypothesized that the increase in premature beats was due to beta adrenergic stimulation at the higher altitude brought on by the early release of catecholamines.

Patients with stable CHD have also been evaluated. In a previously described study, 10 older adult patients with exercise-induced ischemic changes at sea level were studied at 2500 meters (8200 feet), both acutely and after five days of acclimatization [34]. Ventricular premature beats were significantly increased with acute exposure but returned to sea level values after acclimatization. This suggests that early sympathetic stimulation on acute exposure to altitude is driving these changes.

Pacemaker function — The issue of pacemaker safety at altitude and the possibility of alterations in stimulation thresholds are uncertain since data sources cite conflicting findings:

●In one study simulating altitude with inhalation of 10 percent oxygen, a significant but reversible increase in stimulation thresholds was noted [64]. In another phase of threshold testing, hypocapnia (low level of carbon dioxide in the blood), induced by mechanic hyperventilation, led to a reduction in pacing stimulation thresholds.

●In another report, stepwise simulated hypobaric chamber ascent from 450 to 4000 meters (1480 to 13,120 feet) produced no change in stimulation threshold, despite a significant fall in the partial pressure of oxygen in arterial blood (PaO₂) [65].

It seems likely that the competing effects of hypoxia and hypocapnia, each pushing the pacing stimulation threshold in a different direction, may balance each other out in some cases and prevent any net change during the physiologic stress of high-altitude exposure.

Based on the limited data, it appears that pacing thresholds can be expected to remain unchanged at the moderate altitudes seen with air travel and recreational skiing. The safety of pacemakers at the extreme altitudes, as with trekking and mountaineering, is not known. However, the development of advanced pacing algorithms and the active fixation of placement leads are innovations that have improved pacemaker function/reliability.

Airport security gates may detect pacemakers and defibrillators but do not appear to interfere with device function [35]. By contrast, there is a theoretical risk that handheld metal detectors may interfere with personal electronic devices and, hence, pacemakers and defibrillators. (See 'Implanted devices' below.)

Congenital heart disease — When advising a child or adult with congenital heart disease who is contemplating high-altitude exposure, the guidelines must be individualized and based upon the nature of the congenital defect and expected stresses. Patients most at risk are those with intracardiac communication defects and the propensity to worsen right-to-left shunting in the presence of elevated right-sided pressure. Consultation with a pediatric or adult cardiologist specializing in congenital defects should precede high-altitude exposure.

Congenital heart disease associated with intracardiac or extracardiac shunts may be associated with a net shunting of blood from the left, high-pressure side of the heart to the right, low-pressure side. However, with exposure to high altitude and hypobaric hypoxia, pulmonary vascular resistance and right-sided pressures are increased [14]. This results in an increase in right-to-left shunting, leading to arterial oxygen desaturation [66-68]. The extent to which arterial oxygen desaturation occurs will depend upon many factors, including the size of the communication, baseline right-sided pressures, and extent of altitude-induced pulmonary hypertension.

It is important to appreciate that there may be an increased prevalence of congenital heart disease (ie, atrial septal defect/patent foramen ovale [PFO] or patent ductus arteriosus) in individuals who live at high altitudes. This is likely due to a persistence of the fetal pattern of the pulmonary vasculature (thick, smooth muscle cells; narrow lumens; small pulmonary vessels; increased pulmonary and right ventricular pressures) [69-71]. In a prospective study of 1116 schoolchildren, there was a high prevalence of patent ductus arteriosus and atrial septal defect at three high-altitude sites, as well as a graded effect as altitude increased [72]. One explanation is that lower oxygen tension fails to constrict the ductus and thus closure of both the ductus and the foramen ovale is inhibited.

A large cross-sectional study examined children aged 4 to 18 years in the Qinghai province of China, where 1633 cases of congenital heart disease were discovered. Of those, the prevalence of congenital heart disease was found to increase in a gradient-like fashion as the altitude increased by 4.9 per thousand at 2535 meters (8320 feet), 5.7 per thousand at 3600 meters (11,810 feet), and 8.7 per thousand at 4200 meters (13,780 feet) [73].

Another study demonstrated higher pulmonary artery pressures in children with atrial septal defects born at higher altitudes compared with both those without such defects at the higher altitudes and those with similar defects born at sea level [74]. Similar findings were noted in another report in which children with ventricular septal defects born in Denver (1609 meters [5280 feet]) had twice the pulmonary vascular resistance of children born with such defects at sea level [75].

Exaggerated pulmonary hypertension and right ventricular dysfunction has also been found in patients with PFO living at high altitude. The presence of PFO was associated with right ventricular enlargement at rest, an exaggerated increase in the right ventricular pressure gradient and dysfunction (25±7 versus 15±9 mmHg, p<0.001), and a blunted increase in fractional area change of the right ventricle (3 [-1, 5] versus 7 percent [3, 16], p = 0.008) during mild exercise [76]. Individuals who undergo successful closure of their PFO are able to travel or live at high altitude without difficulty [77].

Moreover, in a small study of adults with cyanotic congenital defects, it was reported that exposure to moderate altitude (1500 to 2500 meters [4920 to 8200 feet]) is safe [78]. The upper range of the altitude in this study is relevant in that commercial airplanes are pressurized to this altitude when flying.

Lastly, data from a limited study suggest that it is safe for Eisenmenger patients to travel in commercial airlines as long as the airplanes are adequately pressurized [79]. Supplemental oxygen should be available, although its efficacy in this specific population is unproven. The approach to patients with Eisenmenger syndrome who wish to either travel in commercial airlines or visit geographies at altitude is discussed in detail elsewhere within this report [79]. (See "Evaluation of patients for supplemental oxygen during air travel" and "Pulmonary hypertension in adults with congenital heart disease: General management and prognosis", section on 'High altitude'.)

Blood pressure patterns — There is a subsegment of patients with hypertension who do not exhibit the normal nocturnal fall in blood pressure (sometimes referred to as "nondippers") compared with other hypertensive patients with a normal circadian rhythm (sometimes referred to as "dippers") [80]. One study examined the effects of high altitude on these two groups, finding that those who did not have a nocturnal fall in blood pressure showed poor cardiac compensatory and inadequate adaptation abilities to acute high altitude [81].

AIR TRAVEL

Incidence of in-flight medical events — In-flight emergency medical events (IEMEs) are uncommon, and in-flight deaths are rare. The reported incidence of IEMEs ranges from 21 to 63 per million passengers per year [82,83]. In-flight deaths occur at reported frequencies of 1 death per 1.5 to 4.7 billion passenger miles flown [84].

●In-flight cardiac events – Cardiac events during air travel are also relatively uncommon. As an example, one study of five domestic and international commercial airlines reported that the most common causes of IEMEs were syncope or presyncope (37 percent), respiratory symptoms (12 percent), and nausea or vomiting (10 percent) [85]. Cardiac events were less common (8 percent); however, they disproportionately resulted in aircraft diversions and subsequent transport to a hospital (17 and 45 percent of all cardiac events, respectively).

The reported use of automated external defibrillators (AEDs) is also infrequent, with one study reporting AED use in only 1 percent of all IEMEs [82]. (See "Automated external defibrillators".)

Reported frequencies of IEMEs are likely underestimates due to limited reporting requirements for airlines and misclassifications of event types [86].

●In-flight events in patients with coronary artery disease – The incidence of in-flight problems in patients with known coronary artery disease has not been well studied in patients receiving contemporary medical and revascularization therapies. One study investigated the frequency of in-flight cardiac symptoms after a recent myocardial infarction (MI) among patients undergoing medical repatriation (returning a person back to one's place of origin or citizenship) [87]. A total of 213 patients were transported 6 to 38 days (mean 12.9 days) following presentation with ST elevation MI or non-ST elevation MI. No serious complications occurred. Only three individuals experienced angina, and all of these had had an ST elevation MI fewer than 14 days before travel.

Preflight assessment — Individuals with normal cardiopulmonary reserve can easily compensate for the reduced arterial partial pressure of oxygen (PO₂) that occurs at commercial cabin pressures. In contrast, patients with limited cardiopulmonary reserve can potentially experience profound arterial desaturation and cardiopulmonary decompensation (see 'Barometric pressure and PiO2' above). Resultant tissue hypoxia can lead to chest pain, lightheadedness, dyspnea, hyperventilation, palpitations, and tingling in the extremities [3-5,88]. In patients with coronary artery disease, it can provoke the onset of angina and ischemic electrocardiogram (ECG) changes [34,37].

Other physiologic stressors may also increase the risk of cardiac events, such as alteration of circadian rhythms, sleep deprivation, noise, vibration, low humidity, and anxiety related to flying [51,88,89].

Risk stratification — Clinicians should assess patients with cardiac disease prior to air travel. Evaluation of the patient with established cardiovascular disease should include a careful history and physical examination to identify signs or symptoms of recent angina, volume overload, or dysrhythmia [89]. Most patients with well-compensated heart disease can travel without difficulty. However, air travel is risky or contraindicated for selected high-risk patients or may need to be postponed after cardiac events (eg, MI) or procedures (eg, device implantation or coronary artery bypass graft [CABG] surgery).

Contraindications to air travel — Patients with severe or poorly controlled heart disease and those with recent cardiac events should ideally avoid or postpone air travel. Key cardiac contraindications for air travel are listed in the table (table 2). They include [51,89,90]:

●Unstable angina.

●Acute decompensated heart failure (HF) within the past six weeks.

●High-grade ventricular premature beats or uncontrolled ventricular or supraventricular arrhythmias.

●Congenital heart disease with severe pulmonary hypertension.

●Symptomatic valvular heart disease (relative contraindication).

●Severe hypertension (≥180/120 mmHg).

●Recent MI. Recommended time intervals during which to avoid air travel after an MI vary. (See 'Myocardial infarction' below.)

●Percutaneous coronary intervention within two days.

●CABG surgery within 10 to 14 days. (This time interval varies according to individual practice patterns.)

●Cerebrovascular accident within 14 days.

Recommendations for all travelers with cardiovascular disease — Clinicians should obtain a resting ECG and give a copy to the patient to carry during all air travel.

They should also advise such individuals to plan for any anticipated needs well in advance. These may include requesting airport assistance, special meals, or oxygen. Practical guidelines for all travelers appear in the table (table 3), and disease-specific recommendations are detailed below. These guidelines are consistent with the British Cardiovascular Society's document "Fitness to fly for passengers with cardiovascular disease" [51].

Assess the need for supplemental oxygen — Patients who require supplemental oxygen at sea level require supplemental oxygen during air travel [89]. Additionally, some individuals who do not require supplemental oxygen at sea level should undergo assessment to evaluate their need for oxygen while flying. This includes those with cyanotic congenital heart disease, moderate to severe chronic HF (New York Heart Association [NYHA] class III or IV), and moderate to severe ischemic heart disease (Canadian Cardiovascular Society [CCS] class III or IV). This is summarized in the algorithm (algorithm 1) and discussed in detail elsewhere. (See "Evaluation of patients for supplemental oxygen during air travel".)

Disease-specific recommendations — In addition to the recommendations for all travelers, we offer disease-specific guidance as follows. This is consistent with the 2010 British Cardiovascular Society's document "Fitness to fly for passengers with cardiovascular disease" [51]. In most cases, there is not an empirical evidence basis for this guidance; rather, this represents a conservative approach to risk based upon physics, physiology, and limited clinical observations.

Acute decompensated heart failure — Patients with a recent HF exacerbation should delay travel for six weeks and then follow recommendations for those with chronic HF.

Stable chronic heart failure — Specific recommendations for individuals with chronic, stable heart failure vary according to the severity of the patient's symptoms. Patients with NYHA class III or IV HF (table 4) should be carefully assessed to determine whether they will need in-flight oxygen. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Evaluation of patients for supplemental oxygen during air travel".)

●NYHA class I or II HF symptoms (no or slight limitation with ordinary physical activity) – No restrictions.

●NYHA class III HF symptoms (marked limitation of physical activity) – Consider medical assistance, and assess the need for supplemental oxygen.

●NYHA class IV HF symptoms (symptoms with minimal activity or at rest) – Advise to fly with medical assistance and in-flight oxygen.

Stable coronary artery disease — Specific recommendations for individuals with stable coronary artery disease vary according to the severity of the patient's symptoms [51]. The following guidance is based on functional classification of angina severity by the CCS [91,92] (table 4). Routine stress testing prior to air travel is not necessary unless there has been a recent significant change in clinical status.

●CCS class I or II angina (chest pain only with considerable exertion) – No restrictions.

●CCS class III angina (chest pain with minimal exertion) – Consider medical assistance, and assess the need for supplemental oxygen.

●CCS class IV angina (chest pain at rest or change in symptoms) – Advise to defer travel until medically stabilized or to travel with medical escort and in-flight oxygen available.

Myocardial infarction

●General approach – Individuals who have recently experienced an MI should follow general recommendations for all air travelers (table 3).

In addition, they should request airport transportation to avoid rushing, carry nitroglycerin, and, ideally, travel with a companion.

●Timing of air travel after MI – Passengers should be stratified into low-, medium-, and high-risk groups based on age, symptoms, left ventricular ejection fraction (LVEF), and any additional planned diagnostic or therapeutic interventions [51].

Patients in low- or medium-risk groups can reasonably travel after 3 and 10 days, respectively. Patients in the high-risk group should defer air travel until clinically stable and delay altitude exposure for a minimum of six weeks.

These three groups are defined as follows:

•Low risk – <65 years of age, first event, successful reperfusion, LVEF >45 percent, no complications, and no cardiac investigations or interventions pending. Air travel is reasonable after three days.

•Medium risk – LVEF >40 percent, no symptoms of HF, no evidence of inducible ischemia or arrhythmia, and no further cardiac investigations or interventions pending. Air travel is reasonable after 10 days.

•High risk – LVEF <40 percent with signs and symptoms of HF, pending further investigations for revascularization or device therapy. Patients should defer air travel until medically stable and, ideally, for a minimum of six weeks.

Observational data among air travelers after acute MI are scarce [51]. As an example, a retrospective cohort examined outcomes of 288 individuals who traveled on commercial airlines after a recent acute coronary syndrome (average number of days postevent 10.5). Sixty percent had experienced an acute MI, and the remainder experienced unstable angina. Four (1.4 percent) had an adverse in-flight event, and there were no in-flight deaths [93].

Guidelines on the timing of air travel for such patients vary between different professional organizations [51,90,94,95]. Recommendations are largely based on extrapolations of prognostic risk in nontravelers after MI. For example, guidelines from the American College of Cardiology/American Heart Association recommend that air travel within the first two weeks after an MI should only be undertaken if the patient has no angina, no dyspnea at rest, and no fear of flying [96]. A different approach from the Aerospace Medical Association recommends that no air travel be undertaken within two to three weeks of an uncomplicated MI and within six weeks of a complicated MI [90]. We concur with recommendations from the British Cardiovascular Society's report "Fitness to fly for patients with cardiovascular disease," which recommends risk stratification of patients to determine optimal timing for air travel and is summarized above.

●Role of exercise testing – Exercise testing prior to air travel may aid clinicians in risk stratification. Exercise testing can evaluate for residual ischemia as well as assess functional capacity, the effectiveness of medical therapy, and the risk of a subsequent cardiac event [94]. The timing and choice of testing strategies are discussed elsewhere. (See "Overview of the nonacute management of ST-elevation myocardial infarction", section on 'Stress testing' and "Stress testing in pre-discharge risk stratification of patients with non-ST elevation acute coronary syndrome".)

Percutaneous coronary intervention — Patients undergoing placement of percutaneous coronary stents should avoid immediate air travel due to the increased risk of acute stent thrombosis [89] (see "Coronary artery stent thrombosis: Incidence and risk factors"). Most in-stent thromboses occur within one week of intervention. Hypoxemia may increase this risk by activating coagulation factors and impairing fibrinolysis [89]. Patients with periprocedural complications should delay travel for a longer interval. (See "Periprocedural complications of percutaneous coronary intervention".)

●Uncomplicated – Avoid air travel for at least two days

●Complicated – Avoid air travel for at least two weeks

Coronary artery bypass graft surgery

●Uncomplicated – We recommend that those who have undergone CABG delay air travel at least 10 days. This reduces the risk of barotrauma by allowing for the reabsorption of intrathoracic gas that was introduced during surgery [97]. Some institutions allow stable, asymptomatic patients to fly a few days earlier.

●Complicated – Patients with complications after CABG should follow recommendations for specific symptoms (eg, HF, perioperative MI).

Implanted devices — Air travel has not been shown to interfere with the function of most pacemakers or implantable cardioverter-defibrillators [98-100]. One exception is leadless pacemakers; their safety during air travel is not well established [101]. Patients should take precautions when passing through airport security and carry a card identifying the type of device [89].

Individuals with wearable defibrillators should inform the airline in advance so that the flight crew can minimize risk for other passengers and crew in the rare event that the device delivers in-flight shocks.

●Air travel after device implantation – Individuals who have recently undergone device implantation should restrict arm movements and carry heavy loads on the contralateral side to minimize mechanical complications, such as lead displacement. We concur with the following recommendations from the British Cardiovascular Society regarding the timing of air travel [51]:

•Pacemaker without pneumothorax or complications (bleeding, electrode problem) – Avoid air travel for two days

•Pacemaker with pneumothorax or complications – Avoid air travel until two weeks after resolution

•Implantable cardioverter-defibrillator placement – Treat any rhythm instability, and time air travel as for pacemaker

●Airport security – Although electronic security systems can potentially interfere with pacemakers and implantable defibrillators, passing through airport security gates has not been found to interfere with implanted device function [51]. We suggest that when passing through airport security, patients should walk through the security gate at a normal pace and not linger in its vicinity. If a handheld search is required, patients should request a nondetector hand search [89]. If a handheld detector must be used, the patient should request that it not be held over the implanted device for more than a few seconds and that at least 30 seconds should elapse between passes. This is discussed separately. (See "Cardiac implantable electronic device interactions with electromagnetic fields in the nonhospital environment", section on 'Security systems'.)

TREKKING AND MOUNTAINEERING — The allure of the high-altitude environment is attracting an increasing number of adventurers to travel to mountains all over the world. Although the most extreme ascents are still performed by young and middle-aged adults who appear to be at risk only from altitude-related illness and trauma (as opposed to exacerbation of cardiopulmonary disease), an increasing number of older individuals are venturing into the mountains as well. In one report of tourists seeking visas in Nepal (where approximately one-third come for trekking), 20 percent were 50 years or older [102].

Acute mountain sickness and high-altitude illness — High-altitude illness prevention and acute mountain sickness (AMS) prevention and treatment are described in detail elsewhere. (See "High-altitude illness: Physiology, risk factors, and general prevention" and "Acute mountain sickness and high-altitude cerebral edema".)

Risk of adverse cardiovascular events — The risk of adverse events is low. Among tourists trekking in Nepal, cardiac illness contributed to only approximately 5 percent of helicopter evacuations and none of the reported deaths [102]. Another review examined sudden deaths among participants engaging in high-mountain hiking, skiing, or both in Austria between 1985 and 1991 [103]. A total of 416 deaths were deemed sudden, representing approximately 30 percent of all mountain sport-related deaths [103]. Most of the deaths occurred at altitudes between 1100 to 2100 meters (3600 to 6900 feet). Hikers were more than two times as likely as skiers to die. Among the hikers, the risk of death was highly influenced by age and lack of prior physical activity. The relatively low incidence of cardiac complications among trekkers and mountaineers most likely results from the low incidence of cardiovascular disease in this population. For instance, in a survey of ski mountaineers in the Austrian Alps, only 5.7 percent of women and 12.0 percent of men over the age of 40 reported any type of cardiovascular disease [60].

Prior myocardial infarction (MI) appears to be the greatest predictor of risk regarding sudden cardiac death (SCD) among those who snow ski. In a case-control study of 68 skiers who lost their lives to SCD, compared with 204 controls, those with a previous MI had a 93-times higher adjusted SCD risk. Alternatively, those with hypertension had a ninefold higher risk and those with known coronary heart disease (CHD) without prior MI a 4.8-fold increased risk [104].

Mitigating cardiovascular risk — Exercising at high altitudes should be approached carefully, and individuals should consider their own fitness level as they make their plans. Aerobic exercise intensifies as the height of altitude increases. We suggest not exercising the first day at altitude and planning out gradual increases in intensity as a trip moves forward. Paying attention to adequate hydration and avoiding alcohol are also critically important.

Physiologic studies show that metabolic demands of aerobic exercise (especially high-intensity interval training) are beyond the requirements of standard climbing and trekking mechanics [105-107]. If a person regularly exercises at sea level altitudes, they will be more likely to properly handle the added stressors experienced at higher altitudes [79]. Other individuals should avoid extreme aerobic exercise at altitude because previously asymptomatic heart conditions are likely to be more severe in such conditions.

Because available automated external defibrillators (AEDs) can be lifesaving, medical personnel who care for persons at high altitude should prioritize having an AED available in potentially high-risk situations. A 36-year-old man exposed to high altitude while climbing Mount Fuji had chest pain and lost consciousness. He was saved after receiving electroshocks from an AED [108]. Medical personnel charged with caring for persons at high altitude should review the application of AEDs and cardiopulmonary resuscitation in special circumstances [109], especially in the case of high-altitude climbing where core body temperature will have a significant impact on the effectiveness of cardiopulmonary resuscitation.

Portable technology can provide real-time biofeedback, alerts about worsening medical conditions, and lifesaving treatment. High-altitude trekking has the potential to benefit from these technologic advances, with heart rate variability (HRV) and cognitive monitoring available via portable technology [110,111]. HRV, the variation in the time intervals between heartbeats, can be measured in normoxic and simulated hypoxic environments prior to ascending to altitude, as well as during a climb. Studies suggest that monitoring HRV may have promise to determine the likelihood of AMS incidence and/or severity [110,112,113].

As medicine advances, the opportunities to evaluate the success of major transplants are presenting themselves as people with significant medical conditions adventure at high altitudes. For example, a high-altitude expedition was coordinated that only included lung transplant patients and their accompanying medical personnel [114]. With 8 of the 10 transplant patients and all 24 escorting personnel reaching the peak, this 94 percent success rate was significantly higher than the reported 85 percent for that route.

With regards to tracking peripheral oxygen saturation (SpO₂) and heart rate, the use of a simple pulse oximeter can be valuable in assessing the body's response to high altitude. As expected, tracking how SpO₂ decreases during ascent, how heart rate increases, and then how the opposite occurs during periodic pauses/acclimatation breaks can be informative and provide important feedback. Additionally, the development of AMS has been shown to be consistently associated with lower SpO₂ values [115].

Advice for patients — There are few studies and no randomized trials upon which recommendations can be made for people with heart disease who want to travel to or exercise at high altitude [116]. Every patient must be assessed on an individual basis. Nevertheless, reasonable recommendations can be made when accounting for the following:

●Baseline functional capacity

●Expected altitude that will be encountered

●Anticipated activity level and expected duration of time to be spent at high altitude

An exercise stress test can be performed to evaluate heart disease before planning any activity at altitude if there are concerns about cardiovascular status or any changes in status [117]. However, exercise stress testing is not routinely recommended without cause.

Potential trekkers should be evaluated on the basis of known heart disease, as discussed above, and should be reminded of the importance of adequate training and conditioning before entering this extreme environment. Acute altitude-related illness remains a frequent cause of morbidity and mortality for trekkers either with or without cardiac disease.

For patients with heart disease who seek medical attention prior to such a trip, advice should include [4]:

●Maintain adequate control of blood pressure, arrhythmias, and other cardiac issues prior to ascent.

●Pay strict attention to taking usual medications and dealing with cardiac symptoms should they arise.

●Plan a slow ascent to allow time for acclimatization. A rule of thumb during mountaineering is to ascend no more than 305 meters (1000 feet) per day and to allow a day of rest (no ascent) after every third day [21].

●Pay close attention to the unusual physical exertion that occurs on the first day at altitude, daily during late morning hours, and under conditions of prolonged abstinence from food and fluid intake [118].

●Plan load weight in a conditioned climber not to exceed 32 percent of body weight. This percentage should be lower in a deconditioned climber [119].

●Be aware and plan for compromised sleep efficacy due to hypoxia-induced cardiovascular responses [120].

●Adhere to the usual prophylactic measures to prevent altitude sickness. (See "High-altitude illness: Physiology, risk factors, and general prevention".)

●Remember that descent is the safest and quickest path to resolution of altitude-related symptoms.

●Consider a personal AED, or ensure that a device is within treatment distance when traveling to high altitude.

●Wear a pulse oximeter to track SpO₂ changes, and adjust your ascent accordingly.

●Limit activity at moderate (1500 to 2500 meters [5000 to 8200 feet]) or high (>2500 meters [>5000 feet]) altitudes to a lower maximal level than typically performed at sea level (80 to 90 percent). This is especially true during the first few days.

●Achieve a moderate degree of physical conditioning at sea level before exercising at high altitude [89].

●Patients with coronary artery disease, arrhythmia, or congestive heart failure (HF) may become symptomatic at lower exercise workloads at high altitudes (>2500 meters [8200 feet]) [32,35]. Patients with poorly controlled hypertension should not travel to high altitude, and those with controlled hypertension should consider taking their own blood pressure during travel and adjust medications as needed.

●Patients who have undergone revascularization with either percutaneous coronary intervention or coronary artery bypass graft (CABG) surgery within three weeks should not exercise above low altitude (<1500 meters [5000 feet]).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of inflight medical events".)

SUMMARY AND RECOMMENDATIONS

●Preflight assessment and advice – Travelers with cardiovascular disease should undergo assessment prior to travel and plan ahead to anticipate specific medical needs (table 3). (See 'Preflight assessment' above.)

This assessment should also identify need for supplemental oxygen and identify contraindications to air travel (see table).

Most individuals with cardiovascular disease can travel without difficulty, including most patients with chronic stable angina, compensated heart failure (HF), and implanted devices. (See 'Stable coronary artery disease' above and 'Stable chronic heart failure' above and 'Implanted devices' above.)

●Contraindications to air travel – Patients with unstable angina, acute decompensated HF, uncontrolled ventricular or supraventricular arrhythmias, or symptomatic valvular heart disease should travel only in an emergency (table 2). (See 'Contraindications to air travel' above.)

●Air travel after myocardial infarction (MI) – Patients who have had a recent MI should take extra precautions, including requesting airport assistance and carrying nitroglycerin. Patients in low- or medium-risk groups can reasonably travel after 3 and 10 days, respectively. Patients in the high-risk group should defer air travel until clinically stable and delay altitude exposure for a minimum of six weeks. Exercise testing may aid in risk stratification. (See 'Myocardial infarction' above.)

●Air travel after cardiac interventions – Patients should delay air travel after percutaneous coronary intervention, coronary artery bypass surgery, or device implantation. (See 'Percutaneous coronary intervention' above and 'Coronary artery bypass graft surgery' above and 'Implanted devices' above.)

●Ascent to high altitude – The ascent to high altitude without acclimatization can put patients with heart disease at risk for cardiac events. This is especially true in patients who have marginal cardiopulmonary function at sea level or unstable acute coronary syndromes. (See 'Altitude stress in heart disease' above and 'Risk of adverse cardiovascular events' above.)

●Exercise at high altitude – Stable patients who exercise at sea level without symptoms can generally exercise at altitude. Patients should vigilantly monitor their heart rate and blood pressure, adhere to medications, and decrease the total intensity and duration of exercise. Patients with unstable cardiovascular conditions should ideally refrain from any altitude exposure. (See 'Risk of adverse cardiovascular events' above and 'Mitigating cardiovascular risk' above and 'Advice for patients' above.)