management and cardiac risk in altitude and cold weather

1. Altitude and cold weather:
are they vascular risks?

2. INTRODUCTION
• The number of individuals exposed to high altitude through air travel and
recreational activities has been greatly increasing in the past few decades, with
tens of millions of people per year traveling to high-altitude destinations .
• Changes in physiological functions during high altitude exposure vary with
- an individual’s physical fitness,
- rate of ascent,
- severity and/or duration of exposure,
- cultural habits,
- geographical locations, and
- genetic variation

3. • 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

4. Partial pressure of oxygen
• PiO2 = FiO2 x barometric pressure
partial pressure of oxygen in inspired air - PiO2, in mmHg
FiO2 is the same at all altitudes.
As the barometric pressure changes, the FiO2 remains constant while the partial
pressure of oxygen is altered with the change in barometric pressure. Specifically,
the partial pressure of arterial oxygen decreases with altitude

6. NORMAL CARDIOVASCULAR RESPONSE TO HIGH ALTITUDE
Short-term altitude exposure

7. • Heart rate increase
• Stroke volume increase
• Cardiac output increase
• Blood flow-blood are shunted away from major organs such as kidney, liver,
stomach, intestine
• Blood pressure increase
• The difference in oxygen content of arterial and venous blood increase

8. • 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.

9. • Several changes are observed ECG and ECHO for normal individuals exposed to high altitude
(17,500, 20,500 and 26,200 feet, respectively)
●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
●Increase in resting heart rate (HR)
●Prolongation of the QT interval
●ST-T wave flattening
●Rightward shift in the frontal QRS
axis
●Increase in P-wave amplitude in
lead II

10. Long-term altitude exposure
After three to four days, the initial sympathetic nervous system manifestations of
altitude exposure resolve as early acclimatization begins.
• 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 alveolar-arterial oxygen gradient.
• Reduced parasympathetic nervous activity as a key mechanism for the elevated
heart rate in chronic hypoxia

11. ALTITUDE STRESS IN HEART DISEASE

12. ALTITUDE STRESS IN HEART DISEASE
• The effects of high altitude exposure may have important implications for
patients with various types of heart disease.
• In addition to the baseline changes to the cardiovascular system, the possible
development of high altitude diseases (mountain sickness or pulmonary or
cerebral edema) can add further stress to the cardiovascular system.

13. CAD
• Exercise at real or simulated altitude in patients with stable CHD appears to be
relatively safe, provided patients take the same precautions as they would at sea
level. However, the acute hemodynamic changes associated
with altitude/hypoxemia result in an earlier onset of angina symptoms or ECG
changes
• 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 sea level and 1000
meters (3280 feet), the following findings were noted
1) Patients with CHD, who were more often receiving therapy with a beta
blocker and angiotensin-converting enzyme (ACE) inhibitor, had a lower peak rate-
pressure product (beta blocker effect) than controls at both altitudes.

14. 2) In both patients and controls, exercise capacity was lower at high
altitude compared with baseline, while the maximal heart rate was the same at
baseline and 2500 meters (8200 feet).
3) 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.
Erdmann J. Effects of exposure to altitude on men with coronary artery disease and impaired left
ventricular function. Am J Cardiol 1998; 81:266.

15. So, in CAD
• In patients with recent acute coronary syndromes who have not had
revascularization, there should be no ascent to altitude 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.

16. • 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
altitude.
• Therefore, acclimatization for at least five days is advised. Access to appropriate
medicines and medical care should also be confirmed prior to high altitude travel.
• Optimization of CHD medications and discussions regarding compliance of
medications should be performed prior to high altitude exposure.
Levine BD. Going High with Heart Disease: The Effect of High Altitude Exposure in Older Individuals and
Patients with Coronary Artery Disease. High Alt Med Biol 2015; 16:89.

17. Heart failure
Patients with heart failure (HF) are especially susceptible to the physiologic changes
from high altitude exposure. The increased sympathetic activity elevates the
systemic vascular resistance, blood pressure, and heart rate, which results in a
reduced exercise capacity
• Chronically elevated catecholamine levels Increased transcapillary permeability in
the lung
• Poor skeletal muscle metabolism
• High oxygen extraction in the periphery
• Poor pulmonary function
• Concurrent CHD
Kraus WE. Taking heart failure to new heights: its pathophysiology at simulated altitude. Am J Med 2000;
109:504

20. HEART FAILURE
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, even the stress of air flight may be significant and should
be approached with caution.

21. • In such patients, oxygen therapy should be considered and for patients already
on oxygen, increased flow rates can be used to alleviate symptoms.
• By comparison, patients with only mild functional issues at sea level will probably
tolerate moderate altitudes but should be warned that they will become
symptomatic at lesser degrees of exercise.

22. Valvular heart disease
In patients with pre existing valvular disease, the acute hemodynamic changes
induced by the additional hypoxic stress of altitude may result in decompensation
of their condition.
• 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
aortic and mitral regurgitation, worsening symptoms.

23. • 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 altitude exposure may increase risk of valvular thrombosis,
especially if the anticoagulation level is not in the desired range

24. • For those who are asymptomatic with mild to moderate valvular disease, exercise
testing and transthoracic echocardiography at rest/stress is recommended for
evaluating their current status and response to exercise .
• For those with symptomatic and/or severe valvular disease, exposure to altitude
is contraindicated .
• 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.

25. • Education about blood pressure self-monitoring and treatment titration is
needed if uncontrolled hypertension or hypotension develops .
• For those on anticoagulation, instructions for self-monitoring and dose
adjustment should also be given.
• Alcohol consumption should be avoided or used with caution.

26. Arrhythmias
• The incidence of arrhythmias at altitude 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
• 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 or 29,020 feet) . No arrhythmias or
conduction defects were seen
Malconian M, et al. The electrocardiogram at rest and exercise during a simulated ascent of Mt. Everest
(Operation Everest II). Am J Cardiol 1990; 65:1475

27. • Examining a more advanced age group, a Holter monitor study of healthy middle-
aged men found the incidence of both supraventricular and ventricular
premature beats (VPBs) nearly doubled at an altitude of 1350 meters (4430 feet)
as compared with 200 meters (660 feet). At a still-higher altitude (2630 meters
[8630 feet]), the frequency of ectopy was increased six- to sevenfold.
• Patients with stable CHD that is 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. VPBs were significantly increased
with acute exposure but returned to sea level values after acclimatization

28. Pacemaker function
• The issue of pacemaker safety at altitude and the possibility of alterations in
stimulation thresholds are uncertain since data are conflicting
• In a report, stepwise simulated hypobaric chamber ascent from 450 meters to
4000 meters (1480 to 13,120 feet, respectively) produced no change in
stimulation threshold, in spite of a significant fall in partial pressure of oxygen in
arterial blood (PaO2)
Weilenmann D,et al. Influence of acute exposure to high altitude and hypoxemia on ventricular
stimulation thresholds in pacemaker patients. Pacing Clin Electrophysiol 2000; 23:512.

29. Congenital heart disease
• 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 .
• This results in an increase in right-to-left shunting, leading to arterial oxygen
desaturation.
• The extent to which arterial oxygen desaturation occurs will depend upon many
factors, including the size of the communication, baseline right-sided pressures,
and the extent of altitude-induced pulmonary hypertension

30. • It is important to appreciate that there may be an increased prevalence of
congenital heart disease (ie, atrial septal defect/patent foramen ovale, or patent
ductus arteriosus) at high altitudes.
• One explanation is that lower oxygen tension fails to constrict the ductus and
thus both ductus and foramen ovale closure is inhibited.
So, when advising a child or adult with congenital heart disease who is contemplating
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

31. hypoxia altitude simulation test
• 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
altitude, which may be additionally affected by cold temperature, humidity,
exercise, stress, and their functional reserve.
• One protocol used to gain significant insight into how a patient will respond to air
travel is the hypoxia altitude simulation test.

32. 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
Smith D, Toff W, Joy M, et al. Fitness to fly for passengers with cardiovascular disease. Heart 2010; 96 Suppl
2:ii1.

33. British Cardiovascular Society “Fitness to fly
for passengers with cardiovascular disease”

34. British Cardiovascular Society “Fitness to fly for
passengers with cardiovascular disease”
• Arrive at the airport in sufficient time to avoid rushing
• Warn the carrier and/or airport authority well in advance of the date of
departure of any requirements for assistance, including the requirement for in-
flight oxygen
• Carry an appropriate supply of medication, as well as a clear list of all medications
and doses
• Carry a letter from the appropriate caregiver(s) explaining the condition, drugs,
allergies, and devices (such as a pacemaker or implantable cardioverter
defibrillator [ICD])

35. • Uncomplicated MI within two to three weeks.
• Complicated MI within six weeks.
• Uncontrolled hypertension.
• Coronary artery bypass graft surgery within 10 to 14 days Cerebrovascular accident
within two weeks.
• Unstable angina.
• High-grade ventricular premature beats or uncontrolled ventricular or supraventricular
arrhythmias.
• Severe decompensated heart failure (HF). Patients with class III or IV New York Heart
Association HF should be carefully assessed to determine whether they will need in-flight
oxygen.
• Symptomatic valvular heart disease (relative contraindication).
• Eisenmenger’s syndrome and pulmonary hypertension
Heart 2010;96:ii1eii16. doi:10.1136/hrt.2010.203091 ii5

36. • Supplemental oxygen -Patients who require supplemental oxygen at sea level will
require supplemental oxygen during air travel. As a practical matter, a PaO2 less
than 72 mmHg at sea level predicts the need for supplemental in-flight oxygen in
most subjects
• Stable coronary artery disease — Evaluation of the patient with known coronary
disease before flying should include a careful history and physical examination to
identify signs or symptoms of recent angina, volume overload, or dysrhythmia

37. • Myocardial infarction
ACC/AHA guidelines on air travel after STEMI 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 .
It is also suggest that early, low-level exercise testing after a STEMI may be
reasonable to assess functional capacity and the ability to perform tasks at home
and at work, evaluate the efficacy of medical therapy, and assess the risk of a
subsequent cardiac event.
Two low-level exercise testing protocols have been suggested if the following
requirements are met: 1) Low-level exercise during in-hospital cardiac
rehabilitation; 2) no symptoms of angina or HF; and 3) stable ECG 48 to 72 hours
prior to testing.

38. • Submaximal stress testing (done at three to five days in patients without
complications) or a symptom-limited exercise test (done at five days or later) is
reasonable to “permit detection of profound ischemia or other indicators of high
risk that could be associated with post-discharge cardiac events.”
• So, the patient should have a companion, carry nitroglycerin, and request airport
transportation to avoid rushing.
• Patients with an MI complicated by severely depressed cardiac function or
another significant complication (eg, HF, sudden cardiac arrest, or cardiogenic
shock) should not fly until two weeks after they are deemed medically stable

39. Risk group
• Very low risk: <65 years of age, first event, successful reperfusion, left ventricular
ejection fraction (LVEF) >45 percent, no complications, and no cardiac
investigations or interventions pending.
• Low (or medium) risk: LVEF >40 percent, no symptoms of HF, no evidence of
inducible ischemia or arrhythmia, and no further cardiac investigations or
interventions pending.
• High risk: LVEF <40 percent with signs and symptoms of HF, pending further
investigations for revascularization or device therapy.

40. • Percutaneous coronary intervention — Immediately after coronary stent
placement, airline travel should be avoided due to the increased risk of acute
stent thrombosis during this time. Following this procedure, postponing travel
arrangements for at least two days in uncomplicated cases or two weeks in
complicated cases is recommended.
• Coronary artery bypass graft surgery — Those who have undergone coronary
artery bypass grafting should wait at least 10 days
• Implanted devices — Air travel has not been shown to interfere with the function
of pacemakers or ICDs . Patients should carry a card identifying the type of device

41. • Deep vein thrombosis and pulmonary embolism — Patients at risk of pulmonary
embolism (PE) should be advised to exercise their limbs at regular intervals and,
with especially long flights, take walks within the aisle every hour.

42. COLD

43. EFFECT ON HEART

44. • Temperature, hot or cold, has a significant but different cardiovascular mortality
effect.
• In Finland, an estimated 2000–3000 extra deaths occur during cold. most involve
individuals aged above 65 years, but over 20% occur in the younger working-age
group.
Nayha S. Environmental temperature and mortality. Int J Circumpolar Health 2005; 64:451–458.

45. • Cold causes increased BP and hemoconcentration with increased thrombosis risk
vs
• heat causes hemoconcentration from perspiration with increased blood viscosity
and thrombosis risk.
• Data from Beijing showed that heat effects are immediate. Cold involves longer
lag times

46. COLD
• High altitude and cold weather are frequently linked. However, whether
associated or individual, each one involves cardiovascular risk. Several aspects of
both conditions have been considered.
• Globally a higher occurrence of cardiovascular morbidity and mortality during the
cold season, or in association with prolonged periods of unusually low
temperatures (cold spells) have been documented.

47. wintertime is associated with a higher amount of
• Cardiac symptoms (angina, arrhythmias or dyspnoea) and
health events such as
- hypertensive crisis,
- deep venous thrombosis,
- pulmonary embolism,
- aortic ruptures/dissection,
- stroke, intracerebral hemorrhage,
- heart failure, atrial fibrillation, ventricular arrhythmias, angina
pectoris,
- acute myocardial infarctions and sudden cardiac deaths

48. • Either acute lowering of temperature, or its seasonal effects increases
cardiovascular strain in healthy persons through physiological responses targeted
to maintain heat balance.
• However, these may be aggravated in persons with cardiovascular diseases
involving altered nervous system, cardiac and circulatory function

49. Acute effects of cold
• Blood pressure- systolic, diastolic and mean pressure will increase also
centralaoricpressure
• Heart rate – usually increased, but depends on exposure site
• Myocardial work and oxygen supply- increased

51. Stroke
• Matsumoto et al. performed a multicommunity cohort study in Japan and found
that, among women, low temperatures and number of cold days per year were
both associated with increased stroke incidence independent of conventional
risk.
Matsumoto M, Ishikawa S, Kajii E. Cumulative effects of weather on stroke incidence: a
multicommunity cohort study in Japan. J Epidemiol 2010; 20:136–142.

52. Thrombosis
• Changes in the circulating blood because of cold exposure may be a major factor
in associated problems.
• Hampel et al. studied coagulation and inflammatory responses in 57 men with
coronary artery disease during winter. A 10oC decrease in the 5-day temperature
average increased platelet counts, increased fibrinogen, and decreased C-reactive
protein.
• Platelets from the Raynaud’s study group responded more to epinephrine,
showed more thromboxane A2 production, and demonstrated more resistance to
prostaglandin inhibitors of platelet aggregation, compared with controls
Physiological and haematological responses to cold exposure in the elderly. Int J Circumpolar Health
2000; 59:216–221.

53. risk factor causing CVD
• Mercer studied 11 young healthy males with 1-h cold exposure to 110C compared
with essentially neutral conditions of 26oC.
• there were significant increases in SBP, whole blood viscosity, plasma
norepinephrine, angiotensin, low-density lipoprotein cholesterol, total
cholesterol, and fibrinogen, consistent with increased cardiovascular risk from
cold exposure
Mercer JB, Osterud B, Tveita T. The effect of short-term cold exposure on risk factors for
cardiovascular disease. Thromb Res 1999; 95:93– 104.

54. CONCLUSION
• Altitude and cold can cause CVD individually, but it is difficult to separate these
factors
• High altitude and cold weather increase cardiovascular risk. Both add significant
problems to a world population with high cardiovascular risk in many areas.
• The complex genetics, physiology, and clinical results represent a challenge to
scientists and clinicians.
• Such knowledge is essential for improving overall cardiovascular disease
prevention, separate from the usual clinical and public health problems.
• Prior cardiac consultation, adherence with medications and non-invasive cardiac
test in selected case may prevent major cardiac events.