Download apnea-induced hypoxia and heart failure

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Apnea-induced hypoxia and heart failure
By Regina Patrick, RPSGT
H
eart failure is a condition in which the heart does not pump
blood efficiently. Inefficient pumping can occur if the heart
can not fill with enough blood or if heart contractions are not
sufficiently strong enough. A person with heart failure may have
either of these problems or both. An estimated 40 percent of
people with heart failure have obstructive sleep apnea (OSA, the
intermittent cessation of breathing during sleep).1 Heart failure
patients have a worse prognosis if they also have OSA. Why OSA
worsens the course of heart failure is unclear. One possibility may
be that changes in intrathoracic pressures during apnea episodes
alter the heart’s pumping action, further impairing an alreadyweakened heart’s ability to pump blood. Another possibility may
be that repeated arousals resulting from hypoxia in OSA induce
activation of the sympathetic nervous system; this increases blood
pressure, the heart rhythm, and the heart’s oxygen needs, further
stressing an already-weakened heart.2,3 Recent studies point to hypoxia, rather than arousals, as the factor that worsens heart failure.
The right atrium of the heart collects unoxygenated blood and,
on contracting, expels it into the right ventricle. Once the right
ventricle is filled, it contracts, sending the unoxygenated blood to
the lungs. After the blood is oxygenated in the lungs, it is transported to the left atrium. When the left atrium contracts, it expels
the oxygenated blood into the left ventricle. The subsequent contraction of the left ventricle sends the oxygenated blood through
the aorta. The blood then travels throughout the body, bringing
oxygen to the body’s tissues.
Heart failure typically involves damage to one or both ventricles,
although damage to the atria can increase the risk of heart failure.
Heart failure due to dysfunction of the left ventricle primarily
produces pulmonary symptoms (e.g., dyspnea [difficulty breathing], wheezing, hypoxia, cyanosis), while heart failure due to
dysfunction of the right ventricle produces primarily systemic
symptoms (e.g., peripheral edema, jugular vein distention, ascites
[fluid retention in the abdominal cavity], fainting). Heart failure
symptoms may be treated by medications (e.g., diuretics, vasodilators, digoxin); lifestyle changes (e.g., bed rest, dietary changes);
devices (e.g., defibrillator); or surgery (e.g., heart transplant).
OSA has long been associated with an increased risk of cardiovascular problems such as cardiac arrhythmias, coronary artery
disease, left ventricular dysfunction, and hypertension (i.e., high
blood pressure).3 In OSA, the cessation of breathing (i.e., apnea)
occurs when upper airway tissue collapses into and obstructs the
upper airway during sleep, preventing air flow through the respiratory tract. During an obstructive apnea episode, a person continues
Regina Patrick, RPSGT
Regina Patrick, RPSGT, has been in the
sleep field for more than 20 years and
works as a sleep technologist at the St.
Anne Mercy Sleep Disorders Center in
Toledo, Ohio.
to make efforts to breathe, but no air − or an insufficient amount
of air − enters the lungs. The effort involved in trying to breathe,
and the reduction of oxygen, impacts the heart’s function in several
different ways.
The inspiratory efforts during an apneic episode can significantly decrease intrathoracic pressure, which allows the right
ventricle to expand and fill with an increased amount of blood.2
This distends the right ventricle, which leaves less room for the left
ventricle to expand. As a result, the left ventricle is less able to fill
with blood. The decreased amount of blood in the left ventricle,
combined with the increased force exerted against it by the extra
blood in the right ventricle, increases the left ventricle’s afterload
(i.e., the pressure against which the ventricle contracts). A chronically increased left ventricular afterload can result in hypertrophy
(i.e., increased muscle mass) of the left ventricle. This stiffens the
ventricle and reduces its ability to contract efficiently. In a person
with heart failure, left ventricular hypertrophy can decrease the
pumping action of the heart, thereby worsening heart failure.
Another impact of OSA on the heart is that frequent OSAinduced arousals increase sympathetic activity, which triggers
vasoconstriction of the peripheral blood vessels (thereby increasing
blood pressure) and the release of catecholamines such as epinephrine (thereby increasing the heart rate and the heart’s oxygen
needs).2 In people with heart failure for whom the heart is already
insufficiently providing oxygen to the body’s tissues, the increased
oxygen demand may worsen heart failure by further depleting the
heart of needed oxygen.
Scientists remain unsure which aspect of OSA – arousals or
hypoxia – is more responsible for worsening the course of heart
failure. Researchers Joshua Gottlieb and colleagues investigated
this subject in a recent study.1 They used brain (B-type) natriuretic
peptide (BNP) as a marker of heart stress. This peptide is secreted
by heart muscle cells in response to stretching. They hypothesized
that the stress placed on the heart during an apneic episode would
increase the ventricular production of BNP and, therefore, people
with severe apnea would have a significantly greater amount of
BNP than someone with no or mild apnea.
The patients involved in the study were being treated for heart
failure. All of the patients underwent a baseline sleep study. Afterward, they were divided into three groups: a no/mild OSA group
(an apnea-hypopnea index [AHI] of less than 5 respiratory events
per hour); an intermediate OSA group (an AHI of 6 to 39.9); and
a severe OSA group (an AHI greater than 40). The intermediate
OSA group was not studied after the baseline night. By comparing
the no/mild OSA group with the severe OSA group, the researchers aimed to maximize the sensitivity of their results in detecting
significant effects of sleep apnea on BNP levels. The no/mild OSA
group and the severe OSA group underwent a second sleep study
during which their blood was sampled for BNP levels every 20
minutes throughout the night. Two weeks later the severe OSA
group came back for a third night, during which the patients were
administered oxygen during sleep while their blood was sampled
every 20 minutes for BNP levels. The researchers measured the
ejection fraction of each patient’s heart to assess its pumping
ability. The ejection fraction is the portion of blood that is ejected
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from the ventricles on contraction. About 68 percent of the blood
volume is normally ejected on the contraction of the ventricles;
an ejection fraction less than 68 percent can indicate ventricular
dysfunction.
The researchers found that patients with moderate or severe
apnea had a lower ejection fraction (i.e., less efficient cardiac
pumping) than the no/mild OSA group. The ejection fraction of
patients in the severe OSA group was less than that of the moderate OSA group. They concluded that the heart’s ability to pump is
increasingly reduced with increasing severity of OSA.
They also found that, although the addition of oxygen in the
severe OSA group reduced the total amount of apneic events by
27 percent, there was no significant difference between the BNP
levels on night two and night three in this group. This indicated
that the number of apnea episodes did not stress the heart.
Then they analyzed the collective BNP level results of the no/
mild OSA group and severe OSA group to compare the impact
of apnea vs. hypoxia on BNP levels. In doing this, the researchers
noted that the BNP levels rose and fell in association with the rise
and fall of blood oxygen saturation. By contrast, the BNP level
did not rise and fall in association with the frequency of apneic
events. Gottlieb and colleagues concluded that changes in the level
of BNP were related to the severity of hypoxemia, but not to the
frequency of the apnea episodes.
A Brazilian research team, headed by Cristiana Marques de
Araújo, similarly found that the frequency of apnea events may not
be correlated with heart dysfunction.4 Rather than using BNP, the
researchers used ischemia (i.e., low blood flow) as a marker of cardiac stress and a measure of the impact of OSA on heart function.
The study involved 53 patients who had OSA and were being
treated for angina or for ischemic heart disease resulting from
myocardial infarction, narrowing of the coronary arteries or multivessel disease. The patients underwent simultaneous polysomnography and continuous electrocardiographic recording using a Holter monitor. From the patients’ electrocardiograms, the researchers
determined the number of ischemia episodes that occurred. Based
on the patients’ AHI, they were placed in either a control group
(an AHI of less than 15); an apnea group (an AHI greater than
15); or a severe apnea group (an AHI greater than 30).
They found that the number and duration of ischemic episodes
significantly decreased during sleep in all groups. During wakefulness, patients with severe apnea had fewer and shorter ischemic
episodes than the controls. From this, they concluded that there
was no link between the frequency of apnea episodes (i.e., severity
of OSA) and myocardial ischemia.
Several studies indicate that OSA treatment – in particular, continuous positive airway pressure (CPAP) therapy – significantly
improves heart function in people with heart failure. For example,
Canadian researcher Yasuyuki Kaneko and colleagues treated one
group of heart failure patients with the normal medical therapy
alone.5 They treated a second group of heart failure patients with
the normal medical therapy plus CPAP therapy, which prevents
apnea by blowing pressurized air into the airway to prevent collapse of tissues into the upper airway during sleep. By preventing
apnea, a person’s blood oxygen saturation remains at normal levels,
and arousals are eliminated during sleep. The researchers assessed
the left ventricular ejection fraction in both groups and found no
improvement in the group that received medical therapy alone. By
contrast, the left ventricular ejection fraction improved by 35 percent in the group that had been treated with medical therapy and
CPAP. Kaneko and colleagues concluded that CPAP treatment
could improve left ventricular function in heart failure patients.
Another group of Canadian researchers assessed the left ventricular ejection fraction in heart failure patients before and after
CPAP therapy.6 They found that the ejection fraction increased, on
average, by 32 percent after one month of treatment with CPAP.
Some of the patients were then withdrawn from CPAP treatment
for one week, and the ejection fraction was re-assessed. This time
the researchers found that the ejection fraction decreased by 15
percent. From these results, they also concluded that CPAP can
improve left ventricular function.
About 5 million people (both children and adults) in the U.S.
have heart failure, and about 300,000 people die from heart failure
every year.7 Improving heart function can improve the course of
heart failure in some people. People with both OSA and heart failure have a worse prognosis, and treating OSA in people with heart
failure improves left ventricular function and other aspects of heart
function. Therefore, treating OSA could improve the prognosis
of some people with heart failure. However, studies have not yet
proven that treating OSA reduces cardiac mortality in heart failure
patients. The finding that BNP increases with hypoxia – indicating
increased stress on the heart – suggests that preventing hypoxia
may be especially important in heart failure patients. Therefore,
patients with heart failure may need to be assessed and treated for
OSA or other sleep-disordered breathing problems to reduce the
impact of intermittent episodes of hypoxia on the heart.
REFERENCES
1. Gottlieb JD, Schwartz AR, Marshall J, et al. Hypoxia, not
frequency of sleep apnea, induces acute hemodynamic stress
in patients with chronic heart failure. J Am Coll Cardiol.
2009 Oct 27;54(18):1706-12.
2. Dorasamy P. Obstructive sleep apnea and cardiovascular risk.
Ther Clin Risk Manag. 2007 Dec;3(6):1105-11.
3. Chaicharn J, Carrington M, Trinder J, Khoo MCK. The
effects on cardiovascular autonomic control of repetitive
arousal from sleep. Sleep. 2008 Jan 1;31(1):93-103.
4. Marques de Araújo C, Solimene MC, Grupi CJ, et al.
Evidence that the degree of obstructive sleep apnea may not
increase myocardial ischemia and arrhythmias in patients
with stable coronary artery disease. Clinics (Sao Paulo).
2009;64(3):223-30.
5. Kaneko Y, Floras JS, Usui K, et al. Cardiovascular effects of
continuous positive airway pressure in patients with heart
failure and obstructive sleep apnea. N Engl J Med. 2003 Mar
27;348(13):1233-41.
6. Malone S, Liu PP, Holloway R, et al. Obstructive sleep
apnea in patients with dilated cardiomyopathy: effects of
continuous positive airway pressure. Lancet. 1991 Dec
14;338(8781):1480-4.
7. Department of Health and Human Services. National
Institutes of Health (NIH). National Heart, Lung, and
Blood Institute. Heart failure: what is heart failure? 2007
December. Available at: http://www.nhlbi.nih.gov/health/
dci/Diseases/Hf/HF_WhatIs.html. Accessed Dec. 17,
2009. 
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