A number of recent studies show a link between sleep apnea and congestive heart failure
Everybody knows the importance of a good night’s sleep. Shakespeare knew its importance, rhapsodizing about sleep as “great nature’s second course, chief nourisher in life’s feast.” Sadly, though, many people can’t get the nourishment they need from sleep.
An estimated 20 million Americans suffer from sleep apnea, a sleep disorder in which a person stops breathing repeatedly while sleeping. Deprived of a good night’s sleep, sleep apnea sufferers wake up in the morning feeling tired, moody and depressed and they frequently fall asleep during the day — hardly the condition for coping with the stresses and strains of modern day living.
So what does lost sleep have to do with cardiology? A lot it seems, according to some leading-edge research. A spate of recent studies show a link between sleep apnea and congestive heart failure (CHF) — a linkage that has profound implications for both the understanding and treatment of these two diseases; and beyond these, economic implications that carry potentially big cost-savings for healthcare providers.
Taken collectively, these studies indicate that more than 50 percent of the CHF population of four million Americans have sleep-disordered breathing. A third of this population, while asleep, also experience Cheyne-Stokes respiration (CSR), a form of sleep apnea marked by a halt in breathing alternating with rapid, heavy breathing. CSR can cause higher morbidity and mortality rates if untreated. There also are indications that CSR itself may accelerate deterioration in cardiac function. And, that in some cases, sleeping disorders may be the cause of CHF, and in other cases, the consequence of it.
Among the leading researchers linking sleep apnea with CHF is Shahrokh Javaheri, M.D., professor of Medicine, University of Cincinnati (Ohio) School of Medicine and director of the Sleep Disorder Program, VA Medical Center, Cincinnati. In a recent study, Javaheri and his research team showed that about 50 percent of patients with stable heart failure suffered from sleep apnea. These sufferers stopped breathing on average 44 times per hour during the night. That’s considered fairly high — modest to severe — on the Sleep Apnea index. (A measurement of the variations between successive oxygen saturation data points at constant time intervals.) The CHF patients also had excessive arousals throughout the night and their levels of oxyhemoglobin saturation went down as low as 76 percent; the amount of oxygen bound to hemoglobin normally remains about 90 percent at night. The CHF patients with sleep apnea spent 50 minutes, or about 20 percent of their total sleep time at or below the saturation level of 90 percent; compared to four minutes, or 1 percent of total sleep time for those CHF patients without sleep apnea.
“At night, a person is supposed to be sleeping more quietly, calmly with lower heart rate and lower blood pressure,” says Javaheri. “But in the face of sleep apnea with desaturation and arousals, a considerable amount of sympathetic activity occurs which isn’t good for a fading heart. We think in the long run it could result in excess morbidity and maybe mortality for CHF patients.”
Javaheri thinks that the more severe the patient’s CHF, the more likely he or she is to develop sleep apnea. “This is especially so for patients with CHF and atrial fibrillation,” he says. “It also is very conceivable that a number of patients with CHF die probably because of ventricular tachycardia.”
In their latest study, which confirms and extends earlier findings, Javaheri’s team found that of the CHF patients with sleep apnea, 11 percent have obstructive sleep apnea (OSA) and 40 percent have central sleep apnea (CSA). OSA, the most common form of sleep apnea, occurs when muscle tissues in the throat collapse and block the flow of air into the lungs during sleep. CSA results from the brain not signaling the body to breathe. There is no airflow because there is no effort to breathe. While CSA is less common in the general population, it is much more common in the CHF population.
“We also are dealing with a large part of the population who don’t know they have sleep apnea,” Javaheri says. “Particularly, the 40 percent CHF population who have CSA. We have shown that heart failure patients with OSA have symptoms similar to OSA patients without CHF. For example, they are overweight and snore very loudly. CSA patients, on the other hand, are thinner and snore less frequently than the general population. CSA is very occult. Importantly, though, both CSA and OSA result in sleep disruption and desaturation, and therefore, may be harmful to CHF patients.”
Another group of researchers, this one at the Mayo Clinic, Jacksonville, Fla., also conducted a major study that supports the link between CHF and sleep apnea. The research team was led by Joseph Blackshear and Joseph Kaplan, both associate professors at the Mayo Medical School. Kaplan, a pulmonologist, is co-director of the Sleep Disorder Center at the Mayo Clinic. Blackshear is chairman of the Cardiology Division at the Mayo Clinic.
“Cheyne-Stokes respiration was frequently noted in previous studies to occur in highly selected groups of patients with CHF,” Kaplan says. “But its prevalance in an unselected population with CHF was undefined. We undertook a study in 1994 in which we looked at 100 unselected patients with all degrees of CHF — mild, moderate and severe. Of those 100 patients, 27 percent had CSR, and an additional 43 percent had some form of breathing difficulty at night. Only 30 percent were entirely normal. Two predictors told us of the presence of CSR in this population: (1) if the patient had a history of awakening in the night short of breath — known as paroxysmal nocturnal dyspnea; and (2) the presence of atrial fibrillation.”
Cause or consequence?
The critical question is: does sleep apnea exacerbate CHF? Kaplan doesn’t think that CSR, if untreated, leads to CHF. “If you put a new heart in a CSR patient, the CSR goes away,” he says. “CSR occurs as a consequence of CHF, not as a cause.”
But others aren’t so sure. A 1996 study led by Patrick Hanly, M.D., of the Department of Medicine, Wellesley Hospital, University of Toronto, Canada, concluded that mortality is higher in CHF patients who develop CSR during sleep than CHF patients without CSR. “Although the development of CSR may simply reflect more severe cardiac impairment,” the study says, “we suggest that CSR itself accelerates the deterioration in cardiac function.”
Other researchers tend to support this view. Javaheri posits that severe untreated sleep-disordered breathing may adversely affect the left ventricular function, resulting in a vicious cycle that could contribute to death in patients with CHF. And in a 1998 study, Douglas Bradley, M.D., and Matthew Naughton, M.D., researchers at the Sleep Research Laboratory, Rehabilitaton Institute of Toronto, University of Toronto, Ontario, Canada, report that: “OSA may lead to the development or progression of left ventricular dysfunction by increasing LV afterload through the combined effects of elevations in systemic blood pressure and a generation of exaggerated negative intrathoracic pressure, and by activating the sympathetic nervous system through the influence of hypoxia and arousals from sleep.”
Virend Somers, M.D., associate professor of cardiology at the University of Iowa, Iowa City, Iowa, believes that the research (especially from Toronto and Cincinnati) has shown that sleep apnea is very important to track in patients with heart failure. “It’s far more common than thought,” says Somers, who has followed Javaheri’s sleep apnea studies with great interest. “We do know the worse your heart failure is the more likely you’ll have CSR. That is, you’ll hyperventilate, slow down and stop breathing for a while and then start the cycle over again. There’s good evidence, but it isn’t unequivocal that people with heart failure who have CSR may have a poor prognosis. I’m not yet convinced that people with heart failure are more likely to develop sleep apnea. I just don’t know. It’s very difficult to prove theories of whether sleep apnea causes CHF or is a consequence of CHF. The concepts are exciting, but a huge amount of work to prove this still needs to be done.”
There are a number of drugs for treating congestive heart failure, such as ACE inhibitors and Beta blockers, which can improve the symptoms of CHF that cause limitations and distress.
Now with the compelling link established between sleep apnea and heart failure, treating sleep apnea has been added to the arsenal for improving cardiac function.
A number of studies support this approach. In a study published in March, researchers at the Sleep Research Laboratory, University of Toronto found that the elimination of obstructive sleep apnea by continuous positive airway pressure (CPAP) can improve cardiac function in patients with CHF. The study also found that treating Cheyne-Stokes respiration and central sleep apnea with supplemental oxygen, theophylline, and CPAP can alleviate central apneas. Of these treatments, however, only CPAP was shown to improve cardiac function and symptoms of heart failure. The researchers concluded that effective treatments of OSA and CSR-CSA may prove to be useful adjuncts to the standard pharmacologic therapy of patients with CHF.
In another study, led by Javaheri, researchers used theophylline to treat central apnea associated with Cheyne-Stokes respiration. “We studied the effect of short-term oral theophylline therapy on periodic breathing associated with stable heart failure due to systolic dysfunction,” says Javaheri. “We concluded that in patients with stable heart failure, oral theophylline therapy reduced the number of episodes of apnea and hypopnea and the duration of oxyhemoglobin desaturation during sleep.”
Researchers at the Mayo Clinic in Jacksonville just finished a three-year study looking at the effect of nocturnal oxygen on patients with CHF. “We concluded that the presence of Cheyne-Stokes respiration is associated with poor sleep quality. Chronic oxygen improves the sleep quality and reduces the abnormal breathing pattern in patients with congestive heart failure. Oxygen therapy should be included for symptomatic patients with disturbed sleep and may justify the expense. But so far we haven’t proved that it improves cardiac function or tolerance for exercise,” says Kaplan. “On-going review of our data should help clarify the role of nocturnal oxygen in these patients.”
Whatever the precise linkage is between CHF and sleep apnea, clinical studies show that of the estimated four million Americans who have CHF, more than 50 percent have sleep disordered breathing. That’s a population three times larger than the more familiar chronic obstructive pulmonary disease (COPD) population.
More to the point, as studies show, sleep apnea has a negative impact on CHF patients. “So if you treat sleep apnea, you may reduce its impact,” says Bradley of Toronto’s Rehabilitation Institute.
The most commonly prescribed oxygen therapy for sleep apnea is CPAP. This device delivers a small amount of air pressure through a mask while the patient sleeps. The pressured air prevents the airway from collapsing so that air can flow freely to and from the lungs.
The cost of a CPAP machine runs anywhere from $1,200 to $1,500. Homecare oxygen therapy costs about $300 per month. Add on the $2,000 to $3,000 cost for a sleep study to diagnose and prescribe a treatment for the patient. Then compare those costs with the $1,200 to $1,600 per night cost for the average hospital stay. Those nightly hospital stays account for the costs that CHF patients typically tally up spending a lot of time in the hospital.
Then it’s clear that “oxygen therapy offers a tremendous potential for large-scale savings to hospitals,” says Bradley. “In tracking our CHF patients who had CPAP therapy vs. those who didn’t, we found an 80 percent reduction in hospital admissions from the CPAP patient group–about $5,000 less per case for a CHF patient receiving CPAP therapy.”
While the economics of treating sleep apnea in CHF patients are tantilizing to contemplate, questions remain about the relationship between sleep apnea and heart failure. Does sleep apnea exacerbate CHF? Can untreated sleep apnea, as Javaheri posits, adversely affect cardiac function, resulting in a vicious cycle that could cause death in patients with CHF?
“We don’t know whether this is true or not,” says Brydon Grant, M.D., professor of Medicine and Physiology at the School of Medicine and Biomedical Sciences, University of Buffalo, N.Y. “In our sleep studies, we’re taking a short cut. Rather than trying to prove or disprove the vicious cycle hypothesis regarding mortality, it’s easier to see whether treating sleep apnea actually improves the quality of life of the heart patient.
Another reason for our approach relates to health care costs, Grant says. “Looking at patients with CHF, one of the questions that comes up is should they have a heart transplant. Our thinking is that if you can improve the quality of life of these patients you may be able to delay their need for transplants, perhaps, forever.”
Grant’s point is that the end-of-stage disease is becoming very expensive — both in terms of money and emotional stress. That’s when a decision must be made as to whether to have a transplant. “If you save putting someone on a transplant list, you’ve personally saved a lot of difficulties associated with transplants,” he says. “You can’t guarantee they’ll get an organ. And it’s very difficult to tell someone that ‘we might be able to get a transplant for you, but I don’t know whether your donor will come up.’ They sit on tenderhooks. You wonder if it was the right thing to do because only one in 10 patients gets a transplant. I showed the patient a lifeline, but I haven’t been able to get him to catch it. Had he been better off in not knowing this option? You put people in a very difficult position. You offer the patient a ray of hope which he may never catch.
“That’s why there is a lot of interest now in trying to find [diagnosis and treatment] methods to give patients a more satisfactory quality of life instead of a transplant,” Grant says. “That’s the hope.”
This article originally appeared in the November/December 1998 issueof Cardiology Management. Copyright c 1998 HealthTech Publishing Company, Inc.