Sleep Apnea in Heart Transplant Recipients: Type, Symptoms, Risk Factors, And Response to Nasal Continuous Positive Airway Pressure
Emmanouil S. Brilakis, MD, et al
The term sleep apnea describes several syndromes characterized by disordered respiration during sleep that result in intermittent disruptions in gas exchange and sleep fragmentation. Encompassed syndromes include obstructive sleep apnea (OSA), central sleep apnea and mixed sleep apnea. OSA describes repetitive episodes of airflow cessation because of upper atrway occlusion, whereas central apnea is defined by lack of airflow and absent respiratory effort. The combination of obstructive and central features is termed “mixed apnea.” According to cross-sectional studies, sleep apnea is common in the general population. Sleep apnea has been associated with neurobehavorial deficits and cardiovascular diseases, including hypertension, arrhythmias including bradyarrhythmias, atrial fibrillation, and venthcular arrhythmias, and heart failure. However, the strength of these associations has been questioned recently.
Sleep apnea, both obstructive and central is common in patients with heart failure. Sleep apnea in heart transplant recipients has not been studied extensively. Some events of the posttransplant period (e.g., the weight gain with the use of glucocorticoids) could precipitate or exacerbate OSA, and OSA itself could adversely affect the transplanted heart. We did a retrospective study with follow-up telephone interviews of 17 heart transplant recipients with sleep apnea in a tertiary care institution to determine the type, presenting symptoms, and risk factors for sleep apnea, as well as the response to nasal continuous airway pressure (nCPAP).
[Abridgement of Materials and Methods]
Sleep apnea, primarily OSA, is common in the general population. The most widely cited prevalence estimate tomes from a community-based survey of middle-aged Wisconsin state employees in which 4% of men and 2% of women were found to have OSA, defined as AHI greater than 5 and daytime sleepiness.2 prevalence of sleep apnea in heart transplant recipients has been reported to range between 2.5% and 43%. Sleep apnea was present in 11.6% of our population, yet its prevalence was almost certainly underestimated because universal screening was not performed. Only patients with typical OSA symptoms (n = 17) underwent polysomnography, and sleep apnea was found in all of them.
Underdetection of sleep apnea remains an important public health issue. Reasons for inadequate identification include the non-specific nature of many of the symptoms, the unavailability of collateral history from a bed partner, and the lack of formal sleep education for most health care providers. In the case of heart transplant recipients, the difficulties diagnosing sleep apnea may be compounded by the use of multiple medications, which may affect sleep, and the complexity of the posttransplant course.
Central sleep apnea is common in patients awaiting heart transplantation. Even in the setting of stable congestive heart failure, periodic breathing with central apneas followed by crescendo-decrescendo respiration (Cheyne-Stokes breathing) may occur in 40& to 50% of patients mostly during, stages 1 and 2 of non-rapid eye movement sleep. Central sleep apnea is thought to result primarily from an increased propensity of heart failure patients to hyperventilate, which maintains the Pco2, tenuously close to the apneic threshold. The ventilatory instability manifests clinically as paroxysmal nocturnal dyspnea, insomnia, and daytime sleepiness and is possibly a marker of increased mortality in heart failure patients. Cheyne-Stokes respiration usually resolves after heart transplantation. In this report and in others, OSA was the predominant form of sleep apnea post-transplant.
Upper airway obstruction during sleep is the result of a complex interaction of anatomic, neuromuscular and mechanical factors. The strongest risk factors for OSA in the general population are obesity and male sex. Obesity is thought to act through upper airway fat deposition and thoracoabdominal mass loading. Androgenic hormones may alter upper airway musculature or central respiratory drive. These risk factors were well represented in our heart transplant patients found to have sleep apnea. All except one were men and 16 of the 17 patients had gained an average of 10 kg since transplant. Conventional craniofacial risk factors for OSA were also common in our population.
Several features associated with the post-transplant period may influence the modifiable risk factors for OSA, as suggested by Klink and colleagues. Central adiposity due to glucocorticoid administration may increase the propensity to upper airway narrowing during sleep. Cushingoid features were present in 59% of our sleep apnea patients(10 of 17), and 82% (14 of 17) were receiving prednisone at the time of polysomnography. Diabetes mellitus simultaneously developed post-transplant in 24% of the patients (4 of 17). Diabetes has been implicated in the pathogenesis of OSA. The commonly used post-transplant combination of glucocorticoids and cyclosporine may negatively modulate insulin release and action, which could aggravate both OSA and diabetes mellitus. All of the patients, except one, were receiving cyclosporine at the time of polysomnography.
The treatment of choice for most cases of OSA is nCPAP, yet initial acceptance of and compliance with nCPAP have been problematic occasionally. Initial studies incorporating objective measures of compliance demonstrated that patients tended to subjectively overestimate nCPAP use and that actual use was frequently suboptimal. However, a more recently reported study of more than 500 patients with an AHI greater than 15 revealed an initial acceptance rate for nCPAP of 79% and an objectively documented acceptance rate of greater than The same authors reported the case of a history (eliciting the presence of snoring, 85% over 7 years. The poor compliance with nCPAP in our cohort is striking and difficult to explain retrospectively. The telephone follow-up disclosed that the majority of patients discontinued the use of nCPAP because of inconvenience. Admittedly, side effects from the pressure and nasal interfaces are common. Other potential explanations for poor compliance include insufficient, nCPAP titration during the split-night protocol or overshadowing of the importance of nCPAP by other post- transplant challenges. Finally, it is possible that prednisone dose tapering with the concomitant weight loss contributed to the spontaneous improvement of the patients' symptoms, obviating the need for nCPAP.
To the best of our knowledge, this study is the first to reveal a high prevalence (29%) of periodic limb movement disorder in heart transplant recipients. Periodic limb movements are repetitive, stereotypic actions primarily of the legs that cause symptoms as a result of sleep fragmentation. Periodic limb movements have been reported to occur in association with medical conditions, including heart failure. Hanly and Zuberi-Khokhar noted that approximately 50% of their severe, stable heart failure patients had periodic limb movements during sleep.
The same authors reported the case of a patient with heart failure and periodic limb movement disorder, who improved after heart transplantation. Conclusions regarding the impact of heart transplantation on periodic limb movements cannot be drawn from our data given the lack of pre-transplant polysomnography in our patients.
The repetitive intrathoracic pressure changes, hypoxia, and sleep fragmentation characteristic of OSA could negatively impact the transplanted heart. Heart transplant recipients with sleep apnea may be at increased risk for arrhythmias because the bradycardiac response to apnea and hypoxia is abolished.
Although there are no large-scale longitudinal studies on the consequence of sleep apnea on heart transplant recipients, data are emerging to suggest that it may be deleterious to both quality of life and survival: a heart transplant recipient with severe OSA was reported to develop cor pulmonale. Post-transplant survival appeared to be worse in our patients with sleep apnea, though the difference was not statistically significant.
Screening all heart transplant recipients with polysomnography, the standard for diagnosis, is impractical. Other methods for a rapid assessment of the risk for sleep apnea are necessary. In severe cases, a careful history (eliciting the presence of snoring, witnessed apneas, daytime somnolence, and morning fatigue) and physical examination (focusing on the presence of obesity, cushingoid features, and craniofacial abnormalities) may be enough to prompt referral for polysomnography. For less obvious cases, there are mathematical models that can predict the presence of OSA. One such model has been proposed recently by Kushida et al.
It is a morphometric model, which combines measurements of the oral cavity with BMI and neck circumference to estimate the risk for OSA. Routine use of such a model could increase the rate of sleep apnea detection in the pre-transplant and the post-heart transplant settings.
From this retrospective review, we conclude that sleep apnea, especially OSA, is common in hearth transplant recipients. Heart transplant recipients with OSA have typical risk factors and present with the classic symptoms. Compliance with nCPAP may be poor despite polysomnographic evidence of efficacy. Given the common thread of immunosuppressants, OSA may be an important management issue across the post-transplant spectrum.
Journal of Heart & Lung Transplantation, Vol. 19, No. 10,pp. 330-35
10 Things Your HMO Dr. Won't Tell You
Following are some things your doctor won't tell you as you sit across from him on the examining table, backside to the breeze. He may not even admit them to himself - or if you're lucky enough to have a conscientious doctor, they may not matter much. Not every HMO uses all these measures to pressure docs into limiting care. But you can bet the contract your doctor signed with your HMO contains a few.
1. "If I order expensive treatments for you, the cost might come out of my pocket."
In the Texas case, Harris ranked physicians based on how much their patients cost the HMO. It then withheld up to 50% of the base pay of doctors who ordered a lot of care, with the holdback dangled as an incentive to get their numbers in line. Otherwise, they'd lose the money. Plus, doctors who prescribed more than a set limit for drugs had to make up as much as 35% of the excess, deducted from their pay.
2. "On the other hand, if I order up less care, your HMO might send me a bonus check."
Cynthia Herdrich, the Illinois patient in the Supreme Court case, waited 14 days after going to her HMO doctor for pain in her groin before getting the expensive test that diagnosed her problem. Unfortunately, by then her appendix had burst, infecting her abdominal cavity. After finding out that her HMO gave year-end bonuses to doctors who, among other things, economized on the use ofdiagnostic tests, she sued it, claiming it had violated its fiduciary duty to her as a patient. The Supreme Court held that an HMO's fiduciary duty doesn't stretch that far under federal law.
3. "That cheap HMO you signed up for pays me only $8, or maybe $10 to $12 a month to treat you, so I hope you don't come around too often." Under a system called capitation, many HMOs pay primary-care doctors a set amount per month for each patient assigned to them. Even that amount can drop if a doctor orders too many expensive referrals or hospital stays. So, sick patients become a financial burden.
Just ask Dr. Beatrice Murray, a pediatrician in Grand Rapids, Mich. She got a good reputation for treating the many problems of children born prematurely. That's what put her out of business.
"The number of our special needs cases just exploded," she explains. But the monthly stipend from the HMOs didn't. The amount varied by the child's age and the HMO contract, but for a two-year-old, she says she usually got $6 to $9 a month. Which might be fine if the child was healthy. Her patients weren't.
Dr. Murray says she tried to explain to the HMOs, but they seemed all too willing to lose her and her patients. The 52-year- old doctor lost her private practice this past May. She's now a salaried employee for a federally funded clinic for the poor.
4. "If you become too much of a financial drain, I have ways to make you walk."
Some doctors head off the problem by saying they don't treat a certain type of (read expensive) patient. Dr. Murray recalls the mothers who brought their triplets to her, complaining they couldn't find another pediatrician who treated multiples.
But sometimes the doctor already has a patient before he develops diabetes or cancer, or contracts AIDS. For those situations, there's "turf and surf," says a Texas lawyer representing seven patients who claim their health-care group discriminated against them because of their disabilities - illnesses like cancer, rheumatoid arthritis and heart problems. Doctors use tactics to grind unwanted patients into the turf, then surf them out to other doctors, says attorney Robert J. Provan, himself disabled from a bout with polio at age five.
In a lawsuit and separate complaint to the U.S. Department of Justice, Provan's clients say they were left alone in exam rooms for more than an hour, forced to come to the office to pick up prescriptions that had been phoned in to their pharmacists before and made to wait inordinately long periods to get an appointment. The San Antonio clinic involved denies their claims, as well as those of a former doctor who's also a plaintiff in the case. The doctor alleges the medical group fired him because he attracted disabled patients, then refused to cut corners on their care. Which brings us to...
5. "If I treat you too aggressively, I could get kicked out of the HMO."
Those contracts doctors sign with HMOs expire every one or two years. Plus, many have clauses allowing the HMO to terminate them without cause. A doctor with many contracts doesn't have to worry about losing one. But in areas where one HMO is dominant, a physician can watch his practice - and income - shrivel if the HMO deselects him.
6. "HMOs have sophisticated computer programs that let them track exactly how much my patient care is costing them. And they let me know."
Many doctors receive monthly report cards from HMOs they do business with, pointing out how much care they ordered for each patient, or spent for hospital stays, tests and specialists. Those who rack up more than the average - or more than some predetermined target - may get a call from the HMO. Or maybe they'll get pinched by the methods described above.
7. "Ordering expensive treatments for you could tie me and my staff up on the phone for hours with your HMO to get approval."
Dr. Linda Peeno used to be on the receiving end of such calls. Working as a medical reviewer for giant Humana, she admits she looked for reasons to reject coverage. After years of turning down treatments - including a heart transplant for a Nevada man who later died - she now works as head ethics consultant at the University of Louisville Hospital and as a paid consultant for David Boies, a lawyer better known for representing the government in its antitrust suit against Microsoft, but who's fast gaining a reputation for suing HMOs as well.
Dr. Peeno remembers the early days of HMOs when doctors "would rant and rave and call me names. They were much more strongly patient advocates than they are now," she says. Docs "became slowly compliant out of fatigue and utility."
8. "You might rate less of my time if you're with one of those penny- pinching HMOs."
Kenna Nevill, a 45-year-old Dallas woman, remembers asking her doctor to call her after office hours with a test result she was worried about, and being struck by his response. "He said, `You know, I wouldn't do that for my HMO patients. But I'll do it for you.'" She had recently switched from an HMO to a PPO, or preferred provider organization. "I remember feeling like a second-class patient with an HMO."
How conscious is your doctor of the kind of medical coverage you have when he sits across from you? The Texas doctor who treated Dudley said each of his patients' charts had a large stamp on the front indicating HMO, PPO or old-fashioned indemnity-type coverage.
9. "The drug I prescribe may not be the best one for you - but it's what your HMO will cover."
HMOs give doctors lists of the drugs they want used. And those lists can change in the middle of a patient's treatment, says Dr. Joe Cunningham, an internist in Waco, Texas.
That can mean a drug that's working might be replaced by one that won't, at least until the HMO can be convinced the more expensive medication is necessary. While this may not pose much of a problem for most patients, for those with life-threatening conditions - like seizures - it's potentially fatal, says Dr. Cunningham.
10. "If you have to go to the hospital, I may turn your care over to a doctor who works directly for the HMO."
The use of doctors called hospitalists to manage patients once they're in the hospital began in the early '90s, says Dr. Peeno. These specialists have even more incentive to deny you admission or hustle you out. They're on the payroll of the HMO and, explains Peeno, "It doesn't take anybody with much sense to figure out where the incentives are there."
Of course, it's naive to think that health care has ever been free of financial considerations. Under the old fee-for-service system, doctors had an incentive to provide more - perhaps harmful - care, says Dr. Charles M. Cutler, chief medical officer with the American Association of Health Plans, a trade organization representing managed- care plans. HMO incentives, he argues, are designed to "encourage physicians to think more critically about what it is that we do and to avoid waste - not to limit care."
Adds Dr. Thomas Reardon, past president of the American Medical Association, "I think a doctor generally does what is right for the patient and if it hurts his income, he just absorbs that."
But Dr. Cunningham, who worked on a Texas task force that studied such incentives, isn't sure that is always the case. "You don't want to walk in as a patient to a physician who is thinking, `You know, I've spent all my allocation for this month.'"
PVCSMy goodness how the tributes have been rolling in to the UpBeat Medical Center with the publication of our basic research on the insect repellant qualities of cyclosporine last month. At the risk of too much flag waving, we have to admit that there was even mention of a Nobel Prize. The fact that the suggestion came from the patient’s father should be weighted just a bit. There were others who suggested that the technician should be “freed from her bondage”, whatever that means. Then the most compelling statement, I think was the comment written across a returned copy that said, “Consider the source!” Now that can only be interpreted as a statement of how much respect the UpBeat medical Center has earned over time.
Research in progress — Here is a preliminary report on the basis for our next research project.
Tired of cydosporine? How about scorpion venom? Scorpion venom?
Well it turns out that it contains a chemical that suppresses the immune system.
Researchers at the University of California, Irvine, are working with a chemical from scorpion venom that they believe may lead to a drug to treat autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and lupus. In theory, it could also be useful in preventing rejection of transplanted organs. The synthesized version of the chemical, called TRAM, which suppresses the immune system’s T-cells, does not appear to have the same sort of side effects as other immunosuppressant drugs.
But don’t throw out the cyclosporine just yet. TRAM-34 may be 10 years away. Assuming it works as promised, it still has to be patented and financed and tested for Food and Drug Administration approval. “We’re just dong the basic scientific work right now.” (reORGANized Newsletter — The American Transplant Assoc. Sept. ‘00)
Now you can probably see where this is leading — UpBeat Medical Center is nothing if not at the forefront of “basic” research. We are presently looking for transplant patients willing to drop their cyclosporine and then be treated for anti-rejection with a daily scorpion bite. One of the inhibiting factors, in addition to a distinct shortage of volunteers, is the fact that there are no scorpions here in the swamps. In addition, the previously loyal principal caregiver, nee technician, nee wife has said rather firmly to the negative as to working on this project, “One scorpion, even in this county, and I’m gone!” Hummm, we do have a few black widows, wonder if they’d have the same effect...
Then there was the man arrested for stealing corneas intended for transplantation. He took the plastic foam package from a bus station in Boston. State Police said, “I think that it was just a crime of opportunity. I don’t believe he’s involved in any type of stolen human body part ring. He thought they were lobsters” (reORGANized) Well, then again perhaps he couldn’t clearly see what he was doing. ED.
Sleep Apnea - It’s wonderful that medical science continues to study we recipients in depth, as for example the sleep apnea study. Sleep apnea could be a dangerous situation, except that the researchers overlooked one very important variable —just about any transplant recipient on cyclosporine, of either sex, is bound to be up more than enough times per night to “hit the head” that they don’t possibly have the time to stop breathing and die between trips! Then again, imagine the principal caregiver confronted by a masked patient trailing tubes coming out of the bathroom in the dark of night!
Still could use some cartoons for the December UpBeat.
Organ Donation Increases
WASHINGTON (AP 9/12/00) - Organ donation increased by nearly 4 percent during the first half of 2000 after remaining flat in 1999, the government said Tuesday. This compares to 2,875 during the first six months of 1999, according to statistics compiled by the Department of Health and Human Service and the Association of Organ Procurement Organizations.
"Our efforts to raise awareness about the importance of organ donation appear to be paying off, but with 71,000 people on the transplant waiting list, we still have a long way to go," HHS Secretary Donna Shalala said in a statement. "I'm sure you'll agree, we don't want an epidemic."
Organ donation rose 6 percent in 1998, the first substantial increase since 1995, but was unchanged in 1999. Also Tuesday, HHS release guidelines to help hospitals and organ banks implement new rules that require hospitals to notify organ banks whenever someone dies in the hospital. The goal is to be sure that organ donation professionals evaluate each potential donor and talk with their families when appropriate.
Studies have shown that many potential donors are never identified or approached about donation.
More Evidence That Infections Cause Heart Disease — Also in Transplants
Italy-Organ Donation Symbol
A Further Report from Dr. Goodpump’s Garage Doctors Announce New, Smaller Artificial Heart
First-Ever Transplant Telemedicine Program Brings...
U.S. Blood Shortage Puts Operations on Hold
Disclaimer: The material in this document has been collected by Don Marshall and friends. New ideas and materials are welcome all the time. Nothing herein is ever to be construed as medical advice. As a policy, Upbeat is sent upon request to heart and heart/lung transplant recipients and other interested parties. Donations of $15 per year, or more, from TX recipients, if not a burden, are vital. From all others the donation is specifically requested. The date shown after the name on the address label indicates the last time a donation was received. Please make checks payable to Don Marshall, as we cannot afford to become nonprofit. Send materials, letters, or checks to:
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