Sleep Disordered Breathing

I. Sleep Disordered Breathing: What every physician needs to know.

Sleep disordered breathing is common in patients with cardiovascular disease and is associated with hypertension, atrial fibrillation, ventricular arrhythmias, vascular disease, and diabetes. In particular, sleep disordered breathing has been linked to worsening heart failure, decreased left ventricular function, and left ventricular hypertrophy both directly through its mechanical effects, as well as indirectly by its impact on the adrenergic nervous system and other risk factors.

Sleep disordered breathing, also known as sleep apnea, occurs in two primary forms, obstructive sleep apnea where lax tissue in the pharynx leads to airway closure and significant negative intrathoracic pressure and central sleep apnea, where the respiratory control center in the brain fails to adequately regulate breathing during sleep, leading to cyclical hyperventilation and apnea known as Cheyne-Stokes respiration.

In both forms of sleep apnea, hypoxia leads to surges in adrenergic tone and arousals that stress the cardiovascular system and disrupt sleep. In addition, both forms of sleep apnea are associated with increased inflammatory mediators that may be the mechanism of worsening vascular disease and metabolic abnormalities. The relationship between sleep apnea and heart failure is complex as worsening heart failure can lead to the development of sleep apnea but the presence of sleep apnea also appears to worsen heart failure.

Central sleep apnea is associated with systolic heart failure but can also be seen in stroke patients. One proposed mechanism of the development of central sleep apnea in heart failure is decreased cardiac output leading to a prolonged circulation time to the chemoreceptors in the brain that regulate respiration.

This leads to a delay in the sensing of carbon dioxide, oxygen, and pH and causes the chemoreceptors in the brain to overcompensate for changes in blood chemistry. As cardiac output falls, central sleep apnea can appear or worsen but as the cardiac output improves, central sleep apnea may also improve.

For this reason, therapeutic interventions that improve cardiac output may help to treat central sleep apnea and the diagnosis should not be made during an acute heart failure decompensation. There is increasing evidence that central sleep apnea activates the adrenergic nervous system leading to worsening left ventricular function and arrhythmias both atrial and ventricular.

Treatment of central sleep apnea can be challenging but includes nocturnal oxygen, traditional CPAP, and BPAP, as well as novel forms of servo-ventilators. There are recent reports of the use of an experimental phrenic nerve stimulator similar to a pacemaker that may treat central sleep apnea. Successful treatment of central sleep apnea has led to improved ejection fraction, improved functional capacity as measured by the 6-minute walk test and a trend toward improved transplant-free survival for those successfully treated.

Obstructive sleep apnea is associated with obesity but can also be seen in nonobese individuals. The mechanism of obstructive sleep apnea is airway closure during inspiration that prevents airflow to the lungs. As hypoxia and hypercarbia ensues, a surge of adrenergic activity leads to an arousal from sleep that opens the airway and restores airflow to the lungs.

There is now evidence that fluid shifts in heart failure patients, especially while supine can cause edema in the pharyngeal tissues leading to the development of obstructive sleep apnea. This suggests that the incidence of obstructive sleep apnea may be higher in volume overloaded heart failure patients and nonobese heart failure patients are likely at higher risk than nonobese, non–heart failure patients.

Obstructive sleep apnea impacts heart failure through both direct mechanical and neurohormonal effects. Mechanically, increased negative intrathoracic pressure during an apneic episode leads to increased afterload, myocardial wall stress and myocardial oxygen demand.

Simultaneously, the surge of adrenergic activity leads to increased blood pressure and afterload, and lowers the threshold for arrhythmia and ischemia. Treatment of obstructive sleep apnea includes the use of positive airway pressure with CPAP and BPAP, as well as weight loss and oral appliances.

Surgical procedures that remove pharyngeal tissue, as well as the uvula, have also been used to treat obstructive sleep apnea but have been only modestly effective. Successful treatment of obstructive sleep apnea has been demonstrated to decrease adrenergic activity and blood pressure even during the day, as well as decrease left ventricular hypertrophy and episodes of atrial fibrillation.

Adrenergic neurohormone levels, in particular norepinephrine levels also decrease. Similar to central sleep apnea, successful treatment can also lead to improvements in left ventricular ejection fraction in systolic heart failure and improved diastolic function in patients with heart failure with preserved ejection fraction. Large scale randomized clinical trials of treatment of sleep disordered breathing in heart failure are lacking, leading to significant gaps in evidence for treatment strategies and how treatments impact cardiovascular outcomes.

II. Diagnostic Confirmation: Are you sure your patient has Sleep Disordered Breathing?

The gold standard for diagnosing sleep apnea is a sleep study performed in an accredited sleep laboratory. Recently, home sleep studies using portable equipment have been approved to diagnose sleep apnea and this should allow for more widely available and convenient testing, as well as improved patient acceptance.

Several centers are studying other strategies, including performing sleep studies while patients are hospitalized just prior to discharge to allow for rapid and more convenient diagnosis and treatment initiation. Oxygen saturation monitors worn overnight, either in the hospital or at home, have been used to screen for the presence of sleep apnea but themselves do not differentiate between the types of sleep disordered breathing and therefore should be used primarily for screening.

Patients with positive results on an overnight oxygen saturation study should be sent for a more definitive sleep study. Sleep apnea can also be detected via algorithms in implantable cardiac devices. This can be accomplished either directly via respiratory sensors or indirectly through the detection of arrhythmias: bradycardia or nocturnal atrial fibrillation or ventricular tachycardia.

There are several diagnostic questionnaires that ask about fatigue, napping, snoring, and witnessed apneas. These can be used to decide which patients should be referred for home or in laboratory sleep testing. It is important to note that patients with heart failure often do not score highly on questionnaires evaluating daytime somnolence or fatigue.

A. History Part I: Pattern Recognition:

Classically, patients with sleep apnea describe fatigue, napping during the day, not feeling rested when they wake in the morning, and falling asleep while not physically active. Witnesses to the patient sleeping describe snoring, apneic episodes, and irregular respiratory patterns.

In patients with heart failure, fatigue is less of a hallmark of sleep apnea and traditional screening questionnaires like the Epworth Sleepiness Scale fail to detect sleep apnea at the traditional score cut-offs in heart failure patients.

Some investigators have reported that lower threshold cut-offs on the Epworth Sleepiness Scale may be more sensitive in the heart failure population. In heart failure patients, the most potent predictor of a positive sleep study is witnessed apneas reported by a family member.

Several comorbidities can accompany sleep apnea including hypertension, atrial fibrillation, vascular disease, left ventricular hypertrophy, and heart failure. For obstructive sleep apnea, several other markers have been associated with the diagnosis.

A body mass index (BMI) greater than 32 in men, as well as a neck circumference of 17 or more inches in men, significantly increases the risk of obstructive sleep apnea. Obstructive sleep apnea is relatively uncommon in premenopausal women in the absence of morbid obesity but the incidence rapidly increases postmenopause to a similar incidence as in men.

In central sleep apnea, more advanced heart failure symptoms, decreased ejection fraction, and atrial fibrillation are associated the presence of the syndrome.

B. History Part 2: Prevalence:

In the heart failure population, the prevalence of obstructive sleep apnea has been reported to range from 11% to 37%. For systolic heart failure, one prospective study estimated an incidence of 26%.

For diastolic heart failure, the incidence of obstructive sleep apnea is estimated to be greater than 50%. The prevalence of central sleep apnea has been estimated to be 33% to 40%. In all heart failure patients, approximately 50% of patients will have some form of sleep disordered breathing.

This makes the yield of screening for sleep disordered breathing in the heart failure population relatively high. With the addition of just a few risk factors combined with the diagnosis of heart failure, the likelihood of screening positive for sleep disordered breathing is very high.

Risk factors for the presence of obstructive sleep apnea in heart failure include male sex and an increased body mass index in men. In women with heart failure, increasing age increases the risk of obstructive sleep apnea.

Risk factors for the presence of central sleep apnea in heart failure include male sex, atrial fibrillation, and age greater than 59 years. In addition, resting PCO2 less than 39 mm hg has also been reported to increase the odds of central sleep apnea in heart failure patients.

C. History Part 3: Competing diagnoses that can mimic Sleep Disordered Breathing.

Fatigue is relatively common in patients with heart failure and may mimic the symptoms of sleep apnea. In addition, hypothyroidism, depression, and medication side effects in particular beta-blockers and antiarrhythmics can lead to symptoms that mimic sleep apnea.

Narcotics, anxiolytics, and hypnotics, as well as alcohol can worsen or unmask sleep apnea and these agents often produce side effects that can imitate sleep disordered breathing. Patients who have experienced a stroke or other neurologic injury can also manifest central sleep apnea as can those who have traveled to a high altitude.

D. Physical Examination Findings.

Assessment of height and body weight, including the calculation of a body mass index, can identify those at risk for obstructive sleep apnea although obstructive sleep apnea can occur in nonobese patients. Measurement of neck circumference, especially in men, may identify a subgroup at higher risk of obstructive sleep apnea. In general, a neck circumference of 17 inches (43 centimeters) or more places a man at increased risk.

An assessment of the oral pharynx using the Mallampati score can predict the risk of obstructive sleep apnea. This score evaluates whether the base of the uvula, fuacial pillars (arches in front and behind the tonsils), and the soft palate are visible.

A score of 4 indicating that only the hard palate can be seen when the patient opens their mouth and extends their tongue predicts a higher incidence of obstructive sleep apnea. Difficult to treat hypertension as defined as requiring more than two medications to treat also warrants an assessment for obstructive sleep apnea.

E. What diagnostic tests should be performed?

The definitive diagnostic test for sleep apnea involves overnight polysomnography, which includes electroencephalogram, electromyogram, respiration, continuous ECG monitoring, and electrooculogram. Obstructive and central apneas can occur in the same patient with the appropriate form being determined by which form is predominant.

Recently, portable devices that can perform a sleep study at home have been approved for use in the United States. These devices have a reasonable sensitivity and specificity. Continuous overnight oxygen saturation monitoring is inexpensive and easy to perform but should only be used for screening, as this device cannot differentiate between central and obstructive apneas.

Implantable cardiac rhythm devices collect vast amounts of physiologic data that have been proposed to be used to screen for sleep disordered breathing. Patients with systolic heart failure frequently have these devices for sudden death prophylaxis and/or biventricular pacing and there is optimism that the data collected will simplify the screening process, identifying those who may benefit from treatment of sleep disordered breathing.

The routine interrogation of implantable cardiac devices or the interpretation of Holter or other temporary cardiac monitors can lead clinicians to suspect sleep disordered breathing. For example, the presence of nocturnal arrhythmias, either atrial fibrillation or ventricular tachycardia, and episodic nocturnal bradycardia should increase the suspicion of sleep disordered breathing.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specific laboratory studies that can be ordered to help establish the diagnosis of sleep disordered breathing. To screen for central sleep apnea, an arterial blood gas that reveals a PaCO
2 of less than or equal to 38 mm Hg suggests a higher risk.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specific imaging studies routinely ordered to help establish the diagnosis of sleep disordered breathing.

III. Management.

There is some controversy as to whether patients who are asymptomatic from their sleep disordered breathing get benefit from treatment. Until there are more definitive outcome trials, most clinicians managing heart failure patients consider sleep disordered breathing another therapeutic target. The rationale for this is the theoretical reduction in adrenergic activation that treating sleep disordered breathing can achieve without the addition of another pharmacologic agent.

Partnering with a qualified and engaged sleep clinician is how most cardiovascular clinicians manage sleep disordered breathing. This partnership allows for each to focus on their areas of expertise.

The cardiology team can optimize medical and device therapy for heart failure, and the sleep team can establish the diagnosis of sleep disordered breathing, select the appropriate therapy, and ensure that the therapy is tolerated and used by the patient. Both teams must educate the patient on the importance of diagnosing and treating sleep disordered breathing and share in the responsibility of ensuring that patients are compliant with their treatment.

For obstructive sleep apnea, the most common treatment is continuous positive airway pressure or CPAP. CPAP applies pressure to the inside of the airway, splinting it open, and preventing lax tissue from blocking airflow.

CPAP requires the use of either a nasal or full facial mask that needs to be fitted properly. Oxygen can be administered through the CPAP machine if necessary and the pressure applied to the airway can be adjusted based on the needs of the patient.

CPAP has been shown to improve oxygen saturation, adrenergic tone, sleep quality, reduces daytime somnolence, improves neurocognitive function and can reduce both daytime and nocturnal blood pressure. Newer CPAP machines have algorithms to promote patient comfort including delays before the pressure is applied to allow patients to fall asleep, titration of pressure based on the needs of the patient and built in humidifiers.

Nocturnal oxygen can also be used and has demonstrated modest positive effects. Recently, mandibular advance devices or oral appliances have been shown to be nearly as effective as CPAP in treating obstructive sleep apnea. Whether this will hold true specifically for heart failure patients is unknown but these devices may be a reasonable alternative for the patient who will not or cannot use CPAP.

Finally, surgical procedures designed to increase the size of the airway—uvulopalatopharyngoplasty and laser assisted uvulopalatoplasty—have been studied to treat obstructive sleep apnea but appear to be effective in only about 50% of patients. These procedures may have increased surgical risk in those with advanced heart failure.

For central sleep apnea, the first step in management is to optimize the heart failure treatments. This includes neurohormonal blockade, volume control, restoration of normal sinus rhythm if possible, and the appropriate use of biventricular pacing. Opioid narcotics can cause central sleep apnea and should be avoided if feasible. Nocturnal oxygen has been shown to abolish central sleep apnea in some patients but this has not translated into improved cardiovascular outcomes or improved cardiac function in the short term.

Like obstructive sleep apnea, either CPAP or BPAP (bilevel positive airway pressure), can be used to support respiration during sleep. CPAP can be difficult to titrate in patients with central sleep apnea and has the potential of worsening hyperventilation in the hyperventilatory phase of Cheyne-Stokes respiration.

The largest trial to date in patients with heart failure and central sleep apnea did not show an improvement in transplant-free survival but in an analysis of just those who used effective CPAP there appeared to be a survival benefit. An alternative form of positive airway pressure that can sense respiratory pattern and provide positive pressure ventilation during apneic periods is the adapto-servo ventilator (ASV).

Small trials with ASV have found it to be more effective in abolishing Cheyne-Stokes respiration than CPAP. These trials have also shown improved left ventricular ejection fraction and 6-minute walk distance but larger and longer trials will be necessary to assess the impact of this technology on cardiovascular outcomes.

There are two medications that have some evidence for the treatment of central sleep apnea, acetazolamide and theophylline Acetazolamide is a carbonic anhydrase inhibitor that increases the excretion of bicarbonate, leading to a metabolic acidosis.

This is thought to shift the apneic threshold of PaCO2. Acetazolamide has been used to treat edema in heart failure but is not frequently used to treat central sleep apnea in heart failure. Theophylline is hypothesized to work by stimulating central respiratory drive. Theophylline has significant side effects, including arrhythmogenesis and therefore is not a long-term treatment for central sleep apnea in heart failure patients.

There was a single report of overdrive atrial pacing leading to markedly decreased central sleep apnea but this was not reproduced in other studies and will require additional trials. Finally, there is a novel pacemaker-like device that stimulates the phrenic nerve during sleep that has shown some promise in treating central sleep apnea in the heart failure population.

A. Immediate management.

If possible, avoid sedatives, alcohol, and narcotics as these can worsen or even unmask sleep disordered breathing. For patients experiencing volume overload, diuresis can decrease pharyngeal tissue swelling and mechanical obstruction and can improve overall cardiac performance. Nocturnal oxygen can be used acutely and may decrease the degree of oxygen desaturations but usually does not fully treat sleep disordered breathing.

B. Physical Examination Tips to Guide Management.

Over time, weight loss, or gain may indicate the need to rescreen for sleep disordered breathing, In addition, worsening heart failure over time or new atrial fibrillation could indicate the need to assess for sleep disordered breathing.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.


D. Long-term management.

For patients with obstructive sleep apnea who are obese, weight loss has been shown in most patients to improve and can eliminate the sleep disordered breathing. In central sleep apnea, interventions to improve cardiac output, including medical management with appropriate neurohormonal blockade for heart failure, the placement of a biventricular pacemaker or appropriate cardiac surgery (coronary bypass or valve surgery) all can lead to positive ventricular remodeling and improved cardiac performance.

E. Common Pitfalls and Side-Effects of Management

Many patients with heart failure struggle to tolerate the mask necessary to provide CPAP, BPAP, or adapto-servo ventilation. This is multifactorial but for many patients, orthopnea, paroxysmal nocturnal dyspnea, and anxiety are hallmarks of their heart failure syndrome.

The masks often exacerbate these symptoms and can therefore be a significant challenge to patients and clinicians. A sleep clinician with special knowledge of CPAP masks, techniques for desensitization, and judicious use of anxiolytics can improve treatment compliance.

In addition, an engaged cardiologist, primary care, or other clinician who emphasizes the importance of the treatment of sleep disordered breathing, as well as educating the patient about the impact of sleep disordered breathing on the heart and heart disease can help a patient overcome treatment resistance. Many practices now ask about CPAP compliance at every visit treating CPAP as another therapy on the patient’s medication list.

The CPAP mask can lead to irritation and even ulcers on the face. Careful mask fitting, as well as periodic review of the mask is critical.

Newer CPAP machines can store data on cards that can be downloaded or can transmit data directly through phone lines, Internet, or cellular networks. This allows clinicians to monitor compliance, adjust settings, and troubleshoot problems like mask leaks.

Some patients complain of nasal congestion when using CPAP, BPAP, or adapto-servo ventilation. This can sometimes be alleviated by adding a humidifier to the CPAP machine. The judicious use of nasal sprays can also help with symptoms of congestion.

CPAP has occasionally been shown to worsen central sleep apnea if it exacerbates the hyperventilatory phase of Cheyne-Stokes respiration. This is often the reason to convert to the adapto-servo ventilation form of CPAP.

IV. Management with Co-Morbidities

Narcotic analgesics as well as certain hypnotics and anxiolytics can worsen sleep disordered breathing. In addition, alcohol can worsen obstructive sleep apnea.

CPAP, BPAP, or ASV may not be a safe in patients with certain types of chronic lung disease, including bullous lung disease or a pneumothorax.

Patients need a consistent message to use their sleep disordered breathing treatment. Emphasizing the connections between sleep disordered breathing and cardiovascular disease, in particular worsening heart failure, myocardial ischemia, and arrhythmias can help patients understand the importance of treatment.

Counseling regarding weight loss is critical for patients with obesity and obstructive sleep apnea. The avoidance of alcohol, narcotics, and certain anxiolytics is important in reducing the burden of sleep disordered breathing on the cardiovascular system.

Aggressively managing heart failure with maximally tolerated neurohormonal blockade, volume control, and device therapies can improve central sleep apnea but there is little data that management of heart failure, with the exception of volume status, can have much impact on obstructive sleep apnea.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Use of CPAP, BPAP, or ASV more than 4 hours every night is the minimum to begin accruing a treatment benefit. There is some evidence that the presence of sleep disordered breathing increases the risk of heart failure readmission. For this reason, some centers are piloting the concept of performing sleep studies just prior to discharge and then prescribing treatment. It is hoped that treating sleep disordered breathing will translate into reduced heart failure hospital readmissions.

B. What’s the Evidence for specific management and treatment recommendations?

C. DRG Codes and Expected Length of Stay.