Introduction to Central Sleep Apnea

As opposed to obstructive sleep apnea (OSA), central sleep apnea is characterized by repetitive cessation of ventilation during sleep resulting from lack of ventilatory effort or drive to breathe. Whereas OSA is extremely common in the adult population, central sleep apnea (CSA) affects less than 10% of patients referred to sleep laboratories. A single central apnea event is a ≥10-second pause in ventilation with no associated respiratory effort; greater than five such events per hour are considered abnormal. CSA is present when a patient has greater than five central apneas per hour of sleep with associated symptoms of disrupted sleep (such as excessive daytime somnolence). Because central apneas also may occur in an individual with obstructive apneas, clinicians may struggle to determine if CSA or OSA is the principal problem, or if a combination of the 2 disorders may need therapy.

Pearl: CSA does not have any single cause as a number of syndromes may result in CSA.

Of the causes of CSA, several are highly relevant to the cardiology community:

Cheyne-Stokes respiration (CSR) generally occurs in patients with heart failure, although it has been described in association with neurological disorders, including neurovascular disorders and dementia. It is characterized by a crescendo-decrescendo pattern of breathing with a central apnea or hypopnea at the nadir of ventilatory effort (Figure 1). In patients with heart failure, CSR is believed to result from a high-gain ventilatory control system (increased hypercapnic responsiveness) combined with a prolonged circulation time. This combination leads to unstable ventilatory control and this particular pattern of periodic breathing. Unstable ventilatory control in patients with both CSR and CSA can promote obstructive events (apneas and hypopneas) in an individual with a collapsible pharyngeal airway resulting from diminished upper airway muscle activation at the nadir of the cycling respiration. Thus, both central and obstructive events are commonly seen in these patients.

Central nervous system depressants such as narcotics, hypnotic medications, alcohol and muscle relaxants may lead to CSA. Many individuals taking such medications have a high incidence already of heart diseases.

High altitude can similarly produce CSA physiology.

The effect then of any Central Sleep Apnea syndrome is recurrent and/or persistent hypoxemia which may lead to increased short-term and long-term risk of cardiovascular diseases (Figure 2). Cardiovascular diseases associated with CSA include congestive heart failure, coronary artery disease, left and/or right ventricular dysfunction and a number of cardiac dysrhythmias. Clinicians need to be aware of these risks and be knowledgeable in some basic evaluation and treatment steps. However, the identification and even the management of this disorder then becomes even more challenging because CSA and OSA can co-exist in the same patient.

Pearl: Patients with Central Sleep Apnea have similar symptoms to patients with OSA, and the two disorders often co-exist.

Diagnostic Evaluation

The diagnostic evaluation of CSA consists of evaluating the patient's signs and symptoms in concert with diagnostic testing. These factors are imperative in deciding on treatment options.

Signs and Symptoms: A number of signs and symptoms of CSA are identical to those in OSA, and distinguishing the two can be challenging.

• Non-restorative sleep
• Excessive daytime sleepiness, sometimes with an inability to stay awake during routine or important tasks
• Excessive fatigue
• Mood disorders
• Memory loss
• Witnessed apneas
• Morning headaches
• Dry mouth
• Nocturia
• Snoring (this is generally a sign and symptom of OSA, but often co-exists with CSA)

Importantly, patients with CSA and heart failure may well have fewer symptoms of sleepiness than what might be expected for their degree of physiological derangement, and sleepiness may be a poor predictor of CSA.

Pearl: Symptoms of sleepiness may be poor predictors in CSA.

Objective Testing: Since diagnosing CSA may be challenging, full-night polysomnogram (sleep study) is recommended to determine the frequency and pattern of central apnea. Home sleep studies (often referred to as "portable monitoring") in the diagnosis of CSA have not been broadly accepted as of yet, and overnight oximetry alone does not provide sufficient physiological detail to discriminate CSA from OSA.

Treatment Options

There are several types of treatment options for CSA, starting with treating the underlying cause. Because no randomized trials of therapy for CSA in heart failure have established a significant benefit with respect to hospitalization or mortality, there is no consensus as to whether CSA should be treated in such patients and, if so, what the optimal therapeutic strategy may be.

Pearl: Treating the underlying cause of CSA (e.g. heart failure in Cheyne-Stokes respirations, reduction of respiratory depressant dosing), is generally recommended first.

Non-Positive-Airway-Pressure Treatment options:

• In patients with heart failure and CSA, medical management of heart failure seems to be overall helpful in treating CSA.

• Diuresis with a reduction in cardiac filling pressure has been shown to reduce the severity of CSA
• Angiotensin-Converting Enzyme inhibition can lower the AHI and reduce the nocturnal desaturation of patients with mild to moderate heart failure
• β-adrenergic blockade has been reported to decrease AHI in patients with CSA

• Supplemental Nocturnal Oxygen alone has been shown to eliminate apnea-related hypoxia and CSA. Yet to date it has not been shown to improve symptoms or improve long-term cardiovascular outcomes when given for CSA alone.
• Novel therapies such as atrial overdrive pacing, are as of yet considered investigational.

Positive-Airway-Pressure (PAP) Treatment Options: There are actually several PAP solutions for patients with OSA and CSA.

1. Continuous positive airway pressure therapy (CPAP) is prescribed to maintain airway patency in obstructive events. CPAP is generally a "fixed" pressure that does not differ during inhalation or exhalation phases (see figure), but several advancements to traditional CPAP have made CPAP more comfortable and thereby effective:


• Addition of Expiratory Pressure Relief (EPR or C-Flex), allowing an adjustable pressure drop upon sensing exhalation to facilitate comfort with exhalation.
• Bilevel Therapies (BiPAP) may be used in certain instances to improve ventilation with a different inspiratory and expiratory pressure.
• Heated humidification, either through the device or nowadays sometimes through the tubing itself to minimize condensation. li>
• Automated CPAP and BiPAP devices that sense obstructions and respiratory effort, therefore auto-adjust the pressures within a prescribed therapeutic range.
• Newer masks, newer materials, and quieter machines


2. Adaptive servo-ventilation (ASV) is an advanced BiPAP device that has an exquisite automated algorithm that not only detects central apneas, but also adjusts the rate delivery of the backup breath depending on the respiratory needs. There are theoretical benefits to this mode of delivery in patients with Cheyne-stokes respiration and some smaller studies demonstrating a reduction in overall respiratory events.

Pearl: Newer forms of ventilatory support (such as ASV devices) allow better overall treatment efficacy and tolerability than traditional CPAP, especially for patients who have CSA (with or without OSA).

Efficacy of PAP Therapies for CSA: There are a number of smaller studies that suggest cardiovascular benefit with PAP therapies for CSA which have been reviewed in the attached references, including:

• Reduced ventricular ectopy
• Increased left ventricular ejection fraction
• Reduction of mitral regurgitation
• Improved quality of life
• Decreased catecholamine levels

However, in a multicenter randomized trial of 258 patients with heart failure and CSA [the Canadian Positive Airway Pressure Trial for Patients with Congestive Heart Failure and Central Sleep Apnea (CANPAP)], CPAP reduced nocturnal desaturations but did not improve survival. There were likely important limitations to this study and the findings may not be applicable to all CSA and/or heart failure patients, but this study did raise questions on the efficacy of PAP therapies.

Despite the lack of substantial proven cardiovascular benefit, PAP therapies also have the advantage of having very little health risk. Therefore therapeutic trials, with clinical reassessment and follow-up, leave patients with little to lose, which is why many sleep specialists still recommend a trial of therapy if patients have clinical symptoms or are at increased perceived cardiovascular risk.

There are several PAP and non-PAP treatment options for CSA being utilized. Currently, treatment recommendations for CSA are driven by taking into account clinical symptoms, severity of CSA (as defined by testing methods), clinical risk profile, and individual patient and provider preferences.

Conclusion

In summary, although CSA is much less common than OSA, it has been associated with increased morbidity and mortality in heart failure patients and may have important clinical implications. A number of treatment strategies for CSA have been tested, but presently none is ideal with respect to both efficacy and tolerance, nor has any available therapy yet demonstrated to improve survival.

Clearly more research is needed in the field of sleep medicine, its impact in cardiovascular diseases, and specifically in defining better treatment options for syndromes such as CSA. But many of us in sleep medicine are hopeful that cardiologists will be able to add to their armamentarium of cardiovascular disease management by better understanding and treating such sleep disorders.

Key Learning Points

• Central Sleep Apnea is much less common than Obstructive Sleep Apnea, and the two disorders often co-exist.
• In patients with Central sleep apnea and heart failure, symptoms of sleepiness may be poor predictors of pathological breathing.
• Cheyne-stokes respiration is a type of CSA, commonly associated with heart failure, that is thought to be a dysfunction of ventilator control, or a 'high loop gain" physiological derangement.
• Treatment of CSA focuses first on the underlying cause of the disorder.
• Advances in CPAP and BiPAP have improved tolerability and perhaps efficacy, while newer forms of PAP therapies (such as ASV devices) may be particularly better for patients with CSA.
• Although to date none of the currently available therapies have improved long-term cardiovascular outcomes, a number of studies support treating central sleep apnea.

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References

1. Arzt M, Young T, Finn L, et al. Arch Intern Med 2006;166:1716-1722.
2. Javaheri S. (2005). Heart Failure. In Kryger MH, Roth T, Dement WC (Eds.) Principles and Practice of Sleep Medicine (1208-1217). Philadelphia: Elsevier, Inc.
3. Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular diseases: a bidirectional relationship. Circulation 2012;126:1495-1510.
4. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing Council. J Am Coll Cardiol 2008;52:686–717.

Keywords: Apnea, Respiration, Sleep Apnea, Central, Sleep Apnea, Obstructive

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