Mechanisms and Clinical Consequences of Untreated Central Sleep Apnea in Heart Failure | Journal Scan

Costanzo MR, Khayat R, Ponikowski P, et al.
J Am Coll Cardiol 2015;65:72-84.
The following are 10 points to remember about untreated central sleep apnea (CSA) in patients with heart failure (HF):

1. CSA occurs in 30-50% of HF patients.

2. A temporary withdrawal of central (brainstem-driven) respiratory drive results in cessation of respiratory muscle activity and airflow in CSA, whereas in obstructive sleep apnea, repeated episodes of partial or complete upper airway obstruction results in apnea and hypoxia during sleep.

3. CSA commonly occurs in the form of Cheyne-Stokes respiration (a form of periodic breathing with recurring cycles of crescendo-decrescendo ventilation that culminates in a prolonged apnea or hypopnea).

4. Risk factors for CSA in HF patients include male gender, higher New York Heart Association class, lower ejection fraction, waking hypocapnia (PaCO2 <38 mm Hg), higher prevalence of atrial fibrillation, higher B-type natriuretic peptide levels, and frequent nocturnal ventricular arrhythmias.

5. The gold standard test for diagnosing CSA is polysomnography, or overnight sleep study, which is performed in a sleep laboratory. Characteristic polysomnographic findings of CSA include an onset near the transition into or out of Stage 1; nonrapid eye movement sleep; cycles of deep, rapid, crescendo-decrescendo breathing followed by periods of hypopnea and/or apnea along with concomitant changes in blood oxygen saturation; and apneic periods accompanied by the absence of chest or abdominal wall activity.

6. An apnea-hyponea index (AHI) of 22.5 events/hour has the greatest sensitivity and specificity in predicting mortality associated with CSA, and mortality rises progressively with every 5 event/hour increase in AHI.

7. The pathogenesis of CSA is attributed to an increased respiratory control response to changes in PaCO2 above and below the apneic threshold due to an interaction of three main factors including hyperventilation, circulatory delay, and cerebrovascular reactivity.

8. The apnea-induced hypoxia-reoxygenation and arousal at night results in activation of the sympathetic nervous system, oxidative stress, systemic inflammation, and endothelial dysfunction.

9. There is lack of large-scale, prospective, randomized clinical trials for CSA and therefore the focus is on either improving HF or reducing CSA itself.

10. Potential therapies for CSA include:

• Noninvasive ventilatory support: Continuous positive airway pressure therapy (CPAP) was associated with variable effects and poor compliance in the CANPAP (Canadian Positive Airway Pressure Trial for Patients with Congestive Heart Failure and Central Sleep apnea) study. Adaptive pressure support servo-ventilation (ASV) was introduced to address shortcoming of CPAP. Ongoing trials with ASV are awaited.

• Nocturnal oxygen supplementation: Although short-term studies have suggested that it improves AHI, exercise capacity, and left ventricular ejection fraction, it does not appear to improve daytime sleepiness, cognitive function, or quality of life. It is, therefore, best reserved for those individuals where pressure support therapies are ineffective or are poorly tolerated.

• Nocturnal supplemental carbon dioxide is currently not recommended for treating CSA in HF due to variable effects including possibly adverse effects.

• Cardiac pacing: The benefits of cardiac resynchronization therapy and atrial overdrive pacing need to be substantiated in long-term, prospective, randomized clinical trials.

• Theophylline: Overall, the cardiostimulatory and arrhythmogenic effects limit use of theophylline in clinical practice.

• Acetazolamide: The lack of larger long-term studies of its overall safety and efficacy and the potential for urinary potassium wasting and resulting hypokalemia currently limits regular use of this agent.

• Phrenic nerve stimulation: A neurostimulation lead is placed either into the right brachiocephalic vein or the left pericardiophrenic vein to stimulate the phrenic nerve. Early clinical experience is encouraging. Data from large studies are still needed to confirm safety and efficacy.
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