Sleep-Disordered Breathing and Heart Failure

Most patients with heart failure (HF) have sleep-disordered breathing (SDB), with central (rather than obstructive) sleep apnea becoming the predominant form in patients with more severe disease. Cyclical apnea and hypopneas are associated with sleep disturbance, hypoxemia, hemodynamic changes, and sympathetic activation. These patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and can partially normalize the sleep and respiratory physiology.

However, recent randomized trials of cardiovascular outcomes in central sleep apnea in chronic HF with reduced ejection fraction have had neutral findings or suggested the possibility of harm, likely from an increased rate of sudden death. Further randomized outcome studies are required to determine whether mask-based treatment is appropriate for patients with chronic HF with reduced ejection fraction and obstructive sleep apnea, for patients with heart failure with preserved ejection fraction, and for patients with decompensated heart failure. New therapies for sleep apnea (e.g., implantable phrenic nerve stimulators) also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with HF and sleep apnea. The following are key points to remember about this excellent review of sleep-disordered breathing (SDB) among patients with heart failure (HF):

1. What are the two types of SDB?
   In general, there are two types of SDB: obstructive and central. Obstructive sleep apnea (OSA) is the most common form of SDB among the general population, while central sleep apnea (CSA) is more common in HF, with prevalence rates ranging between 50% and 75% in both reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The article includes a Table of the large randomized trials using mask therapy to treat SDB in HF as well as a color graphic diagram illustrating pathophysiologic abnormalities in SDB and HF.


2. What is ASV and how is it different from conventional PAP therapy?
   Adaptive servo-ventilation (ASV) is a mask therapy that delivers controlled inspiratory pressure on top of expiratory positive airway pressure (PAP). ASV is better tolerated than PAP therapy and is effective in both CSA and OSA. Conversely, PAP continuously delivers ventilation via mask, eliminating airway obstruction and improving hypoxemia.


3. What is the primary benefit of treating OSA with mask therapy?
   At the moment, cardiologists can recommend to patients with OSA that PAP therapy can improve sleepiness and physical function. Despite the association between SDB and adverse cardiovascular outcomes, in a recent meta-analysis of 10 randomized trials, the use of PAP compared to sham or no treatment was not associated with lowering cardiovascular outcomes or death among patients with OSA.


4. What do the guidelines recommend for treating OSA/CSA in HF?
   The 2013 American College of Cardiology/American Heart Association HF guidelines state that treating HF patients with OSA using continuous PAP (CPAP) does have benefit (see below). The 2016 European Society of Cardiology guidelines state that ASV is not recommended for HFrEF patients and predominantly CSA, based on randomized controlled data (see the following SERVE-HF comment).


5. Are there any SDB treatments to avoid in HFrEF?
   Yes. Avoid ASV, based on the SERVE-HF trial, which randomized 1,325 patients with HFrEF (<45%) and apnea-hypopnea index (AHI) >15 (moderate to severe SDB with predominance of CSA events) to ASV or guideline HF therapy alone. All-cause mortality and death from cardiovascular causes was increased in the ASV arm.


6. How can one explain the findings of the SERVE-HF trial?
   Two explanations are offered: Among HFrEF with CSA, PAP could be harmful or perhaps CSA is a positive adaptive mechanism for HFrEF and abolishing CSA with ASV could be doing harm.


7. Are experimental trials for treating CSA in HF on the horizon?
   Phrenic nerve stimulation, aims to provide normal respiratory contraction of the diaphragm by stimulating the phrenic nerve to reduce central events in CSA. In one small randomized trial, there was a 50% reduction in respiratory events, but at the cost of a 10% adverse event rate. A second experimental device involving stimulation of the hypoglossal nerve to improve apnea did reduce AHI in one small nonrandomized trial, which did not include HF patients. Last, a small randomized trial in HF with CSA using acetazolamide is underway to reduce AHI and treat hypoxemia.


8. Overall Conclusions:
   Improvement in AHI (respiratory events) or sleepiness are not adequate outcomes to measure alone when treating HF. Based on current evidence, cardiologists best focus on treating HF itself at present. Further studies addressing which subsets of patients with HF (such as acute decompensated or HFpEF) will benefit from ASV are needed.