Update on Apneas of Heart Failure With Reduced Ejection Fraction: Emphasis on the Physiology of Treatment: Part 2: Central Sleep Apnea

Central sleep apnea/Hunter-Cheyne-Stokes breathing (CSA/HCSB) is prevalent in patients with heart failure with reduced ejection fraction (HFrEF). The acute pathobiologic consequences of CSA/HSCB eventually lead to sustained sympathetic overactivity, repeated hospitalization, and premature mortality. A few randomized controlled trials (RCTs) have shown statistically significant and clinically important reduction in sympathetic activity when CSA/HCSB is attenuated by oxygen or PAP therapy. Yet, the two largest PAP RCTs in patients with HFrEF, one with CPAP and the other with adaptive servoventilation (ASV), were negative with respect to their primary outcomes, and both were associated with excess mortality. However, both trials suffered from significant deficiencies, casting doubt on their results. A second RCT evaluating an ASV device with an advanced algorithm is ongoing. A new modality of therapy, unilateral phrenic nerve stimulation, has undergone an RCT that demonstrated an improvement in CSA that was associated with a reduction in arousals, improvement in sleepiness, and improvement in quality of life. However, a long-term mortality trial has not been performed with this modality. Most recently, the National Institutes of Health has funded a long-term, phase 3 RCT of low-flow oxygen vs sham for the treatment of CSA/HCSB in HFrEF. The composite primary outcome includes all-cause mortality and hospitalization for worsening HF. In this article, we focus on various therapeutic options for the treatment of CSA/HCSB and, when appropriate, emphasize the importance of identifying CSA/HCSB phenotypes to tailor treatment.