Nonhypercapnic CSA
Heart Failure–Induced CSA
The leading medical diagnosis causing CSA is congestive HF (CHF), and there is a correlation between HF severity and presence of CSA. In patients with stable CHF with HF reduced ejection fraction (HFrEF), CSA is highly prevalent, occurring in 25% to 40% of patients.9 In contrast to other subtypes of CSA where literature regarding prognosis is lacking, the literature is clear that patients with HFrEF with CSA have a worse prognosis, with increased risk of death independent of the severity of HF. This may be the result of CSA promoting malignant ventricular arrhythmias. The prevalence of CSA in HF with preserved ejection fraction (HFpEF) is about 18% to 30%.10,11
A significant reduction in cardiac output results in circulatory delay between the lungs and chemoreceptors that produces CSB periodic breathing, which is characteristic of the most recognized form of CSA. Per the ICSD-3, CSA with CSB requires the following 4 findings: (1) PSG reveals ≥ 5 CSAs and/or central hypopneas per hour of sleep; there are at least 3 consecutive CSAs and/or central hypopneas separated by crescendo-decrescendo breathing with a cycle length of at least 40 seconds (ie, CSB pattern), and the number of CSAs and/or central hypopneas is > 50% of the total number of apneas and hypopneas; (2) the patient reports sleepiness, awakening with shortness of breath, snoring, witnessed apneas, or insomnia; (3) the breathing pattern is associated with atrial fibrillation/flutter, CHF, or a neurologic disorder; and (4) the disorder is not better explained by another current sleep disorder, medication use (eg, opioids), or SUD.8
Treatment of HF-induced CSA begins with guideline-based medical management with the goal of reducing pulmonary capillary wedge pressure or increasing left ventricular ejection fraction through means that may include cardiac resynchronization therapy or left ventricular assist devices, when clinically indicated. If medical optimization is not sufficient, the next step is continuous positive airway pressure (CPAP or PAP), followed by adaptive servo-ventilation (ASV) if the apnea-hypopnea index (AHI) remains > 15 events per hour and is clinically indicated.
ASV is a second-line PAP therapy modality that uses proprietary algorithms to provide variable amounts of pressure that alternate between expiratory and inspiratory phases of the respiratory cycle in combination with physician-set or automatic backup respiratory rate designed to stabilize ventilation in patients with CSA and CSB. The inability to adjust tidal volume, potentially resulting in insufficient tidal volumes or ventilation, results in the contraindication for its use in patients with CSA with comorbid conditions that may result in hypercapnic respiratory failure. These conditions include chronic hypoventilation in obesity hypoventilation syndrome (OHS), moderate-to-severe chronic obstructive pulmonary disease, chronic elevation of PaCO2 on arterial blood gas > 45 mm Hg, and restrictive thoracic or neuromuscular disease.12
Although ASV is more effective in normalizing AHI in patients with HF and CSA than is CPAP therapy, the clinical indications for ASV in the setting of HFrEF changed drastically with the publication of the landmark SERVE-HF trial, which investigated the effects of adding ASV to guideline-based medical management on survival and cardiovascular outcomes in patients with HFrEF and predominant CSA.13 The study did not show a difference between the ASV and control groups for the primary endpoint: a composite of time to first event of death from any cause, lifesaving cardiovascular intervention (transplantation, implantation of a long-term ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening HF. However, the study showed a statistically and clinically significant increased risk of all-cause and cardiovascular mortality in the ASV group compared with the control group.13 A possible explanation for the increased all-cause and cardiovascular mortality is that CSA potentially serves a protective mechanism that when eliminated results in deleterious clinical outcomes. This resulted in significant changes in the treatment algorithm for HF-induced CSA with left ventricular ejection fraction of at least 45% becoming the cutoff for therapeutic decisions.