When CPAP has not worked: central sleep apnea with Cheyne-Stokes breathing in heart failure with reduced ejection fraction

Clinical scenario

This protocol applies to patients with central sleep apnoea (CSA) accompanied by Cheyne-Stokes breathing — a form of periodic breathing with waxing and waning flow and tidal volume — occurring in the context of heart failure with reduced ejection fraction (HFrEF) and a left ventricular ejection fraction below 45%.

Previous treatment line did not achieve the target

The prior step was continuous positive airway pressure (CPAP) therapy, with or without supplemental oxygen, for symptomatic CSA. Escalation to this protocol is indicated when CPAP fails to bring the apnoea-hypopnoea index (AHI) below 15 events per hour — that is, when adequate control of CSA is not achieved.

Next-step approach (overview — incomplete)

For patients in this situation, the protocol involves a neuromodulatory intervention targeting the phrenic nerve. Non-device-based and non-PAP alternatives are also part of this line for patients who cannot tolerate positive airway pressure mask interfaces. Notably, one specific class of ventilatory support is explicitly not recommended in this HFrEF population.

The complete regimen, sequencing, clinical criteria, and specific options are in the full structured protocol →

Clinical goal

The primary measure of response is reduction in the apnoea-hypopnoea index (AHI) at 3 months of therapy.

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References

CSA, often with concurrent CSB (a form of periodic breathing with waxing and waning amplitude of flow/tidal volume), can be observed in low cardiac output states including heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF; impaired cardiac filling/relaxation) and cardiac arrhythmia.
Nonetheless, after the SERVE-HF (Treatment of Predominant Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure) trial, ASV is no longer recommended in CSA–CSB among heart failure patients with LVEF <45%.
Transvenous phrenic nerve stimulator (TPNS) offers an alternative method to regulate breathing and stabilise CO2 levels while bypassing the surgical risk seen in intrathoracic stimulator implantation.
Currently, TPNS is considered an option for symptomatic CSA in patients who fail or do not tolerate CPAP therapy.
Nocturnal oxygen therapy (NOT) is also an alternative in HFrEF with CSA, and may be better accepted in patients who cannot tolerate positive airway pressure (PAP) mask interfaces.
As upper airway obstruction is a triggering factor in generating CSA episodes, other methods to reduce upper airway collapsibility, such as positioning devices or elevating the head of the patient's bed, can also be considered as non-PAP alternatives.
The post hoc analysis of the CSA subgroup with heart failure from the redemé System Pivotal Trial (CSA with AHI >20 events per h, 1:1 randomisation to stimulation or no stimulation post TPNS implantation) showed improvement in sleep metrics from baseline (55% reduction in AHI after 3 months of therapy) and trends towards improved LVEF and time to first hospitalisation with no increased mortality.

DOI: 10.1183/20734735.0235-2023 View source ↗