Transvenous phrenic nerve stimulation improves central sleep apnea, sleep quality, and quality of life regardless of prior positive airway pressure treatment

Abstract

Study objective: Positive airway pressure (PAP) therapy for central sleep apnea (CSA) is often poorly tolerated, ineffective, or contraindicated. Transvenous phrenic nerve stimulation (TPNS) offers an alternative, although its impact on previously PAP-treated patients with CSA has not been examined.

Methods: TPNS responses among PAP-naïve and prior PAP-treated patients from the remedē^® System Pivotal Trial were assessed. Of 151, 56 (37%) used PAP therapy before enrolling in the trial. Patients were implanted with a TPNS device and randomized to either active or deferred (control) therapy for 6 months before therapy activation. Apnea-hypopnea index (AHI) and patient-reported outcomes (PRO) were assessed at baseline, and 6 and 12 months following active therapy.

Results: Patients had moderate-severe CSA at baseline, which was of greater severity and more symptomatic in the PAP-treated vs. PAP-naïve group (median AHI 52/h vs. 38, central apnea index (CAI) 32/h vs. 18, Epworth Sleepiness Scale 13 vs. 10, fatigue severity scale 5.2 vs. 4.5). Twelve months of TPNS decreased AHI to <20/h and CAI to ≤2/h. Both groups showed reductions in daytime sleepiness and fatigue, improved well-being by patient global assessment, and high therapeutic acceptance with 98% and 94% of PAP-treated and PAP-naïve patients indicating they would undergo the implant again. Stimulation produced discomfort in approximately one-third of patients, yet <5% of prior PAP-treated participants discontinued therapy.

Conclusion: Polysomnographic and clinical responses to TPNS were comparable in PAP-naïve and prior PAP-treated CSA patients. TPNS is a viable therapy across a broad spectrum of CSA patients.

Trial registration: ClinicalTrials.gov Identifier NCT01816776; March 22, 2013.

Keywords: Central sleep apnea; Positive airway pressure; Transvenous phrenic nerve stimulation.

Fig. 1

The remedē^® System shown with the pulse generator implanted in the right pectoral region, stimulation lead implanted in the left pericardiophrenic vein adjacent to the phrenic nerve, and sensing lead implanted in the azygos vein. The phrenic nerve is stimulated, which travels to and activates the diaphragm to generate a breath

Fig. 2

CONSORT Diagram. Patient accountability by prior PAP use subgroup through 1 year of active therapy. PAP positive airway pressure

Fig. 3

Sleep indices by visit for prior PAP-treated (a) and PAP-naïve (b) subgroups. Median sleep indices from centrally scored in-laboratory polysomnogram displayed by visit for the prior mask use (left) and no prior mask use subgroups (right). *Paired change from baseline p value <.001. AHI apnea-hypopnea index, ArI arousal index, CAI central apnea index, OAI obstructive apnea index, ODI4 4% oxygen desaturation index, PAP positive airway pressure

Fig. 4

Sleep stages by visit for prior PAP-treated (a) and PAP-naïve subgroups (b). Median percentage of total sleep time in N1, N2, N3, and REM sleep. The percentage of sleep in light stage sleep (N1) decreased in both subgroups at 1 year. Note that the sum of the medians of the sleep stages does not add to 100%. *Paired change from baseline p value < 0.05. PAP positive airway pressure, REM rapid eye movement

Fig. 5

Daytime symptoms for prior PAP-treated (a) and PAP-naïve subgroups (b). Median scores for ESS and FSS by subgroup at 1 year. The ESS score ranges from 0 to 24 with scores >10 considered excessive daytime sleepiness. The FSS score ranges from 0 to 9 with scores >4 considered excessive fatigue. *Paired change from baseline p value. ESS Epworth Sleepiness Scale, FSS Fatigue Severity Scale, PAP positive airway pressure