Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea

Olaf Oldenburg, Maria Rosa Costanzo, Robin Germany, Scott McKane, Timothy E Meyer, Henrik Fox, Olaf Oldenburg, Maria Rosa Costanzo, Robin Germany, Scott McKane, Timothy E Meyer, Henrik Fox

Abstract

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remedē System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.

Trial registration: ClinicalTrials.gov NCT01816776.

Keywords: Central sleep apnea; Hypoxemic burden; Phrenic nerve stimulation.

Conflict of interest statement

The authors have the following conflicts of interest to declare: Fox: no conflict of interest to declare regarding this manuscript. Oldenburg: no conflict of interest to declare regarding this manuscript. Costanzo: was the Primary Investigator for the trial. Germany, McKane and Meyer: Employees of Respicardia.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8043931/bin/12265_2020_10061_Figa_HTML.jpg
Graphical Abstract
Fig. 1
Fig. 1
CONSORT Diagram, Composition of the per protocol population with sleep study results through the 6-month visit, PSG = polysomnogram
Fig. 2
Fig. 2
Central Apnea Index Percentage Reduction from baseline to 6 Months for each subject, each vertical bar represents the percentage reduction (improvement) in the central apnea index from baseline to 6 months for a subject. The green bars (> 0%) represent reduction and red (

Fig. 3

Median (interquartile range) of minutes…

Fig. 3

Median (interquartile range) of minutes with oxygen saturation A) and the subgroup…

Fig. 3
Median (interquartile range) of minutes with oxygen saturation A) and the subgroup with heart failure and ejection fraction ≤ 45% (B). P value from Mann–Whitney test for difference in change from baseline between groups (2-sided)

Fig. 4

Oxygen saturation 0%) represent reduction…

Fig. 4

Oxygen saturation 0%) represent reduction and red (

Fig. 4
Oxygen saturation  0%) represent reduction and red (
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Fig. 3
Fig. 3
Median (interquartile range) of minutes with oxygen saturation A) and the subgroup with heart failure and ejection fraction ≤ 45% (B). P value from Mann–Whitney test for difference in change from baseline between groups (2-sided)
Fig. 4
Fig. 4
Oxygen saturation  0%) represent reduction and red (

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