Analysis by sex of safety and effectiveness of transvenous phrenic nerve stimulation

Abstract

Purpose: Little is known about sex differences in the treatment of central sleep apnea (CSA). Our post hoc analysis of the remedē System Pivotal Trial aimed to determine sex-specific differences in the safety and effectiveness of treating moderate to severe CSA in adults with transvenous phrenic nerve stimulation (TPNS).

Methods: Men and women enrolled in the remedē System Pivotal Trial were included in this post hoc analysis of the effect of TPNS on polysomnographic measures, Epworth Sleepiness Scale, and patient global assessment for quality of life.

Results: Women (n = 16) experienced improvement in CSA metrics that were comparable to the benefits experienced by men (n = 135), with central apneas being practically eliminated post TPNS. Women experienced improvement in sleep quality and architecture that was comparable to men post TPNS. While women had lower baseline apnea hypopnea index than men, their quality of life was worse at baseline. Additionally, women reported a 25-percentage point greater improvement in quality of life compared to men after 12 months of TPNS therapy. TPNS was found to be safe in women, with no related serious adverse events through 12 months post-implant, while men had a low rate of 10%.

Conclusion: Although women had less prevalent and less severe CSA than men, they were more likely to report reduced quality of life. Transvenous phrenic nerve stimulation may be a safe and effective tool in the treatment of moderate to severe CSA in women. Larger studies of women with CSA are needed to confirm our findings.

Clinical trial registration: ClinicalTrials.gov NCT01816776; March 22, 2013.

Keywords: Central sleep apnea; Female; Transvenous phrenic nerve stimulation.

Fig. 1

Changes in the apnea hypopnea index by sex. The apnea hypopnea index (AHI) components are shown at baseline and after 12 months of transvenous phrenic nerve stimulation. Females and males both had a large, statistically significant reduction in the AHI, with most of the improvement from the reduction in the central apnea index. The median (Q1, Q3) AHI paired change from baseline was − 21 events/h (− 24, − 10) in females (change from baseline P = 0.002) and − 22 (− 40, − 6) in males (P < 0.001), with corresponding changes in the central apnea index of − 14 (− 21, − 10) (P = 0.002) and − 21 (− 35, − 12) (P < 0.001). Abbreviations: AHI, apnea hypopnea index; hr, hour; P, P-value

Fig. 2

Changes in rapid eye movement sleep by sex. Rapid eye movement sleep increased for females and males after 12 months of transvenous phrenic nerve stimulation. The median (Q1, Q3) paired change from baseline was 4 (− 1, 7) for females (P = 0.049) and 3 (− 3, 10) for males (P = 0.001). Abbreviations: P, P-value; REM, rapid eye movement

Fig. 3

Patient global assessment by sex. The patient global assessment (PGA) is a single question asking “Specifically in reference to your overall health, how do you feel today as compared to how you felt before having your device implanted: Markedly improved, moderately improved, mildly improved, no change, slightly worse, moderately worse, or markedly worse?”. After 12 months of transvenous phrenic nerve stimulation therapy, 82% of females and 57% of males indicated marked or moderate improvement. Abbreviations: CI, confidence interval

Fig. 4

Changes in the Epworth Sleepiness Scale by sex. The Epworth Sleepiness Scale (ESS) is a measure of daytime sleepiness with scores ranging from 0 to 24. A score greater than 10 is considered excessive daytime sleepiness. The median (Q1, Q3) paired change from baseline was − 2 (− 9, − 1) for females (P = 0.008) and − 3 (− 7, 0) for males (P < 0.001) after 12 months of transvenous phrenic nerve stimulation. Abbreviations: P, P-value