Benefit of phrenic nerve stimulation on central sleep apnea sustained to 5 years
Presenter: Shahrokh Javaheri, MD
At 5 years, patients with moderate to severe central sleep apnea who underwent transvenous phrenic nerve stimulation showed durability of improvements in the apnea-hypopnea index (AHI), sleep arousals, daytime sleepiness, and other outcomes.1 Further, 78% of patients were still alive at the 5-year follow-up, including 68% of those with heart failure, reported Shahrokh Javaheri, MD, from the Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH.
The implantable transvenous phrenic nerve stimulation device (remedē System; Respicardia Inc.) was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of severe central sleep apnea in adults. The device, implanted similar to the way a pacemaker is implanted, stimulates the phrenic nerve to activate the diaphragm, thereby restoring a more normal breathing pattern during sleep.
As a condition of FDA approval, data from the 6-month randomized controlled trial on which approval was based were collected through 5 years postimplant to assess long-term safety, effectiveness, and mortality. All patients in the follow-up were randomized to active therapy in the controlled trial.
At 5 years, the median number of AHI events per hour in a paired sample of 42 patients with 5-year polysomnograms decreased from 42/hour at baseline to 17/hour at 5 years (median change [interquartile range], -22/hour; P < .001). The reduction occurred predominantly in central apnea events, with little change in the obstructive apnea index, said Dr. Javaheri.
Parallel changes in the arousal index were observed. In a paired analysis of 35 patients, the arousal index decreased from a median of 36/hour at baseline to 23/hour at 5 years, for a median reduction [interquartile range] of 14/hour (P < .001).
“Consistent with the reduction in AHI over 5 years was a progressive improvement in sleep architecture,” he said, with a shift away from light-stage sleep (N1) to deeper-stage sleep (N2-REM). Paired analysis of 35 patients showed a median reduction in N1 sleep of 19% at 5 years and a median increase in REM sleep of 14%.
At baseline, 45% of the 131 patients enrolled had an Epworth Sleepiness Scale (ESS) score greater than 10. At 5 years, 62% of patients with a baseline score greater than 10 shifted to a score of 10 or lower. Paired changes in ESS from baseline in 50 patients showed a median reduction in ESS score from 12 at baseline to 6 at year 5 (median change [interquartile range] -3; P < .001).
An independent clinical events committee found no unanticipated adverse device effects and no deaths related to the implant procedure, device, or delivered therapy. Most serious adverse events occurred in the first year after implantation. With increased experience in implanting the device, the number of side effects has been reduced, said Dr. Javaheri. Beyond 3 years, there were 2 stimulation lead component failures and 1 lead dislocation that required surgical replacement, and 1 implant site infection.
In randomized controlled trials, use of continuous positive airway pressure in patients with sleep apnea has been associated with excess mortality, noted Dr. Jahaveri. “One of the hypotheses was that with positive airway pressure therapy, the increased intrathoracic pressure could result in adverse effects, particularly in the subset of patients with heart failure,” he said. “Therefore, therapeutic modalities that do not cause increased intrathoracic pressure, such as oxygen therapy, medications, or phrenic nerve stimulation, could have a different impact.”
Reference
- Javaheri S, Schwartz A, Abraham W, et al. Effects of transvenous phrenic nerve stimulation on central sleep apnea and sleep architecture: the 5-year analysis. CHEST 2020; 158(4 Suppl):A2412–A2413. DOI: https://doi.org/10.1016/j.chest.2020.09.011