Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes

Abstract

Background The remedē System Pivotal Trial was a prospective, multi-center, randomized trial demonstrating transvenous phrenic nerve stimulation (TPNS) therapy is safe and effectively treats central sleep apnea (CSA) and improves sleep architecture and daytime sleepiness. Subsequently, the remedē System was approved by FDA in 2017. As a condition of approval, the Post Approval Study (PAS) collected clinical evidence regarding long-term safety and effectiveness in adults with moderate to severe CSA through five years post implant. Methods Patients remaining in the Pivotal Trial at the time of FDA approval were invited to enroll in the PAS and consented to undergo sleep studies (scored by a central laboratory), complete the Epworth Sleepiness Scale (ESS) questionnaire to assess daytime sleepiness, and safety assessment. All subjects (treatment and former control group) receiving active therapy were pooled; data from both trials were combined for analysis. Results Fifty-three of the original 151 Pivotal Trial patients consented to participate in the PAS and 52 completed the 5-year visit. Following TPNS therapy, the apnea-hypopnea index (AHI), central-apnea index (CAI), arousal index, oxygen desaturation index, and sleep architecture showed sustained improvements. Comparing 5 years to baseline, AHI and CAI decreased significantly (AHI baseline median 46 events/hour vs 17 at 5 years; CAI baseline median 23 events/hour vs 1 at 5 years), though residual hypopneas were present. In parallel, the arousal index, oxygen desaturation index and sleep architecture improved. The ESS improved by a statistically significant median reduction of 3 points at 5 years. Serious adverse events related to implant procedure, device or delivered therapy were reported by 14% of patients which include 16 (9%) patients who underwent a pulse generator reposition or lead revision (primarily in the first year). None of the events caused long-term harm. No unanticipated adverse device effects or related deaths occurred through 5 years. Conclusion Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01816776.

Patienten relevanter Nutzen und Therapieeffekte in der Stimulationstherapie bei schlafbezogenen Atmungsstörungen

“…Hereby, an improvement from initially 10.2 and 9.5 points, respectively, was observed by -3.6 in the treatment arm compared to+0.1 in the ESS of the control arm (p<0.0001). This reduction to a median of 9 or a reduction by 3 points could be maintained in the 5-year follow-up of 53 patients 60 . In the long-term follow-up, 62% of the patients revealed an improvement of at least 3 points.…”

“…In the pilot study with 6-month perspective [58], the therapy was active during 5.4 of 5.8 hours of potential sleeping time with the mentioned preconditions. The following publications as well as the 5-year follow-up of the key study [59,60], however, do not provide results on therapy times.…”

“…Die Daten für die transvenöse Stimulation des Nervus phrenicus beruhen im Wesentlichen auf der Pilotstudie mit 57 [58] und der anschließenden Schlüsselstudie mit initial 151 eingeschlossenen Teilnehmern [59] sowie die Folgestudien letzterer zu den Langzeitergebnissen nach u. a. 5 Jahren [60]. Insgesamt muss bei der Betrachtung der ESS-Werte zu Tagesschläfrigkeit beachtet werden, dass in diesen beiden Kohorten der Anteil von herzinsuffizienten Patienten mit NYHA ≥ II bei 70 bzw.…”

Novel Therapeutic Devices in Heart Failure

“…It was meant to provide phrenic nerve stimulation and demonstrated a significant reduction in the apnea-hypopnea index (AHI), central apnea index, arousal index, oxygen desaturation ≥4% index, percentage of sleep with rapid eye movement and sleepiness (Epworth Sleepiness Scale (ESS)) [ 41 ]. Those findings were sustained in a 5-year follow-up [ 11 ].…”

Angiologie und schlafbezogene Atmungsstörungen: Neues im DGK-Positionspapier?

“…Eine Alternative zu den maskenbasierten Überdruck-Ventilationstherapien stellen neuartige implantierbare Nervenstimulations-Devices dar [13,14]. Für die prädominant zentralen SBAS konnte mit dem transvenös implantierbaren remede-System eine effektive AHI-Reduktion von mehr als 50 % dargelegt werden [15].…”