Transvenous phrenic nerve stimulation is associated with normalization of nocturnal heart rate perturbations in patients with central sleep apnea

Mathias Baumert; Dominik Linz; Scott McKane; Sarah Immanuel

doi:10.1093/sleep/zsad166

Transvenous phrenic nerve stimulation is associated with normalization of nocturnal heart rate perturbations in patients with central sleep apnea

Sleep. 2023 Sep 8;46(9):zsad166. doi: 10.1093/sleep/zsad166.

Authors

Mathias Baumert¹, Dominik Linz^{2

3

4}, Scott McKane⁵, Sarah Immanuel^{1

6}

Affiliations

¹ Discipline of Biomedical Engineering, School of Electrical and Mechanical Engineering, The University of Adelaide, Adelaide, Australia.
² Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute, Maastricht, The Netherlands.
³ Centre for Heart Rhythm Disorders, The University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.
⁴ Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵ ZOLL Respicardia, Inc. Minnetonka, MN, USA.
⁶ School of Business Information Systems, Torrens University, Adelaide, Australia.

Abstract

Study objectives: To determine the effect of transvenous phrenic nerve stimulation (TPNS) on nocturnal heart rate perturbations in patients with CSA.

Methods: In this ancillary study of the remedē System Pivotal Trial, we analyzed electrocardiograms from baseline and follow-up overnight polysomnograms (PSG) in 48 CSA patients in sinus rhythm with implanted TPNS randomized to stimulation (treatment group; TPNS on) or no stimulation (control group; TPNS off). We quantified heart rate variability in the time and frequency domain. Mean change from baseline and standard error is provided.

Results: TPNS titrated to reduce respiratory events is associated with reduced cyclical heart rate variations in the very low-frequency domain across REM (VLFI: 4.12 ± 0.79% vs. 6.87 ± 0.82%, p = 0.02) and NREM sleep (VLFI: 5.05 ± 0.68% vs. 6.74 ± 0.70%, p = 0.08) compared to the control group. Further, low-frequency oscillations were reduced in the treatment arm in REM (LFn: 0.67 ± 0.03 n.u. vs. 0.77 ± 0.03 n.u., p = 0.02) and NREM sleep (LFn: 0.70 ± 0.02 n.u. vs. 0.76 ± 0.02 n.u., p = 0.03).

Conclusion: In adult patients with moderate to severe central sleep apnea, transvenous phrenic nerve stimulation reduces respiratory events and is associated with the normalization of nocturnal heart rate perturbations. Long-term follow-up studies could establish whether the reduction in heart rate perturbation by TPNS also translates into cardiovascular mortality reduction.

Clinical trial: A Randomized Trial Evaluating the Safety and Effectiveness of the remedē® System in Patients With Central Sleep Apnea, ClinicalTrials.gov, NCT01816776.

Keywords: central sleep apnea; heart rate variability; transvenous phrenic nerve stimulation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Electric Stimulation Therapy*
Heart Rate
Humans
Phrenic Nerve
Prospective Studies
Quality of Life
Sleep Apnea, Central* / therapy
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT01816776