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

Abstract

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