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

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 remede 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.