title: Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial.
abstract: Chronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T-wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat-to-beat heart rate dynamics have not been systematically characterized in humans.
  
  
  
  We evaluated acute effects of VNS on R-R-interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM-HF trial by quantifying effects during continuous cyclic VNS (14-seconds on-time, 66-seconds off-time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10-week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right-sided stimulation (-2.22 ± 0.13 bpm) than in the 31 patients with left-sided stimulation (-0.60 ± 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R-R interval was stronger among the 28 patients with right-sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left-sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+0.08 ± 0.06 bpm, P < 0.001).
  
  
  
  Instantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left- and right-sided stimulation.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.affiliation: LivaNova PLC, Houston, Texas, USA.
authors.forename: Imad
authors.initials: I
authors.lastname: Libbus
authors.affiliation: LivaNova PLC, Houston, Texas, USA.
authors.forename: Badri
authors.initials: B
authors.lastname: Amurthur
authors.affiliation: LivaNova PLC, Houston, Texas, USA.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Kenknight
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. rverrier@bidmc.harvard.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000200:Action Potentials; D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods
keywords: ANTHEM-HF trial; autonomic regulation therapy; heart failure; heart rate; vagus nerve stimulation