title: Novel method to assess intrinsic heart rate recovery in ambulatory ECG recordings tracks cardioprotective effects of chronic autonomic regulation therapy in patients enrolled in the ANTHEM-HF study.
abstract: BACKGROUND
  Postexercise heart rate recovery (HRR) is a powerful and independent predictor of mortality. Autonomic regulation therapy (ART) with chronic vagus nerve stimulation (VNS) has been shown to improve ventricular function in patients with chronic heart failure. However, the effect of ART on HRR in patients with heart failure remains unknown.
  
  
  METHODS
  A new measure involving quantification of intrinsic HRR was developed for 24-hr ambulatory ECG (AECG) recordings based on spontaneous heart rate changes observed during daily activity in patients with symptomatic heart failure and reduced ejection fraction. Intrinsic HRR values were compared in 21 patients enrolled in the ANTHEM-HF study (NCT01823887) before and after 12 months of chronic ART (10 Hz, 250 μs pulse width, 18% duty cycle, maximum tolerable current amplitude after 10 weeks of titration) and to values from normal subjects (PhysioNet database, n = 54).
  
  
  RESULTS
  With chronic ART, average intrinsic HRR was improved as indicated by a shortening of the rate-recovery time constant by 8.9% (from 12.3 ± 0.1 at baseline to 11.2 ± 0.1 s, p < .0001) among patients receiving high-intensity stimuli (≥2 mA). In addition, mean heart rate decreased by 8.5 bpm (from 75.9 ± 2.6 to 67.4 ± 2.9 bpm, p = .005) and left ventricular ejection fraction (LVEF) increased by 4.7% (from 32.6 ± 2.0% to 37.3 ± 1.9%, p < .005).
  
  
  CONCLUSIONS
  Using a new technique adapted for 24-hr AECG recordings, intrinsic HRR was found to be impaired in patients with symptomatic HF compared to normal subjects. Chronic ART significantly improved intrinsic HRR, indicating an improvement in autonomic function.
authors.affiliation: LivaNova (Cyberonics, Inc.), Houston, TX, USA.
authors.forename: Gerrard M
authors.initials: GM
authors.lastname: Carlson
authors.affiliation: LivaNova (Cyberonics, Inc.), Houston, TX, USA.
authors.forename: Imad
authors.identifier: http://orcid.org/0000-0002-0675-8790
authors.initials: I
authors.lastname: Libbus
authors.affiliation: LivaNova (Cyberonics, Inc.), Houston, TX, USA.
authors.forename: Badri
authors.initials: B
authors.lastname: Amurthur
authors.affiliation: LivaNova (Cyberonics, Inc.), Houston, TX, USA.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: KenKnight
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D015716:Electrocardiography, Ambulatory / Q000379:methods* / Q000706:statistics & numerical data; D005080:Exercise Test / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: autonomic reflexes; autonomic regulation therapy; baroreflex sensitivity; heart failure; heart rate recovery; vagus nerve stimulation