title: Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study.
abstract: BACKGROUND
  Autonomic regulation therapy (ART) with chronic vagus nerve stimulation improves ventricular function in patients with chronic heart failure, but its effects on quantitative T-wave alternans (TWA), ventricular tachycardia (VT), baroreflex sensitivity, and autonomic tone remained unknown.
  
  
  OBJECTIVE
  Effects on TWA, a marker of risk of life-threatening arrhythmias; heart rate turbulence (HRT), an indicator of baroreflex sensitivity; heart rate variability; and VT incidence were studied in 25 patients with chronic symptomatic heart failure and reduced ejection fraction enrolled in the ANTHEM-HF study (NCT01823887).
  
  
  METHODS
  Twenty-four-hour ambulatory electrocardiographic recordings made before ART system (Cyberonics, Inc., Houston, TX) implantation involving the left or right vagus nerve and after 6 and 12 months of chronic therapy (10-Hz frequency, 250-μs pulse width, maximum tolerable current amplitude after 10 weeks of titration) at low-intensity (<2 mA; n = 10, 40%) or high-intensity (≥2 mA; n = 15, 60%) stimulation levels were analyzed.
  
  
  RESULTS
  At 12 months, peak TWA levels were reduced by 29% from 71.0 ± 4.6 to 50.5 ± 1.8 μV (P < .0001). The number of patients with severely abnormal TWA (≥60 μV) was reduced by 76% from 17 to 4 (P < .0005), and the number of patients with nonsustained VT decreased by 73% from 11 to 3 (P < .025). HRT slope (P < .025), high frequency heart rate variability (HRV) (P = .05), and square root of the mean squared differences of successive normal-to-normal interval HRV (P = .013) increased. The mean heart rate derived from 24-hour Holter electrocardiograms decreased by 10% from 77 ± 2 to 69 ± 2 beats/min (P = .0002). HRT onset was unchanged.
  
  
  CONCLUSIONS
  Chronic ART in patients with symptomatic heart failure improves cardiac electrical stability, as reflected by reduced TWA levels and heart rate, suppresses VT, and increases baroreceptor sensitivity. These observations deserve study in a larger population.
authors.affiliation: Cyberonics, Inc., Houston, Texas.
authors.forename: Imad
authors.initials: I
authors.lastname: Libbus
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.affiliation: Cyberonics, Inc., Houston, Texas.
authors.forename: Badri
authors.initials: B
authors.lastname: Amurthur
authors.affiliation: Cyberonics, Inc., Houston, Texas.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: KenKnight
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: rverrier@bidmc.harvard.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D017704:Baroreflex / Q000502:physiology*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: Autonomic reflexes; Autonomic regulation therapy; Autonomic tone; Baroreceptor sensitivity; Heart failure; Heart rate turbulence; Heart rate variability; T-wave alternans; Vagus nerve stimulation; Ventricular tachycardia