title: Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial.
abstract: OBJECTIVE
  ANTHEM-HF evaluated a novel autonomic regulation therapy (ART) via either left or right vagus nerve stimulation (VNS) in patients with heart failure (HF) and reduced ejection fraction (HFrEF).
  
  
  RESULTS
  Sixty subjects (New York Heart Association [NYHA] functional class II-III, left ventricular ejection fraction (LVEF) ≤ 40%, left ventricular end-diastolic diameter ≥ 50 mm to < 80 mm) receiving optimal pharmacologic therapy were randomized at 10 sites. VNS systems were randomly implanted on the left (n = 31) or right (n = 29) side. All patients were successfully implanted and 59 were titrated over 10 weeks to a well tolerated stimulation intensity. One patient died 3 days after an embolic stroke that occurred during implantation. Common device-related adverse events after VNS titration were transient mild dysphonia, cough, and oropharyngeal pain, which were similar for left- and right-side VNS. After 6 months of ART, the adjusted left-right differences in LVEF, left ventricular end-systolic volume (LVESV), and left ventricular end-systolic diameter (LVESD) were 0.2% (95% CI -4.4 to 4.7), 3.7 mL (95% CI -7.0 to 14.4), and 1.3 mm (95% CI -0.9 to 3.6), respectively. In the combined population, absolute LVEF improved by 4.5% (95% CI 2.4-6.6), LVESV improved by -4.1 mL (95% CI -9.0 to 0.8), and LVESD improved by -1.7 mm (95% CI -2.8 to -0.7). Heart rate variability improved by 17 ms (95% CI 6.5-28) with minimal left-right difference. Six-minute walk distance improved an average of 56 m (95% CI 37-75); however, improvement was greater for right-side ART (77 m [95% CI 49-105]). NYHA functional class improved in 77% of patients (baseline to 6 months).
  
  
  CONCLUSIONS
  Chronic open-loop ART via left- or right-side VNS is feasible and well tolerated in HFrEF patients. Safety and efficacy measures are encouraging and warrant further study.
authors.affiliation: Department of Cardiology, Krishna Institute of Medical Sciences, Secunderabad, India.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Premchand
authors.affiliation: Department of Cardiology, Sanjivani Super Specialty Hospitals, Ahmedabad, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Department of Cardiology, Medanta, Medicity, Haryana, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Department of Cardiology, Vintage Hospital, Goa, India.
authors.forename: Rufino
authors.initials: R
authors.lastname: Monteiro
authors.affiliation: Department of Cardiology, Sanjivani Super Specialty Hospitals, Ahmedabad, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Dixit
authors.affiliation: Emerging Therapies, Cyberonics, Houston, Texas.
authors.forename: Imad
authors.initials: I
authors.lastname: Libbus
authors.affiliation: Biodev, San Francisco, California.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: DiCarlo
authors.affiliation: Department of Medicine, University of California, Los Angeles, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.affiliation: Department of Medicine University of Minnesota, Minneapolis, Minnesota.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rector
authors.affiliation: Emerging Therapies, Cyberonics, Houston, Texas.
authors.forename: Badri
authors.initials: B
authors.lastname: Amurthur
authors.affiliation: Emerging Therapies, Cyberonics, Houston, Texas.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: KenKnight
authors.affiliation: Department of Medicine University of Minnesota, Minneapolis, Minnesota. Electronic address: anand001@umn.edu.
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
mesh_terms: D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013318:Stroke Volume / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling
keywords: Heart failure; autonomic regulation therapy; nonpharmacologic therapy; vagus nerve stimulation