title: Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial.
abstract: Heart failure (HF) is increasing in prevalence and is a major cause of morbidity and mortality despite advances in medical and device therapy. Autonomic imbalance, with excess sympathetic activation and decreased vagal tone, is an integral component of the pathophysiology of HF.
  
  
  
  The INOVATE-HF (Increase of Vagal Tone in Heart Failure) trial assessed the safety and efficacy of vagal nerve stimulation (VNS) among patients with HF and a reduced ejection fraction.
  
  
  
  INOVATE-HF was a multinational, randomized trial involving 85 centers including patients with chronic HF, New York Heart Association functional class III symptoms and ejection fraction ≤40%. Patients were assigned to device implantation to provide VNS (active) or continued medical therapy (control) in a 3:2 ratio. The primary efficacy endpoint was composite of death from any cause or first event for worsening HF.
  
  
  
  Patients (n = 707) were randomized and followed up for a mean of 16 months. The primary efficacy outcome occurred in 132 of 436 patients in the VNS group, compared to 70 of 271 in the control group (30.3% vs. 25.8%; hazard ratio: 1.14; 95% confidence interval: 0.86 to 1.53; p = 0.37). During the trial, the estimated annual mortality rates were 9.3% and 7.1%, respectively (p = 0.19). Quality of life, New York Heart Association functional class, and 6-min walking distance were favorably affected by VNS (p < 0.05), but left ventricular end-systolic volume index was not different (p = 0.49).
  
  
  
  VNS does not reduce the rate of death or HF events in chronic HF patients. (INcrease Of VAgal TonE in CHF [INOVATE-HF]; NCT01303718).
authors.affiliation: Cardiology Division, Medical University of South Carolina, Charleston, South Carolina. Electronic address: goldmr@musc.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gold
authors.affiliation: Cardiovascular Division, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.affiliation: Cardiology Division, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hauptman
authors.affiliation: 1st Department of Medicine-Cardiology, University Medical Centre Mannheim, Mannheim, Germany, and DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.affiliation: BioControl Medical, New Hope, Minnesota.
authors.forename: Spencer H
authors.initials: SH
authors.lastname: Kubo
authors.affiliation: Detroit Medical Center, Detroit, Michigan.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Lieberman
authors.affiliation: Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Milasinovic
authors.affiliation: Chula Vista Cardiac Center, Chula Vista, California.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Berman
authors.affiliation: Clinical Hospital Center "Bezanijska Kosa," Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Djordjevic
authors.affiliation: Lone Star Heart Center, Amarillo, Texas.
authors.forename: Suresh
authors.initials: S
authors.lastname: Neelagaru
authors.affiliation: IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D014630:Vagus Nerve / Q000503:physiopathology; D055536:Vagus Nerve Stimulation / Q000379:methods*; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling
keywords: autonomic modulation; clinical trials; heart failure; outcomes; vagus nerve stimulation