title: Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial.
abstract: OBJECTIVE
  The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy.
  
  
  METHODS
  Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers.
  
  
  RESULTS
  Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group.
  
  
  CONCLUSIONS
  Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.
authors.affiliation: Inserm, CIC 1433, Centre Hospitalier Universitaire, Department of Cardiology, Nancy University, Université de Lorraine, Nancy, France f.zannad@chu-nancy.fr.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Department of Cardiology and Cardiovascular Clinical Research Center, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy.
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.affiliation: Department of Cardiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Anton E
authors.initials: AE
authors.lastname: Tuinenburg
authors.affiliation: Department of Cardiology, Liverpool Heart and Chest, Liverpool, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Thorax Institute, Hospital Clinic, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Heart Centre Brandenburg Hospital, Bernau, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Butter
authors.affiliation: Division of Cardiology, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Klein
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Stolen
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Stein
authors.affiliation: Guidant Europe, Diegem, Belgium.
authors.forename: Agnes
authors.initials: A
authors.lastname: Ramuzat
authors.affiliation: Guidant Europe, Diegem, Belgium.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schubert
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Doug
authors.initials: D
authors.lastname: Daum
authors.affiliation: Department of Cardiology, Homolka Hospital, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Neuzil
authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Botman
authors.affiliation: Thorax Institute, Hospital Clinic, Barcelona, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Castel
authors.affiliation: Azienda Ospedaliera dei Colli - Monaldi, Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Onofrio
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wold
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Ruble
mesh_terms: D015716:Electrocardiography, Ambulatory; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011788:Quality of Life; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000009:adverse effects / Q000379:methods*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy; D020257:Ventricular Remodeling / Q000502:physiology
keywords: Autonomic nervous system; Heart failure; Vagal stimulation