title: Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy.
abstract: OBJECTIVE
  Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT.
  
  
  RESULTS
  New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control.
  
  
  CONCLUSIONS
  BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT.
authors.affiliation: Division of Cardiology, Department of Medicine, Medical University of South Carolina, 114 Doughty Street, Thurmond/Gazes, 323, Charleston, SC 29425, USA and Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Weaver
authors.affiliation: Department of Cardiology, Immanuel Heart Center Bernau-Medical School Brandenburg, Bernau, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Butter
authors.affiliation: Montreal Heart Institute, University of Montréal, Montreal, Quebec, Canada.
authors.forename: Anique
authors.initials: A
authors.lastname: Ducharme
authors.affiliation: Department of Internal Medicine III, University Hospital of Cologne, Cologne, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Halbach
authors.affiliation: Department of Cardiology A, University Hospital, Lille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Klug
authors.affiliation: Department of Research, CVRx, Inc., Minneapolis, MN, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Lovett
authors.affiliation: Department of Medicine, Asklepios Klinik Altona, Hamburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Müller-Ehmsen
authors.affiliation: Department of Statistics, NAMSA, Inc., Minneapolis, MN, USA.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Schafer
authors.affiliation: Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Senni
authors.affiliation: Department of Electrophysiology, Arizona Heart Hospital, Phoenix, AZ, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Swarup
authors.affiliation: Clinic for Cardiology and Pneumology, University Medicine Göttingen and German Cardiovascular Research Center (DZHK), Göttingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.affiliation: Division of Cardiology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Little
mesh_terms: D000368:Aged; D017704:Baroreflex / Q000502:physiology; D058406:Cardiac Resynchronization Therapy; D004599:Electric Stimulation Therapy; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D058542:Implantable Neurostimulators; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D016277:Ventricular Function, Left
keywords: Autonomic nervous system; Baroreflex; Heart failure; Randomized controlled trial; Resynchronization