Baroreflex activation therapy for the treatment of heart failure with reduced ejection fraction in patients with and without coronary artery disease Marcel Halbach a, ⁎, William T. Abraham b , Christian Butter c , Anique Ducharme d , Didier Klug e , William C. Little f,1 , Hannes Reuter a , Jill E. Schafer g , Michele Senni h , Vijay Swarup i , Rolf Wachter j , Fred A. Weaver k , Seth J. Wilks l , Michael R. Zile m,o , Jochen Müller-Ehmsen n a Department of Internal Medicine III, University Hospital of Cologne, Cologne, Germany b Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA c Department of Cardiology, Immanuel Heart Center Bernau - Medical School Brandenburg, Bernau, Germany d Montreal Heart Institute, University of Montréal, Montreal, Quebec, Canada e Department of Cardiology A, University Hospital, Lille, France f Division of Cardiology, University of Mississippi Medical Center, Jackson, MS, USA g Department of Statistics, NAMSA, Inc., Minneapolis, MN, USA h Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy i Department of Electrophysiology, Arizona Heart Hospital, Phoenix, AZ, USA j Clinic and Policlinic for Cardiology, University Hospital Leipzig, Leipzig, Germany k Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA l Department of Research, CVRx, Inc., Minneapolis, MN, USA m Medical University of South Carolina, Charleston, SC, USA n Department of Medicine, Asklepios Klinik Altona, Hamburg, Germany o Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA abstract article info Article history: Received 27 February 2018 Received in revised form 1 April 2018 Accepted 17 April 2018 Available online 21 April 2018 Background: In a randomized trial, baroreflex activation therapy (BAT) improved exercise capacity, quality of life and NT-proBNP in patients with heart failure with reduced ejection fraction (HFrEF). In view of different mech- anisms underlying HFrEF, we performed a post-hoc subgroup analysis of efficacy and safety of BAT in patients with and without coronary artery disease (CAD). Methods and results: Patients with left ventricular ejection fraction b35% and NYHA Class III were randomized 1:1 to guideline-directed medical and device therapy alone or plus BAT. Patients with a history of CAD, prior myocardial in- farction or coronary artery bypass graft were assigned to the CAD group with all others assigned to the no-CAD group. Of 71 BAT treated patients, 52 had CAD and 19 had no CAD. In the control group, 49 of 69 patients had CAD and 20 had no CAD. The system- or procedure-related major adverse neurological or cardiovascular event rate was 3.8% in the CAD group vs. 0% in the no-CAD group (p = 1.0). In the whole cohort, NYHA Class, Minnesota Living with Heart Failure score, 6-minute hall walk distance and NTproBNP were improved in BAT treated patients compared with controls. Statistical analyses revealed no interaction between the presence of CAD and effect of BAT (all p N 0.05). Conclusion: No major differences were found in BAT efficacy or safety between patients with and without CAD, in- dicating that BAT improves exercise capacity, quality of life and NTproBNP in patients with ischemic and non- ischemic cardiomyopathy. ClinicalTrials.gov identifier: NCT01471860 and NCT01720160. © 2018 Elsevier B.V. All rights reserved. Keywords: Baroreflex activation therapy Coronary artery disease Device Heart failure 1. Introduction Heart failure (HF) with reduced ejection fraction (HFrEF) is associ- ated with increased sympathetic and decreased parasympathetic tone [1], related to a lower sensitivity of the inhibitory baroreflex [2]. This sympathovagal imbalance causes vasoconstriction, activation of the renin-angiotensin-aldosterone system and cardiac remodeling, leading to further decline in left ventricular (LV) function [1,3]. Baroreflex acti- vation therapy (BAT) electrically stimulates carotid sinus baroreceptors and can cause a ~30% reduction in sympathetic nerve activity, which may disrupt this vicious circle [4,5]. The first randomized trial comparing guideline-directed medical and device-based therapy (GDMDT) alone with GDMDT plus BAT in patients International Journal of Cardiology 266 (2018) 187–192 ⁎ Corresponding author at: Department of Internal Medicine III, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany. E-mail address: marcel.halbach@uk-koeln.de. (M. Halbach). 1 Deceased July 9, 2015. https://doi.org/10.1016/j.ijcard.2018.04.075 0167-5273/© 2018 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard