Michael R Zile1, William T Abraham2, Fred A Weaver3, Christian Butter4, Anique Ducharme5, Marcel Halbach6, Didier Klug7, Eric G Lovett8, Jochen Müller-Ehmsen9, Jill E Schafer10, Michele Senni11, Vijay Swarup12, Rolf Wachter13, William C Little14. 1. 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. 2. Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA. 3. Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 4. Department of Cardiology, Immanuel Heart Center Bernau-Medical School Brandenburg, Bernau, Germany. 5. Montreal Heart Institute, University of Montréal, Montreal, Quebec, Canada. 6. Department of Internal Medicine III, University Hospital of Cologne, Cologne, Germany. 7. Department of Cardiology A, University Hospital, Lille, France. 8. Department of Research, CVRx, Inc., Minneapolis, MN, USA. 9. Department of Medicine, Asklepios Klinik Altona, Hamburg, Germany. 10. Department of Statistics, NAMSA, Inc., Minneapolis, MN, USA. 11. Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 12. Department of Electrophysiology, Arizona Heart Hospital, Phoenix, AZ, USA. 13. Clinic for Cardiology and Pneumology, University Medicine Göttingen and German Cardiovascular Research Center (DZHK), Göttingen, Germany. 14. Division of Cardiology, University of Mississippi Medical Center, Jackson, MS, USA.
Abstract
AIMS: 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. METHODS AND 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.
RCT Entities:
AIMS: 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. METHODS AND 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: John S Clemmer; W Andrew Pruett; Robert L Hester; Radu Iliescu; Thomas E Lohmeier Journal: Am J Physiol Heart Circ Physiol Date: 2018-07-13 Impact factor: 4.733