PMID- 29754812
OWN - NLM
STAT- MEDLINE
DCOM- 20191115
LR  - 20230104
IS  - 2213-1787 (Electronic)
IS  - 2213-1779 (Linking)
VI  - 6
IP  - 10
DP  - 2018 Oct
TI  - A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac 
      Contractility Modulation.
PG  - 874-883
LID - S2213-1779(18)30303-2 [pii]
LID - 10.1016/j.jchf.2018.04.010 [doi]
AB  - OBJECTIVES: This study sought to confirm a subgroup analysis of the prior 
      FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With 
      Moderate-to-Severe Heart Failure) study showing that cardiac contractility 
      modulation (CCM) improved exercise tolerance (ET) and quality of life in patients 
      with ejection fractions between 25% and 45%. BACKGROUND: CCM therapy for New York 
      Heart Association (NYHA) functional class III and IV heart failure (HF) patients 
      consists of nonexcitatory electrical signals delivered to the heart during the 
      absolute refractory period. METHODS: A total of 160 patients with NYHA functional 
      class III or IV symptoms, QRS duration <130 ms, and ejection fraction >/=25% 
      and </=45% were randomized to continued medical therapy (control, n = 86) or CCM 
      (treatment, n = 74, unblinded) for 24 weeks. Peak Vo(2) (primary endpoint), 
      Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 
      6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian 
      repeated measures linear modeling was used for the primary endpoint analysis with 
      30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage 
      of patients free of device-related adverse events with a pre-specified lower 
      bound of 70%. RESULTS: The difference in peak Vo(2) between groups was 0.84 (95% 
      Bayesian credible interval: 0.123 to 1.552) ml O(2)/kg/min, satisfying the 
      primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), 
      NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better 
      in the treatment versus control group. There were 7 device-related events, 
      yielding a lower bound of 80% of patients free of events, satisfying the primary 
      safety endpoint. The composite of cardiovascular death and HF hospitalizations 
      was reduced from 10.8% to 2.9% (p = 0.048). CONCLUSIONS: CCM is safe, improves 
      exercise tolerance and quality of life in the specified group of HF patients, and 
      leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the 
      OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172).
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Abraham, William T
AU  - Abraham WT
AD  - Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio. 
      Electronic address: William.Abraham@osumc.edu.
FAU - Kuck, Karl-Heinz
AU  - Kuck KH
AD  - Department of Cardiology, ASKLEPIOS Klinik St. Georg, Hamburg, Germany.
FAU - Goldsmith, Rochelle L
AU  - Goldsmith RL
AD  - Exercise Physiology Laboratory, Columbia University Medical Center, New York, New 
      York.
FAU - Lindenfeld, JoAnn
AU  - Lindenfeld J
AD  - Department of Heart Failure and Transplant, Vanderbilt Heart, Nashville, 
      Tennessee.
FAU - Reddy, Vivek Y
AU  - Reddy VY
AD  - Department of Cardiac Arrhythmia Services, The Mount Sinai Hospital, New York, 
      New York.
FAU - Carson, Peter E
AU  - Carson PE
AD  - Medical Intensive Care Unit, Washington VA Medical Center, Washington, DC.
FAU - Mann, Douglas L
AU  - Mann DL
AD  - Cardiovascular Division, Medicine, Washington University School of Medicine, St. 
      Louis, Missouri.
FAU - Saville, Benjamin
AU  - Saville B
AD  - Berry Consultants, Austin, Texas.
FAU - Parise, Helen
AU  - Parise H
AD  - R. P. Chiacchierini Consulting, Gaithersburg, Maryland.
FAU - Chan, Rodrigo
AU  - Chan R
AD  - Chan Heart Rhythm Institute, Mesa, Arizona.
FAU - Wiegn, Phi
AU  - Wiegn P
AD  - Department of Clinical Cardiac Electrophysiology, Dallas VA Medical Center, 
      Dallas, Texas.
FAU - Hastings, Jeffrey L
AU  - Hastings JL
AD  - Department of Clinical Cardiac Electrophysiology, Dallas VA Medical Center, 
      Dallas, Texas.
FAU - Kaplan, Andrew J
AU  - Kaplan AJ
AD  - Department of Clinical Cardiac Electrophysiology, Cardiovascular Associates of 
      Mesa, Mesa, Arizona.
FAU - Edelmann, Frank
AU  - Edelmann F
AD  - Department of Cardiology and Pneumology, Universitat Gottingen, Gottingen, 
      Germany.
FAU - Luthje, Lars
AU  - Luthje L
AD  - Department of Cardiology and Pneumology, Universitat Gottingen, Gottingen, 
      Germany.
FAU - Kahwash, Rami
AU  - Kahwash R
AD  - Department of Heart Failure & Transplantation, The Ohio State University Heart 
      and Vascular Center, Columbus, Ohio.
FAU - Tomassoni, Gery F
AU  - Tomassoni GF
AD  - Department of Clinical Cardiac Electrophysiology, Baptist Health Lexington, 
      Lexington, Kentucky.
FAU - Gutterman, David D
AU  - Gutterman DD
AD  - Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
FAU - Stagg, Angela
AU  - Stagg A
AD  - Clinical Trials, Impulse Dynamics, Orangeburg, New York.
FAU - Burkhoff, Daniel
AU  - Burkhoff D
AD  - Cardiovascular Research Foundation, New York, New York.
FAU - Hasenfuss, Gerd
AU  - Hasenfuss G
AD  - Heart Center of Gottingen, University Medical Center Gottingen, Gottingen, 
      Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01381172
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180510
PL  - United States
TA  - JACC Heart Fail
JT  - JACC. Heart failure
JID - 101598241
SB  - IM
CIN - Nat Rev Cardiol. 2018 Jul;15(7):382. PMID: 29789626
EIN - JACC Heart Fail. 2023 Jan;11(1):132. PMID: 36599543
MH  - Electric Stimulation/adverse effects/instrumentation/*methods
MH  - Electrodes, Implanted
MH  - Exercise Test
MH  - Exercise Tolerance
MH  - Female
MH  - Heart Failure/mortality/physiopathology/*therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Myocardial Contraction
MH  - Quality of Life
MH  - Stroke Volume/physiology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - QRS duration
OT  - exercise tolerance
OT  - heart failure
OT  - peak Vo(2)
OT  - quality of life
EDAT- 2018/05/15 06:00
MHDA- 2019/11/16 06:00
CRDT- 2018/05/15 06:00
PHST- 2018/04/13 00:00 [received]
PHST- 2018/04/24 00:00 [revised]
PHST- 2018/04/24 00:00 [accepted]
PHST- 2018/05/15 06:00 [pubmed]
PHST- 2019/11/16 06:00 [medline]
PHST- 2018/05/15 06:00 [entrez]
AID - S2213-1779(18)30303-2 [pii]
AID - 10.1016/j.jchf.2018.04.010 [doi]
PST - ppublish
SO  - JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 
      2018 May 10.