A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation

William T. Abraham; Karl Heinz Kuck; Rochelle L. Goldsmith; Jo Ann Lindenfeld; Vivek Y. Reddy; Peter E. Carson; Douglas L. Mann; Benjamin Saville; Helen Parise; Rodrigo Chan; Phi Wiegn; Jeffrey L. Hastings; Andrew J. Kaplan; Frank Edelmann; Lars Luthje; Rami Kahwash; Gery F. Tomassoni; David D. Gutterman; Angela Stagg; Daniel Burkhoff; Gerd Hasenfuß

doi:10.1016/j.jchf.2018.04.010

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation

William T. Abraham, Karl Heinz Kuck, Rochelle L. Goldsmith, Jo Ann Lindenfeld, Vivek Y. Reddy, Peter E. Carson, Douglas L. Mann, Benjamin Saville, Helen Parise, Rodrigo Chan, Phi Wiegn, Jeffrey L. Hastings, Andrew J. Kaplan, Frank Edelmann, Lars Luthje, Rami Kahwash, Gery F. Tomassoni, David D. Gutterman, Angela Stagg, Daniel BurkhoffGerd Hasenfuß

Research output: Contribution to journal › Article › peer-review

169 Scopus citations

Abstract

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 Vo₂ (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 Vo₂ between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O₂/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.

Original language	English (US)
Pages (from-to)	874-883
Number of pages	10
Journal	JACC: Heart Failure
Volume	6
Issue number	10
DOIs	https://doi.org/10.1016/j.jchf.2018.04.010
State	Published - Oct 2018

Keywords

QRS duration
exercise tolerance
heart failure
peak Vo
quality of life

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jchf.2018.04.010

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Abraham, W. T., Kuck, K. H., Goldsmith, R. L., Lindenfeld, J. A., Reddy, V. Y., Carson, P. E., Mann, D. L., Saville, B., Parise, H., Chan, R., Wiegn, P., Hastings, J. L., Kaplan, A. J., Edelmann, F., Luthje, L., Kahwash, R., Tomassoni, G. F., Gutterman, D. D., Stagg, A., ... Hasenfuß, G. (2018). A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC: Heart Failure, 6(10), 874-883. https://doi.org/10.1016/j.jchf.2018.04.010

Abraham, WT, Kuck, KH, Goldsmith, RL, Lindenfeld, JA, Reddy, VY, Carson, PE, Mann, DL, Saville, B, Parise, H, Chan, R, Wiegn, P , Hastings, JL, Kaplan, AJ, Edelmann, F, Luthje, L, Kahwash, R, Tomassoni, GF, Gutterman, DD, Stagg, A, Burkhoff, D & Hasenfuß, G 2018, 'A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation', JACC: Heart Failure, vol. 6, no. 10, pp. 874-883. https://doi.org/10.1016/j.jchf.2018.04.010

@article{a89982a7a5ca437e9d94c3b3cce63fe7,

title = "A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation",

abstract = "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 Vo2 (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 Vo2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/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.",

keywords = "QRS duration, exercise tolerance, heart failure, peak Vo, quality of life",

author = "Abraham, {William T.} and Kuck, {Karl Heinz} and Goldsmith, {Rochelle L.} and Lindenfeld, {Jo Ann} and Reddy, {Vivek Y.} and Carson, {Peter E.} and Mann, {Douglas L.} and Benjamin Saville and Helen Parise and Rodrigo Chan and Phi Wiegn and Hastings, {Jeffrey L.} and Kaplan, {Andrew J.} and Frank Edelmann and Lars Luthje and Rami Kahwash and Tomassoni, {Gery F.} and Gutterman, {David D.} and Angela Stagg and Daniel Burkhoff and Gerd Hasenfu{\ss}",

note = "Funding Information: This study was supported by research grants from Impulse Dynamics. Ms. Stagg is an employee of Impulse Dynamics. Drs. Abraham, Parise, Gutterman, Burkhoff, and Hasenfu{\ss} have served as consultants to Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = oct,

doi = "10.1016/j.jchf.2018.04.010",

language = "English (US)",

volume = "6",

pages = "874--883",

journal = "JACC: Heart Failure",

issn = "2213-1779",

publisher = "Elsevier BV",

number = "10",

}

TY - JOUR

T1 - A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation

AU - Abraham, William T.

AU - Kuck, Karl Heinz

AU - Goldsmith, Rochelle L.

AU - Lindenfeld, Jo Ann

AU - Reddy, Vivek Y.

AU - Carson, Peter E.

AU - Mann, Douglas L.

AU - Saville, Benjamin

AU - Parise, Helen

AU - Chan, Rodrigo

AU - Wiegn, Phi

AU - Hastings, Jeffrey L.

AU - Kaplan, Andrew J.

AU - Edelmann, Frank

AU - Luthje, Lars

AU - Kahwash, Rami

AU - Tomassoni, Gery F.

AU - Gutterman, David D.

AU - Stagg, Angela

AU - Burkhoff, Daniel

AU - Hasenfuß, Gerd

N1 - Funding Information: This study was supported by research grants from Impulse Dynamics. Ms. Stagg is an employee of Impulse Dynamics. Drs. Abraham, Parise, Gutterman, Burkhoff, and Hasenfuß have served as consultants to Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2018 The Authors

PY - 2018/10

Y1 - 2018/10

N2 - 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 Vo2 (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 Vo2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/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.

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 Vo2 (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 Vo2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/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.

KW - QRS duration

KW - exercise tolerance

KW - heart failure

KW - peak Vo

KW - quality of life

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A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation

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