A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure

Alan Kadish, Koonlawee Nademanee, Kent Volosin, Steven Krueger, Suresh Neelagaru, Nirav Raval, Owen Obel, Stanislav Weiner, Marc Wish, Peter Carson, Kenneth Ellenbogen, Robert Bourge, Michael K. Parides, Richard P. Chiacchierini, Rochelle Goldsmith, Sidney Goldstein, Yuval Mika, Daniel Burkhoff, William T. Abraham

Research output: Contribution to journalArticle

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Abstract

Background: Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction. Methods: We tested CCM in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤35% randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak Vo2 (pVo2), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5% allowable delta). Results: The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26% ± 7% vs 26% ± 7%), pVo2 (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg-1 min-1), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pVo2 and MLWHFQ (by 0.65 mL kg-1 min-1 [P = .024] and -9.7 points [P < .0001], respectively) over OMT. Forty-eight percent of OMT and 52% of CCM patients experienced a safety end point, which satisfied the noniferiority criterion (P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥25% and New York Heart Association class III symptoms) in which all parameters were improved by CCM. Conclusions: In the overall target population, CCM did not improve VAT (the primary end point) but did improve pVo2 and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.

Original languageEnglish (US)
JournalAmerican Heart Journal
Volume161
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

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Anaerobic Threshold
Randomized Controlled Trials
Heart Failure
Safety
Hospitalization
Therapeutics
Mortality
Health Services Needs and Demand

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. / Kadish, Alan; Nademanee, Koonlawee; Volosin, Kent; Krueger, Steven; Neelagaru, Suresh; Raval, Nirav; Obel, Owen; Weiner, Stanislav; Wish, Marc; Carson, Peter; Ellenbogen, Kenneth; Bourge, Robert; Parides, Michael K.; Chiacchierini, Richard P.; Goldsmith, Rochelle; Goldstein, Sidney; Mika, Yuval; Burkhoff, Daniel; Abraham, William T.

In: American Heart Journal, Vol. 161, No. 2, 01.02.2011.

Research output: Contribution to journalArticle

Kadish, A, Nademanee, K, Volosin, K, Krueger, S, Neelagaru, S, Raval, N, Obel, O, Weiner, S, Wish, M, Carson, P, Ellenbogen, K, Bourge, R, Parides, MK, Chiacchierini, RP, Goldsmith, R, Goldstein, S, Mika, Y, Burkhoff, D & Abraham, WT 2011, 'A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure', American Heart Journal, vol. 161, no. 2. https://doi.org/10.1016/j.ahj.2010.10.025
Kadish, Alan ; Nademanee, Koonlawee ; Volosin, Kent ; Krueger, Steven ; Neelagaru, Suresh ; Raval, Nirav ; Obel, Owen ; Weiner, Stanislav ; Wish, Marc ; Carson, Peter ; Ellenbogen, Kenneth ; Bourge, Robert ; Parides, Michael K. ; Chiacchierini, Richard P. ; Goldsmith, Rochelle ; Goldstein, Sidney ; Mika, Yuval ; Burkhoff, Daniel ; Abraham, William T. / A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure. In: American Heart Journal. 2011 ; Vol. 161, No. 2.
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abstract = "Background: Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction. Methods: We tested CCM in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤35{\%} randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak Vo2 (pVo2), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5{\%} allowable delta). Results: The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26{\%} ± 7{\%} vs 26{\%} ± 7{\%}), pVo2 (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg-1 min-1), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pVo2 and MLWHFQ (by 0.65 mL kg-1 min-1 [P = .024] and -9.7 points [P < .0001], respectively) over OMT. Forty-eight percent of OMT and 52{\%} of CCM patients experienced a safety end point, which satisfied the noniferiority criterion (P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥25{\%} and New York Heart Association class III symptoms) in which all parameters were improved by CCM. Conclusions: In the overall target population, CCM did not improve VAT (the primary end point) but did improve pVo2 and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.",
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AU - Nademanee, Koonlawee

AU - Volosin, Kent

AU - Krueger, Steven

AU - Neelagaru, Suresh

AU - Raval, Nirav

AU - Obel, Owen

AU - Weiner, Stanislav

AU - Wish, Marc

AU - Carson, Peter

AU - Ellenbogen, Kenneth

AU - Bourge, Robert

AU - Parides, Michael K.

AU - Chiacchierini, Richard P.

AU - Goldsmith, Rochelle

AU - Goldstein, Sidney

AU - Mika, Yuval

AU - Burkhoff, Daniel

AU - Abraham, William T.

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N2 - Background: Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction. Methods: We tested CCM in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤35% randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak Vo2 (pVo2), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5% allowable delta). Results: The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26% ± 7% vs 26% ± 7%), pVo2 (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg-1 min-1), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pVo2 and MLWHFQ (by 0.65 mL kg-1 min-1 [P = .024] and -9.7 points [P < .0001], respectively) over OMT. Forty-eight percent of OMT and 52% of CCM patients experienced a safety end point, which satisfied the noniferiority criterion (P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥25% and New York Heart Association class III symptoms) in which all parameters were improved by CCM. Conclusions: In the overall target population, CCM did not improve VAT (the primary end point) but did improve pVo2 and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.

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