title: A randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure.
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.
authors.affiliation: Northwestern University, Chicago IL, USA. a-kadish@northwestern.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Kadish
authors.forename: Koonlawee
authors.initials: K
authors.lastname: Nademanee
authors.forename: Kent
authors.initials: K
authors.lastname: Volosin
authors.forename: Steven
authors.initials: S
authors.lastname: Krueger
authors.forename: Suresh
authors.initials: S
authors.lastname: Neelagaru
authors.forename: Nirav
authors.initials: N
authors.lastname: Raval
authors.forename: Owen
authors.initials: O
authors.lastname: Obel
authors.forename: Stanislav
authors.initials: S
authors.lastname: Weiner
authors.forename: Marc
authors.initials: M
authors.lastname: Wish
authors.forename: Peter
authors.initials: P
authors.lastname: Carson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ellenbogen
authors.forename: Robert
authors.initials: R
authors.lastname: Bourge
authors.forename: Michael
authors.initials: M
authors.lastname: Parides
authors.forename: Richard P
authors.initials: RP
authors.lastname: Chiacchierini
authors.forename: Rochelle
authors.initials: R
authors.lastname: Goldsmith
authors.forename: Sidney
authors.initials: S
authors.lastname: Goldstein
authors.forename: Yuval
authors.initials: Y
authors.lastname: Mika
authors.forename: Daniel
authors.initials: D
authors.lastname: Burkhoff
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
mesh_terms: D058406:Cardiac Resynchronization Therapy; D018450:Disease Progression; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D011446:Prospective Studies; D016037:Single-Blind Method