title: Subgroup analysis of a randomized controlled trial evaluating the safety and efficacy of cardiac contractility modulation in advanced heart failure.
abstract: BACKGROUND
  Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the absolute refractory period intended to improve contraction. We previously tested the safety and efficacy of CCM in 428 NYHA functional class III/IV heart failure patients with EF ≤35% and narrow QRS randomized to optimal medical treatment (OMT) plus CCM (n = 215) versus OMT alone (n = 213) and found no significant effect on ventilatory anaerobic threshold (VAT), the study's primary end point. In the present analysis, we sought to identify if there was a subgroup of patients who showed a response to CCM.
  
  
  RESULTS
  The protocol specified that multiregression analysis would be used to determine if baseline EF, NYHA functional class, pVO(2), or etiology of heart failure influenced the impact of CCM on AT. Etiology and baseline pVO(2) did not affect efficacy. However, baseline NYHA functional class III and EF ≥25% were significant predictors of increased efficacy. In this subgroup (comprising 97 OMT and 109 CCM patients, ∼48% of the entire population) VAT increased by 0.10 ± 2.36 in CCM versus -0.54 ± 1.83 mL kg(-1) min(-1) in OMT (P = .03) and pVO(2) increased by 0.34 ± 3.11 in CCM versus -0.97 ± 2.31 (P = .001) at 24 weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed improvement of ≥1 class in NYHA functional class (P = .002), and 59% of CCM versus 42% of OMT subjects showed a ≥10-point reduction in Minnesota Living with Heart Failure Questionnaire (P = .01). All of these findings were similar to those seen at 50 weeks.
  
  
  CONCLUSIONS
  The results of this retrospective hypothesis-generating analysis indicate that CCM significantly improves objective parameters of exercise tolerance in a subgroup of patients characterized by normal QRS duration, NYHA functional class III symptoms, and EF >25%.
authors.affiliation: Ohio State University Heart Center, Columbus, Ohio, USA. william.abraham@osumc.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
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: Alan
authors.initials: A
authors.lastname: Kadish
mesh_terms: D000368:Aged; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects / Q000592:standards*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D011446:Prospective Studies; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D016896:Treatment Outcome