title: Randomized controlled trial comparing simultaneous versus optimized sequential interventricular stimulation during cardiac resynchronization therapy.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) reduces morbidity and mortality and improves symptoms in patients with systolic heart failure (HF) and ventricular dyssynchrony. This randomized, double-blind, controlled study evaluated whether optimizing the interventricular stimulating interval (V-V) to sequentially activate the ventricles is clinically better than simultaneous V-V stimulation during CRT.
  
  
  METHODS
  Patients with New York Heart Association (NYHA) III or IV HF, meeting both CRT and implantable cardioverter-defibrillator indications, randomly received either simultaneous CRT or CRT with optimized V-V settings for 6 months. Patients also underwent echocardiography-guided atrioventricular delay optimization to maximize left ventricular filling. The V-V optimization involved minimizing the left ventricular septal to posterior wall motion delay during CRT. The primary objective was to demonstrate noninferiority using a clinical composite end point that included mortality, HF hospitalization, NYHA functional class, and patient global assessment. Secondary end points included changes in NYHA classification, 6-minute hall walk distance, quality of life, peak VO(2), and event-free survival.
  
  
  RESULTS
  The composite score improved in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized patients (P < .001, for noninferiority). A prespecified test of superiority showed that more optimized patients improved (P = .03). New York Heart Association functional class improved in 58.0% of simultaneous patients versus 75.0% of optimized patients (P = .01). No significant differences in exercise capacity, quality of life, peak VO(2), or HF-related event rate between the 2 groups were observed.
  
  
  CONCLUSIONS
  These findings demonstrate modest clinical benefit with optimized sequential V-V stimulation during CRT in patients with NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool for increasing the proportion of patients who respond to CRT.
authors.affiliation: The Ohio State University Heart Center, Columbus, OH 43210-1252, USA. william.abraham@osumc.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.forename: Angel R
authors.initials: AR
authors.lastname: León
authors.forename: Martin G
authors.initials: MG
authors.lastname: St John Sutton
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Keteyian
authors.forename: Ann M
authors.initials: AM
authors.lastname: Fieberg
authors.forename: Ed
authors.initials: E
authors.lastname: Chinchoy
authors.forename: Garrie
authors.initials: G
authors.lastname: Haas
mesh_terms: D000328:Adult; D000368:Aged; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D058406:Cardiac Resynchronization Therapy; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016138:Walking