title: Meta-analysis of symptomatic response attributable to the pacing component of cardiac resynchronization therapy.
abstract: OBJECTIVE
  Prognostic benefit from CRT compared with controls is well established. Symptomatic response rates, however, are controversial and have never been systematically evaluated with standard subtraction of control rates to establish the incremental symptomatic response effect of CRT pacing.
  
  
  RESULTS
  First, we identified 150 consecutive CRT papers and assessed researchers' perceptions of the symptomatic response to CRT. The mean quoted response rate was 66%. Only 26 studies acknowledged the existence of response without the device. Secondly, we examined actual symptomatic response rates in the randomized trials (CARE-HF, COMPANION, CONTAK-CD, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, MUSTIC, and REVERSE) totalling 3904 patients. The NYHA status improved in 51% of those randomized to CRT vs. 35% of controls (incremental effect 16%). This incremental improvement was significantly greater in open studies (with no device for controls) than in blinded studies (control arm receiving a device but no CRT, such as a defibrillator or a CRT programmed off), 20% vs. 13%, P < 0.001.
  
  
  CONCLUSIONS
  Quoting CRT responder rates in isolation without recognizing spontaneous 'response' is common but unwise. The incremental symptomatic response rate from CRT pacing is ∼16%, much lower than widely reported. This value is similar to that for drugs in heart failure and should not be considered disappointing: they both exert powerful prognostic benefits. For scientific purposes, e.g. to explore potential improvements, symptomatic benefit from CRT should be quantified, like all other effects, by comparison with a control.
authors.affiliation: International Centre for Centre for Circulatory Health, Imperial College, London, UK.
authors.forename: S M Afzal
authors.initials: SM
authors.lastname: Sohaib
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Chen
authors.forename: Zachary I
authors.initials: ZI
authors.lastname: Whinnett
authors.forename: Sonia
authors.initials: S
authors.lastname: Bouri
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.forename: David L
authors.initials: DL
authors.lastname: Hayes
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Manisty
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D017147:Defibrillators, Implantable; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D017063:Outcome Assessment, Health Care; D010138:Pacemaker, Artificial; D015990:Placebo Effect; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology / Q000628:therapy
keywords: Cardiac resynchronization therapy; Heart failure; Minnesota Living with Heart Failure Score; NYHA class; Placebo effect