title: Opportunity to increase life span in narrow QRS cardiac resynchronization therapy recipients by deactivating ventricular pacing: evidence from randomized controlled trials.
abstract: OBJECTIVE
  This study examined the time course of clinical events in cardiac resynchronization therapy (CRT) trials.
  
  
  BACKGROUND
  Recent randomized controlled trial results suggest that in heart failure with narrow QRS, biventricular pacing (CRT) may increase mortality. The authors proposed implant complications as the cause, rather than a progressive adverse physiological effect.
  
  
  METHODS
  The study identified all trials comparing CRT with no CRT, which reported Kaplan-Meier curves in groups defined by QRS: narrow, non-left bundle branch block (LBBB) broad, and LBBB broad. For each trial, the change in life span every 3 months up to 3.5 years (the longest time for which data are available) was calculated and a power law was fitted, that is, ∝ time(n).
  
  
  RESULTS
  Four trials (MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial], REVERSE [REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction], and EchoCRT [Echocardiography Guided Cardiac Resynchronization Therapy]), totaling 4,717 patients, reported curves for mortality or heart failure-related hospitalization, or for mortality. In patients with LBBB broad QRS (within MADIT-CRT), life span gain increased in proportion to time(1.94). In contrast, in patients with non-LBBB broad QRS (within MADIT-CRT) and patients with narrow QRS (EchoCRT), life span was lost in proportion to time(1.92) and time,(1.96) respectively. Hospitalization-free survival showed similar patterns.
  
  
  CONCLUSIONS
  The nonlinear growth of life span gained when a CRT device is implanted in patients with LBBB broad QRS is unfortunately mirrored by a similarly progressive loss in life span in narrow QRS heart failure. This suggests the culprit is a progressive physiological effect of pacing rather than implant complications. If these data are not sufficient, a randomized controlled trial of deactivating CRT in patients with narrow QRS may now be needed, with a primary endpoint of increasing survival.
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: S M Afzal
authors.initials: SM
authors.lastname: Sohaib
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Finegold
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Sukhjinder S
authors.initials: SS
authors.lastname: Nijjer
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Ruhella
authors.initials: R
authors.lastname: Hossain
authors.affiliation: Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: Division of Cardiology, University of Washington, Seattle, Washington.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Prapa
authors.initials: P
authors.lastname: Kanagaratnam
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom. Electronic address: darrel@drfrancis.org.
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.affiliation: National Heart & Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Zachary I
authors.initials: ZI
authors.lastname: Whinnett
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000379:methods* / Q000401:mortality; D017147:Defibrillators, Implantable; D018572:Disease-Free Survival; D004562:Electrocardiography; D006333:Heart Failure / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008017:Life Expectancy; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
keywords: QRS morphology; cardiac resynchronization therapy; heart failure; survival