title: Quantification of survival gain from cardiac resynchronization therapy: nonlinear growth with time, and greater gain in low-risk patients, make raw trial data an underestimate of real-world behavior.
abstract: OBJECTIVE
  The goal of this study was to examine the impact of calculation-window duration on lifespan gain (as observed in trials) and on who gains most.
  
  
  BACKGROUND
  The landmark trials of biventricular pacing (cardiac resynchronization therapy [CRT]) typically ran for <1 device battery life, and they may therefore underestimate lifespan benefit over longer durations.
  
  
  METHODS
  We conducted a meta-analysis of biventricular pacing trials to calculate lifespan gained: first, within the duration of randomized controlled trial data up to 2 years; second, over a 5-year typical battery life; and third, over >1 battery life. Importantly, we applied the Gompertz method for age-related increase in mortality from non-CRT-preventable causes.
  
  
  RESULTS
  Five landmark trials (COMPANION [Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure], CARE-HF (CArdiac REsynchronization-Heart Failure), MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure)) provided data for 2 years (6,561 patients), with an average hazard ratio of 0.71. Lifespan gained across all trials increased nonlinearly with time from 0.1 month at 1 year, to 0.5 month at 2 years, and a projected 6.5 months at 5 years (65 times more than at 1 year). After multiple devices, it reached 14 months, involving on average 1.6 devices (i.e., 8.8 months per device implanted). Moreover, while over a short window (e.g., 2 years), lower-mortality patients may gain less than higher-mortality patients (1.4 vs. 2.3 months), their positions reverse by 15 years (16.0 vs. 13.7 months).
  
  
  CONCLUSIONS
  Lifespan gain from biventricular pacing rises nonlinearly with time. Early on, higher-risk patients exhibit more gain, but later, lower-risk patients exhibit more gain. Quantifying gain over less than a patient's lifetime underestimates lifespan gain. Over the first 1 or 2 years, lower-risk patients may seem to gain less, although they may ultimately be the ones who gain the most.
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, London, United Kingdom. Electronic address: judyfinegold@doctors.org.uk.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Finegold
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Raphael
authors.affiliation: Division of Cardiology, University of Washington, Seattle, Washington.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Whinnett
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, London, United Kingdom.
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000401:mortality / Q000639:trends*; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D017711:Nonlinear Dynamics; D016032:Randomized Controlled Trials as Topic / Q000639:trends; D012307:Risk Factors; D013223:Statistics as Topic / Q000639:trends*; D016019:Survival Analysis; D013997:Time Factors
keywords: CRT; NNT; QALY; cardiac resynchronization therapy; follow-up studies; lifespan gain; number-needed-to-treat; quality-adjusted life-year; survival