Mortality reduction in relation to implantable cardioverter defibrillator programming in the multicenter automatic defibrillator implantation trial-reduce inappropriate therapy (MADIT-RIT)

Anne Christine Ruwald, Claudio Schuger, Arthur J. Moss, Valentina Kutyifa, Brian Olshansky, Henry Greenberg, David S. Cannom, N. A.Mark Estes, Martin H. Ruwald, David T. Huang, Helmut Klein, Scott McNitt, Christopher A. Beck, Robert Goldstein, Mary W. Brown, Josef Kautzner, Morio Shoda, David Wilber, Wojciech Zareba, James P. Daubert*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

101 Scopus citations

Abstract

Background: The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. Methods and Results: In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03). Conclusions: In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome.

Original languageEnglish
Pages (from-to)785-792
Number of pages8
JournalCirculation: Arrhythmia and Electrophysiology
Volume7
Issue number5
DOIs
StatePublished - 1 Oct 2014
Externally publishedYes

Keywords

  • Cardiac
  • Mortality
  • arrhythmias

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