• 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, and James P Daubert.
• From the Heart Research Follow-up Program, University of Rochester Medical Center, NY (A.-C.R., A.J.M., V.K., M.H.R., D.T.H., H.K., S.M., C.A.B., M.W.B., W.Z.); Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark (A.-C.R., M.H.R.); Division of Cardiology, Henry Ford Hospital, Detroit, MI (C.S.); Department of Medicine, University of Iowa Health Care, Iowa City (B.O.); St Luke's and Roosevelt Hospitals, Departments of Medicine and Epidemiology, Columbia University, New York, NY (H.G.); Division of Cardiology, Hospital of the Good Samaritan, Los Angeles, CA (D.S.C.); Cardiology Division, Cedars-Sinai Heart Institute, Los Angeles, CA (D.S.C.); New England Cardiac Arrhythmia Center, Tufts-New England Medical Center, Boston, MA (N.A.M.E.); Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD (R.G.); Cardiology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic (J.K.); Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan (M.S.); Cardiovascular Institute, Loyola University Medical Center, Chicago, IL (D.W.); and Cardiology Division, Department of Medicine, Duke University Medical Center, Durham, NC (J.P.D.).
• Circ Arrhythm Electrophysiol. 2014 Oct 1; 7 (5): 785-92.

BackgroundThe 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 ResultsIn 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).ConclusionsIn 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.Clinical Trial Registration Urlclinicaltrials.gov Unique identifier: NCT00947310.© 2014 American Heart Association, Inc.

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