Mortality Reduction in Relation to Implantable Cardioverter Defibrillator Programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT)

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. Clinical Trial Registration-URL: clinicaltrials.gov; Unique identifier: NCT00947310.(Circ Arrhythm Electrophysiol. 2014;7:785-792.)

Inappropriate ICD Shocks in Pediatric and Congenital Heart Disease Patients

“…Analyses of the MADIT-II and SCD-HeFT data first demonstrated an independent association between IS and a twofold increase in mortality in adult patients. 16,25 A similar association has been subsequently demonstrated in other studies, 26,27 and supported by two recent meta-analyses. 28,29 The data from these studies conflict, however, with those from another meta-analysis that demonstrated equivocal results, and other recent studies that found no association between IS and mortality.…”

“…In larger adult studies, the rate of IS has been reported to range from 10% to 15%. 16,25,27 However, most studies of ICD use in pediatric and CHD patients have found rates of IS to be between 20% and 30% in these patient populations, 10,11,13,14,[34][35][36][37][38][39][40] with some studies observing IS in up to 40% to 50% of patients and, in some instances, with inappropriate shocks being more frequent than appropriate shocks. 12,19,41,42 This is likely a result of a more active lifestyle, faster rates of sinus tachycardia, longer duration of implantation, smaller patient size, and a higher rate of device and lead complications relative to adult patients.…”

2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing

“…The use of ATP during ICD capacitor charging has been clinically validated as safe and effective [163]. It is important to recognize that inappropriate therapies including inappropriate ATP, delivered primarily in the setting of supraventricular arrhythmias, have been associated with increased mortality in the MADIT-RIT and MADIT-CRT trials [156,179]. However, the overall safety of ATP and its role as a contributor to improved survival are well established, particularly in terms of preventing avoidable ICD shocks.…”

Safety and efficacy of high-rate cutoff and long detection interval ICD programming in secondary prevention patients

“…The incidence of appropriate ATP and shock significantly decreased in strategic setting (conventional and strategic settings: 21.2 and 4. 8 ATPs per year, respectively, OR 0.18, 95 % CI 0.06-0.54, p = 0.002, 26.1 and 7.8 shocks per year, respectively, OR 0.29, 95 % CI 0.09-0.88, p = 0.03). The incidence of overall inappropriate therapy significantly decreased (conventional and strategic settings: 17.6 and 2.8 therapies per…”

“…However, shock therapies have been reported to be associated with pain, depression, proarrhythmia, and increased risk of all-cause mortality [4][5][6][7]. Several trials demonstrated that a long detection window and a high-rate cutoff reduced ICD therapies in primary prevention (PP) patients [8][9][10][11][12]. As for secondary prevention (SP) patients, only one subanalysis of the ADVANCE III randomized clinical trial reported that the ICD setting that combined a long detection window for ventricular tachyarrhythmias ≤320 ms with antitachycardia pacing (ATP) during charge reduced overall ICD therapies in SP patients [13].…”