The Multicenter Automatic
Defibrillator Implantation Trial-Reduce Inappropriate
Therapy (MADIT-RIT) randomized 1500 patients to 3 different
implantable cardioverter-defibrillator programming arms: (1) Conventional programming with
therapy for
ventricular tachycardia ≥170 bpm; (2) high-rate cutoff with
therapy for
ventricular tachycardia ≥200 bpm and a monitoring zone at 170 to 199 bpm, and (3) prolonged 60-second delay with a monitoring zone before
therapy.
Syncope was a prespecified safety end point that was adjudicated independently. Multivariable Cox models were used to identify risk factors associated with
syncope and to analyze subsequent risk of mortality. During follow-up, 64 of 1500 patients (4.3%) had
syncope. The incidence of
syncope was similar across the 3 treatment arms. Prognostic factors for all-cause
syncope included the presence of ischemic
cardiomyopathy (hazard ratio [HR], 2.48; 95% confidence interval [CI], 1.42-4.34; P=0.002), previous ventricular arrhythmias (HR, 2.99; 95% CI, 1.18-7.59; P=0.021), left ventricular ejection fraction ≤25% (HR, 1.65; 95% CI, 0.98-2.77; P=0.059), and younger age (by 10 years; HR, 1.25; 95% CI, 1.00-1.52; P=0.046).
Syncope was associated with increased risk of death regardless of its cause (arrhythmogenic
syncope: HR, 4.51; 95% CI, 1.39-14.64, P=0.012; nonarrhythmogenic
syncope: HR, 2.97; 95% CI, 1.07-8.28, P=0.038).
CONCLUSIONS: CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00947310.