Syncope in high-risk cardiomyopathy patients with implantable defibrillators: frequency, risk factors, mechanisms, and association with mortality: results from the multicenter automatic defibrillator implantation trial-reduce inappropriate therapy (MADIT-RIT) study.

Abstract

There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter-defibrillators, and it is controversial whether nonarrhythmogenic syncope is associated with increased mortality. 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). Innovative programming of implantable cardioverter-defibrillators with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (<200 bpm) is a rare event. The clinical risk factors associated with syncope are related to increased cardiovascular risk profile, and syncope is associated with increased mortality irrespective of the cause. http://www.clinicaltrials.gov. Unique identifier: NCT00947310.