Syncope in High-Risk Cardiomyopathy Patients With Implantable Defibrillators: Frequency, Risk Factors, Mechanisms, and Association With Mortality

Abstract

BACKGROUND: There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter defibrillators (ICD) and it is controversial whether non-arrhythmogenic syncope is associated with increased mortality.METHODS AND RESULTS: The MADIT-RIT study randomized 1500 patients to three different ICD programming arms: A) conventional with VT therapy ≥ 170; B) high-rate cut-off with VT therapy ≥ 200 and monitor zone 170-199, and C) prolonged 60 sec delay with monitor zone before therapy. Syncope was a pre-specified safety endpoint independently adjudicated. 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 (4.3%) patients had syncope. The incidence of syncope was similar across the three treatment arms. Prognostic factors of all-cause syncope included the presence of ischemic cardiomyopathy (HR=2.48, CI: 1.42-4.34, p=0.002), previous ventricular arrhythmias (HR=2.99, CI: 1.18-7.59, p=0.021), LVEF≤ 25% (HR=1.65, CI: 0.98-2.77, p=0.059), and younger age (by 10 years, HR=1.25, CI: 1.00-1.52, p=0.046). Syncope was associated with increased risk of death irrespective of the etiology (arrhythmogenic syncope: HR=4.51, CI: 1.39-14.64, p=0.012 and non-arrhythmogenic syncope: HR=2.97, CI: 1.07-8.28, p=0.038).CONCLUSIONS: Innovative ICD programming with a VT therapy ≥ 200 bpm or long delay is not associated with increased risk of arrhythmogenic or all-cause syncope and syncope due to slow VTs (<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 etiology.CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov. Identifier: NCT00947310.