Syncope in High-Risk Cardiomyopathy Patients with Implantable Defibrillators: Frequency, Risk Factors, Mechanisms and Association with Mortality: Results from the MADIT-RIT Study
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
- inappropriate ICD therapy
- appropriate ICD therapy
- ICD programming
- implanted cardioverter defibrillator
- heart failure
- Received June 3, 2013.
- Revision received October 25, 2013.
- Accepted October 26, 2013.