title: 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: BACKGROUND
  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.
  
  
  RESULTS
  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
  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.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00947310.
authors.affiliation: Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, NY (M.H.R., V.K., A.-C.H.R., S.M., W.Z., A.J.M.); Department of Cardiology, Gentofte Hospital, Hellerup, Denmark (M.H.R., A.-C.H.R.); Department of Cardiology, Hirosaki University Hospital, Hirosaki, Japan (K.O.); Department of Cardiology, Kyoto University Hospital, Kyoto, Japan (T.K.); Department of Cardiology, Tsukuba University Hospital, Tsukuba, Japan (K.A.); and Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan (M.S.).
authors.forename: Martin H
authors.initials: MH
authors.lastname: Ruwald
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
authors.forename: Morio
authors.initials: M
authors.lastname: Shoda
authors.forename: Valentina
authors.initials: V
authors.lastname: Kutyifa
authors.forename: Anne-Christine H
authors.initials: AC
authors.lastname: Ruwald
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
mesh_terms: D000368:Aged; D009202:Cardiomyopathies / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*; D017147:Defibrillators, Implantable / Q000009:adverse effects; D004554:Electric Countershock / Q000379:methods / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013575:Syncope / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*
keywords: heart failure; implantable cardioverter-defibrillators; prognosis; syncope; ventricular tachycardia