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. METHODS AND 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. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00947310.
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A history of syncope in patients with structural heart disease or inheritable arrhythmia syndromes is associated with a two- to four-fold increased risk of death, but this varies between specific conditions.
“In general, a history of syncope in patients with structural heart disease or inheritable arrhythmia syndromes is associated with a two- to four-fold increased risk of death, 348,350-353 but varies between specific conditions. 354-356”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [348]
When indicated, ICD prevents sudden cardiac death but may be unable to prevent syncope due to ventricular tachycardia recurrence.
“When indicated, ICD prevents SCD but it may be unable to prevent syncope due to VT recurrence. 31,348”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [348]
ICD may not prevent syncope recurrence in patients with syncope and depressed cardiac function and ventricular tachycardia or ventricular fibrillation without correctable cause.
“Although ICD may not prevent syncope recurrence in these patients, 31,348 it is indicated to reduce the risk of SCD”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [348]
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- Authors
- Ruwald, M. H., Okumura, K., Kimura, T., Aonuma, K., Shoda, M., Kutyifa, V., Ruwald, A.-C. H., McNitt, S., Zareba, W., & Moss, A. J.
- Affiliations
- Hirosaki University (JP)
- From the 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...
- ORCID
- Venue
- Circulation
- Published
- 2014-02-04
- Volume
- 129
- Issue
- 5
- Pages
- 545-552
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1997607454
- Cited by
- 50
- References
- 14
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 5
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23591077)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- syncope, implantable cardioverter-defibrillator, ischemic cardiomyopathy, heart failure, syncope mechanism, mortality, ventricular arrhythmias, left ventricular ejection fraction, risk factors
- MeSH terms
- Aged, Electric Countershock, Female, Follow-Up Studies, Humans, Male, Middle Aged, Cardiomyopathies, Risk Factors, Syncope, Defibrillators, Implantable
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