Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis
Open accessAbstract
BACKGROUND: The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain. METHODS AND RESULTS: We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden cardiac arrest who underwent programmed ventricular stimulation. We estimated incidence rates and relative hazards of cardiac arrest or implantable cardioverter-defibrillator shock. We analyzed individual-level data from 8 studies comprising 1312 patients who experienced 65 cardiac events (median follow-up, 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (hazard ratio, 2.66; 95% confidence interval [CI], 1.44-4.92, P<0.001), with the greatest risk observed among those induced with single or double extrastimuli. Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction. The lowest risk occurred in individuals without syncope and with drug-induced type 1 patterns (0.23%, 95% CI, 0.05-0.68 for no induced arrhythmia with up to double extrastimuli; 0.45%, 95% CI, 0.01-2.49 for induced arrhythmia), and the highest risk occurred in individuals with syncope and spontaneous type 1 patterns (2.55%, 95% CI, 1.58-3.89 for no induced arrhythmia; 5.60%, 95% CI, 2.98-9.58 for induced arrhythmia). CONCLUSIONS: In patients with Brugada syndrome, arrhythmias induced with programmed ventricular stimulation are associated with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk, particularly in patients with high-risk clinical features.
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In a recent meta-analysis, the risk of arrhythmic events was slightly increased in patients with a history of unexplained syncope or a spontaneous type 1 pattern, and who had induction of VT or VF with one or two extra stimuli.
“In a recent meta-analysis, 220 the risk of arrhythmic events was slightly increased in patients with a history of unexplained syncope or a spontaneous type 1 pattern, and who had induction of VT or VF with one or two extra stimuli.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [220]
The Results and Discussion associate syncope, a spontaneous type 1 pattern, and arrhythmia induction with higher event risk, particularly when induction occurs with one or two extrastimuli. The Discussion describes a two- to three-fold increase with induction, so “slightly increased” understates the reported magnitude. The supplied passages refer to syncope or suspected arrhythmogenic syncope, not specifically unexplained syncope; page numbers were not supplied. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA drug-induced type 1 ECG pattern has a lower risk of sudden death than a spontaneous type 1 response in Brugada syndrome.
“A drug-induced type 1 ECG pattern has a lower risk of sudden death than a spontaneous type 1 response.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [220]
The Results report that spontaneous type 1 ECG patterns were significantly associated with the primary outcome in adjusted models, and the Discussion describes lower event risk in asymptomatic patients with drug-induced patterns than in patients with syncope and spontaneous patterns. But the measured outcome was cardiac arrest or appropriate defibrillator shock—not sudden death—and the reported risk extremes also differ by syncope history. (LLM, conf=0.86)
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References 38 · Cited by 242
- Authors
- Sroubek, J., Probst, V., Mazzanti, A., Delise, P., Hevia, J. C., Ohkubo, K., Zorzi, A., Champagne, J., Kostopoulou, A., Yin, X., Napolitano, C., Milan, D. J., Wilde, A., Sacher, F., Borggrefe, M., Ellinor, P. T., Theodorakis, G., Nault, I., Corrado, D., Watanabe, I., Antzelevitch, C., Allocca, G., Priori, S. G., & Lubitz, S. A.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- From Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (J.S.); Service de Cardiologue du CHU de Nantes, CHU de Nantes, Hôpital Nord, Nantes, France (V.P.); Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (A.M., C.N., S.G.P.); Dipartimento di Medicina, Molecolare Università di Pavia, Pavia, Italy (S.G.P.); Division of Cardiology, Casa di Cura Pederzoli, Peschiera del Garda, Verona, Italy (P.D.); Arrhythmia Unit, Cardiovascular Surgery and Cardiology...
- ORCID
- Sroubek, Jakub
- Probst, Vincent
- Mazzanti, Andrea
- Delise, Pietro
- Zorzi, Alessandro
- Champagne, Jean
- Yin, Xiaoyan
- Napolitano, Carlo
- Milan, David J.
- Wilde, Arthur
- Borggrefe, Martin
- Ellinor, Patrick T.
- Nault, Isabelle
- Corrado, Domenico
- Watanabe, Ichiro
- Antzelevitch, Charles
- Allocca, Giuseppe
- Priori, Silvia G.
- Lubitz, Steven A.
- Venue
- Circulation
- Published
- 2016-02-16
- Volume
- 133
- Issue
- 7
- Pages
- 622-630
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4758872
- OpenAlex
- W2264508662
- Cited by
- 242
- References
- 38
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 23 · 2023: 18 · 2022: 18 · 2021: 31 · 2020: 30 · 2019: 22 · 2018: 30 · 2017: 31 · 2016: 16
- FWCI
- 27.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Doris Duke Charitable Foundation (2014105)
- Boston Scientific Corporation
- Impulse Dynamics
- National Heart, Lung, and Blood Institute (HL-47678, R01HL047678, K23HL114724, R01HL092577)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- Brugada syndrome, programmed ventricular stimulation, sudden cardiac death, risk stratification, ventricular arrhythmia induction, extrastimuli, syncope, implantable cardioverter-defibrillator shocks, cardiac arrest
- MeSH terms
- Humans, Prospective Studies, Ventricular Fibrillation, Defibrillators, Implantable, Tachycardia, Ventricular, Risk Assessment, Brugada Syndrome, Observational Studies as Topic
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