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Risk Stratification in Brugada Syndrome
Open accessAbstract
Objectives The PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) prospective registry was designed to assess the predictive accuracy of sustained ventricular tachycardia/ventricular fibrillation (VTs/VF) inducibility and to identify additional predictors of arrhythmic events in Brugada syndrome patients without history of VT/VF.Background Brugada syndrome is a genetic disease associated with increased risk of sudden cardiac death. Even though its value has been questioned, inducibility of VTs/VF is widely used to select candidates to receive a prophylactic implantable defibrillator, and its accuracy has never been addressed in prospective studies with homogeneous enrolling criteria.Methods Patients with a spontaneous or drug-induced type I electrocardiogram (ECG) and without history of cardiac arrest were enrolled. The registry included 308 consecutive individuals (247 men, 80%; median age 44 years, range 18 to 72 years). Programmed electrical stimulation was performed at enrollment, and patients were followed-up every 6 months.Results During a median follow-up of 34 months, 14 arrhythmic events (4.5%) occurred (13 appropriate shocks of the implantable defibrillator, and 1 cardiac arrest). Programmed electrical stimulation performed with a uniform and pre-specified protocol induced ventricular tachyarrhythmias in 40% of patients: arrhythmia inducibility was not a predictor of events at follow-up (9 of 14 events occurred in noninducible patients). History of syncope and spontaneous type I ECG (hazard ratio [HR]: 4.20), ventricular refractory period <200 ms (HR: 3.91), and QRS fragmentation (HR: 4.94) were significant predictors of arrhythmias.Conclusions Our data show that VT/VF inducibility is unable to identify high-risk patients, whereas the presence of a spontaneous type I ECG, history of syncope, ventricular effective refractory period <200 ms, and QRS fragmentation seem useful to identify candidates for prophylactic implantable cardioverter defibrillator.
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“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 [371]
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“In contrast, the FINGER study (5), conducted in 638 patients, found a negative predictive value of 60% for the lack of inducibility, which was also confirmed by our PRELUDE study in 308 patients, because 9 of 14 patients who experienced an arrhythmic episode at follow-up were noninducible at PES (6).”
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“In addition, syncope is a known predictor of sudden cardiac arrest in patients with BrS (10).”
BackgroundResultPlasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome
Ikeuchi, Y., Ochi, H., Motoda, C., Tokuyama, T., Okubo, Y., Okamura, S., Miyauchi, S., Miyamoto, S., Uotani, Y., Onohara, Y., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0261390 · Cited by 5
When Brugada syndrome is at risk of sudden death: clinical and anatomical aspects
Stazi, F., & Battisti, P. (2022) · European Heart Journal Supplements · doi:10.1093/eurheartjsupp/suac088 · Cited by 4
Shinohara, T., Takagi, M., Kamakura, T., Komatsu, Y., Aizawa, Y., Sekiguchi, Y., Yokoyama, Y., Aihara, N., Hiraoka, M., Aonuma, K., et al. (2024) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.16205 · Cited by 6
“In fact, Nademanee et al. reported 17 that fibrosis of the epicardial surface and interstitium and decreased gap junction expression of RVOT were associated with VF occurrence in patients with BrS.”
MethodResultInfluentialCabrera‐Bueno, F., Alzueta, J., Ruíz-Zamora, I., Molina-Mora, M. J., Barrera, A., & de Teresa–Galván, E. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.04.109 · Cited by 4
Risk Stratification and Therapeutic Approach in Brugada Syndrome
Probst, V., Chatel, S., Gourraud, J., Marec, H. L., Project Manager, & Professor, A. (2012) · Arrhythmia & Electrophysiology Review · doi:10.15420/aer.2012.1.17 · Cited by 4
Life threatening causes of syncope: Channelopathies and cardiomyopathies
Herman, A. R. M., Bennett, M. T., Chakrabarti, S., & Krahn, A. D. (2014) · Autonomic Neuroscience · doi:10.1016/j.autneu.2014.04.003 · Cited by 4
“The presence of unexplained syncope is a marker for risk of SCD leading to a recommendation of an ICD (Brugada et al., 2005; Priori et al., 2012).”
BackgroundPolidori, E., Stocchi, L., Potenza, D. R., Cucchiarini, L., Stocchi, V., & Potenza, L. (2020) · Journal of Genetics · doi:10.1007/s12041-020-01228-4 · Cited by 4
Prognostic significance of a low T/R ratio in Brugada syndrome
Delinière, A., Baranchuk, A. M., Bessière, F., Defaye, P., Marijon, É., Vavasseur, O. L., Dobreanu, D., Scridon, A., Costa, A. D., Delacrétaz, E., et al. (2020) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2020.08.023 · Cited by 4
Brugada Syndrome: Fatal Consequences of a Must-Not-Miss Diagnosis
Smith, L. D., Gast, S., & Guy, D. F. (2021) · Critical Care Nurse · doi:10.4037/ccn2021499 · Cited by 4
El-Azrak, M., Darar, C., Boutaybi, M., Ouafi, N. E., & Bazid, Z. (2023) · Current Cardiology Reports · doi:10.1007/s11886-023-01842-5 · Cited by 4
Latrofa, S., Hartwig, V., Bachi, L., Notarstefano, P., Garibaldi, S., Panchetti, L., Nesti, M., Seghetti, P., Startari, U., Mirizzi, G., et al. (2024) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.16244 · Cited by 4
Implantable cardioverter defibrillator and catheter ablation in Brugada syndrome
Pappone, C., & Santinelli, V. (2016) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000449 · Cited by 4
Self-citationBrugada Syndrome: Evolving Insights and Emerging Treatment Strategies
Duffett, S., & Roberts, J. D. (2017) · Journal of Innovations in Cardiac Rhythm Management · doi:10.19102/icrm.2017.080205 · Cited by 4
“The role of invasive electrophysiology study in identifying BrS has been controversial, with disagreement regarding its clinical utility, a notion currently reflected in that it has a class IIb indication as a tool for risk stratification.(54) Debate surrounding its utility partially stems from variable results having…”
BackgroundResultInfluentialGoldstein, S. A., Ward, C., & Al‐Khatib, S. M. (2017) · Journal of Innovations in Cardiac Rhythm Management · doi:10.19102/icrm.2018.090103 · Cited by 4
Wakamiya, A., Kamakura, T., Shinohara, T., Yodogawa, K., Murakoshi, N., Morita, H., Takahashi, N., Inden, Y., Shimizu, W., Nogami, A., et al. (2020) · Circulation Journal · doi:10.1253/circj.cj-19-0910 · Cited by 4
Electrophysiologic Study Indications And Evaluation
Majeed, H., & Sattar, Y. (2021) · StatPearls · Cited by 4
Lopez-Blazquez, M., Field, E., Tollit, J., Walsh, H., Addis, A., French, N., Starling, L., & Kaski, J. P. (2021) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2021.03.011 · Cited by 4
Is There Anyone Left With a Normal Electrocardiogram?
Viskin, S. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.06.037 · Cited by 4
“tomatic individuals who have non-type I ST-segment elevation in V1 to V3 have an excellent long-term prognosis even if their ECG pattern converts to type I when challenged with a sodium channel blocker, even if they also have inducible VF during electrophysiological studies (16).”
BackgroundRisk stratification in Brugada syndrome: Where is the finish line?
Postema, P. G., & Wilde, A. A. M. (2016) · Heart Rhythm · doi:10.1016/j.hrthm.2016.08.008 · Cited by 4
“The absence of a VF history as a risk marker is not understandable (but maybe not even modeled), and the irrelevance of parameters such as QRS fractionation is somewhat unexpected.(14) Fourth, the parameters in the model are interesting as well.”
BackgroundDrug-induced type 1 Brugada ECG: Lights and shadows
Giustetto, C., Cerrato, N., & Gaïta, F. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.12.044 · Cited by 4
Palacios-Rubio, J., Roessel, A. M.-V., Brito, V. G., Expósito-Pineda, C., & Morales, C. E. G. (2020) · Cardiology · doi:10.1159/000511496 · Cited by 4
Kumar, A., Tantray, J., Kosey, S., Devi, C. H., & Prajapati, B. G. (2025) · Health Sciences Review · doi:10.1016/j.hsr.2025.100238 · Cited by 3
Brugada syndrome risk scores: what we've learned and what's next
Rattanawong, P., & Shen, W.-K. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1715146 · Cited by 3
Zhu, Y., Zhang, J., Ji, Y.-Y., Hu, Y., Wang, H., Ruan, D., Meng, X.-R., Lin, X.-F., Luo, J.-W., & Chen, W. (2022) · Cardiology Research and Practice · doi:10.1155/2022/9716045 · Cited by 3
Chiotis, S., Pannone, L., Doundoulakis, I., Rocca, D. G. D., Zafeiropoulos, S., Sorgente, A., Marcon, L., Vetta, G., Koliastasis, L., Monte, A. D., et al. (2024) · Heart Rhythm O2 · doi:10.1016/j.hroo.2024.11.022 · Cited by 4
Implantable Cardioverter-Defibrillator Therapy in Brugada Syndrome
Monaco, C., Fernández, M. C., Pannone, L., Monte, A. D., Rocca, D. G. D., Gauthey, A., Mouram, S., Marcon, L., Vetta, G., Audiat, C., et al. (2025) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2025.01.013 · Cited by 3
Clinical outcome and risk stratification in Brugada syndrome
Wada, T., & Morita, H. (2013) · Journal of Arrhythmia · doi:10.1016/j.joa.2012.12.008 · Cited by 2
“Although most of the European studies failed to prove an association between family history of sudden death and VF events [3,4,7,21], frequent sudden deaths in family members were recognized [22].”
BackgroundResultInfluentialICD-Therapie zur Primär- und Sekundärprophylaxe kongenitaler arrhythmogener Erkrankungen
Duncker, D., König, T., Hohmann, S., & Veltmann, C. (2015) · Herzschrittmachertherapie + Elektrophysiologie · doi:10.1007/s00399-015-0372-8 · Cited by 3
Chen, X.-M., Ji, C.-C., Cheng, Y., Liu, L., Zhu, W.-Q., Huang, Y., Chen, W., & Wu, S. (2016) · Clinical Cardiology · doi:10.1002/clc.22587 · Cited by 3
Risk stratification and criteria for diagnosis in Brugada syndrome: current status and developing
Serguladze, S. Y., & Проничева, И. В. (2020) · Annaly aritmologii · doi:10.15275/annaritmol.2020.1.6 · Cited by 3
“ELectrical stimUlation preDictive valuE – прогностическая ценность программированной электрической стимуляции), в рамках которого проспективно наблюдали 308 пациентов с СБ без остановки сердца в прошлом [12].”
InfluentialShinohara, T., Takagi, M., Kamakura, T., Sekiguchi, Y., Yokoyama, Y., Aihara, N., Hiraoka, M., Aonuma, K., & Japan Idiopathic Ventricular Fibrillation Study (J‐IVFS) Investigators (2021) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12831 · Cited by 3
“This registry was launched in 2002 prior to the 2013 consensus report (Priori et al., 2013)), which defined only spontaneous, drug- induced, or fever- induced type 1 Br- ECG as BrS.”
MethodExercise Stress Test in The Assessment of Brugada Syndrome Patients
Miná, C. P. C., Rocha, E. A. Q., Mont’Alverne, D. G. B., & Rocha, E. A. (2023) · International Journal of Cardiovascular Sciences · doi:10.36660/ijcs.20220079 · Cited by 3
Seghetti, P., Latrofa, S., Biasi, N., Giannoni, A., Hartwig, V., Rossi, A., & Tognetti, A. (2024) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.16341 · Cited by 3
“2,3,13,14 Recently, it has been shown that PVS can be used to distinguish between high ‐ risk and low ‐ risk asymptomatic patients in selected cohorts of patients, 15,16 however it is not suitable for mass screening and both sensitivity and specificity of the test depend on the PVS protocol used.”
Brugada Syndrome 26 Years Later: More Questions than Answers
Delise, P., Allocca, G., & Sitta, N. (2019) · Journal of Clinical & Experimental Cardiology · Cited by 3
Metadata
- Authors
- Priori, S. G., Gasparini, M., Napolitano, C., Della Bella, P., Ottonelli, A. G., Sassone, B., Giordano, U., Pappone, C., Mascioli, G., Rossetti, G., De Nardis, R., & Colombo, M.
- Affiliations
- University of Pavia (IT)
- IRCCS Humanitas Research Hospital (IT)
- NYU Langone Health (US)
- Ospedale Versilia (IT)
- Azienda USL di Bologna (IT)
- Maria Cecilia Hospital (IT)
- Humanitas Gavazzeni (IT)
- Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT)
- Corresponding author
- Priori, Silvia G.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 59
- Issue
- 1
- Pages
- 37-45
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W140924846
- Cited by
- 581
- References
- 26
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 26 · 2023: 25 · 2022: 26 · 2021: 44 · 2020: 43 · 2019: 44 · 2018: 44 · 2017: 68 · 2016: 60 · 2015: 45 · 2014: 31 · 2013: 66 · 2012: 30
- FWCI
- 28.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- Medtronic
- Boston Scientific Corporation
- 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, risk stratification, programmed electrical stimulation, implantable cardioverter-defibrillator, sudden cardiac death, syncope, ventricular effective refractory period, QRS fragmentation, arrhythmic events
- MeSH terms
- Adolescent, Adult, Aged, Cause of Death, Electric Stimulation, Electrocardiography, Female, Humans, Male, Middle Aged, Registries, Severity of Illness Index, Ventricular Fibrillation, Cohort Studies, Incidence, Survival Rate, Confidence Intervals, Defibrillators, Implantable, Tachycardia, Ventricular, Age Distribution, Sex Distribution, Risk Assessment, Patient Selection, Statistics, Nonparametric, Kaplan-Meier Estimate, Brugada Syndrome, Young Adult
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