{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T09:48:40Z","timestamp":1767260920831,"version":"3.37.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the prognostic significance of heterogeneity in the refractoriness of right ventricular (RV) outflow tract (RVOT) and RV apex at the electrophysiological study (EPS) in Brugada syndrome (BrS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>A cohort of BrS patients (primary prevention) from five Italian centres was retrospectively analysed. Patients with spontaneous or drug-induced Type-1 electrocardiogram (ECG) + symptoms were offered an EPS for prognostic stratification. The primary endpoint was a composite of sudden cardiac death (SCD), resuscitated cardiac arrest, or appropriate intervention by the implantable cardioverter-defibrillator (ICD). Three hundred and seventy-two patients with BrS were evaluated (44 \u00b1 15 years, 69% males, 23% with ICD): 4 SCDs and 17 ICD interventions occurred at follow-up (median 48, interquartile range: 36\u201360 months). Family history of SCD, syncope, and a spontaneous Type-1 ECG pattern were univariate predictors of the primary endpoint in the whole population. In patients undergoing EPS (n = 198, 53%, 44 \u00b1 12 years, 71% males, 39% with ICD), 3 SCD and 15 ICD interventions occurred at follow-up. In this subset, the primary endpoint was not only predicted by ventricular tachycardia\/fibrillation inducibility but also by a difference in the refractory period between RVOT and RV apex (\u0394RPRVOT-apex) &amp;gt;60 ms. \u0394RPRVOT-apex &amp;gt; 60 ms remained an independent predictor of SCD\/ICD shock at bivariate analysis, even when adjusted for the other univariate predictors, showing the highest predictive power at C-statistic analysis (0.75, 95% confidence interval 0.63\u20130.86).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Heterogeneity of RV refractory periods is a strong, independent predictor of life-threatening arrhythmias in BrS patients, beyond VT\/VF inducibility at EPS and common clinical predictors.<\/jats:p><\/jats:sec>","DOI":"10.1093\/europace\/euac168","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T05:29:00Z","timestamp":1664947740000},"page":"651-659","source":"Crossref","is-referenced-by-count":8,"title":["Prognostic value of right ventricular refractory period heterogeneity in Type-1 Brugada electrocardiographic pattern"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-6821","authenticated-orcid":false,"given":"Andrea","family":"Rossi","sequence":"first","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-2005","authenticated-orcid":false,"given":"Alberto","family":"Giannoni","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"},{"name":"Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8995-3884","authenticated-orcid":false,"given":"Martina","family":"Nesti","sequence":"additional","affiliation":[{"name":"Cardiovascular and Neurological Department, San Donato Hospital , Arezzo , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-0464","authenticated-orcid":false,"given":"Pasquale","family":"Notarstefano","sequence":"additional","affiliation":[{"name":"Cardiovascular and Neurological Department, San Donato Hospital , Arezzo , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-2328","authenticated-orcid":false,"given":"Vincenzo","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Solarino","sequence":"additional","affiliation":[{"name":"Cardiology Division, Versilia Hospital , Lido di Camaiore , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5626-0336","authenticated-orcid":false,"given":"Lucio","family":"Teresi","sequence":"additional","affiliation":[{"name":"Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Mirizzi","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-0360","authenticated-orcid":false,"given":"Vincenzo","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Monaldi Hospital , Naples , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Panchetti","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Startari","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ripoli","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7453-3748","authenticated-orcid":false,"given":"Francesco","family":"Gentile","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-4372","authenticated-orcid":false,"given":"Amato","family":"Santoro","sequence":"additional","affiliation":[{"name":"Cardiology Division, Azienda Ospedaliera Universitaria Senese , Siena , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-3610","authenticated-orcid":false,"given":"Nicoletta","family":"Botto","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Casolo","sequence":"additional","affiliation":[{"name":"Cardiology Division, Versilia Hospital , Lido di Camaiore , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Sieira","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Centre, Universitair Ziekenhuis Brussel , Brussels , Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-4292","authenticated-orcid":false,"given":"Maurizio","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Cardiovascular and Neurological Department, San Donato Hospital , Arezzo , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Santangeli","sequence":"additional","affiliation":[{"name":"Electrophysiology Section, Cardiovascular Division, Hospital of the University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"},{"name":"Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-7122","authenticated-orcid":false,"given":"Marcello","family":"Piacenti","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio , Pisa , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.joa.2016.07.002","article-title":"J-Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge","volume":"32","author":"Antzelevitch","year":"2016","journal-title":"J Arrhythm"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1540-8167.2011.02075.x","article-title":"Long-Term follow-up in patients with presumptive Brugada syndrome treated with implanted defibrillators","volume":"22","author":"Steven","year":"2011","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.hrthm.2018.01.014","article-title":"Profile of patients with Brugada syndrome presenting with their first documented arrhythmic event: data from the survey on arrhythmic events in BRUgada syndrome (SABRUS)","volume":"15","author":"Milman","year":"2018","journal-title":"Heart Rhythm"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1161\/CIRCULATIONAHA.114.013698","article-title":"Cardiac electrophysiological substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients","volume":"131","author":"Zhang","year":"2015","journal-title":"Circulation"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/eurheartj\/ehq381","article-title":"Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach","volume":"32","author":"Delise","year":"2011","journal-title":"Eur Heart J"},{"key":"2023021623541157000_","first-page":"1","article-title":"Brugada syndrome and reduced right ventricular outflow tract conduction reserve: a final common pathway?","volume":"00","author":"Behr","year":"2021","journal-title":"Eur Heart J"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.jacep.2018.02.009","article-title":"Shanghai Score system for diagnosis of Brugada syndrome: validation of the score system and system and reclassification of the patients","volume":"4","author":"Kawada","year":"2018","journal-title":"JACC Clin Electrophysiol"},{"key":"2023021623541157000_","first-page":"2514","article-title":"Proposed diagnostic criteria for the Brugada syndrome","volume":"106","author":"Wilde","year":"2002","journal-title":"Eur Heart J"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/01.CIR.0000152479.54298.51","article-title":"Brugada syndrome: report of the second consensus conference","volume":"111","author":"Antzelevitch","year":"2005","journal-title":"Circulation"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1161\/CIRCULATIONAHA.115.017885","article-title":"Programmed ventricular stimulation for risk stratification in the Brugada syndrome: a pooled analysis","volume":"133","author":"Sroubek","year":"2016","journal-title":"Circulation"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.amjcard.2010.10.046","article-title":"Sleep-disordered breathing in patients with the Brugada syndrome","volume":"107","author":"Macedo","year":"2011","journal-title":"Am J Cardiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jacc.2011.08.064","article-title":"Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry","volume":"59","author":"Priori","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1093\/eurheartj\/ehx119","article-title":"A score model to predict risk of events in patients with Brugada syndrome","volume":"38","author":"Sieira","year":"2017","journal-title":"Eur Heart J"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jacep.2020.08.032","article-title":"A primary prevention clinical risk score model for patients with brugada syndrome (BRUGADA-RISK)","volume":"7","author":"Honarbakhsh","year":"2020","journal-title":"JACC Clin Electrophysiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1161\/CIRCULATIONAHA.108.771401","article-title":"High-density substrate mapping in Brugada syndrome","volume":"120","author":"Lambiase","year":"2009","journal-title":"Circulation"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00424-011-0989-3","article-title":"Refractory dispersion promotes conduction disturbance and arrhythmias in a Scn5a (+\/\u2212) mouse model","volume":"462","author":"Martin","year":"2011","journal-title":"Pflugers Arch"},{"key":"2023021623541157000_","first-page":"2537","article-title":"Conduction abnormalities in the right ventricular outflow tract in Brugada syndrome detected body surface potential mapping","volume-title":"Ann Int Conf IEEE Eng Med Biol Soc","author":"Guillem","year":"2010"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/europace\/euv300","article-title":"Brugada syndrome: clinical presentation and genotype-correlation with magnetic resonance imaging parameters","volume":"18","author":"Rudic","year":"2016","journal-title":"Europace"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1016\/j.jacc.2018.09.037","article-title":"Electroanatomic and pathologic right ventricular outflow tract abnormalities in patients with Brugada syndrome","volume":"72","author":"Pieroni","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1016\/j.jacc.2015.08.862","article-title":"Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome","volume":"66","author":"Nademanee","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/cvr\/19.10.623","article-title":"Inhomogeneity of ventricular refractory period in canineheart with quinidine-induced long QT interval: a comparative study on effects of heart rate, isoprenaline, and lignocaine","volume":"19","author":"Inoue","year":"1985","journal-title":"Cardiovasc Res"},{"key":"2023021623541157000_","first-page":"905","article-title":"Dispersion of effective refractory period in the ischemic borderzone in canine heart","volume":"45","author":"Isomura","year":"1981","journal-title":"Jpn Circ J"},{"key":"2023021623541157000_","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.hrthm.2007.03.036","article-title":"Heterogeneity and cardiac arrhythmias: an overview","volume":"4","author":"Antzelevitch","year":"2007","journal-title":"Heart Rhythm"}],"container-title":["EP Europace"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/europace\/article-pdf\/25\/2\/651\/49230836\/euac168.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/europace\/article-pdf\/25\/2\/651\/49230836\/euac168.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T23:00:08Z","timestamp":1676761208000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/europace\/article\/25\/2\/651\/6748256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,10,5]]},"published-print":{"date-parts":[[2023,2,16]]}},"URL":"https:\/\/doi.org\/10.1093\/europace\/euac168","relation":{},"ISSN":["1099-5129","1532-2092"],"issn-type":[{"type":"print","value":"1099-5129"},{"type":"electronic","value":"1532-2092"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,10,5]]}}}