{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:21:29Z","timestamp":1793726489758,"version":"4.6.1"},"reference-count":207,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome\u2019s pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.<\/jats:p>","DOI":"10.3390\/ijms24043328","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:01:45Z","timestamp":1675825305000},"page":"3328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification"],"prefix":"10.3390","volume":"24","author":[{"given":"Irene Paula","family":"Popa","sequence":"first","affiliation":[{"name":"Cardiology Clinic, \u201cSt. Spiridon\u201d County Clinical Emergency Hospital, 700111 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragomir N.","family":"\u0218erban","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-9700","authenticated-orcid":false,"given":"Minela Aida","family":"M\u0103r\u0103nduc\u0103","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionela L\u0103cr\u0103mioara","family":"\u0218erban","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-1999","authenticated-orcid":false,"given":"Bogdan Ionel","family":"Tamba","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-2595","authenticated-orcid":false,"given":"Ionu\u021b","family":"Tudorancea","sequence":"additional","affiliation":[{"name":"Cardiology Clinic, \u201cSt. Spiridon\u201d County Clinical Emergency Hospital, 700111 Ia\u0219i, Romania"},{"name":"Department of Physiology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","article-title":"Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report","volume":"20","author":"Brugada","year":"1992","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000076693","article-title":"Brugada syndrome\u2014An under-recognized electrical disease in patients with sudden cardiac death","volume":"101","author":"Juang","year":"2004","journal-title":"Cardiology"},{"key":"ref_3","first-page":"12","article-title":"Current review of Brugada syndrome: From epidemiology to treatment","volume":"9","author":"Khan","year":"2009","journal-title":"Anadolu Kardiyol. Derg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sendfeld, F., Selga, E., Scornik, F.S., P\u00e9rez, G.J., Mills, N.L., and Brugada, R. (2019). Experimental Models of Brugada syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092123"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0735-1097(98)00528-2","article-title":"The Brugada syndrome: Clinical, electrophysiologic and genetic aspects","volume":"33","author":"Gussak","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.jacep.2018.03.006","article-title":"Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy","volume":"4","author":"Wilde","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/32675","article-title":"Genetic basis and molecular mechanism for idiopathic ventricular fibrillation","volume":"392","author":"Chen","year":"1998","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1161\/CIRCULATIONAHA.118.035070","article-title":"Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome","volume":"138","author":"Hosseini","year":"2018","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1161\/CIRCULATIONAHA.118.036889","article-title":"Letter by London Regarding Article, \u201cReappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome\u201d","volume":"139","author":"London","year":"2019","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fcvm.2016.00020","article-title":"Clinical genetic testing for the cardiomyopathies and arrhythmias: A systematic framework for establishing clinical validity and addressing genotypic and phenotypic heterogeneity","volume":"3","author":"Garcia","year":"2016","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.mcna.2019.05.001","article-title":"Inherited cardiac arrhythmias and channelopathies","volume":"103","author":"Kline","year":"2019","journal-title":"Med. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.hlc.2018.09.007","article-title":"Channelopathies that lead to sudden cardiac death: Clinical and genetic aspects","volume":"28","author":"Skinner","year":"2019","journal-title":"Heart Lung Circ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cpcardiol.2015.06.002","article-title":"Brugada syndrome: Clinical, genetic, molecular, cellular, and ionic aspects","volume":"41","author":"Antzelevitch","year":"2016","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1046\/j.1460-9592.2001.01423.x","article-title":"Wolff-Parkinson-White syndrome associated with Brugada syndrome","volume":"24","author":"Eckardt","year":"2001","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1253\/circj.68.473","article-title":"Sinus node function in patients with Brugada-type ECG","volume":"68","author":"Morita","year":"2004","journal-title":"Circ. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1046\/j.0954-6820.2003.01247.x","article-title":"A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill","volume":"255","author":"Takehara","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.ehj.2004.01.004","article-title":"Incidence, clinical implications and prognosis of atrial arrhythmias in Brugada syndrome","volume":"25","author":"Bordachar","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1161\/01.CIR.0000034169.45752.4A","article-title":"Proposed diagnostic criteria for the Brugada syndrome: Consensus report","volume":"106","author":"Wilde","year":"2002","journal-title":"Circulation"},{"key":"ref_19","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: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association","volume":"111","author":"Antzelevitch","year":"2005","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.hrthm.2013.05.014","article-title":"HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013","volume":"10","author":"Priori","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jelectrocard.2012.06.004","article-title":"Current electrocardiographic criteria for diagnosis of Brugada pattern: A consensus report","volume":"45","author":"Brugada","year":"2012","journal-title":"J. Electrocardiol."},{"key":"ref_22","first-page":"e210","article-title":"2017 AHA\/ACC\/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A report of the american college of cardiology\/american heart association task force on clinical practice guidelines and the heart rhythm society","volume":"138","author":"Stevenson","year":"2018","journal-title":"Circulation"},{"key":"ref_23","first-page":"665","article-title":"J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge","volume":"19","author":"Antzelevitch","year":"2017","journal-title":"Europace"},{"key":"ref_24","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":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2147\/RRCC.S182162","article-title":"Brugada syndrome: Updated perspectives","volume":"10","author":"Walia","year":"2019","journal-title":"RRCC"},{"key":"ref_26","first-page":"100468","article-title":"Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies","volume":"26","author":"Li","year":"2020","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1161\/01.CIR.101.5.510","article-title":"Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts","volume":"101","author":"Brugada","year":"2000","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1046\/j.1540-8167.2000.01320.x","article-title":"Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome","volume":"11","author":"Shimizu","year":"2000","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1161\/01.CIR.0000144299.17008.07","article-title":"Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations","volume":"110","author":"Hong","year":"2004","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/j.1540-8167.2006.00531.x","article-title":"Diagnostic value of flecainide testing in unmasking SCN5A-related Brugada syndrome","volume":"17","author":"Meregalli","year":"2006","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1016\/j.ijcard.2008.11.147","article-title":"Sensitivity and specificity of sodium channel blocking test in the diagnosis of Brugada syndrome","volume":"141","author":"Gavrielatos","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.hrthm.2004.11.025","article-title":"Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome","volume":"2","author":"Wolpert","year":"2005","journal-title":"Heart Rhythm"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1540-8159.2000.tb06751.x","article-title":"Arrhythmia induction by antiarrhythmic drugs","volume":"23","author":"Brugada","year":"2000","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1046\/j.1460-9592.2002.01537.x","article-title":"Fever and Brugada syndrome","volume":"25","author":"Antzelevitch","year":"2002","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1161\/CIRCULATIONAHA.107.746495","article-title":"Induced Brugada-type electrocardiogram, a sign for imminent malignant arrhythmias","volume":"117","author":"Junttila","year":"2008","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.hrthm.2013.07.030","article-title":"Fever-induced Brugada pattern: How common is it and what does it mean?","volume":"10","author":"Adler","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1053\/euhj.2001.2691","article-title":"New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives","volume":"22","author":"Sangwatanaroj","year":"2001","journal-title":"Eur. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/1074248406288760","article-title":"Recording of high V1-V3 precordial leads may be essential to the diagnosis of Brugada syndrome during the ajmaline test","volume":"11","author":"Teijeiro","year":"2006","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1093\/europace\/eum229","article-title":"Unmasking the Brugada syndrome with high parasternal leads","volume":"9","author":"Allende","year":"2007","journal-title":"Europace"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1542-474X.2012.00525.x","article-title":"Brugada phenocopy: New terminology and proposed classification","volume":"17","author":"Baranchuk","year":"2012","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_41","first-page":"525","article-title":"Brugada electrocardiographic phenocopy in a patient with chronic Chagasic cardiomyopathy","volume":"17","author":"Arce","year":"2010","journal-title":"Cardiol. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fcvm.2016.00009","article-title":"The Brugada Syndrome: A Rare Arrhythmia Disorder with Complex Inheritance","volume":"3","author":"Gourraud","year":"2016","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_43","first-page":"75","article-title":"Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions","volume":"9","author":"Tse","year":"2015","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1161\/hc5001.100834","article-title":"Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family","volume":"104","author":"Kyndt","year":"2001","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/0002-8703(89)90011-2","article-title":"Ventricular fibrillation without apparent heart disease: Description of six cases","volume":"118","author":"Martini","year":"1989","journal-title":"Am. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Leoni, A.-L., Gavillet, B., Rougier, J.-S., Marionneau, C., Probst, V., Le Scouarnec, S., Schott, J.-J., Demolombe, S., Bruneval, P., and Huang, C.L.H. (2010). Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+\/-) mouse model. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009298"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.1093\/eurheartj\/eht310.4556","article-title":"Generation and characterization of SCN5A loss-of-function mutant mice modeling human brugada syndrome","volume":"34","author":"Schweizer","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1161\/CIRCRESAHA.113.301565","article-title":"Reduced sodium channel function unmasks residual embryonic slow conduction in the adult right ventricular outflow tract","volume":"113","author":"Boukens","year":"2013","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1016\/S0735-1097(02)01888-0","article-title":"Epicardial electrogram of the right ventricular outflow tract in patients with the brugada syndrome","volume":"39","author":"Nagase","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S0002-9149(00)01351-5","article-title":"Electrocardiographic patterns of the Brugada syndrome in right ventricular infarction\/ischemia","volume":"86","author":"Kataoka","year":"2000","journal-title":"Am. J. Cardiol."},{"key":"ref_51","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":"ref_52","doi-asserted-by":"crossref","first-page":"E91","DOI":"10.1161\/01.RES.86.9.e91","article-title":"Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel","volume":"86","author":"Veldkamp","year":"2000","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/europace\/eut379","article-title":"Dependence of phase-2 reentry and repolarization dispersion on epicardial and transmural ionic heterogeneity: A simulation study","volume":"16","author":"Maoz","year":"2014","journal-title":"Europace"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1161\/01.CIR.100.15.1660","article-title":"Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation","volume":"100","author":"Yan","year":"1999","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1016\/j.hrthm.2015.07.029","article-title":"Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome","volume":"12","author":"Maury","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCULATIONAHA.106.668392","article-title":"Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death","volume":"115","author":"Antzelevitch","year":"2007","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1161\/01.CIR.99.10.1385","article-title":"Mechanism linking T-wave alternans to the genesis of cardiac fibrillation","volume":"99","author":"Pastore","year":"1999","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.hrthm.2009.10.007","article-title":"Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch","volume":"7","author":"Hoogendijk","year":"2010","journal-title":"Heart Rhythm"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.hrthm.2010.09.066","article-title":"ST segment elevation by current-to-load mismatch: An experimental and computational study","volume":"8","author":"Hoogendijk","year":"2011","journal-title":"Heart Rhythm"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1161\/CIRCEP.110.937029","article-title":"The Brugada ECG pattern: A marker of channelopathy, structural heart disease, or neither? Toward a unifying mechanism of the Brugada syndrome","volume":"3","author":"Hoogendijk","year":"2010","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1161\/CIRCEP.115.003366","article-title":"ST-Segment Elevation and Fractionated Electrograms in Brugada Syndrome Patients Arise From the Same Structurally Abnormal Subepicardial RVOT Area but Have a Different Mechanism","volume":"8","author":"Coronel","year":"2015","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1161\/CIRCULATIONAHA.105.532614","article-title":"Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: A combined electrophysiological, genetic, histopathologic, and computational study","volume":"112","author":"Coronel","year":"2005","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1161\/CIRCEP.108.790543","article-title":"Slow and discontinuous conduction conspire in Brugada syndrome: A right ventricular mapping and stimulation study","volume":"1","author":"Postema","year":"2008","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/anec.12309","article-title":"Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New Biomarker for the Identification of Patients at Increased Arrhythmic Risk","volume":"21","author":"Robyns","year":"2016","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/europace\/euw280","article-title":"Traditional and novel electrocardiographic conduction and repolarization markers of sudden cardiac death","volume":"19","author":"Tse","year":"2017","journal-title":"Europace"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.yjmcc.2010.07.012","article-title":"The pathophysiological mechanism underlying Brugada syndrome: Depolarization versus repolarization","volume":"49","author":"Wilde","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2169\/internalmedicine.35.637","article-title":"Familial occurrence of electrocardiographic abnormalities of the Brugada-type","volume":"35","author":"Kobayashi","year":"1996","journal-title":"Intern. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1540-8167.1998.tb00947.x","article-title":"Familial sudden cardiac death associated with a terminal QRS abnormality on surface 12-lead electrocardiogram in the index case","volume":"9","author":"Garg","year":"1998","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1053\/euhj.1999.1751","article-title":"Sudden death in patients and relatives with the syndrome of right bundle branch block, ST segment elevation in the precordial leads V(1)to V(3)and sudden death","volume":"21","author":"Brugada","year":"2000","journal-title":"Eur. Heart J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/CIRCGENETICS.109.853374","article-title":"SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome","volume":"2","author":"Probst","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Monasky, M.M., Micaglio, E., Ciconte, G., and Pappone, C. (2020). Brugada syndrome: Oligogenic or mendelian disease?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051687"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3389\/fgene.2019.00547","article-title":"Novel SCN5A frameshift mutation in brugada syndrome associated with complex arrhythmic phenotype","volume":"10","author":"Micaglio","year":"2019","journal-title":"Front. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/cvr\/cvr142","article-title":"A Brugada syndrome mutation (p.S216L) and its modulation by p.H558R polymorphism: Standard and dynamic characterization","volume":"91","author":"Marangoni","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/ng.2712","article-title":"Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death","volume":"45","author":"Bezzina","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Monasky, M.M., Micaglio, E., Giachino, D., Ciconte, G., Giannelli, L., Locati, E.T., Ramondini, E., Cotugno, R., Vicedomini, G., and Borrelli, V. (2019). Genotype-Phenotype Correlation in a Family with Brugada Syndrome Harboring the Novel p.Gln371* Nonsense Variant in the SCN5A Gene. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225522"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/j.bbamcr.2016.02.014","article-title":"The role of mutations in the SCN5A gene in cardiomyopathies","volume":"1863","author":"Zaklyazminskaya","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3389\/fphys.2018.01372","article-title":"SCN5A variants: Association with cardiac disorders","volume":"9","author":"Li","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/humu.23730","article-title":"Genetic interpretation and clinical translation of minor genes related to Brugada syndrome","volume":"40","author":"Campuzano","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.cpcardiol.2019.100454","article-title":"Update on brugada syndrome 2019","volume":"46","author":"Coppola","year":"2021","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jacc.2018.06.037","article-title":"Present Status of Brugada Syndrome: JACC State-of-the-Art Review","volume":"72","author":"Brugada","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1540-8167.2010.02003.x","article-title":"Brugada syndrome caused by a large deletion in SCN5A only detected by multiplex ligation-dependent probe amplification","volume":"22","author":"Eastaugh","year":"2011","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mademont-Soler, I., Pinsach-Abuin, M.L., Riur\u00f3, H., Mates, J., P\u00e9rez-Serra, A., Coll, M., Porres, J.M., Del Olmo, B., Iglesias, A., and Selga, E. (2016). Large genomic imbalances in brugada syndrome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163514"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.hrthm.2018.03.033","article-title":"Copy number variations of SCN5A in Brugada syndrome","volume":"15","author":"Sonoda","year":"2018","journal-title":"Heart Rhythm"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1111\/j.1540-8167.2009.01508.x","article-title":"Genetic modulation of brugada syndrome by a common polymorphism","volume":"20","author":"Lizotte","year":"2009","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1093\/eurheartj\/ehz435","article-title":"Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores","volume":"40","author":"Tadros","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41588-021-01007-6","article-title":"Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility","volume":"54","author":"Barc","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3389\/fphys.2019.00666","article-title":"Genotype\/phenotype relationship in a consanguineal family with brugada syndrome harboring the R1632C missense variant in the SCN5A gene","volume":"10","author":"Monasky","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fgene.2019.00050","article-title":"SCN5A nonsense mutation and NF1 frameshift mutation in a family with brugada syndrome and neurofibromatosis","volume":"10","author":"Micaglio","year":"2019","journal-title":"Front. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Micaglio, E., Monasky, M.M., Resta, N., Bagnulo, R., Ciconte, G., Giannelli, L., Locati, E.T., Vicedomini, G., Borrelli, V., and Ghiroldi, A. (2019). Novel SCN5A p.W697X Nonsense Mutation Segregation in a Family with Brugada Syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194920"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/europace\/euz186","article-title":"Comparable clinical characteristics in Brugada syndrome patients harboring SCN5A or novel SCN10A variants","volume":"21","author":"Monasky","year":"2019","journal-title":"Europace"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.hrthm.2018.08.027","article-title":"A balanced translocation disrupting SCN5A in a family with Brugada syndrome and sudden cardiac death","volume":"16","author":"Yeates","year":"2019","journal-title":"Heart Rhythm"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1161\/JAHA.116.003644","article-title":"Variants in the SCN5A promoter associated with various arrhythmia phenotypes","volume":"5","author":"Yagihara","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"B61","DOI":"10.1093\/eurheartj\/suz028","article-title":"Epicardial ablation in genetic cardiomyopathies: A new frontier","volume":"21","author":"Pappone","year":"2019","journal-title":"Eur. Heart J. Suppl."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1093\/europace\/euz122","article-title":"A cellular model of Brugada syndrome with SCN10A variants using human-induced pluripotent stem cell-derived cardiomyocytes","volume":"21","author":"Albers","year":"2019","journal-title":"Europace"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/cvr\/cvv042","article-title":"Role of common and rare variants in SCN10A: Results from the Brugada syndrome QRS locus gene discovery collaborative study","volume":"106","author":"Behr","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jacc.2014.04.032","article-title":"Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome","volume":"64","author":"Hu","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ng.516","article-title":"Genetic variation in SCN10A influences cardiac conduction","volume":"42","author":"Chambers","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1093\/cvr\/cvu005","article-title":"Nav1.8 channels in ganglionated plexi modulate atrial fibrillation inducibility","volume":"102","author":"Qi","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/gb-2012-13-1-238","article-title":"Transcriptional enhancers in development and disease","volume":"13","author":"Sakabe","year":"2012","journal-title":"Genome Biol."},{"key":"ref_101","unstructured":"(2023, January 12). GWAS Catalog. Available online: https:\/\/www.ebi.ac.uk\/gwas\/home."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/ng.716","article-title":"Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction","volume":"42","author":"Sotoodehnia","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/379257a0","article-title":"A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons","volume":"379","author":"Akopian","year":"1996","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6077","DOI":"10.1523\/JNEUROSCI.21-16-06077.2001","article-title":"Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons","volume":"21","author":"Benn","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neures.2011.01.020","article-title":"Comparative study of voltage-gated sodium channel \u03b1-subunits in non-overlapping four neuronal populations in the rat dorsal root ganglion","volume":"70","author":"Fukuoka","year":"2011","journal-title":"Neurosci. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/CIRCRESAHA.112.274035","article-title":"Functional Nav1.8 channels in intracardiac neurons: The link between SCN10A and cardiac electrophysiology","volume":"111","author":"Verkerk","year":"2012","journal-title":"Circ. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1161\/JAHA.115.002946","article-title":"Contrasting Nav1.8 Activity in Scn10a-\/- Ventricular Myocytes and the Intact Heart","volume":"5","author":"Stroud","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1161\/CIRCRESAHA.112.265173","article-title":"Blocking Scn10a channels in heart reduces late sodium current and is antiarrhythmic","volume":"111","author":"Yang","year":"2012","journal-title":"Circ. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1093\/cvr\/cvy152","article-title":"Differential regulation of sodium channels as a novel proarrhythmic mechanism in the human failing heart","volume":"114","author":"Dybkova","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10557-019-06925-6","article-title":"Absence of Functional Nav1.8 Channels in Non-diseased Atrial and Ventricular Cardiomyocytes","volume":"33","author":"Casini","year":"2019","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1172\/JCI73140","article-title":"A common genetic variant within SCN10A modulates cardiac SCN5A expression","volume":"124","author":"Smemo","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1172\/JCI62613","article-title":"Genetic variation in T-box binding element functionally affects SCN5A\/SCN10A enhancer","volume":"122","author":"Wong","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1038\/s41467-019-12856-5","article-title":"An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo","volume":"10","author":"Man","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Agust\u00edn, A., Pinsach-Abuin, M.L., and Pagans, S. (2020). Role of Non-Coding Variants in Brugada Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228556"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fphys.2018.00178","article-title":"KV4.3 expression modulates nav1.5 sodium current","volume":"9","author":"Portero","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_116","first-page":"153","article-title":"Characterization of N-terminally mutated cardiac Na(+) channels associated with long QT syndrome 3 and Brugada syndrome","volume":"4","author":"Benndorf","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fphar.2012.00062","article-title":"Mexiletine differentially restores the trafficking defects caused by two brugada syndrome mutations","volume":"3","author":"Moreau","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.yjmcc.2015.02.013","article-title":"Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications","volume":"82","author":"Marionneau","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1161\/CIRCEP.111.000206","article-title":"MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome","volume":"6","author":"Chakrabarti","year":"2013","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"H1446","DOI":"10.1152\/ajpheart.00513.2009","article-title":"GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A","volume":"297","author":"Valdivia","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00414-016-1516-z","article-title":"Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population","volume":"131","author":"Huang","year":"2017","journal-title":"Int. J. Legal Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3389\/fphys.2018.01088","article-title":"Calcium in brugada syndrome: Questions for future research","volume":"9","author":"Monasky","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3389\/fphys.2013.00179","article-title":"The genetic component of Brugada syndrome","volume":"4","author":"Nielsen","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.joa.2016.07.012","article-title":"Genetics of Brugada syndrome","volume":"32","author":"Juang","year":"2016","journal-title":"J. Arrhythm."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0092-8674(02)00719-5","article-title":"TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization","volume":"109","author":"Launay","year":"2002","journal-title":"Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"103527","DOI":"10.1016\/j.ejmg.2018.08.008","article-title":"TRPM4 mutations to cause autosomal recessive and not autosomal dominant Brugada type 1 syndrome","volume":"62","author":"Janin","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1161\/CIRCULATIONAHA.113.003077","article-title":"Missense mutations in plakophilin-2 cause sodium current deficit and associate with a Brugada syndrome phenotype","volume":"129","author":"Cerrone","year":"2014","journal-title":"Circulation"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.eplepsyres.2013.02.024","article-title":"Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation","volume":"105","author":"Parisi","year":"2013","journal-title":"Epilepsy Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.mayocp.2013.06.019","article-title":"Electrical storm in the brain and in the heart: Epilepsy and Brugada syndrome","volume":"88","author":"Sandorfi","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1161\/JAHA.116.003379","article-title":"Further insights in the most common SCN5A mutation causing overlapping phenotype of long QT syndrome, brugada syndrome, and conduction defect","volume":"5","author":"Veltmann","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.nrl.2015.03.010","article-title":"Epilepsia y s\u00edndrome de Brugada","volume":"32","year":"2017","journal-title":"Neurolog\u00eda"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ijcard.2003.04.032","article-title":"Results of ajmaline testing in patients with arrhythmogenic right ventricular dysplasia-cardiomyopathy","volume":"95","author":"Peters","year":"2004","journal-title":"Int. J. Cardiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/europace\/euaa277","article-title":"Brugada syndrome and arrhythmogenic cardiomyopathy: Overlapping disorders of the connexome?","volume":"23","author":"Asimaki","year":"2021","journal-title":"Europace"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.febslet.2014.02.008","article-title":"Arrhythmogenic cardiomyopathy and Brugada syndrome: Diseases of the connexome","volume":"588","author":"Cerrone","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e003631","DOI":"10.1161\/CIRCEP.115.003631","article-title":"Relationship between arrhythmogenic right ventricular cardiomyopathy and brugada syndrome: New insights from molecular biology and clinical implications","volume":"9","author":"Corrado","year":"2016","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.tcm.2014.02.001","article-title":"Desmosomes and the sodium channel complex: Implications for arrhythmogenic cardiomyopathy and Brugada syndrome","volume":"24","author":"Cerrone","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.jacep.2020.05.026","article-title":"Worse prognosis in brugada syndrome patients with arrhythmogenic cardiomyopathy features","volume":"6","author":"Scheirlynck","year":"2020","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"652027","DOI":"10.3389\/fcvm.2021.652027","article-title":"Evaluating the use of genetics in brugada syndrome risk stratification","volume":"8","author":"Monasky","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"113970","DOI":"10.1016\/j.biopha.2022.113970","article-title":"Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte modelling of cardiovascular diseases for natural compound discovery","volume":"157","author":"Zhu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1016\/j.jacc.2016.07.779","article-title":"Patient-Specific and Genome-Edited Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Brugada Syndrome","volume":"68","author":"Liang","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3389\/fcell.2019.00261","article-title":"Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes","volume":"7","author":"Zhao","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Blok, M., and Boukens, B.J. (2020). Mechanisms of arrhythmias in the brugada syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197051"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1093\/eurheartj\/ehz308","article-title":"RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome","volume":"40","author":"Belbachir","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/CIRCEP.111.964577","article-title":"Brugada syndrome","volume":"5","author":"Mizusawa","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1161\/CIRCULATIONAHA.109.887026","article-title":"Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry","volume":"121","author":"Probst","year":"2010","journal-title":"Circulation"},{"key":"ref_146","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":"ref_147","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.jacc.2014.12.031","article-title":"Implantable cardioverter-defibrillator therapy in Brugada syndrome: A 20-year single-center experience","volume":"65","author":"Conte","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/europace\/eum174","article-title":"Asymptomatic Brugada syndrome: A cardiac ticking time-bomb?","volume":"9","author":"Viskin","year":"2007","journal-title":"Europace"},{"key":"ref_149","first-page":"1413","article-title":"Brugada syndrome:risk stratification and management","volume":"9","author":"Letsas","year":"2016","journal-title":"J. Atr. Fibrillation"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.hrthm.2015.10.002","article-title":"Implantable devices in young patients: Hitting the reset button on risk versus benefit","volume":"13","author":"Hamilton","year":"2016","journal-title":"Heart Rhythm"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"79","DOI":"10.15420\/aer.2018.2.2","article-title":"Risk stratification in brugada syndrome: Current status and emerging approaches","volume":"7","author":"Honarbakhsh","year":"2018","journal-title":"Arrhythm. Electrophysiol. Rev."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.hrthm.2015.04.017","article-title":"Everybody has Brugada syndrome until proven otherwise?","volume":"12","author":"Viskin","year":"2015","journal-title":"Heart Rhythm"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4330\/wjc.v6.i3.81","article-title":"Brugada phenocopy: A new electrocardiogram phenomenon","volume":"6","author":"Anselm","year":"2014","journal-title":"World J. Cardiol."},{"key":"ref_154","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":"ref_155","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1253\/circj.CJ-14-1059","article-title":"Risk stratification in patients with Brugada syndrome without previous cardiac arrest\u2013prognostic value of combined risk factors","volume":"79","author":"Okamura","year":"2015","journal-title":"Circ. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/j.ijcard.2013.04.146","article-title":"Prognostic value of programmed ventricular stimulation in Brugada syndrome according to clinical presentation: An updated meta-analysis of worldwide published data","volume":"168","author":"Fauchier","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/CIRCEP.108.816892","article-title":"Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3","volume":"2","author":"Kamakura","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/hc0102.101354","article-title":"Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3","volume":"105","author":"Brugada","year":"2002","journal-title":"Circulation"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1540-8167.2006.00455.x","article-title":"Risk stratification of individuals with the Brugada electrocardiogram: A meta-analysis","volume":"17","author":"Gehi","year":"2006","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1161\/hc1102.105288","article-title":"Natural history of Brugada syndrome: Insights for risk stratification and management","volume":"105","author":"Priori","year":"2002","journal-title":"Circulation"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.hrthm.2012.04.013","article-title":"Syncope in Brugada syndrome patients: Prevalence, characteristics, and outcome","volume":"9","author":"Sacher","year":"2012","journal-title":"Heart Rhythm"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1540-8159.2008.01010.x","article-title":"Neurally mediated susceptibility in individuals with Brugada-type ECG pattern","volume":"31","author":"Letsas","year":"2008","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/europace\/eup006","article-title":"Risk stratification of the patients with Brugada type electrocardiogram: A community-based prospective study","volume":"11","author":"Giustetto","year":"2009","journal-title":"Europace"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1161\/CIRCEP.114.002647","article-title":"Prognostic value of programmed electrical stimulation in Brugada syndrome: 20 years experience","volume":"8","author":"Sieira","year":"2015","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.amjcard.2015.03.044","article-title":"Meta-Analysis on Risk Stratification of Asymptomatic Individuals With the Brugada Phenotype","volume":"116","author":"Letsas","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3389\/fphys.2017.00678","article-title":"Meta-analysis of Fragmented QRS as an Electrocardiographic Predictor for Arrhythmic Events in Patients with Brugada Syndrome","volume":"8","author":"Meng","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e12507","DOI":"10.1111\/anec.12507","article-title":"Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta-analysis","volume":"23","author":"Rattanawong","year":"2018","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1161\/CIRCEP.116.004765","article-title":"Distribution and prognostic significance of fragmented QRS in patients with brugada syndrome","volume":"10","author":"Morita","year":"2017","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/jce.13349","article-title":"Identification of electrocardiographic risk markers for the initial and recurrent episodes of ventricular fibrillation in patients with Brugada syndrome","volume":"29","author":"Morita","year":"2018","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1161\/CIRCULATIONAHA.108.770917","article-title":"Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome","volume":"118","author":"Morita","year":"2008","journal-title":"Circulation"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1016\/j.jacc.2014.01.072","article-title":"Electrocardiographic parameters and fatal arrhythmic events in patients with Brugada syndrome: Combination of depolarization and repolarization abnormalities","volume":"63","author":"Tokioka","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.amjcard.2013.06.033","article-title":"Prevalence and prognostic role of various conduction disturbances in patients with the Brugada syndrome","volume":"112","author":"Maury","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1540-8167.2007.01050.x","article-title":"Differences in 12-lead electrocardiogram between symptomatic and asymptomatic Brugada syndrome patients","volume":"19","author":"Junttila","year":"2008","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1111\/j.1540-8167.2007.00971.x","article-title":"Clinical characteristics and risk stratification in symptomatic and asymptomatic patients with brugada syndrome: Multicenter study in Japan","volume":"18","author":"Takagi","year":"2007","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/j.jacc.2005.12.049","article-title":"Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia\/ventricular fibrillation in patients with the Brugada syndrome","volume":"47","author":"Antzelevitch","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_176","first-page":"811","article-title":"Novel conduction-repolarization indices for the stratification of arrhythmic risk","volume":"13","author":"Tse","year":"2016","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_177","first-page":"696","article-title":"(Tpeak-Tend)\/QRS and (Tpeak-Tend)\/(QT \u00d7 QRS): Novel markers for predicting arrhythmic risk in Brugada syndrome","volume":"19","author":"Tse","year":"2017","journal-title":"EP Eur."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.vascn.2013.01.003","article-title":"A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in drug-induced cardiac arrhythmias: Beyond QT-prolongation and Torsades de Pointes (TdPs)","volume":"68","author":"Lu","year":"2013","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_179","first-page":"813","article-title":"Both transmural dispersion of repolarization and of refractoriness are poor predictors of arrhythmogenicity: A role for iCEB (QT\/QRS)?","volume":"13","author":"Tse","year":"2016","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijcha.2018.03.001","article-title":"High risk electrocardiographic markers in Brugada syndrome","volume":"18","author":"Asvestas","year":"2018","journal-title":"IJC Heart Vasc."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.hrthm.2004.11.011","article-title":"In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine","volume":"2","author":"Xia","year":"2005","journal-title":"Heart Rhythm"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1253\/circj.CJ-10-0903","article-title":"Risk determinants in individuals with a spontaneous type 1 Brugada ECG","volume":"75","author":"Miyamoto","year":"2011","journal-title":"Circ. J."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1540-8167.2007.00967.x","article-title":"Clinical significance of macroscopic T-wave alternans after sodium channel blocker administration in patients with Brugada syndrome","volume":"19","author":"Tada","year":"2008","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/clc.22386","article-title":"Brugada syndrome, exercise, and exercise testing","volume":"38","author":"Masrur","year":"2015","journal-title":"Clin. Cardiol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.jacc.2010.06.033","article-title":"Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome","volume":"56","author":"Makimoto","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1161\/CIRCEP.109.862441","article-title":"Exercise-induced ECG changes in Brugada syndrome","volume":"2","author":"Amin","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.hrthm.2013.04.009","article-title":"Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: A novel risk factor for Brugada syndrome with ventricular fibrillation","volume":"10","author":"Kawata","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1161\/CIRCEP.108.795153","article-title":"Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome","volume":"2","author":"Sarkozy","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.hrthm.2008.09.021","article-title":"Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome","volume":"5","author":"Letsas","year":"2008","journal-title":"Heart Rhythm"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.hrthm.2007.04.017","article-title":"aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome","volume":"4","author":"Aslani","year":"2007","journal-title":"Heart Rhythm"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/j.1540-8167.1996.tb00472.x","article-title":"The signal-averaged electrocardiogram: Update on clinical applications","volume":"7","author":"Steinberg","year":"1996","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.hrthm.2009.05.007","article-title":"Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: A prospective study","volume":"6","author":"Huang","year":"2009","journal-title":"Heart Rhythm"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1046\/j.1540-8167.2005.04313.x","article-title":"Assessment of markers for identifying patients at risk for life-threatening arrhythmic events in Brugada syndrome","volume":"16","author":"Ajiro","year":"2005","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/j.1540-8167.2006.00508.x","article-title":"Risk stratification in patients with Brugada syndrome: Analysis of daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG)","volume":"17","author":"Tatsumi","year":"2006","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1161\/CIRCEP.117.005107","article-title":"ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG","volume":"10","author":"Leong","year":"2017","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_196","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":"ref_197","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ijcard.2015.04.243","article-title":"Prolonged right ventricular ejection delay identifies high risk patients and gender differences in Brugada syndrome","volume":"191","author":"Kerkhove","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1093\/eurheartj\/ehaa942","article-title":"Brugada syndrome genetics is associated with phenotype severity","volume":"42","author":"Ciconte","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/eurheartj\/ehab071","article-title":"Common modulators of Brugada syndrome phenotype do not affect SCN5A prognostic value","volume":"42","author":"Pappone","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_200","first-page":"39","article-title":"Programmed ventricular stimulation--indications and limitations: A comprehensive update and review","volume":"54","author":"Kossaify","year":"2013","journal-title":"Hellenic J. Cardiol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1093\/europace\/euy301","article-title":"Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: Data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS)","volume":"21","author":"Milman","year":"2019","journal-title":"Europace"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1046\/j.1540-8167.2003.02517.x","article-title":"Natural history of Brugada syndrome: The prognostic value of programmed electrical stimulation of the heart","volume":"14","author":"Brugada","year":"2003","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_203","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":"ref_204","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/eurheartj\/ehac262","article-title":"2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","volume":"43","author":"Zeppenfeld","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_205","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":"ref_206","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1093\/eurheartj\/ehaa763","article-title":"Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome","volume":"42","author":"Probst","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_207","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":"2021","journal-title":"JACC Clin. Electrophysiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3328\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:03Z","timestamp":1760120823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":207,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043328"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043328","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}