{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:22:47Z","timestamp":1793398967995,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included. First-degree family members underwent comprehensive FE and decedents with post-mortem DNA were sequenced with a 36 cardiac gene panel for MA. A Bayesian framework for analysis was performed to identify associations. Among 760 SADS decedents (66% male; mean age 31 \u00b1 12 years) the overall diagnostic yield for an inherited cardiac condition was 37% (32\u201342%) and 9% (6\u201312%) for FE and MA cohorts. In a subset where both FE and MA were performed the diagnostic yield was 45% (38\u201361%). The relative risk of an FE diagnosis of long QT syndrome (LQTS) or Catecholaminergic polymorphic ventricular tachycardia (CPVT) vs. remaining unexplained declined by 5.6% [RR 0.94 (0.91\u20130.98)] and by 11% [RR 0.89 (0.81\u20130.97)], for each year increase in age. Females were more likely to have a diagnosis by both FE [40% (34\u201345%) vs. 36% (31\u201341%)] and MA [15% (10\u201321%) vs. 6% (3\u20138%)]. Females [8.1% (4.1\u201313.4%)], were more likely to be diagnosed with LQTS than males [1.2% (0.2\u20132.7%)] in the MA cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>After a SADS death, the diagnostic yield of comprehensive FE, MA, or both in an expert setting can be up to 45% with a combined approach. Females had higher diagnostic yield than males, most notable with LQTS. CPVT and LQTS diagnoses declined with increasing age. These data highlight the relative utility of FE and MA depending on age and sex for determining underlying diagnoses following SADS deaths.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwae389","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:36:28Z","timestamp":1734507388000},"page":"432-440","source":"Crossref","is-referenced-by-count":12,"title":["Influence of age and sex on the diagnostic yield of inherited cardiac conditions in sudden arrhythmic death syndrome decedents"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-0329","authenticated-orcid":false,"given":"Belinda","family":"Gray","sequence":"first","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]},{"name":"Faculty of Medicine and Health, University of Sydney , Sydney, NSW ,","place":["Australia"]},{"name":"Department of Cardiology, Royal Prince Alfred Hospital , Sydney, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-2853","authenticated-orcid":false,"given":"Elijah R","family":"Behr","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios","family":"Papatheodorou","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Bakalakos","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]},{"name":"Institute of Cardiovascular Science, University College London , London ,","place":["UK"]},{"name":"Inherited Cardiovascular Disease Unit, St Bartholomew\u2019s Hospital , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0000-7520","authenticated-orcid":false,"given":"Hariharan","family":"Raju","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]},{"name":"Faculty of Medicine, Health and Human Sciences, Macquarie University , Sydney ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanushi D","family":"Wijeyeratne","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gherardo","family":"Finocchiaro","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneil","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]},{"name":"Institute of Sport, Manchester Metropolitan University , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-6594","authenticated-orcid":false,"given":"Nicola","family":"Whiffin","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, MRC Laboratory of Medical Sciences, Imperial College , London ,","place":["UK"]},{"name":"Big Data Institute, Centre for Human Genetics, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S","family":"Ware","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, MRC Laboratory of Medical Sciences, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Tome","family":"Esteban","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary N","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Pathology, St George\u2019s University of London , London SW17 ORE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-6138","authenticated-orcid":false,"given":"Sanjay","family":"Sharma","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Institute, City St George\u2019s University of London , Cranmer Terrace, London SW17 0RE ,","place":["UK"]},{"name":"Department of Cardiology, St George\u2019s University Hospitals NHS Foundation Trust , Blackshaw Rd, London SW17 OQT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"2026021723141989200_zwae389-B1","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":"2026021723141989200_zwae389-B2","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"Priori","year":"2015","journal-title":"Eur Heart J"},{"key":"2026021723141989200_zwae389-B3","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S0140-6736(03)14692-2","article-title":"Cardiological assessment of first-degree relatives in sudden arrhythmic death syndrome","volume":"362","author":"Behr","year":"2003","journal-title":"Lancet"},{"key":"2026021723141989200_zwae389-B4","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1093\/eurheartj\/ehn219","article-title":"Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families","volume":"29","author":"Behr","year":"2008","journal-title":"Eur Heart J"},{"key":"2026021723141989200_zwae389-B5","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/j.jacc.2017.02.046","article-title":"Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome","volume":"69","author":"Lahrouchi","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2026021723141989200_zwae389-B6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.hrthm.2020.10.010","article-title":"2020 APHRS\/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families","volume":"18","author":"Stiles","year":"2021","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B7","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.hrthm.2022.03.1225","article-title":"European Heart Rhythm Association (EHRA)\/Heart Rhythm Society (HRS)\/Asia Pacific Heart Rhythm Society (APHRS)\/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases","volume":"19","author":"Wilde","year":"2022","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/europace\/euab176","article-title":"Investigation on sudden unexpected death in the young (SUDY) in Europe: results of the European Heart Rhythm Association Survey","volume":"24","author":"Behr","year":"2022","journal-title":"Europace"},{"key":"2026021723141989200_zwae389-B9","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1056\/NEJMoa1510687","article-title":"A prospective study of sudden cardiac death among children and young adults","volume":"374","author":"Bagnall","year":"2016","journal-title":"N Engl J Med"},{"key":"2026021723141989200_zwae389-B10","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.jacc.2018.01.031","article-title":"The diagnostic yield of Brugada syndrome after sudden death with normal autopsy","volume":"71","author":"Papadakis","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026021723141989200_zwae389-B11","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.hrthm.2017.02.026","article-title":"Twelve-lead ambulatory electrocardiographic monitoring in Brugada syndrome: potential diagnostic and prognostic implications","volume":"14","author":"Gray","year":"2017","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B12","doi-asserted-by":"crossref","first-page":"e007453","DOI":"10.1161\/CIRCEP.119.007453","article-title":"Evaluation after sudden death in the young","volume":"12","author":"Gray","year":"2019","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2026021723141989200_zwae389-B13","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.hrthm.2011.05.020","article-title":"HRS\/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA)","volume":"8","author":"Ackerman","year":"2011","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B14","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1016\/j.hrthm.2016.05.024","article-title":"J-Wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge","volume":"13","author":"Antzelevitch","year":"2016","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12265-016-9673-5","article-title":"Development of a comprehensive sequencing assay for inherited cardiac condition genes","volume":"9","author":"Pua","year":"2016","journal-title":"J Cardiovasc Transl Res"},{"key":"2026021723141989200_zwae389-B16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"2026021723141989200_zwae389-B17","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/gim.2017.258","article-title":"CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation","volume":"20","author":"Whiffin","year":"2018","journal-title":"Genet Med"},{"key":"2026021723141989200_zwae389-B18","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1161\/CIRCRESAHA.116.304521","article-title":"The spectrum of epidemiology underlying sudden cardiac death","volume":"116","author":"Hayashi","year":"2015","journal-title":"Circ Res"},{"key":"2026021723141989200_zwae389-B19","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.hrthm.2011.01.048","article-title":"Arrhythmia characterization and long-term outcomes in catecholaminergic polymorphic ventricular tachycardia","volume":"8","author":"Sy","year":"2011","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.mayocp.2012.02.017","article-title":"Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing","volume":"87","author":"Tester","year":"2012","journal-title":"Mayo Clin Proc"},{"key":"2026021723141989200_zwae389-B21","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.jacc.2018.01.078","article-title":"Interplay between genetic substrate, QTc duration, and arrhythmia risk in patients with long QT syndrome","volume":"71","author":"Mazzanti","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026021723141989200_zwae389-B22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1161\/01.CIR.0000020013.73106.D8","article-title":"Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia","volume":"106","author":"Priori","year":"2002","journal-title":"Circulation"},{"key":"2026021723141989200_zwae389-B23","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/j.1528-1167.2010.02952.x","article-title":"Combined analysis of risk factors for SUDEP","volume":"52","author":"Hesdorffer","year":"2011","journal-title":"Epilepsia"},{"key":"2026021723141989200_zwae389-B24","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1056\/NEJMoa071968","article-title":"Sudden cardiac arrest associated with early repolarization","volume":"358","author":"Haissaguerre","year":"2008","journal-title":"N Engl J Med"},{"key":"2026021723141989200_zwae389-B25","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1161\/CIRCEP.114.001854","article-title":"Clinical characteristics and circumstances of death in the sudden arrhythmic death syndrome","volume":"7","author":"Mellor","year":"2014","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2026021723141989200_zwae389-B26","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":"2026021723141989200_zwae389-B27","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.hrthm.2019.11.027","article-title":"Age at diagnosis of Brugada syndrome: influence on clinical characteristics and risk of arrhythmia","volume":"17","author":"Minier","year":"2020","journal-title":"Heart Rhythm"},{"key":"2026021723141989200_zwae389-B28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.tcm.2014.05.009","article-title":"The value of cardiac genetic testing","volume":"24","author":"Ingles","year":"2014","journal-title":"Trends Cardiovasc Med"},{"key":"2026021723141989200_zwae389-B29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1161\/CIRCGENETICS.116.001571","article-title":"New insights into the genetic basis of inherited arrhythmia syndromes","volume":"9","author":"Gray","year":"2016","journal-title":"Circ Cardiovasc Genet"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwae389\/61266695\/zwae389.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/33\/3\/432\/61266695\/zwae389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/33\/3\/432\/61266695\/zwae389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T04:14:27Z","timestamp":1771388067000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/33\/3\/432\/7931537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,12,23]]},"published-print":{"date-parts":[[2026,2,18]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwae389","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2024,12,23]]}}}