{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:24:40Z","timestamp":1767626680245,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondi di Ateneo, Linea D.1, Universit\u00e0 Cattolica del Sacro Cuore"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sudden death is defined as the unexpected death of a healthy person that occurs within the first hour of the onset of symptoms or within 24 h of the victim being last seen alive. In some of these cases, rare deleterious variants of genes associated with inherited cardiac disorders can provide a highly probable explanation for the fatal event. We report the case of a 21-year-old obese woman who lost consciousness suddenly in a public place and was pronounced dead after hospital admission. Clinical autopsy showed an inconclusive gross examination, while in the histopathological analysis an eosinophilic inflammatory focus and interstitial fibrosis in the sino-atrial node were found. Molecular autopsy revealed an intronic variant in the KCNQ1 gene (c.683 + 5G &gt; A), classified as likely pathogenic for long QT syndrome according to the guidelines provided by the American College of Medical Genetics and Genomics. Therefore, there were many anomalies that could have played a role in the causation of the sudden death, such as the extreme obesity, the cardiac anomalies and the KNCQ1 variant. This case depicts the difficult interpretation of rare cardiac structural abnormalities in subjects carrying rare variants responsible for inherited arrhythmic disorders and the challenge for the forensic pathologist to make causal inferences in the determinism of the unexpected decease.<\/jats:p>","DOI":"10.3390\/ijms231911666","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Eosinophilic Infiltration of the Sino-Atrial Node in Sudden Cardiac Death Caused by Long QT Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-6658","authenticated-orcid":false,"given":"Simone","family":"Grassi","sequence":"first","affiliation":[{"name":"Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Health Sciences, Section of Forensic Medical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-5276","authenticated-orcid":false,"given":"Oscar","family":"Campuzano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Cardiovascular Genetics Center, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Girona (IDIBGI), University of Girona, 17190 Girona, Spain"},{"name":"Medical Science Department, School of Medicine, University of Girona, 17003 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f2nica","family":"Coll","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Cardiovascular Genetics Center, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Girona (IDIBGI), University of Girona, 17190 Girona, Spain"},{"name":"Medical Science Department, School of Medicine, University of Girona, 17003 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9707-4249","authenticated-orcid":false,"given":"Francesca","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Cardiovascular Genetics Center, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Girona (IDIBGI), University of Girona, 17190 Girona, Spain"},{"name":"Medical Science Department, School of Medicine, University of Girona, 17003 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Ausania","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Section of Forensic Medicine, University of Verona, 37122 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Scarnicci","sequence":"additional","affiliation":[{"name":"Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6857-8904","authenticated-orcid":false,"given":"Georgia","family":"Sarquella-Brugada","sequence":"additional","affiliation":[{"name":"Medical Science Department, School of Medicine, University of Girona, 17003 Girona, Spain"},{"name":"Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Cardiology Department, Sant Joan de D\u00e9u Hospital de Barcelona, 08950 Barcelona, Spain"},{"name":"European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands"},{"name":"Arr\u00edtmies Pedi\u00e0triques, Cardiologia Gen\u00e8tica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de D\u00e9u, Esplugues de Llobregat, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Brugada","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Cardiology Department, Sant Joan de D\u00e9u Hospital de Barcelona, 08950 Barcelona, Spain"},{"name":"European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, The Netherlands"},{"name":"Arr\u00edtmies Pedi\u00e0triques, Cardiologia Gen\u00e8tica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de D\u00e9u, Esplugues de Llobregat, 08950 Barcelona, Spain"},{"name":"Arrhythmias Unit, Hospital Clinic, University of Barcelona-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Arena","sequence":"additional","affiliation":[{"name":"Area of Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00147 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-9096","authenticated-orcid":false,"given":"Antonio","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Brugada","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Cardiovascular Genetics Center, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Girona (IDIBGI), University of Girona, 17190 Girona, Spain"},{"name":"Medical Science Department, School of Medicine, University of Girona, 17003 Girona, Spain"},{"name":"Cardiology Service, Hospital Josep Trueta, University of Girona, 17007 Girona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grassi, S., Vidal, M.C., Campuzano, O., Arena, V., Alfonsetti, A., Rossi, S.S., Scarnicci, F., Iglesias, A., Brugada, R., and Oliva, A. (2021). Sudden Death without a Clear Cause after Comprehensive Investigation: An Example of Forensic Approach to Atypical\/Uncertain Findings. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050886"},{"key":"ref_2","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","volume":"36","author":"Priori","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_3","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":"ref_4","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Falgueras, A., Sarquella-Brugada, G., Brugada, J., Brugada, R., and Campuzano, O. (2017). Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances. Biology, 6.","DOI":"10.3390\/biology6010007"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e040815","DOI":"10.1136\/bmjopen-2020-040815","article-title":"Incidence of Sudden Cardiac Death in the Young: A Systematic Review","volume":"10","author":"Couper","year":"2020","journal-title":"BMJ Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1159\/000524314","article-title":"Sudden Cardiac Death, Not What You Thought","volume":"147","author":"Teodorovich","year":"2022","journal-title":"Cardiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101712","DOI":"10.1016\/j.legalmed.2020.101712","article-title":"Genetic Variants of Uncertain Significance: How to Match Scientific Rigour and Standard of Proof in Sudden Cardiac Death?","volume":"45","author":"Grassi","year":"2020","journal-title":"Leg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.jacc.2011.01.049","article-title":"Sudden Death in Young Adults","volume":"58","author":"Eckart","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102732","DOI":"10.1016\/j.ebiom.2020.102732","article-title":"Reanalysis and Reclassification of Rare Genetic Variants Associated with Inherited Arrhythmogenic Syndromes","volume":"54","author":"Campuzano","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vallverd\u00fa-Prats, M., Alcalde, M., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Fernandez-Falgueras, A., Coll, M., P\u00e9rez-Serra, A., Puigmul\u00e9, M., and Iglesias, A. (2021). Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later. J. Pers. Med., 11.","DOI":"10.3390\/jpm11030162"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s00439-021-02370-4","article-title":"Clinical Impact of Rare Variants Associated with Inherited Channelopathies: A 5-Year Update","volume":"141","author":"Cesar","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1177\/2047487317751291","article-title":"Obesity and Sudden Cardiac Death in the Young: Clinical and Pathological Insights from a Large National Registry","volume":"25","author":"Finocchiaro","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s11886-022-01671-y","article-title":"The Impact of Obesity on Sudden Cardiac Death Risk","volume":"24","author":"Margolis","year":"2022","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_14","first-page":"e984","article-title":"Obesity and Cardiovascular Disease: A Scientific Statement from the American Heart Association","volume":"143","author":"Poirier","year":"2021","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10654-017-0353-9","article-title":"Body Mass Index, Abdominal Fatness, and the Risk of Sudden Cardiac Death: A Systematic Review and Dose\u2013Response Meta-Analysis of Prospective Studies","volume":"33","author":"Aune","year":"2018","journal-title":"Eur. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cjca.2014.10.027","article-title":"The Implications of Obesity for Cardiac Arrhythmia Mechanisms and Management","volume":"31","author":"Pathak","year":"2015","journal-title":"Can. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.joa.2015.09.010","article-title":"Molecular Autopsy in Victims of Inherited Arrhythmias","volume":"32","author":"Semsarian","year":"2016","journal-title":"J. Arrhythm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zeppenfeld, K., Tfelt-Hansen, J., de Riva, M., Winkel, B.G., Behr, E.R., Blom, N.A., Charron, P., Corrado, D., Dagres, N., and de Chillou, C. (2022). 2022 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Eur. Heart J., ehac262.","DOI":"10.1093\/eurheartj\/ehac699"},{"key":"ref_19","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":"ref_20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.carpath.2016.08.005","article-title":"Anatomopathological Changes of the Cardiac Conduction System in Sudden Cardiac Death, Particularly in Infants: Advances over the Last 25 Years","volume":"25","author":"Ottaviani","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"ref_21","unstructured":"(2022, September 20). The Royal College of Pathologists Guidelines on Autopsy Practice: Sudden Death with Likely Cardiac Pathology. Available online: https:\/\/www.rcpath.org\/uploads\/assets\/3d973908-c2af-46ea-8190b2dc57fa3ba6\/G145-GAP-CardiacDeath_Dec16.pdf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D91","DOI":"10.1093\/nar\/gkr895","article-title":"Ensembl Genomes: An Integrative Resource for Genome-Scale Data from Non-Vertebrate Species","volume":"40","author":"Kersey","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and Accurate Long-Read Alignment with Burrows\u2013Wheeler Transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A Method and Server for Predicting Damaging Missense Mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the Effects of Coding Non-Synonymous Variants on Protein Function Using the SIFT Algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Choi, Y., Sims, G.E., Murphy, S., Miller, J.R., and Chan, A.P. (2012). Predicting the Functional Effect of Amino Acid Substitutions and Indels. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046688"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: Mutation Prediction for the Deep-Sequencing Age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1089\/1066527041410418","article-title":"Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing Signals","volume":"11","author":"Yeo","year":"2004","journal-title":"J. Comput. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/nar\/29.5.1185","article-title":"GeneSplicer: A New Computational Method for Splice Site Prediction","volume":"29","author":"Pertea","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/cmb.1997.4.311","article-title":"Improved Splice Site Detection in Genie","volume":"4","author":"Reese","year":"1997","journal-title":"J. Comput. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/GIM.0b013e31816b5cae","article-title":"ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations: Revisions 2007","volume":"10","author":"Richards","year":"2008","journal-title":"Genet. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.4081\/cardiogenetics.2012.e6","article-title":"Combined Use of In Silico and In Vitro Splicing Assays for Interpretation of Genomic Variants of Unknown Significance in Cardiomyopathies and Channelopathies","volume":"2","author":"Crehalet","year":"2012","journal-title":"Cardiogenetics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1161\/CIRCULATIONAHA.106.665406","article-title":"Clinical Aspects of Type-1 Long-QT Syndrome by Location, Coding Type, and Biophysical Function of Mutations Involving the KCNQ1 Gene","volume":"115","author":"Moss","year":"2007","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1161\/CIRCULATIONAHA.109.863076","article-title":"Genetic Testing for Long-QT Syndrome: Distinguishing Pathogenic Mutations from Benign Variants","volume":"120","author":"Kapa","year":"2009","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1089\/gtmb.2012.0118","article-title":"Results of Genetic Testing in 855 Consecutive Unrelated Patients Referred for Long QT Syndrome in a Clinical Laboratory","volume":"17","author":"Lieve","year":"2013","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.hrthm.2017.04.028","article-title":"Clinical Profile and Mutation Spectrum of Long QT Syndrome in Saudi Arabia: The Impact of Consanguinity","volume":"14","author":"Shafquat","year":"2017","journal-title":"Heart Rhythm."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Koponen, M., Havulinna, A.S., Marjamaa, A., Tuiskula, A.M., Salomaa, V., Laitinen-Forsblom, P.J., Piippo, K., Toivonen, L., Kontula, K., and Viitasalo, M. (2018). Clinical and Molecular Genetic Risk Determinants in Adult Long QT Syndrome Type 1 and 2 Patients: Koponen et al. Follow-up of Adult LQTS Patients. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0574-0"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1161\/CIRCULATIONAHA.111.048041","article-title":"Mutations in Cytoplasmic Loops of the KCNQ1 Channel and the Risk of Life-Threatening Events","volume":"125","author":"Barsheshet","year":"2012","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.hrthm.2015.08.033","article-title":"Stop-Codon and C-Terminal Nonsense Mutations Are Associated with a Lower Risk of Cardiac Events in Patients with Long QT Syndrome Type 1","volume":"13","author":"Ruwald","year":"2016","journal-title":"Heart Rhythm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fendo.2018.00194","article-title":"The Role of KCNQ1 Mutations and Maternal Beta Blocker Use during Pregnancy in the Growth of Children with Long QT Syndrome","volume":"9","author":"Huttunen","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1080\/00016489.2016.1260156","article-title":"Identification of KCNQ1 Compound Heterozygous Mutations in Three Chinese Families with Jervell and Lange-Nielsen Syndrome","volume":"137","author":"Wang","year":"2017","journal-title":"Acta Otolaryngol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/00000433-200203000-00018","article-title":"Sudden Death Resulting from Lesions of the Cardiac Conduction System","volume":"23","author":"Cohle","year":"2002","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/1054-8807(94)90042-6","article-title":"Sudden Death in Athletes\u2014Conduction System: Practical Approach to Dissection and Pertinent Pathology","volume":"3","author":"Bharati","year":"1994","journal-title":"Cardiovasc. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/0735-1097(94)90762-5","article-title":"Conduction System Findings in Sudden Death in Young Adults with a History of Bronchial Asthma","volume":"23","author":"Bharati","year":"1994","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0002-8703(95)90008-X","article-title":"Cardiac Conduction System Involvement in Sudden Death of Obese Young People","volume":"129","author":"Bharati","year":"1995","journal-title":"Am. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fphys.2015.00037","article-title":"Fibrosis: A Structural Modulator of Sinoatrial Node Physiology and Dysfunction","volume":"6","author":"Csepe","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1016\/j.jtcvs.2006.01.031","article-title":"Sinus Node Structural Changes in Patients with Long-Standing Chronic Atrial Fibrillation","volume":"131","author":"Climent","year":"2006","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1161\/CIRCULATIONAHA.108.789677","article-title":"Funny Current Downregulation and Sinus Node Dysfunction Associated with Atrial Tachyarrhythmia","volume":"119","author":"Yeh","year":"2009","journal-title":"Circulation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fphar.2014.00048","article-title":"CaMKII in Sinoatrial Node Physiology and Dysfunction","volume":"5","author":"Wu","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ottaviani, G., Alfonsi, G., Ramos, S.G., and Buja, L.M. (2021). Sudden Unexpected Death Associated with Arrhythmogenic Cardiomyopathy: Study of the Cardiac Conduction System. Diagnostics, 11.","DOI":"10.20944\/preprints202106.0246.v1"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Grassi, S., Campuzano, O., Coll, M., Cazzato, F., Sarquella-Brugada, G., Rossi, R., Arena, V., Brugada, J., Brugada, R., and Oliva, A. (2021). Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084124"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0379-0738(00)00401-1","article-title":"Organ Weight in 684 Adult Autopsies: New Tables for a Caucasoid Population","volume":"119","author":"Clairand","year":"2001","journal-title":"Forensic Sci. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1001\/archinte.1987.00370100039008","article-title":"Overweight and Sudden Death. Increased Ventricular Ectopy in Cardiopathy of Obesity","volume":"147","author":"Messerli","year":"1987","journal-title":"Arch. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0002-8703(88)90891-5","article-title":"Cardiac Failure and Sudden Death in the Framingham Study","volume":"115","author":"Kannel","year":"1988","journal-title":"Am. Heart J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/CIRCULATIONAHA.106.171016","article-title":"Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss","volume":"113","author":"Poirier","year":"2006","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1111\/j.1540-8167.2012.02390.x","article-title":"QRS Fragmentation and the Risk of Sudden Cardiac Death in MADIT II","volume":"23","author":"Brenyo","year":"2012","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Narayanan, K., Zhang, L., Kim, C., Uy-Evanado, A., Teodorescu, C., Reinier, K., Zheng, Z., Gunson, K., Jui, J., and Chugh, S.S. (2015). QRS Fragmentation and Sudden Cardiac Death in the Obese and Overweight. J. Am. Heart Assoc., 4.","DOI":"10.1161\/JAHA.114.001654"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1111\/jce.12742","article-title":"Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy","volume":"26","author":"Konno","year":"2015","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chi, P.-C., Chang, S.-C., Yun, C.-H., Kuo, J.-Y., Hung, C.-L., Hou, C.J.-Y., Liu, C.-Y., Yang, F.-S., Wu, T.-H., and Bezerra, H.G. (2016). The Associations between Various Ectopic Visceral Adiposity and Body Surface Electrocardiographic Alterations: Potential Differences between Local and Remote Systemic Effects. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158300"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.atherosclerosis.2015.05.025","article-title":"Pericardial Fat Is Associated with Ventricular Tachyarrhythmia and Mortality in Patients with Systolic Heart Failure","volume":"241","author":"Wu","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1586\/14779072.2014.952283","article-title":"Sudden Cardiac Death and Obesity","volume":"12","author":"Plourde","year":"2014","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"RC32","DOI":"10.1007\/BF03344061","article-title":"Autonomic Dysfunction Associates with Prolongation of QT Intervals and Blunted Night BP in Obese Women with Visceral Obesity","volume":"25","author":"Esposito","year":"2002","journal-title":"J. Endocrinol. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.hfc.2005.06.013","article-title":"Eosinophilic Myocarditis","volume":"1","author":"Ginsberg","year":"2005","journal-title":"Heart Fail. Clin."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00380-003-0721-0","article-title":"Changes in the Peripheral Eosinophil Count in Patients with Acute Eosinophilic Myocarditis","volume":"18","author":"Morimoto","year":"2003","journal-title":"Heart Vessel."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10875-021-01187-0","article-title":"First Identified Case of Fatal Fulminant Necrotizing Eosinophilic Myocarditis Following the Initial Dose of the Pfizer-BioNTech MRNA COVID-19 Vaccine (BNT162b2, Comirnaty): An Extremely Rare Idiosyncratic Hypersensitivity Reaction","volume":"42","author":"Ameratunga","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Coll, M., Oliva, A., Grassi, S., Brugada, R., and Campuzano, O. (2019). Update on the Genetic Basis of Sudden Unexpected Death in Epilepsy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081979"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/ejhg.2012.280","article-title":"Mild Beckwith-Wiedemann and Severe Long-QT Syndrome Due to Deletion of the Imprinting Center 2 on Chromosome 11p","volume":"21","author":"Gurrieri","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1038\/s41431-019-0445-y","article-title":"European Recommendations Integrating Genetic Testing into Multidisciplinary Management of Sudden Cardiac Death","volume":"27","author":"Fellmann","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102281","DOI":"10.1016\/j.fsigen.2020.102281","article-title":"Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?","volume":"47","author":"Mates","year":"2020","journal-title":"Forensic Sci. Int. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41525-021-00211-x","article-title":"Genetic Variants Associated with Inherited Cardiovascular Disorders among 13,131 Asymptomatic Older Adults of European Descent","volume":"6","author":"Lacaze","year":"2021","journal-title":"NPJ Genom. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1300","DOI":"10.1002\/mgg3.1300","article-title":"Reclassification of Genetic Variants in Children with Long QT Syndrome","volume":"8","author":"Westphal","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"S292","DOI":"10.21037\/cdt.2019.06.06","article-title":"Variant Panorama in 1385 Index Patients and Sensitivity of Expanded next-Generation Sequencing Panels in Arrhythmogenic Disorders","volume":"9","author":"Marschall","year":"2019","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_73","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":"ref_74","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/384078a0","article-title":"KvLQT1 and IsK (MinK) Proteins Associate to Form the IKS Cardiac Potassium Current","volume":"384","author":"Barhanin","year":"1996","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1161\/01.RES.84.3.290","article-title":"Genomic Organization of the KCNQ1 K+ Channel Gene and Identification of C-Terminal Mutations in the Long-QT Syndrome","volume":"84","author":"Neyroud","year":"1999","journal-title":"Circ. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/chd.12011","article-title":"Subclinical Cardiomyopathy and Long QT Syndrome: An Echocardiographic Observation","volume":"8","author":"Haugaa","year":"2013","journal-title":"Congenit. Heart Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jcmg.2014.12.023","article-title":"Cardiac Mechanical Alterations and Genotype Specific Differences in Subjects with Long QT Syndrome","volume":"8","author":"Leren","year":"2015","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0344-0338(85)80051-0","article-title":"Morphologic Alterations in the Long Q-T Syndrome","volume":"180","author":"Bos","year":"1985","journal-title":"Pathol. Res. Pract."},{"key":"ref_79","first-page":"2562","article-title":"Histopathology of the Conduction System in Long QT Syndrome","volume":"10","author":"Rogers","year":"2021","journal-title":"Fetal Pediatr. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11666\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:21Z","timestamp":1760143521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":79,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911666"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911666","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}