[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658296":3},{"organization":4,"outcomesModule":7,"designInfo":37,"detailedDescription":40,"studyPopulation":41,"armGroups":42,"interventions":48,"overallOfficials":36,"centralContacts":62,"locations":68,"responsibleParty":84,"collaborators":36,"id":88,"slug":89,"hasResults":90,"nctId":91,"briefTitle":92,"officialTitle":93,"acronym":36,"eligibilityCriteria":94,"healthyVolunteers":90,"sex":95,"minAge":96,"maxAge":97,"enrollmentInfo":98,"targetDuration":36,"studyType":101,"phases":36,"briefSummary":102,"conditions":103,"keywords":105,"overallStatus":71,"whyStopped":36,"lastUpdateSubmitDate":107,"lastUpdatePostDateStruct":108,"startDateStruct":111,"completionDateStruct":113,"leadSponsor":115,"locationsCount":116},{"fullName":5,"class":6},"University of Sao Paulo","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":36},[9],{"measure":10,"description":11,"timeFrame":12},"Diagnostic yield of molecular autopsy","Proportion of index cases in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease is identified by whole exome sequencing, classified according to ACMG criteria.","From sample collection at autopsy to reporting of genetic results, assessed up to 3 years",[14,17,20,24,28,32],{"measure":15,"description":16,"timeFrame":12},"Frequency of variants of uncertain significance","Proportion of index cases with at least one variant of uncertain significance in genes associated with inherited cardiac disease, according to ACMG criteria.",{"measure":18,"description":19,"timeFrame":12},"Distribution of genetic diagnoses by disease category","Number of index cases with pathogenic or likely pathogenic variants, by gene and disease category (primary arrhythmia syndromes, cardiomyopathies, or other inherited cardiac diseases).",{"measure":21,"description":22,"timeFrame":23},"Histopathological findings in the heart","Proportion of index cases with macroscopic or microscopic cardiac abnormalities (such as myocardial fibrosis, fatty infiltration, hypertrophy, coronary anomalies or ischemic injury) on pathological examination.","From autopsy to completion of pathological analysis, assessed up to 3 years",{"measure":25,"description":26,"timeFrame":27},"Carrier rate among first-degree relatives","Proportion of tested first-degree relatives who carry the pathogenic or likely pathogenic variant identified in the index case, assessed by targeted Sanger sequencing","From the index case genetic report to relative testing, assessed up to 3 year",{"measure":29,"description":30,"timeFrame":31},"Uptake of cascade genetic screening","Number of first-degree relatives tested per index case with a pathogenic or likely pathogenic variant.","From the index case genetic report to relative testing, assessed up to 3 years",{"measure":33,"description":34,"timeFrame":35},"Feasibility of the molecular autopsy workflow","Proportion of eligible cases identified at the Death Verification Service for which family consent was obtained and genetic results were successfully reported.","From case identification to reporting of genetic results, assessed up to 3 years",null,{"allocation":36,"interventionModel":36,"interventionModelDescription":36,"primaryPurpose":36,"observationalModel":38,"timePerspective":39,"maskingInfo":36},"FAMILY_BASED","PROSPECTIVE","Background: Sudden cardiac death (SCD) is defined as an unexpected, non-traumatic death from cardiovascular causes occurring within 1 hour of symptom onset in an apparently healthy individual or, if unwitnessed, within 24 hours of the individual last being seen alive and asymptomatic. In individuals younger than 35 years, inherited causes predominate, including primary arrhythmia syndromes and inherited cardiomyopathies. The concept of molecular autopsy, the post-mortem genetic analysis of victims of unexplained sudden death following conventional autopsy, was introduced in 2001. Data on molecular autopsy have been reported mainly from North American, European and Australian populations, and no data are available for the admixed Brazilian population.\n\nStudy setting: This single-center prospective study involves two units of the University of São Paulo: the Death Verification Service of the City of São Paulo (SVOC-USP), where index cases are identified and samples are collected at autopsy, and the Heart Institute (InCor) of Hospital das Clínicas, University of São Paulo Medical School, where molecular and pathological analyses and cascade screening of relatives are performed.\n\nStudy workflow: At SVOC-USP, eligible cases are identified, and informed consent is obtained digitally from the legally responsible family member through the Brazilian government platform (GOV.BR). A verbal autopsy questionnaire is applied to the family, the autopsy report and death certificate are reviewed, and biological samples are collected. Whole blood (EDTA tubes) or tissue samples are sent to the Laboratory of Genetics and Molecular Cardiology (LGCM) at InCor, and the heart is sent to the InCor Pathology Laboratory.\n\nMolecular analysis: Genomic DNA is extracted with the QIAamp DNA Blood Mini Kit and assessed for integrity (agarose gel electrophoresis), purity and concentration (NanoDrop). Whole exome sequencing is performed on the Illumina NextSeq platform, with an expected mean coverage of 100x over 95% of exonic regions. Reads are aligned to the reference genome, and variants are called with GATK HaplotypeCaller. Variants are annotated and prioritized in Franklin by Genoox, retaining variants with a minor allele frequency below 1% in gnomAD, ExAC, Bravo, Kaviar and ABraOM (a Brazilian genomic database), including intronic variants that may affect splicing. Copy number variants are also analyzed. Variants are classified according to the American College of Medical Genetics and Genomics (ACMG) criteria, and pathogenic, likely pathogenic and uncertain-significance variants are reported. Variants of uncertain significance are periodically reassessed. Secondary findings are reported only when included in the ACMG list of recommended secondary findings. Sanger sequencing is used to confirm variants with low coverage or quality and for targeted testing of relatives.\n\nPathological analysis: The heart is weighed after washing the cavities, and a transmural ventricular myocardial sample is stored in liquid nitrogen. After formalin fixation, the heart is examined macroscopically for myocardial fibrosis, fatty infiltration, hypertrabeculation, wall thickness disproportion, valve and septal integrity, and coronary artery origin, course and patency. Five myocardial samples and the mitral and aortic valves are sampled for histology (hematoxylin-eosin), with C4d immunohistochemistry when acute ischemic injury is suspected.\n\nCascade screening: When a pathogenic or likely pathogenic variant is identified in the index case, first-degree relatives are invited to participate at InCor, where they provide consent and a blood sample for targeted Sanger sequencing. Carriers are referred for clinical cardiovascular screening.\n\nEpidemiological analysis: Data on sudden death in individuals aged 5 to 50 years are obtained from the Brazilian Ministry of Health database (DATASUS).\n\nData management and analysis: Data are collected and stored in REDCap, with participants identified only by a coded center and sequential number. Results are summarized using descriptive statistics.","individuals aged 1 to 50 years with unexplained sudden death who undergo autopsy at the Death Verification Service of the City of São Paulo (SVOC-USP), São Paulo, Brazil. First-degree relatives: parents, siblings and children of index cases in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease is identified, evaluated at the Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School.",[43],{"label":44,"type":36,"description":44,"interventionNames":45},"Observation",[46,47],"Genetic: Molecular autopsy by whole exome sequencing","Genetic: Cascade genetic screening by targeted Sanger sequencing",[49,56],{"type":50,"name":51,"description":52,"armGroupLabels":53,"otherNames":54},"GENETIC","Molecular autopsy by whole exome sequencing","Post-mortem genetic testing of index cases using whole exome sequencing of DNA extracted from blood or tissue collected at autopsy, with variant classification according to ACMG criteria. Performed together with a verbal autopsy questionnaire, review of the autopsy report and death certificate, and histopathological analysis of the heart.",[44],[55],"Index cases",{"type":50,"name":57,"description":58,"armGroupLabels":59,"otherNames":60},"Cascade genetic screening by targeted Sanger sequencing","Targeted Sanger sequencing of the variant identified in the index case, using a peripheral blood sample (about 10 mL) from first-degree relatives. Carriers of pathogenic or likely pathogenic variants are referred for clinical cardiovascular screening.",[44],[61],"First degree relatives",[63],{"name":64,"role":65,"phone":66,"phoneExt":36,"email":67},"Luciana Sacilotto, MD, PhD","CONTACT","551126615342","lu.sacilotto@gmail.com",[69],{"facility":70,"status":71,"city":72,"state":72,"zip":73,"country":74,"countryCode":75,"cosmosGeoPoint":76,"geoPoint":81,"contacts":82},"Heart Institute","RECRUITING","São Paulo","05403-900","Brazil","BR",{"type":77,"coordinates":78},"Point",[79,80],-46.63611,-23.5475,{"lat":80,"lon":79},[83],{"name":64,"role":65,"phone":66,"phoneExt":36,"email":67},{"type":85,"investigatorFullName":86,"investigatorTitle":87,"investigatorAffiliation":5,"oldNameTitle":36,"oldOrganization":36},"PRINCIPAL_INVESTIGATOR","Luciana Sacilotto","Principal Investigator","100658296","molecular-autopsy-in-young-individuals-with-sudden-cardiac-death-100658296",false,"NCT07849738","Molecular Autopsy in Young Individuals With Sudden Cardiac Death","Molecular Autopsy in Young Individuals With Unexplained Sudden Cardiovascular Death: a Pilot Workflow at the São Paulo Death Verification Service With Cascade Genetic Screening of First-degree Relatives","Index cases\n\nInclusion Criteria:\n\n* Male or female, aged 1 to 50 years at the time of death\n* Unexplained sudden death, defined as an unexpected, non-traumatic death occurring within 1 hour of symptom onset in an apparently healthy individual or, if unwitnessed, within 24 hours of the individual last being seen alive and asymptomatic\n* Autopsy performed at the Death Verification Service of the City of São Paulo (SVOC-USP)\n* Informed consent provided by the legally responsible family member\n\nExclusion Criteria:\n\n\\- Suspected death from intoxication by toxic substances\n\nFirst-degree relatives\n\nInclusion Criteria:\n\n* First-degree relative (parent, sibling or child) of an index case in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease was identified\n* Informed consent provided by the participant or, when applicable, by a legal representative","ALL","5 Years","50 Years",{"count":99,"type":100},200,"ESTIMATED","OBSERVATIONAL","The goal of this observational study is to create and test a pilot workflow for molecular autopsy (genetic testing after death) in children and adults aged 1 to 50 years who died suddenly from an unexplained cause and were examined at the Death Verification Service of the city of São Paulo, Brazil.\n\nThe main questions it aims to answer are:\n\n* How often can a genetic cause of sudden death be found in young people in Brazil?\n* Can first-degree relatives who carry the same genetic change be identified and referred for heart screening before they have symptoms?\n\nSudden cardiac death in young people is often caused by inherited heart diseases, such as heart rhythm disorders and diseases of the heart muscle. Death may be the first sign of the disease in a family. Most of what is known comes from studies in North America, Europe and Australia, and there are no such data for the Brazilian population.\n\nAfter a family member gives consent, the researchers will:\n\n* Interview the family using a verbal autopsy questionnaire and review the autopsy report and death certificate\n* Collect blood or tissue during the autopsy for genetic testing (whole exome sequencing)\n* Examine the heart under the microscope\n\nWhen a genetic cause is found, the results will be given to the responsible family member, and first-degree relatives (parents, siblings and children) will be invited to take part. Relatives who agree will give a small blood sample (about 10 mL) to test for the same genetic change. Relatives who carry the change will be referred for heart screening.",[104],"Tachycardia",[106],"TVPC","2026-10-01",{"date":109,"type":110},"2026-10-05","ACTUAL",{"date":112,"type":110},"2025-01-08",{"date":114,"type":100},"2028-07",{"name":5,"class":6},1]