Molecular Autopsy in Young Individuals With Sudden Cardiac Death

NCT07849738 | Recruiting

• 2 other identifiers: 85756625.5.0000.00688.676.160
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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. The main questions it aims to answer are:

• How often can a genetic cause of sudden death be found in young people in Brazil?
• Can first-degree relatives who carry the same genetic change be identified and referred for heart screening before they have symptoms? Sudden 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. After a family member gives consent, the researchers will:
• Interview the family using a verbal autopsy questionnaire and review the autopsy report and death certificate
• Collect blood or tissue during the autopsy for genetic testing (whole exome sequencing)
• Examine the heart under the microscope When 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.

Conditions

Tachycardia

Keywords

TVPC

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Frequency of variants of uncertain significance

  From sample collection at autopsy to reporting of genetic results, assessed up to 3 years

• Distribution of genetic diagnoses by disease category

  From sample collection at autopsy to reporting of genetic results, assessed up to 3 years

• Histopathological findings in the heart

  From autopsy to completion of pathological analysis, assessed up to 3 years

• Carrier rate among first-degree relatives

  From the index case genetic report to relative testing, assessed up to 3 year

• Uptake of cascade genetic screening

  From the index case genetic report to relative testing, assessed up to 3 years

Study Arms (1)

Observation

Observation

Genetic: Molecular autopsy by whole exome sequencing; Genetic: Cascade genetic screening by targeted Sanger sequencing

Interventions

Molecular autopsy by whole exome sequencing GENETIC

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.

Also known as: Index cases

Observation

Cascade genetic screening by targeted Sanger sequencing GENETIC

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.

Also known as: First degree relatives

Observation

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Male or female, aged 1 to 50 years at the time of death
• 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
• Autopsy performed at the Death Verification Service of the City of São Paulo (SVOC-USP)
• Informed consent provided by the legally responsible family member

You may not qualify if:

• \- Suspected death from intoxication by toxic substances
• First-degree relatives
• 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
• Informed consent provided by the participant or, when applicable, by a legal representative

Sponsors & Collaborators

• University of Sao Paulo: lead

Study Sites (1)

Heart Institute

São Paulo, São Paulo, 05403-900, Brazil

RECRUITING

MeSH Terms

Conditions

Tachycardia

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Luciana Sacilotto, MD, PhD

CONTACT

551126615342; lu.sacilotto@gmail.com

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 24, 2026
• First Posted: September 30, 2026
• Study Start: January 8, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)