TachycardiaNCT07849738
Molecular Autopsy in Young Individuals With Sudden Cardiac Death
An observational study of Tachycardia, run by University of Sao Paulo at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 50 years
- Conditions the study is for
- Tachycardia
- What is being tested?
- Molecular autopsy by whole exome sequencing and Cascade genetic screening by targeted Sanger sequencing
- How many people
- 200 participants
- Where
- 1 siteBrazil
- Study dates
- 8 Jan 2025to Jul 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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
- 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
Who cannot join
- Suspected death from intoxication by toxic substances
- First-degree relatives
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Heart Institute
São Paulo, São Paulo, 05403-900
Luciana Sacilotto, MD, PhD, 551126615342, lu.sacilotto@gmail.com
About this study
Official title: 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
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:
Read more
- 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.
Read the detailed description
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.
Study 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.
Study 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.
Molecular 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.
Pathological 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.
Cascade 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.
Epidemiological analysis: Data on sudden death in individuals aged 5 to 50 years are obtained from the Brazilian Ministry of Health database (DATASUS).
Data 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.
- Conditions
- Tachycardia
- Being tested
- Molecular autopsy by whole exome sequencing, Cascade genetic screening by targeted Sanger sequencing
- Keywords
- TVPC
- Medical subject headings
- Tachycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Molecular autopsy by whole exome sequencingGenetic
Also called Index cases
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.
Cascade genetic screening by targeted Sanger sequencingGenetic
Also called First degree relatives
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.
| Study group | Role | What they receive |
|---|---|---|
| Observation | Observation Receives: Genetic: Molecular autopsy by whole exome sequencing; Genetic: Cascade genetic screening by targeted Sanger sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
Secondary outcomes (6)
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.
Measured: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
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).
Measured: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
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.
Measured: From autopsy to completion of pathological analysis, assessed up to 3 years
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
Measured: From the index case genetic report to relative testing, assessed up to 3 year
Uptake of cascade genetic screening
Number of first-degree relatives tested per index case with a pathogenic or likely pathogenic variant.
Measured: From the index case genetic report to relative testing, assessed up to 3 years
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.
Measured: From case identification to reporting of genetic results, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2026
- Study start8 Jan 2025
- Primary completionJan 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TachycardiaStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luciana Sacilotto, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07849738
- Sponsor's protocol ID
- 85756625.5.0000.0068
- Other IDs
- 8.676.160
- Status last verified
- Sep 2026
- First submitted
- 24 Sep 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared. The dataset includes whole exome sequencing data from deceased index cases and genetic data from their living relatives, which are highly sensitive and difficult to fully de-identify. The informed consent obtained from participants and legally responsible family members does not cover data sharing with third parties, and genetic data are classified as sensitive personal data under the Brazilian General Data Protection Law (LGPD). Aggregate results will be made available through scientific publications.
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07849738
- Acronym / sponsor ID
- 85756625.5.0000.0068
- Conditions
- Tachycardia
- Keywords
- TVPC
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- 8 Jan 2025 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 30 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study 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.
Study 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.
Molecular 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.
Pathological 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.
Cascade 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.
Epidemiological analysis: Data on sudden death in individuals aged 5 to 50 years are obtained from the Brazilian Ministry of Health database (DATASUS).
Data 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.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observation | – | Genetic: Molecular autopsy by whole exome sequencing, Genetic: Cascade genetic screening by targeted Sanger sequencingObservation |
Who may qualify
- Ages
- 5 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (6 listed)
- 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
- 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
Key exclusion criteria (2 listed)
- Suspected death from intoxication by toxic substances
- First-degree relatives
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Molecular autopsy by whole exome sequencingAlso: Index casesPost-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. | Genetic | Observation |
| Cascade genetic screening by targeted Sanger sequencingAlso: First degree relativesTargeted 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. | Genetic | Observation |
Primary outcome
Diagnostic yield of molecular autopsy
Time frame: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
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.
6 secondary outcomes
Frequency of variants of uncertain significance
Time frame: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
Distribution of genetic diagnoses by disease category
Time frame: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years
Histopathological findings in the heart
Time frame: From autopsy to completion of pathological analysis, assessed up to 3 years
Carrier rate among first-degree relatives
Time frame: From the index case genetic report to relative testing, assessed up to 3 year
Uptake of cascade genetic screening
Time frame: From the index case genetic report to relative testing, assessed up to 3 years
Feasibility of the molecular autopsy workflow
Time frame: From case identification to reporting of genetic results, assessed up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared. The dataset includes whole exome sequencing data from deceased index cases and genetic data from their living relatives, which are highly sensitive and difficult to fully de-identify. The informed consent obtained from participants and legally responsible family members does not cover data sharing with third parties, and genetic data are classified as sensitive personal data under the Brazilian General Data Protection Law (LGPD). Aggregate results will be made available through scientific publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tachycardia, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luciana Sacilotto, MD, PhD (551126615342, lu.sacilotto@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic yield of molecular autopsy (time frame: From sample collection at autopsy to reporting of genetic results, assessed up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.