Evidence map›Paper›PMID 39708038›Full record

ArticleJACC. Clinical electrophysiology2025

Heritable Burden of Community Sudden Death by Autopsy and Molecular Phenotyping for Precision Genotype Correlation.

Zian H Tseng, James W Salazar, Julianne Wojciak, W Patrick Devine, Brielle A Kinkead, Matthew Yee, David Eik, Jean Feng, Andrew J Connolly, Ellen Moffatt

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. Clinical electrophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Countywide burden, pathology, and genetics of lethal hypertrophic cardiomyopathy: from the POST SCD study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Zian H TsengSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA; Cardiovascular Genetics Center, University of California-San Francisco, San Francisco, California, USA. Electronic address: zhtseng@medicine.ucsf.edu.
James W SalazarSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA. Electronic address: https://twitter.com/JamesSalazarMD.
Julianne WojciakCardiovascular Genetics Center, University of California-San Francisco, San Francisco, California, USA; Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
W Patrick DevineDepartment of Pathology, University of California-San Francisco, San Francisco, California, USA.
Brielle A KinkeadSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
Matthew YeeSchool of Medicine, University of California-San Francisco, San Francisco, California, USA.
David EikSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
Jean FengDepartment of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California, USA.
Andrew J ConnollyDepartment of Pathology, University of California-San Francisco, San Francisco, California, USA.
Ellen MoffattOffice of the Chief Medical Examiner, City and County of San Francisco, San Francisco, California, USA.

Funding

Molecular Phenotyping for Autopsy-Defined Sudden Cardiac DeathR01HL147035 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TSENG, ZIAN H · 2020 to 2023
$3.2M
Comprehensive autopsy characterization of sudden cardiac deathR01HL102090 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TSENG, ZIAN H · 2010 to 2014
$2.8M
NHLBI NIH HHS R01 HL102090NHLBI NIH HHS R01 HL147035
6 · The paper itself

Abstract

backgroundSudden cardiac death (SCD) genetic studies neglect the majority occurring in older decedents with cardiovascular pathology.

objectivesThis study sought to determine the burden of genetic disease in unselected adult sudden deaths by precision genotype-postmortem phenotype correlation.

methodsThe authors used autopsy, histology, and toxicology to adjudicate cause and identify high-suspicion phenotypes (eg, hypertrophic cardiomyopathy) among presumed SCDs aged 18 to 90 years referred to the county medical examiner from February 2011 to January 2018. They tested 231 genes associated with sudden death and correlated genotype with postmortem phenotypes, including myocardial analysis. Family history in high-suspicion phenotype cases was obtained.

resultsOf 856 autopsied presumed SCDs, families of 359 consented and 306 cases (66% cardiac cause) ultimately underwent genetic testing (mean age 62 years, 74% male). Seventy-five cases met high-suspicion phenotype criteria (8.8%), of which 36 underwent testing; 18 families met with a genetic counselor. We found 14 cases with autosomal dominant or X-linked pathogenic/likely pathogenic (P/LP) variants (apparent yield 4.6%); 6 had concordant cause (corrected yield 2%). Yields restricted to autopsy-confirmed cardiac causes (2.5%) and high-suspicion phenotypes (2.7%) were similar. Myocardial genotyping in 14 high-suspicion decedents matched negative blood genotyping, thus did not support somatic mosaicism. Myocardial RNA in a P/LP PKP2 carrier without phenotype demonstrated nonsense-mediated escape as potential mechanism for incomplete penetrance. One-half of high-suspicion cases had a family history of a related condition or sudden death.

conclusionsIn this 7-year countywide study, 2% of total sudden deaths and 2.5% of confirmed SCDs had identifiable genetic cause, corrected for genotype-phenotype concordance. These results do not support routine genetic testing for community sudden deaths, particularly without autopsy.

Indexed as

Death, Sudden, CardiacAdolescentAdultAgedAged, 80 and overAutopsyFemaleGenetic Association StudiesGenetic TestingGenotypeHumansMaleMiddle AgedPhenotypeYoung Adultautopsygeneticssudden cardiac death

Identifiers

PMID39708038
PMCPMC12117619

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.