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Pathogenic Variants Tied To Unexplained Sudden Cardiac Death In U.S. Adults

Discussion in 'Hospital' started by The Good Doctor, Jun 9, 2021.

  1. The Good Doctor

    The Good Doctor Golden Member

    Aug 12, 2020
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    Close to 20% of U.S. adults dying from unexplained sudden cardiac death (SCD) carried pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes in a large genetic association study.

    "These clinically significant variants were predominantly associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and long QT syndrome," Dr. Aloke Finn of the CVPath Institute in Gaithersburg, Maryland told Reuters Health by email. Yet, he noted, the affected individuals had normal cardiac exams at autopsy.

    "These data suggest the need to assess a strategy of integrating genetic testing into risk assessment for the prevention of sudden death, especially in persons with a family history of this phenomenon," he said.


    "Ideally," he added, "we would like to follow this work up by screening a large number of patients for genetic variants for cardiomyopathies and examining rates of sudden death in carriers versus non carriers with phenotypically normal hearts. These data will help us understand whether carriers of such variants are at risk of sudden death in the absence of clinically detectable disease."

    As reported in JAMA Cardiology, the genetic association study included 683 African-American and white adults who died of unexplained SCD and were part of an autopsy registry; of those, 413 had DNA of acceptable quality for genetic sequencing.

    The team sequenced 30 CM genes and 38 arrhythmia genes; variants, curated as P/LP, were assessed for their frequency.

    The median age at death from SCD was 41; 63% were men; and about half were African-American; 12.6% carried variants considered P/LP for CM; 5.3% had P/LP variants for arrhythmia; and 0.5% had P/LP variants for both conditions.

    Overall, 10.9% had P/LP variants for hypertrophic CM; 2.7%, for dilated CM; and 2.7% for long QT syndrome.

    No significant differences in clinical and heart characteristics were found between individuals with or without P/LP variants, and both African-American and white patients were equally likely to harbor them.

    Dr. Sadiya Khan of Northwestern University Feinberg School of Medicine in Chicago, commented on the study in an email to Reuters Health. "Investigating inherited causes (of SCD), such as cardiomyopathies and arrhythmia syndromes with genetic testing can offer important life-saving information for first-degree family members and direct earlier screening and closer surveillance to prevent SCD in those family members."

    "Clinical genetic testing in decedents of sudden cardiac death is ready for prime time and should be considered, based on these findings," she said.

    "One of the biggest barriers (is) a lack of infrastructure or standardized federal policy that requires postmortem genetic testing," she noted. "The question remains who is responsible for this type of evaluation - physicians of the loved ones left behind, if the decedent had a physician? Or the coroner? There is significant heterogeneity across counties and states and I would argue we need federal policies to establish standards in 2021 for postmortem genetic testing routinely after SCD."

    —Marilynn Larkin


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