After sudden cardiac death, genetic testing may provide answers, identify risks for family
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Key takeaways:
- A novel genetic test may provide clues to what caused a person’s sudden cardiac death.
- Testing can then be extended to family members who may be at risk for the same genetic condition.
Sudden death from cardiac causes is among the leading causes of death in the United States, yet predicting who might be at high risk remains a difficult task.
According to the Sudden Cardiac Arrest Foundation, 436,852 people in the U.S. experienced sudden cardiac death in 2020, and many people are unaware that they are living with a genetic condition that greatly increases their risk for an unexpected cardiac event. Additionally, an underlying genetic disorder that predisposes a person to high risk for sudden death likely extends to first-degree relatives. Detecting such conditions among relatives could improve prevention strategies.
Currently, Mayo Clinic offers the only CLIA lab in the country that performs genetic testing for postmortem purposes on a specific sample type. New tests use formalin-fixed paraffin-embedded (FFPE) tissue to identify disease-causing genetic variants.
The lab’s multidisciplinary team interprets the results of 24 different test panels that cover more than 300 genes linked to inherited CV disorders, including four post-mortem gene panels for FFPE analysis, and then can extend testing to family members who may potentially have the same genetic disorder. The findings could lead to better preventive care and potentially prevent sudden cardiac deaths.
Healio spoke with Linnea Baudhuin, PhD, FACMG, clinical molecular geneticist and professor of laboratory medicine at Mayo Clinic, about how genetic testing after death works, the insight it can provide for family members and what research is needed to improve the testing technology.
Healio: What is the prevalence of sudden cardiac death in the U.S.?
Baudhuin: The incidence of sudden death is about 50 to 100 per 100,000 population per year, so about 180,000 to 450,000 cases of sudden death per year. Of those, sudden cardiac death is the predominant cause, about 60% of sudden death is due to sudden cardiac death. The most common cause of sudden cardiac death is arrhythmia or cardiomyopathy. Especially among athletes, a sudden cardiac death is usually due to a cardiomyopathy.
Healio: How does sudden cardiac death affect family members?
Baudhuin: It is shocking for the family and it does cause a ripple effect. There is often an unknown about what caused it. Many times, with sudden death, a cause cannot be identified based on autopsy analysis, also called an autopsy-negative sudden death. But the cause could still be sudden cardiac death if it were due to an arrhythmia. With arrhythmia, there are usually no morphological changes in the heart.
Healio: How could genetic testing help family members better understand what happened to their loved one, and how does it work?
Baudhuin: Genetic testing is a way to potentially explore if an arrhythmia caused the sudden death or, if there was another CV cause, whether that CV cause had an underlying genetic component. Many times, genetic testing is not done, so family members do not have those answers. Often, genetic testing is not done because the appropriate specimen type, which is blood, is not collected at autopsy. The blood sample needs to be collected in a certain type of tube and within a tight time frame. We do almost all of our genetic testing with blood.
However, our postmortem tests use formalin fixed paraffin embedded tissue, or FFPE tissue, which is ubiquitously collected at autopsy. Formalin-fixed tissue undergoes tissue processing and then is embedded in paraffin to create a FFPE block or paraffin block. We are one of the only labs to perform genetic testing with FFPE and we can do it 10 or even 20 years after death, in the events where family members still do not have an answer and want to explore that option. Often, our test is the last hope for the family in getting an answer.
The good thing about getting an answer is it provides closure for the family, which is so important. And, if we do find a genetic cause, we can then perform targeted genetic testing for any at-risk family members if that is desired. Family members can be screened, appropriately monitored with imaging or receive other care to prevent this happening in those individuals in the family.
Healio: What are some of the drawbacks to testing FFPE?
Baudhuin: The FFPE is challenging to test. We still prefer to have blood because you get a better DNA specimen. With FFPE, the DNA is very fragmented.
Thus, we cannot test for everything that we could using a blood sample. For example, we cannot sequence a whole genome and look for copy number variants with FFPE. We do have more of a limited approach with the FFPE, so it would be great to develop new technologies that allow us to test FFPE more comprehensively. We also must get the word out that pathologists should consider collecting blood from the decedents. That would be helpful. Advancing our genomic technologies and providing a comprehensive test based on the sample we are provided is a goal.
Healio: What other research is needed?
Baudhuin: Another interesting area is to correlate the genetic findings to exactly what happened with the cause of death. What genetic findings might cause a more severe phenotype? That could lead to certain therapies or better management strategies, especially if we already know that those individuals have the genetic variant.
We have a large team of people who are involved in this testing — genetic counselors, lab directors and CV pathologists. An added benefit of these tests is we also have the expertise to look at the phenotype or the way the decedent passed away along with the genetic data and try to correlate those. We are aways available to answer questions and provide insights for the family.
Reference:
- Mayo Clinic Labs. Available at: www.mayocliniclabs.com. Accessed Jan. 25, 2024.
- Sudden Cardiac Arrest Foundation. Highlights of 2023 sudden cardiac arrest statistics. Available at: www.sca-aware.org/sca-news/highlights-of-2023-sudden-cardiac-arrest-statistics. Published Feb. 1, 2023. Accessed Jan. 24, 2024.
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