Seemingly healthy young people suddenly die genetically or behind the scenes

□ Chutian Metropolis Daily Jimu news reporter Yan Wen correspondent Du Weiwei Yang Cen

Dialogue characters

Hu Dan is a professor of cardiology at Wuhan University People's Hospital. He specializes in basic research and clinical diagnosis and treatment of arrhythmias, heart failure, cardiomyopathy, myocardial ischemia and sudden cardiac death. He has pioneered or participated in the discovery of multiple heart disease-causing genes internationally, and has in-depth exploration of the development of anti-arrhythmia drugs.

Dialogue background

Recently, the news of the sudden death of a 28-year-old man in Changsha after high-intensity work has attracted attention. It is the middle of youth, but it is suddenly dead, which makes people feel overwhelmed. What causes sudden death? Can it be prevented?

Recently, the latest issue of the international top journal in the field of cardiovascular, the Journal of the American Society of Cardiology, published the latest research progress on arrhythmias by Professor Hu Dan's research group of the Department of Cardiovascular Medicine of Wuhan University People's Hospital (Hubei Provincial People's Hospital). Studies have found that the likelihood of sudden death is strongly correlated with individual genes. If genetic testing were used to screen out "lethal" genes and carry out precision treatment, perhaps such tragedies could be reduced. This study has great clinical significance for the early detection and prevention of sudden cardiac death due to early futurism.

In young people who die suddenly, two-thirds have abnormal cardiac development

Extreme Eye News: How can a physically strong athlete suddenly die while exercising? How could a well-mannered young man leave in his sleep without warning?

Hu Dan: Unlike coronary heart disease, which can easily lead to sudden death in middle-aged and elderly people, the main "black hand" behind the sudden death of "seemingly healthy" young people is often genetically inherited cardiomyopathy or hereditary fatal arrhythmia.

Many single-gene genetic diseases, such as hypertrophic cardiomyopathy, dilated cardiomyopathy, and early catalytic syndrome, are the causes of sudden cardiac death. In fact, these diseases are very insidious. Therefore, there are many strong young people, usually may just be a little flustered, or no symptoms, once they work overtime and stay up late or run a marathon, there is a possibility of sudden death. Studies have found that two-thirds of young people who die suddenly have abnormal cardiac development.

Polar News: Sudden death, and sudden cardiac death, what is the relationship between genes and genes?

Hu Dan: It is estimated that sudden cardiac death accounts for more than 80% of the total population of sudden death, and the number of sudden cardiac deaths in China is 544,000 per year, and less than 1% of the survivors. Coronary heart disease, cardiomyopathy and hereditary fatal arrhythmias are the three main causes of sudden cardiac death.

About 70% to 80% of sudden cardiac death is caused by malignant arrhythmias caused by coronary heart disease, which occurs mainly in middle-aged and elderly people; and about 15% to 20% of sudden death is caused by cardiomyopathy, most of which is related to genes. Cardiomyopathy is divided into hypertrophic cardiomyopathy and dilated cardiomyopathy, 80% of hypertrophic cardiomyopathy has a clear genetic problem, and 50% of dilated cardiomyopathy is currently determined to be caused by genes.

Patients with early catalarization syndrome that we focused on in this study belong to the remaining 5% or so of the high-risk population without any symptoms and sudden death, mainly due to hereditary fatal arrhythmias. Almost the vast majority of sudden deaths in this group of people are genetically related, as if they had a switch in the body, there was no trace of it before the onset of the disease, and once the switch was pressed, they may lose their lives.

Genes cannot be changed, but precision treatment can rewrite fate

Polar News: How many genes are known to be found to be associated with sudden cardiac death?

Hu Dan: Genes are fragments of DNA that have a genetic effect. All life phenomena such as the birth, growth, decay, disease, old age, and death of an organism are related to genes, and it is also an intrinsic factor that determines the health of life.

Genetic testing, in simple terms, is to extract DNA from human blood, saliva and other samples, and through genetic technology, the genetic information of DNA molecules is detected to check whether there are genetic mutations, and information including disease risk and precision medication is analyzed.

According to incomplete statistics, genetic testing can find more than 200 genes that cause sudden cardiac death, including more than 100 cardiomyopathy pathogenic genes and nearly 100 inherited fatal arrhythmia pathogenic genes.

Jimu News: Many people think that there is no way to change the genetic problems that are checked. If genetic problems are found, what kind of treatments and interventions can doctors do?

Hu Dan: Genes not only find out the cause, but also help doctors find the best solution. Once the patient's gene type is clarified, the doctor can adopt targeted and precise treatment strategies according to the clinical characteristics and specific conditions of this gene type. For example, the European Heart Association's guidelines have made it clear that patients with three dilated cardiomyopathy mutations should actively implant buried cardioversion defibrillators to prevent sudden death.

PRKAG2 cardiac syndrome is also a genetic disorder in which patients have a higher risk of arrhythmias and sudden cardiac death. Last year I published an article in the Lancet about PRKAG2 heart syndrome, which mentioned a patient in Wuhan who developed the disease at the age of 15 and was included in our study at the age of 19. In the study, we found his genetic mutation through genetic testing. Follow-up studies showed that the mutation of the gene type he carried was very malignant, and then we broke the norm and prospectively recommended that he have a heart transplant in time. Soon after, the patient developed heart failure from pneumonia, but fortunately, our precision treatment bought him valuable time. After a successful change of heart, he also successfully stepped into the dream university door at the age of 23, and turned a new page in his life.

Unfortunately, the article also mentions that three patients, even if there are confirmed patients in the family, still refuse genetic testing, do not receive corresponding treatment, and finally die due to heart failure. These cases remind us of the importance of timely genetic testing and targeted treatment in genetic disorders.

Do not blindly test genes, but should be judged comprehensively in combination with clinical symptoms

Extreme Eye News: If you are worried about carrying a sudden death gene, can you do a genetic screening?

Hu Dan: First of all, I would like to express the idea that genetic testing cannot be used as a routine examination, and blindly testing genes such as finding a needle in a haystack is not recommended by doctors. In general, people with a history of sudden family death, frequent syncope of unknown causes, or cardiac arrest are at high risk of sudden death, and heart disease genetic testing is recommended. If there are confirmed patients with cardiomyopathy and hereditary lethal arrhythmias in the family, then other family members should be very careful, and it is best to identify whether they carry this gene through genetic testing, whether they have genetic mutations, and take preventive measures as soon as possible, which can significantly reduce the occurrence of sudden death. At present, the clinical guidelines in Europe and the United States have strongly recommended class I genetic testing for such patients.

But it is worth noting that it is not the discovery of genetic mutations that will cause 100% sudden death. Genetic mutations only represent a higher risk of sudden death, but how likely it is to occur sudden death needs to be comprehensively judged based on whether there is a family history of sudden death and whether the patient has clinical symptoms.

Genetic interpretation is more important than genetic testing, and the psychological burden caused by excessive interpretation should be avoided. At present, the "2023 International Guide to genetic interpretation of hereditary heart disease" is being written, hoping to bring more guidance and help to clinicians and patients at that time.

Source: Chutian Metropolis Daily