Jimu news reporter Yan Wen
Correspondent Du Weiwei Yang Cen
Dialogue background
Not long ago, a junior high school student in Beihai, Guangxi Province, unfortunately fell to the ground while running at school; a 28-year-old man in Changsha who worked in the real estate industry died suddenly after high-intensity work... They are all fancy years, and they have died suddenly, which makes people feel overwhelmed. Such examples always appear in people's field of vision. What causes sudden death? Can it be prevented in advance? 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, perhaps such tragedies could be reduced.
Screenshot of the publication of the paper
Recently, the latest issue of the international top journal in the field of cardiovascular,"Journal of the American College of Cardiology", published the latest research progress of arrhythmia in the research group of Professor Hu Dan of the Department of Cardiovascular Medicine of Wuhan University People's Hospital (Hubei Provincial People's Hospital): SCN5A, which encodes the sodium ion channel of the heart, is the main pathogenic gene of early fupolar syndrome (ERS) that can lead to sudden cardiac death. The success of this study has great clinical significance for the early detection and prevention of sudden cardiac death caused by early futurism syndrome. On November 1, Jimu News interviewed Professor Hu Dan to decipher the relationship between sudden death and genes.
Schematic diagram of research results
Biography
Hu Dan is a professor of cardiology at Wuhan University People's Hospital. He was a Senior Research Fellow II/Associate Professor at The Masonic Medical Research Laboratory, a clinical laboratory consultant, and the chairman of the SCRO of the MMRL Stem Cell Center.
Hu Dan
Pioneered or participated in the discovery of multiple heart disease-causing genes internationally; there has been an in-depth exploration of the development of anti-arrhythmia drugs. He specializes in basic research and clinical diagnosis and treatment of arrhythmias, heart failure, cardiomyopathy, myocardial ischemia and sudden cardiac death, epidemiology of cardiovascular diseases, cardiovascular pharmacology (including traditional Chinese medicine), genetics, therapeutics, and translational research of stem cells.
He has the CLIA license of the director of the American Clinical Genetic Testing Laboratory, won the title of Chutian Distinguished Professor, and is an editorial board member and reviewer of more than 40 mainstream journals in the world. He has been invited to become a senior member of several international associations (Member of the Heart Rhythm Society/FHRS, Member of the American Association of Cardiovascular Diseases/FAHA, Member of the American Society of Cardiovascular Diseases/FACC, Member of the Asia-Pacific Heart Rhythm Society/FAPHRS), Former Vice President of the Genetics Branch of the Chinese Heart Rhythm Society (CHRS), etc. In 2020, he was awarded the title of "Young and Middle-Aged Cardiovascular Elite" by the Chinese Medical Association.
"Seemingly healthy" sudden death in young people, the answer may be in the genetic code
Jimu News: How can a physically strong athlete suddenly die while exercising? How can a well-mannered young man stay up late or be tired, or even leave in his sleep without warning? What is the "black hand" behind the sudden death of young people?
Professor Hu Dan: Unlike coronary heart disease, which can easily lead to sudden death of middle-aged and elderly people, the main behind-the-scenes "black hand" that causes the sudden death of "seemingly healthy" young people is often genetically inherited cardiomyopathy or hereditary lethal heart rate disorders.
Many single-gene genetic diseases such as hypertrophic cardiomyopathy, dilated cardiomyopathy, long QT syndrome, early compounding syndrome, Brugada syndrome, etc., are very classic causes of sudden cardiac death, which are very insidious. Among them, there are indeed many strong young people, who may just be a little flustered and dizzy, or have no symptoms, and once they stay up late or run marathons, they may die suddenly.
Current studies have confirmed that sudden cardiac death in young people is closely linked to single-gene diseases, and many patients die in a hurry at the first episode. One study found that 2/3 of all young people who died suddenly had abnormal cardiac development. Mutations in pathogenic genes associated with these diseases can cause abnormal development of the myocardium and associated regulatory systems, leading to morbidity.
Extreme Eye News: Now, there are always many young people who laugh at themselves: it is not good to be young at a young age, it is not good to have a low blood pressure at a young age, and a heart is not good at a young age... In addition to what you mentioned above, sudden death in young people is more likely to be caused by genetics. In other areas of heart disease, is the onset of young people genetically related?
Professor Hu Dan: Now more and more clinical studies have found that there are some very serious patients with high blood pressure, congenital heart disease, hyperlipidemia, atrial fibrillation, etc., who develop the disease at a young age, and there are no other precipitating factors, and the onset of the disease is very serious, and then through genetic testing, it is found that it is often related to genetic inheritance.
Take atrial fibrillation, once considered a patent for the elderly population, and the higher the age, the greater the risk. However, clinically, it is common to see young patients with atrial fibrillation who have no history of hypertension, do not smoke and drink, but have the disease at the age of twenty or thirty. Later, I found through genetic testing for them that most of the young patients with atrial fibrillation carry the atrial fibrillation susceptibility gene, although it is not 100% pathogenic, but if he also has the predisposing factors of atrial fibrillation (such as obesity, sleep apnea syndrome, tumors, etc.), the symptoms of atrial fibrillation will appear very early.
Not long ago, I also diagnosed a very specific case of young hypertension, which is caused by genetic inheritance. This is completely different from what we usually say that high blood pressure has a genetic predisposition, in the past it was only said that heredity is a predisposing factor and a probability problem, but those who carry this gene are 100% sick.
This patient is 28 years old, very young, very thin, when he came to the hospital, his blood pressure was as high as 220/160mmHg, his hypertension was abnormally serious, and the doctor used a variety of antihypertensive drugs, even if five or six antihypertensive drugs were combined, they could not control blood pressure. And another check, such a thin guy's blood vessel blockage is very serious, all three coronary veins are narrowed, and renal insufficiency. Finally, the gene gave the answer, he was due to renal epithelial cell sodium channel mutation caused by high blood pressure, called lidde syndrome. His mother, like him, had a related genetic mutation, but the symptoms were relatively less severe.
Professor Hu Dan rounds the room
Genes cannot be changed, but precision therapy can rewrite the fate of patients
Pole News: What is the clinical significance of genetic testing? Many people think that if the genetic problems are not checked, the money is spent in vain, and if they are checked, they will bear the psychological shadow of the "family curse" and have no way to change the genes. What do you think about this?
Professor Hu Dan: Genes can not only find the cause and give an answer to a disease, but also often provide the best solution in treatment.
Take the young man who inherits hypertension above, after determining the type of gene that causes his hypertension, I adjusted the hypertension medication for him, using only a few cents of Beijing Antihypertensive No. 0, the cheapest, now rarely used in clinical antihypertensive drugs, to control his stubborn hypertension.
Usually, if you see patients with high blood pressure using this drug, I will actively recommend that they switch to a new generation of antihypertensive drugs. But for this patient, instead, he had to give up the expensive antihypertensive drugs, because for his mutation in this gene, the triamterene contained in Beijing Antihypertensive No. 0 was shown to correct the primary hypertension caused by such genetic mutations, better than any expensive antihypertensive drugs. In the end, he and her mother controlled their blood pressure very well through this very cheap medicine.
Extreme Eye News: If a patient with a sudden death gene is found, what kind of treatment and intervention can doctors carry?
Professor Hu Dan: Before the diagnosis of genes, the treatment is based on the symptomatic treatment of the clinician's experience, but the diagnosis of the gene type is clear, and the doctor can adopt targeted and precise treatment strategies according to the clinical characteristics and specific conditions of the patient's gene type. For example, current European Heart Association (ESC) guidelines have directed that patients with three dilated cardiomyopathy mutations should actively implant buried cardioversion defibrillators (ICDs) to prevent sudden death.
Take an article on PRKAG2 heart syndrome that I published in The Lancet last year, PRKAG2 cardiac syndrome is also a genetic disorder with a higher risk of arrhythmias and sudden cardiac death. One of our patients from Wuhan was onset at the age of 15 and was included in this study at the age of 19. In the study, we genetically tested him to find mutations. 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 after contracting pneumonia, but fortunately, our precision medicine strategy bought him valuable time, and he became the first PRKAG2 patient in China to receive a heart transplant. After a successful change of heart, at the age of 23, he also successfully stepped into the door of the dream university and turned a new page in his life.
In contrast, unfortunately, there are three more Chinese patients in the text, even when the family's pre-witnesses have been clearly diagnosed, they still refuse genetic testing for various reasons, do not receive corresponding treatment, and finally die due to heart failure. These realities remind us of the importance of timely genetic testing and targeted treatment in genetic disorders.
Genetic testing is only meaningful if clinical symptoms are combined
Extreme Eye News: If you are worried about carrying a sudden death gene, can you do a genetic screening? At present, in the clinic, how popular is the screening for the sudden death gene, and how accepted is it?
Professor Hu Dan: First of all, I would like to express a point of view 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. Genetic interpretation is more important than genetic testing, and the psychological burden caused by over-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.
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. Or, if there are confirmed patients with cardiomyopathy and hereditary fatal 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 there is a genetic mutation, 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 highly recommended (class I) genetic testing for such patients.
But there is also another extreme that can be encountered in the clinic. Many patients are very resistant to genetic screening, even if they already have a very serious patient in the family, or they already have very clear symptoms. Some of them feel that it is a shame to find genetic abnormalities, some do not want to carry psychological shadows, prefer to hold an ostrich mentality, we respect the personal wishes of patients, but when some patients who really need genetic diagnosis to guide clinical treatment refuse to do further counseling and examination, it is still very painful. In fact, it is not that after finding the mutation of the gene that causes sudden death, sudden death will occur 100%, and then it can only be considered that this person is at high risk of sudden death. How likely the probability of sudden death is, it also needs to be combined with whether there is a history of family sudden death and whether the patient has clinical symptoms to comprehensively judge.
It should be emphasized that the patient's genetic information will be strictly protected, and the domestic requirements in this regard will become more and more standardized. Genetic diagnostics can help identify the risk of sudden death, guide clinical diagnosis and treatment, identify high-risk groups in the family, and potentially prevent similar genetic diseases in the next generation with genetic blockade methods.
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