Far from being rare, genetic heart diseases can cause sudden death. Over the past few decades, the management of patients with these pathologies has improved significantly thanks to a rapidly developing approach: cardiogenetics.
An article to be found in the Inserm magazine n°55
According to the Heart & Research Foundation, each year in France, approximately 60,000 apparently healthy adults die suddenly of cardiac arrest. In people under 45, this accident often results from undetected genetic heart disease. Identifying these pathologies as early as possible is therefore vital. This is precisely the objective of cardiogenetics! ” In full swing, this approach has considerably increased the chances of survival for many patients “, emphasizes Philippe Chevalier, cardiologist at the Louis-Pradel hospital in Lyon.
Genetic heart diseases form a large heterogeneous group that includes no less than twenty pathologies. They are classified into two subgroups: cardiomyopathies, where the heart muscle (myocardium) has anatomical defects (hypertrophic, dilated, arrhythmogenic right ventricular cardiomyopathies, etc.) and “arrhythmia syndromes”, where the heart is structurally normal but beats too slowly, too quickly or irregularly ( Brugada, long QT or short QT syndromes…). Although qualified as “rare”, these diseases still affect several tens of thousands of people in France. For example, on its own, the cardiomyopathy Hypertrophic disease affects 1 in 500 people, or around 135,000 French people, according to Orphanet, the rare disease information portal.
While “classic” heart diseases are often favored by certain lifestyles (unbalanced diet, smoking, sedentary lifestyle, etc.), genetic heart diseases result from anomalies (or “mutations”) in certain key genes involved in the manufacture of proteins essential to the proper functioning of the heart, such as myosin, alpha-actinin 2 or ion channel proteins.
A young estate with a bright future
Born in the early 1990s and booming since the early 2010s, cardiogenetics aims to detect these mutations early and treat the patient appropriately. “Like oncogenetics – dedicated to the study of genetic factors favoring cancer – this approach aims to make precision medicine, personalized to the mutations in question for each patient. “, specifies Philippe Chevalier. In France, activity in this field is organized at the national level around the Cardiogen health sector, coordinated by Philippe Charron at the Pitié-Salpêtrière hospital in Paris. In addition to this center and the Louis-Pradel hospital in Lyon, eight others now offer cardiogenetics consultation (the Necker and Georges-Pompidou hospitals in Paris, the University Hospitals of Nantes, Bordeaux, Grenoble, etc.). The cardiogenetics teams of these centers meet regularly, with the aim of standardizing their practices.
In fact, cardiogenetics involves close collaboration between cardiologists and biologists. In Lyon, patients are received by Philippe Chevalier who, after a clinical examination and an analysis of the results of various other possible examinations (specialized electrocardiograms, cardiac imaging, etc.), establishes a diagnosis. Then the team of Gilles Millat, head of the cardiogenetics laboratory of the Hospices Civils de Lyon, tries to genetically validate this diagnosis. ” Concretely, we extract the patient’s DNA from a blood sample and sequence it. Then, using bioinformatics software, we carry out a targeted analysis of a panel of more than 100 genes known to be involved in the suspected pathology. “, details Gilles Millat. Finally, if the result of the genetic test confirms the diagnosis of the cardiologist, the latter prescribes an appropriate treatment: “ a change in lifestyle, drug or non-drug treatment (pacemaker, defibrillator), and/or the implementation of regular medical supervision “explains the doctor. Finally, the team also offers genetic tests to relatives of the patient (mother, father, brothers and sisters or children).
The effectiveness of this approach? As shown, among others, by works published in 2021 by Gilles Millat’s team, which involved 4,185 patients, genetic tests now make it possible to identify with almost certainty the genetic mutations involved, in 30 to 40% of cases. ” In the future, observe the biochemistthis rate could significantly increase thanks to ongoing research, which aims to confirm or invalidate the involvement of certain mutations whose role in certain genetic heart diseases remains uncertain. »
The organoids to the rescue
This research effort notably mobilizes the team of Vincent Gache, researcher Inserm at the NeuroMyoGène Institute in Lyon, which works in collaboration with the groups of Gilles Millat and Philippe Chevalier. ” We create heart organoids from the patient’s blood cells or stem cells into which we introduce suspicious mutations using genome editing techniques. The comparison and analysis of these different organoids makes it possible to quantify the impact of mutations on the functioning of these “mini-hearts” and thus to validate whether these mutations induce the observed disorders. Moreover, importantly, these organoids also allow us to test new drug molecules. », Explains the cell biologist, who precisely describes the approach of his team in an article published in 2021..
Shunned in its infancy by many cardiologists who did not believe in its effectiveness, cardiogenetics is now becoming more and more essential. ” In our service, nearly 2,000 patients now benefit from genetic tests each year, compared to around 100 in 2010. “, says Philippe Chevalier. In the years to come, this upward trend could be amplified. Because in addition to the “rare” genetic heart diseases mentioned above, cardiogenetics could concern other much more frequent heart pathologies. Including in particular myocardial infarction, linked to the obstruction of an artery irrigating the heart, and which affects around 80,000 French people each year, according to Health Insurance. In effect, ” the existence of “heart attack families”, where the risk of being affected by this disorder is higher than in the average person, suggests that these cases are favored by a combination of multiple genetic mutations which, independently, each have tiny effects but which, combined, would significantly increase the risk of myocardial infarction », Explains Philippe Chevalier. How to save even more lives?
Philippe Chevalier and Gilles Millat are researchers in the Architecture team of the core and cytoskeleton musculardirected by Vincent Gache, at the NeuroMyoGene Institute (unit 1315 Inserm/CNRS/Claude-Bernard Lyon 1 University) in Lyon.
Philippe Charron is responsible for the team Genomics and physiopathology of cardiovascular diseases: from monogenic diseases to multifactorial diseases from the Cardiovascular, Metabolism and Nutritional Diseases Research Unit (unit 1166 Inserm/Sorbonne University), in Paris.
Read also
Source: www.inserm.fr
