A simple blood test to prevent sudden death ⋅ Inserm, From science to health

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