Atrial fibrillation affects more than 6 million people and is the leading cause of embolic stroke. It is also a factor in heart failure and dementia. AF is primarily triggered by ectopic foci in the pulmonary veins. This historical discovery (by members of this team) led to the development of a curative treatment based on pulmonary vein isolation via ablation, now part of international guidelines for AF management. However, the cellular mechanisms of pulmonary vein ectopy and their potential molecular targets remain unknown. In patients with persistent AF, the disease affects a large area of atrial tissue with variable extent and localization of the arrhythmogenic substrate. Consequently, ablation is less effective due to the difficulty in locating the substrate in these patients. The team’s objectives regarding AF are to (i) improve our understanding of the mechanisms that initiate and maintain atrial fibrillation; (ii) develop better ablation tools for safer, faster, and simpler procedures; (iii) develop biomarkers and novel therapeutic strategies.

Ventricular fibrillation or tachycardia is a major cause of sudden death with up to 50,000 deaths per year in France alone. Currently, most individuals at risk for sudden death cannot be identified beforehand, an unacceptable situation since they could benefit from implantable defibrillators or antiarrhythmic treatments. Young patients with genetic predispositions or pure electrical dysfunction may develop this type of arrhythmia. However, most ventricular arrhythmias occur alongside structural heart disease, and the characteristics of fatal structural anomalies remain undefined. About 40% of sudden deaths are complications of acute myocardial infarction and could potentially be prevented through risk factor management. The team’s research has also highlighted the central role of the ventricular conduction system (Purkinje fibers) in initiating and maintaining ventricular fibrillation. The team’s goals in the VF domain are to (i) improve the identification of at-risk individuals through better understanding of molecular and cellular mechanisms and the development of new non-invasive screening methods; and (ii) develop new targeted therapies.

Heart failure affects 9 million people in Europe, including 1 million in France — accounting for 10% of all hospital admissions. This is a severe condition: NYHA stage III and IV heart failure leads to a 50% mortality rate within five years. The team aims to better understand the electromechanical dysfunctions leading to heart failure or contributing to deleterious cardiac remodeling, with particular focus on acute or chronic stretch and ventricular electrical dyssynchrony.

Particular attention is also given to the role of bioenergetics and metabolism in cardiac disease and arrhythmias. Cardiac contraction, triggered by electrical stimulation and excitation-contraction coupling, relies on adequate cellular energy responses (ATP production). These mechanisms are severely impacted in heart diseases. A core focus of the team is on the role of mitochondrial metabolism in excitation-contraction coupling and cardiac rhythm.