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National projects

PURKINJE CRA

Characterization of the Purkinje Network from cell to organ, based on cell tissue imaging and clinical data

 

This project aims to characterise the behaviour and structure of the Purkinje network to better understand its role in the origin of arrhythmia and to develop new interventional therapies. This involves developing new imaging techniques, conducting experiments at cellular and tissue level, acquiring clinical recordings of the Purkinje network’s electrical activity, and integrating all of this data into a computer model. This model allows for better stratification of at-risk patients.

This project received funding from the Aquitaine Limousin Poitou-Charentes region as part of the Research 2016 call for projects (File No. 2016-1R30113).

Equipex MUSIC

Multi-modality platform for specific imaging in cardiology

 

A multimodal platform for specific imaging in cardiology.

A multimodal imaging tool was created through the MUSIC project, combining the various existing technologies in the study of cardiac electrical disorders (MRI, X-rays, 3D catheter tracking systems, invasive and non-invasive electrophysiological mapping systems). The goal is to provide a multiparametric assessment of the disease and treatment guidance on one and the same platform.

MUSIC has been used for therapeutic purposes in an international consortium in more than 20 international hospitals in 2017. This study received state support, managed by the National Research Agency as part of the “Investments for the Future” programme with the reference "ANR-11-EQPX-0030."

To know more MUSIC

WAYLESS

 A new therapy to stop ventricular fibrillation with WAYLESS : wide area yielding low-energy surface stimulation 

 

The WAYLESS strategy is to minimise the energy requirements to stop ventricular fibrillation (VF) by using low-energy DC surface stimulation delivered by electrodes strategically placed over large areas of the heart. This involves combining advanced computer and experimental approaches to determine stimulation protocols and electrode configurations capable of reducing defibrillation energy requirements below tissue damage and pain thresholds. 

CARTLOVE

Monitoring radiofrequency catheter ablation by thermometry (MRI) for the atria and ventricles 

 

The success of radiofrequency catheter ablation procedures for arrhythmias, such as ventricular and atrial fibrillation, is currently restricted by a lack of visualisation of lesion formation during the procedure.

The CARTLOVE project aims to significantly improve the assessment of the extent of the lesion created by providing an instant visualisation during ablation using MRI thermometry.

This would substantially reduce failures due to partial ablations of the arrhythmogenic area.

ECGI

Improvement in non-invasive cardiac imaging by characterisation of the scar

 

Non-invasive electrocardiographic imaging (ECGI) visualises the propagation of electrical activity on the heart's surface, and so identifies re-entry conduction (electrical vortices) present in rhythm disorders.

However, the presence of scars in the heart causes artefacts in the results since the electric potentials in these areas are attenuated and complex. This is problematic, because the patterns that cause the re-entries are found at scar level.

The project aims to significantly improve ECGI by better incorporation of MRI data in a new inverse methodology based on source parameterization.

UNMASC

Understanding remodelling mechanisms during the progression of atrial fibrillation to develop better treatment

 

Atrial fibrillation (AF) is the most common of the heart rhythm disorders associated with a poor prognosis. With progression of the disorder, there is a transition phase characterised by an increased frequency and duration of AF episodes, whose nature and development remain unknown. It is important to understand the mechanisms of these deteriorations, the role of intrinsic factors and to find new biomarkers. This project aims to clarify the remodelling processes occurring during this phase in a sheep model with atrial fibrillation (comparable to humans) to improve the management of AF. 

TARGET

 

 

Micro-structural deteriorations related to ventricular fibrillation: cellular and electrocardiographic characterisation.

 

The main goals of this research project are a better understanding of the mechanisms related to triggering and maintaining ventricular fibrillation. This understanding is via molecular and cellular analysis of the heart’s properties and the application of non-invasive electrocardiography.

This project will possibly lead to the discovery of new therapeutic targets. 

SUDDEN DEATH

Mesuring the risks of sudden death

 

Repolarisation times in arrhythmia patients are generally estimated using ARI calculations from ECG recordings. However, this practice has not been properly validated, and subsequently, the use of such a marker in classifying a patient’s risk of sudden death may be compromised.

By accessing the patient’s ECG recordings, we are able to calculate the dispersion of repolarisation and compare it with the recorded images. Additionally, by developing personalised mathematical models of patients’ hearts, we can rate their individual risk of sudden death depending on the conditions causing arrhythmia.

These studies will improve the effectiveness of the indicators of heart arrhythmias and will pave the way for a better risk classification of sudden death. 

 

ARRHYTHMOGENIC RISK

Arrhythmogenic risk assessment due to heterogeneity of repolarisation in patient-specific models 

 

Despite significant improvements in surgery and drug treatments, most people at risk of sudden cardiac death cannot be identified.

This project studies heart cells and the electrical signalling pathway during arrhythmia. Re-entry arrhythmias, where an electrical signal pathologically follows a circuitous pathway and re-enters, are assumed to play a role in maintaining ventricular fibrillation.

The heterogeneities in the repolarisation times of heart cells are associated with an increased arrhythmogenic risk.

Due to a better understanding and study of the mechanisms at cell level, these studies will therefore help to better assess the arrhythmia risk upstream. 

SPATIO TEMPORAL ANALYSIS

Spatio-temporal analysis of the heart's electrical signals for atrial fibrillation ablation 

 

Atrial fibrillation (AF), the most common heart arrhythmia, is responsible for strokes and cardiovascular diseases. Catheter ablation is one of the most common therapies to treat it. Detection of the arrhythmogenic areas to be targeted is based on the analysis of electrogram (EGM) potentials, measured directly on contact with atrial tissue by mapping catheters introduced via the femoral vein. The success rate of the ablation technique for persistent atrial fibrillation is not satisfactory, partly because analysis of the EGM potentials is still highly visual and manual and subsequently operator-dependent and prone to errors.

This project aims to develop automatic tools based on extracting information from EGMs to guide ablation for persistent atrial fibrillation and hence provide targets for ablation. These tools will increase the procedure's success rate and the patient’s quality of life. 

EPAC

New therapeutic targets in atrial fibrillation: the role of Epac 

 

Despite the significant advances in knowledge of cellular mechanisms associated with atrial fibrillation, a better understanding of the molecular signalling pathways, i.e., the stages which involve molecules to control cellular functions, is essential.

This research project proposes a cross-sectional (from the cell to the living organism via tissue) and translational approach highlighting a new actor in atrial fibrillation, the “exchange protein directly activated by cAMP” (Epac). During this project, we propose to demonstrate Epac's key role in atrial fibrillation and to show the therapeutic potential of its inhibition.

MEGAVOLT

 

Mechano-electrical coupling in the healthy right ventricular infundibulum and pressure overload

 

The right ventricular infundibulum (INF) is one of the main anatomical sources of ventricular arrhythmias and idiopathic sudden death in the context of various heart diseases.

Stretching of the heart muscle is known to modulate cardiac electrical activity by a mechanism: mechano-electrical coupling. Thus, we hypothesise that myocardial stretching is a significant regulator of INF electrophysiology, causing arrhythmias in a healthy and diseased right ventricle.

The MEGaVOLT project is studying the contribution of this acute and chronic stretching in the obstruction of right ventricular outflow. It will identify the mechanisms associated with chronic stretching of the INF. This translational project will benefit from an integrated approach to monitoring the mechanisms which cause arrhythmias and to identifying potential therapeutic targets.

CARDIOVERSION

A new safe and painless version of cardioversion for atrial fibrillation with EPIC:  Painless External Cardioversion

 

The purpose of this project is to demonstrate the feasibility of cardioversion – that is painless atrial defibrillation – for atrial fibrillation and to calculate the administration parameters for the person. The research results will serve as a basis for a new and robust AF electrotherapy which will reduce the physical and economic burdens associated with traditional far-field and high-energy electric shocks. At the end of this project, we will be able to proceed with clinical trials.

CANAL TRPM7

Involvement of the TRPM7 channel in Ca2+ and Mg2+ homeostasis and in the electrical activity of Purkinje fibres, and its pathological implications.

 

The TRPM7 channel is expressed ubiquitously throughout the body. It plays a part in the regulation of calcium and magnesium homeostasis, thus playing a major role in many physiological processes. Preliminary unpublished studies have revealed that its levels of transcripts are 3.5 times higher at the PF level compared to the ventricle in the ewe. These data suggest that the TRPM7 channel would play a predominant role in Purkinje fibres.

The goal of this project is to figure out the involvement of the TRPM7 channel in Mg2+ and Ca2+ homeostasis and in the electrical activity of PFs, and to identify its pathological implications. To achieve this objective, patch-clamp experiments will be carried out on isolated cells of Purkinje fibre sheep. The patch-clamp pairing with calcium and magnesium imaging will determine the impact of the TRPM7 channel on the homeostasis of these two ions. Finally, "double-tank" microelectrode experiments, reproducing the infarction context and the computer model, will determine the involvement of the TRPM7 channel in ventricular arrhythmias leading to sudden death.

ATRIAL FIBRILLATION

 

Chronic disease funds requiring medical and technical assistance

 

Current therapies are based on anti-arrhythmic and anticoagulant treatments to prevent thrombus formation and radiofrequency ablation of arrhythmogenic areas, which are often ineffective in cases of persistent and permanent AF. If these treatments fail, a pacemaker is implanted, requiring invasive intervention and regular follow-up of the patient. Patients with persistent and permanent AF are then followed throughout their lives with strict biological and medical monitoring to control blood pressure, the risk of thrombosis and the development of heart failure.

The main objective of this research project is to bring to light new signalling pathways involved in AF in order to define new therapeutic targets. One particular candidate caught our attention, the "exchange protein directly activated by cAMP" (Epac), which has until now been mainly studied in ventricular pathologies. During this project, we will study its link with AF through a transversal (from cell to living organism) and translational (on an animal model and human samples) approach.

CARCOI


CARCOI : High resolution CARrdiac MRI-thermometry on a clinical scanner using intracardiac COIls

 

The project aims at developing novel MRI instrumentation and real-time image acquisition / processing methods to monitor temperature during the treatment of cardiac arrhythmias by radiofrequency catheterization. For this purpose, flexible MRI antennas will be constructed and interfaced with a clinical MRI (1.5T). They will have to be able to be deployed in the heart to improve the spatial selectivity and the sensitivity of the images. The security aspects of the device will be analyzed in detail. Several imaging methods will be developed to exploit these sensors in order to obtain real-time temperature images with a resolution of 150 μm or better in vivo in preclinical studies. The instrumentation and methods developed will also benefit from imaging the cardiac substrate underlying arrhythmias with unparalleled spatial resolution. This project is therefore a major step forward to improve the quality of cardiac MRI.

MAESTRO

 

MAESTRO : Magnetic Signal detection of ventricular arrhythmogenic substrates

 

Ventricular arrhythmias are a major cause of sudden cardiac death in Europe (350,000 deaths / year). The majority of these deaths cannot be anticipated and prevented due to the low sensitivity of current risk criteria. Cardiac mapping of surviving patients has shown the presence of distinctive electrical signals in areas generating arrhythmias. These signals are currently recorded by invasive measurement (catheters) as they are not perceived by electrocardiography or electrical mapping on the surface of the thorax. Detection of the magnetic components of these signals would allow a vector measurement including currents electrically invisible consequence of an altered myocardial zone. The aim of the MAESTRO project is to implement a network of ultrasensitive magnetometers on models of pathological hearts (ex-vivo and in-vivo) in order to develop a non-invasive method of identifying signals associated with a high risk of sudden cardiac death.

SIMRIC

SIMRIC : Mechanically Realistic educational Simulator for Cardiac Interventions

 

This project concerns an innovative learning device for the manipulation of cathetersin the heart rhythm disorders treatment. These arrhythmias, caused by electrical dysfunctions of the heart, are a major public health problem and represent a significant but unknown socio-economic burden. If drug treatments exist, the management of these patients is based on procedures consisting of introducing catheters into the heart to burn the diseased area. These procedures require a great deal of technical expertise and the learning of these procedures is usually done directly on the patient. It is essential that physicians have access to a training device during their training to secure interventions.

This is what the SIMRIC project proposes through the development of a realistic simulator for training in cardiac interventions. Like a stand, it allows the manipulation of electrophysiology catheters in a virtual patient model, and reproduces the technological environment of the intervention rooms, allowing a visualization on the screen of a reconstruction of electrical signals and spatial imaging of the heart.

STIMULATION CARDIAQUE


Non-invasive cardiac pacing with focused ultrasound

 

The project aims to develop a non-invasive device for cardiac stimulation using focused extracorporeal ultrasounds. For this purpose, a dedicated instrumentation will be created in collaboration with the regional company Image Guided Therapy. The project includes multidisciplinary skills (medical device engineering, power electronics, ultrasonic instrumentation, computer modelling, clinical electrophysiology). Multiple clinical applications based on temporary cardiac stimulation are being considered :

  • Therapeutic applications : emergency handling of a conduction disorder, relay of a permanent pacemaker when it must be changed or removed due to infection, or for the management of an atrial or ventricular rhythm disorder.
     
  • Diagnostic applications : atrial or ventricular stimulation to highlight arrhythmias, ventricular stimulation to find an optimal site for definitive stimulation.

FIBRE OPTIC PROBE

Faisability of the development of a multimodal fibre optic probe for highly resolved in vivo localization of cardiac fibrosis

 

Suffers are often only diagnosed with SCD, especially women. Only a minority of patients are therefore eligible for targeted curative treatments, such as ablation treatment. There is a gender imbalance and an inability to identify and locate the combined electrical, structural or biochemical substrates that predispose to VF.

The objective of this project is to overcome this deficit by developing an innovative multimodal imaging fiber probe with high optical resolution, capable of combining morphological and biochemical characterization of arrhythmogenic substrates as a guiding tool for cardiac ablation. This approach will also make it possible to evaluate the effectiveness of ablation in real time. As a result, the availability of such a probe will significantly increase the eligibility of patients (regardless of their genders) requiring treatment for electric heart disease for curative ablation therapy.

BMPR2

 MRI characterization of cardiac alterations associated with mutations in the BMPR2 gene

 

Monoallelic mutations in the BMPR2 gene (Bone Morphogenetic Protein Receptor 2) are the main risk factor for inheritable Pulmonary Arterial Hypertension (PAHT). Patients with mutations in BMPR2 display a higher pulmonary arterial pressure, increased resistance in the pulmonary arteries and a lack of adaptation of the right ventricle compared to non-transferred patients. In this project, the transgenic rat line to be used has a monoallelic BMPR2 mutation and has an PAHT penetrance.

The project aims to compare the cardiac phenotype of BMPR2 rats of 3 months aged (without PAHT) and wild rats (WT) in normoxia and chronic hypoxia using MRI technics. In-vivo-MRI provides hemodynamic data on ventricular function. The high-resolution MRI performed ex-vivo on fixed hearts makes it possible to analyse myofibrils’ orientation using 3D acquisitions with a resolution of 200-μm-isotropic.

 

IVF

    Support for patients’ diagnosis and the search for therapeutic targets in idiopathic ventricular fibrillation and associated sudden death

 

Idiopathic ventricular fibrillation (IVF) is the leading cause of unexplained sudden cardiac death, particularly in young patients under 35 years of age. VIF is a diagnosis of exclusion in patients who have survived an episode of VF without an identifiable cause of structure or metabolism Few data are available on the mechanisms related to IVFs, who are responsible for 14% of sudden deaths. The aim of this project is to understand these mechanisms in order to improve patient diagnosis and treatment. For this purpose, we’re proposing to conduct the first multicentre study on IVFs by combining clinical patient data obtained by the innovative exploratory techniques of the Bordeaux University Hospital with scientific research data in laboratory.

This way, IVF patients in the 3 cardiology departments dedicated to cardiac rhythm disorders in France, namely Paris, Nantes and Bordeaux, will benefit from a complete clinical exploration (in Bordeaux) and a total sequencing of their genome (in Nantes). The collected data will make it possible to define new molecular targets (whose role will be studied in Bordeaux), and to carry out a global statistical analysis (in Paris) in order to identify groups of patients with a similar profile and to consider a personalized therapeutic approach.