Electrophysiology and heart modeling institute THE LIRYC BEAT

NEWSLETTER N° 12 /// 1ST HALF 2021

RESEARCH & INNOVATION: RESEARCH 20 MILLION EUROS FROM EXCELLENCE TO BENEFIT EUROPE TO FOSTER CARDIAC RESEARCH

EDITORIAL PATIENTS. _ page 2

As the new Chief Executive Officer of the institute, Iam INNOVATION pleased to lead Liryc to address the major cardiac challenges TIC EPAC : A HOPE FOR in electrophyisiology while keeping in mind our initial goal : NEW THERAPIES, FROM bringing major advances in medical technologies to the hospital, TO ATRIAL to improve patient care. FIBRILLATION _ page 3 y concern is to pursue the strategic orientations adopted in By Pierre PATIENT CARE Mresearch, innovation, care and education, focusing on the Jaïs, DATA MANAGEMENT : Chief scientific excellence of our teams that are recognized worldwide. OPTIMIZING CARE AND Executive This appointment is an opportunity to foster Liryc’s multidisciplinary RESEARCH Officer of Liryc approach, enhancing collaborations within the institute. I feel _ page strongly about the importance of a cross-disciplinary research for 4 the enrichment of Liryc’s ecosystem to make a real difference in patient care. This is TRAINING AND EDUCATION the whole point of the European projects and international collaborations that you A NEW LIRYC-EDUCATION can read in the following pages of this newsletter. I also want to boost synergies to PLATFORM respond to the urgency of cardiac rhythm diseases. Moreover, these collaborations are _ page an opportunity for researchers to obtain grants for their ambitious projects and to be 5 published in the best scientific journals. MANAGEMENT Innovation, both in terms of practices and approaches, will allow us to adress major A NEW CEO FOR LIRYC medical issues. We have already defined an ambitious roadmap for the future with the _ page 6 artificial intelligence and modeling tools, combining the expertise of our teams, in order to accelerate research and patient care. WOMEN AND MEN PORTRAIT OF A RESEARCH Finally, I which to focus on digitalization to be more flexible and to share knowledge in ASSOCIATE the current health context, which requires us to rethink our practice every day. _ page 7 RESEARCH 20 MILLION EUROS FROM EUROPE TO FOSTER CARDIAC RESEARCH

The European Commission has is the selected three scientific projects number involving the Liryc teams as part of of its Horizon 2020 program. These 70 human hearts new grants are opening up new studied since the opportunities in terms of innovation, CADeNCE research by supporting collaborative and program based on interdisciplinary research to address organ donation was medical challenges. launched in March 2015. 6 year after the launch BEAT AF : a revolutionary treatment for of this successful atrial fibrillation program, the multi- The BEAT AF project coordinated by disciplinary teams met Pierre Jaïs, brings together 9 leading to review the results European clinical centers with the aim of and challenges ahead demonstrating the efficacy of Pulsed Electric during a workshop on Field, a new ablation method, supposedly March 26. more effective and safer than radio- frequency, the reference treatment to date. SIMCARDIOTEST : 21st century in-silico2 It will also help to reduce recurrences, which studies are common. This project has received 6 This project, coordinated by Maxime The program is a million euros funding from the EU’s Horizon Sermesant, is funded by the European great opportunity to 2020 program. Commission for 8 million euros. It will provide study human cardiac new insight into designing new predictive pathologies with tools in cardiac pathologies. It brings together MICROCARD : a more sophisticated advanced mapping and 10 international partners to develop a cardiac modeling tool high-resolution imaging The new European Project MICROCARD standardized and secure platform where in- tools that remain led by the IHU Liryc and coordinated by silico clinical trials run seamlessly in order to test currently unavailable in Mark Potse will develop a software able to drugs and medical devices. the clinic. simulate the electrical activity of an entire heart, cell by cell, on new ultra-powerful Pr Olivier Bernus, Scientific Director of the “Exascale”1 supercomputers. This project, 1Exascale computers perform one billion calculations IHU LIRYC involving multidisciplinary experts from 10 per second. partner centers received 6 million euros 2Research or a test performed using numerical funding from the EU. calculations or computer models.

HIGHLIGHTS Two new international experts to guide Liryc’s major scientific orientations

Liryc is honoured to host two new distinguished members on its Scientific Advisory Board, joining Pr. Barbara Casadei and Katja Zeppenfeld.

Pr Srijoy Mahapatra will provide his expertise on new cardiac technologies. Professor of Medicine at the University of Minesota and Associate Dean for Clinical Innovation, he has held several strategics positions over the years within major international industral groups and startups.

Pr Dobromir Dobrev will share his expertise on molecular mechanisms of cardiac . He is director of the institute for Pharmacology at the University of Duisburg-Essen in Germany.

__ page page 2 2 INNOVATION

HIGHLIGHTS

Optimizing the ablation procedures : from the heart to the prostate Dr. Bruno Quesson’s imaging team has demonstrated the effectiveness of temperature mapping in cardiac MRI during radiofrequency ablation procedures in predicting the size of radiofrequency catheter-induced lesions, helping in improving both the efficacy and safety of treatments. This technique, which was originally developed for the heart, may benefit other organs.

With this purpose, the Liryc teams are now working on the ThermoPro research protocol, coordinated by Dr. Clément Marcelin of the Bordeaux University Hospital. The protocol aims at evaluating this imaging method iorder to develop laser ablation of localized prostate tumors under MRI guidance. TIC EPAC: A HOPE FOR NEW THERAPIES, FROM A LOOK BACK AT HEART FAILURE TO ATRIAL AI : a new method to improve remote cardiac monitoring FIBRILLATION

The IHU Liryc provides its potential in several experimental expertise to support and models of heart failure. This participate in the TIC EPAC compound is protected by a project coordinated by Dr. patent. Frank Lezoualc’h, Research Director at INSERM Unit 1048 The international recognition Different sources of noises, such in Toulouse, in collaboration of Liryc in preclinical models as artifacts due to movements, with INSERM Transfert and of atrial fibrillation and heart extra cardiac muscular activity or SATT Toulouse Tech Transfert. failure has aroused the interest interferences due electrical devices, The Institute is involved in of Dr. Lezoualc’h. This is how Dr. can modify the electrocardiogram transfering the first results Fabien Brette, also interested in (ECG) and affect the quality of cardiac on heart failure into atrial the EPAC protein’s involvement monitoring. fibrillation, paving the way for in arrhythmias, was asssociated new therapies. to the project. With the support The cardiac pacing team at the of Dr Alice Récalde, the team Bordeaux University Hospital launched conducts experiments to validate a machine learning challenge to the liryc he team led by Dr. Frank the inhibition of the EPAC protein community for which 4 teams accepted Lezoualc’h has developed with the AM-001 coumpound to participate. The objective was to Ta new promising molecule in atrial fibrillation. This project use clinical telecardiology databases for the treatment of heart failure. is also funded by the French to propose an artificial intelligence Their work first demonstrated National Research Agency algorithm that could identify relevant the involvement of the EPAC (ANR). Another example of the signals and differentiate them from protein (Exchange Protein importance of multidisciplinary noise. After careful analysis, the directly Activated by cAMP) in the scientific collaboration in order to researchers Narimane Gassa and Nejib disease. Toulouse researchers develop new therapies. Zemzemi presented the algorithm with then identified a pharmacological the lowest error rate of under 1%. inhibitor of EPAC1 called AM-001 Congratulations ! and demonstrated its therapeutic

_ page 3 PATIENT CARE DATA MANAGEMENT: OPTIMIZING CARE AND RESEARCH

The management of clinical data is essential for both research and care, and it requires tools to optimize data collection and manage the use of such data. In this context, clinical team of the Bordeaux University Hospital led by Dr Josselin Duchateau have set up the “DARE1” project.

Medical examination results, clinical data… every year, e-health data are increasing considerably. Now, the challenge is to collect, store and analyze all this in information coming from heterogeneous sources. The DARE project has been developed to address this challenge with a double aim.

Optimizing patient management

Better data management will allow patients to have access The teams are working on a first phase of conversion to emerging medical technologies resulting from research and compilation of data to make them accessible after (AI, automatic analysis), but also to improve patient follow- pseudonymization in the next 6 to 12 months. This project has up (automated re-convocations, remote monitoring, practice a regional and national deployment objective. The availability evaluation, etc.). of these data will enrich research projects and allow progress in comprehension benefiting the patient directly at the same Improving the quality of scientific input time. The generated cardiac data will be analyzed and registered so that Liryc researchers can access them for research projects. 1DAta hub and REsearch network in

FOCUS ON UPDATE ON COVID-19 PROJECTS “Recovered” : taking care of patients and their families The ASCCOVID19 study that looks at the direct consequences of the coronavirus on the heart of Sudden cardiac death often affects people with no known cardiac high-level athletes has just completed the inclusion risk factor. This reinforces the trauma and stress for patients phase. This study has required the recruitment of rescued after an episode of ventricular fibrillation. more than 800 athletes who underwent clinical In this respect, the Reference Center for Hereditary Rhythmic examination, electrocardiographic, and a cardiac Diseases and Prevention of Sudden Death is launching this MRI scan in more than 130 subjects. The results spring a two-year study to investigate post-traumatic stress in will be analyzed in detail and communicated these patients. The aim is to evaluate the stress of patients and in the near future. This will allow for a better one of their relatives through a semi-directive interview (one understanding of the direct consequences of week after the episode, and then 3 months later). the infection on the athlete’s heart, as well as the formulation of recommendations on the recovery Then the teams will be able to propose of intense sports activity after the infection, for adapted psychotherapeutic tools to both professional and non-professional athletes. better accompany the patients and their relatives in this traumatic situation. The COVID-CMR study, which evaluates the incidence of silent myocardial scars by high- This study is coordinated by Adeline resolution MRI after COVID-19 and the associated Nogala who is a clinical psychologist. risk of , is still in progress. The study It has been funded by the French has reached the halfway stage of inclusions. We Cardiology Society. can expect the study to be completed before the summer and results to be published in the fall.

_ page 4 FORMATION

A NEW DIGITAL LIRYC-EDUCATION PLATFORM

E-learning, remote training, personalized content accessible anywhere at any time... The COVID-19 crisis has been an opportunity for Liryc to accelerate the transition to digital tools, which are more flexible, accessible and up to date. This is why the institute has launched a new e-learning platform in April. Its mission is to facilitate and accelerate scientific and medical knowledge sharing.

This E-learning platform will include a wide range of training and followed via a dashboard that records the participant’s contents related to electrophysiology, and more specifically progress, regardless of the type of training, whether it is to ablation and cardiac stimulation. This platform will also continuing professional education or academic degree include all the training programs of the Institute. It takes courses. into consideration the increasing need to provide more video content, including case studies, live interventions, An interactive tool transmissions of meetings or more classical teaching contents, including courses, bibliographies and publications. In a health context that has disturbed interpersonal relationships, this platform also helps to create interaction A step towards personalized training with the teaching team and other students thanks to chat The platform also allows for a personalized training modules and forums. It is a great way for the upcoming approach, with access to profile-based contents, which generation of researchers and clinicians in electrophysiology are organized in modules for a step-by-step follow-up of to multiply the opportunities for engaging with world-class the different courses. The modules can be self-managed experts.

A new Training & heart failure at the Bordeaux Education Director University Hospital.Former vice- With the support of a dedicated president of the University of teaching team, I want to In February, Prof. Bordeaux in charge of research, develop an international Pierre Dos Santos he now puts his expertise at training program of excellence, succeeded Prof. the service of Liryc by building in which interdisciplinarity is Pierre Bordachar international training programs of the cornerstone of a strong as Training excellence. scientific culture. My personal & Education He wishes to develop a teaching challenge would be to see that Director of the program designed enhancing within five years, any student or Institute. Liryc’s scientific excellence and professional who wants to learn Prof. Pierre interdisciplinary approach to train about electrophysiology knows Dos Santos is future cardiac electrophysiology that this is happening at Liryc. a cardiologist, experts. A first challenge will be to Pr Pierre Dos Santos professor of involve the whole Liryc community Training & Education Director of physiology and as well as the industrial partners in the IHU LIRYC . head of the cardiology department this training project. specialized in the treatment of __ pagepage 5 MANAGEMENT

HIGHLIGHTS - LIRYC’S A NEW CEO FOR LIRYC TEAMS’S INITIATIVES Professor Pierre Jaïs has been appointed Chief Executive Director of the IHU Liryc by the Administrative Board on February 1st 2021, after an international recruitment procedure.

As Chief Executive Director of the IHU Liryc for a 4-year term, he will lead the institute in its strategic objectives and challenges, both in terms of the scientific and clinical aspects of cardiac electrophysiology as well as Each month, an Artificial the business plan of the institute. Intelligence (AI) working group meets virtually, led by Driven by his passion for the Multimodal Data Science technological innovation and researcher Dr Marta Nunez cardiac electrophysiology, Prof. Garcia. Pierre Jaïs is an internationally recognized expert. He wishes to AI at Liryc is a transversal strengthen the multidisciplinary and and important theme that translational aspect of the Institute. involves several research

and clinical teams. The He succeeds Professor Michel purpose of this group is Haïssaguerre, who founded the to discuss ideas and tools institute and will continue to be to improve practices and involved in the scientific life of Liryc, facilitate the cooperation for and more generally as Honorary future projects. Chairman of the institute.

FUNDRAISING Liryc’s fundraising campaign is also running Two important virtual meetings for Liryc’s internationally. On March 18, in a remote session, the fundraising’s activities institute gave a virtual visit tour of its laboratories and platforms to 50 Americans gathered around Mark and Laura Bailey, donors of the institute. The On March 10, Liryc hosted a plenary session of the ETI event was an opportunity to raise awareness about Club of Nouvelle-Aquitaine. This was an opportunity to heart rhythm disorders and about Liryc’s ambition introduce the institute and its projects to an audience of to develop new diagnostic and therapeutic solutions. 90 regional business leaders. It paves the way to future Many participants became donors of Liryc after this collaboration and fundraising opportunities. Welcoming initiative. the Club at Liryc illustrates the Institute’s desire to engage with regional companies.

Opening the institute, sharing our projects, and meeting the public is essential to us. I am very proud to be part of the dynamic On its own scale, this event allowed us to initative initiated by the ETI Club and to achieve those goals. become a sponsor of Liryc. Dr Mélèze Hocini, Jean-Paul Calès, Deputy Directof of Liryc CEO of Cap Ingelec

_ page 6 WOMEN AND MEN

PORTRAIT OF A RESEARCH ASSOCIATE CONGRATULATIONS !

• Aurélien Bustin and Kanchan Kulkarni received a grant from the Lefoulon Delalande Foundation for their research projects.

• Maxime Sermesant has received a European Horizon 2020 grant for his AI project, Digital Twin & Clinical Trial for a Disruption in Catheter Ablation.

• Aurélien Bustin is the winner of an ISMRM Junior Fellow award 2021, recognizing the Meeting with Richard Walton, associate researcher in outstanding work of the tissue electrophysiology team, at Liryc. young researchers.

• Matthias Stuber Richard, what is your position at of the heart and the impact of electrical received a gold Liryc ? and structural alterations in pathological medal at the Society I am a research associate, specializing in hearts. for Cardiovascular cardiac physiology. Magnetic Resonance What is your greatest pride ? 2021 conference, the When did you join the institute ? My greatest pride is to coordinate a I joined Liryc at the end of 2011, coming collaborative project “MultiFib” with two highest distinction in the from the UK where I was already working European teams. We are developing an profession. with Prof Olivier Bernus, now Scientific innovative catheter to image microscopic Director at Liryc. details of the cardiac tissue. The goal is to characterize electrical activity with What does it mean to be a research an optical approach, to better identify associate at Liryc ? and localize electrical substrates that I work mainly in the experimental predispose to ventricular fibrillation. We laboratory, but I am also involved in should have a working prototype by 2022. the coordination of different research projects, from obtaining funding for these To conclude, do you prefer to work projects to the daily management of the in the UK or in France ? experimental work in the lab. Today, my family is in France and I am also On the scientific side, I am interested in very happy to work in a great international the mechanisms of sudden cardiac death, professional environment, with huge and more particularly in the development research opportunities, right here in of new tools to map ventricular activity. Bordeaux ! I observe the behavior of cardiac cells and tissues with different imaging tools and try to understand the mechanism

_ page 7 A LOOK BACK AT THE KEY EVENTS

JANUARY 29, 2021 APRIL 6, 2021

Second session of remote learning for the 20 students of Dr Mélèze Hocini has taken part in the first ANCRE medical the University Diploma in remote monitoring of implantable program broadcast, a patron of the institute and Allianz, to cardiac devices. discuss research & COVID-19 with other experts.

JANUARY 29-31, 2021

The teams participated to the 26th AFsymposium virtual edition on the latest advances in atrial fibrillation management.

MARCH 25, 2021

The world’s first commercially approved use of pulsed field FEBRUARY 2021 ablation technology to treat patients with atrial fibrillation on March 23rd by the IHU Liryc and Bordeaux University Participation of the institute’s reference center in charge of Hospital, led by Prof. Pierre Jaïs using technology from hereditary rhytmic diseases in the digital awareness campaign Farapulse. for rare diseases and their prevention, to remind the importance of diagnosis and family screening to improve access to treatments.

MARCH 4, 2021

Temporary installation of Intuitive Surgical robots for medical training in robotic surgery.

WE CAN SUPPORT LIRYC TOGETHER TO PREVENT AND CURE HEART RYTHM DISEASES IHU Liryc Make a donation on : www.ihu-liryc.fr Campus Xavier Arnozan Avenue du Haut Lévêque or by bank check : IHU Liryc - FBU 33600 Pessac Campus Xavier Arnozan Avenue du Haut Lévêque 33600 Pessac www.ihu-liryc.fr

NEWSLETTER N° 12 /// APRIL 2021 Printed on 100% recly- Directors of the publication : the bord of directors with P. Jaïs, M. Hocini, P. Jaïs, R. Marthan, cled cyclus paper. P. Bordachar, O. Bernus, J. Boussuge-Rozé, R. Dubois, V. Bitker, H. Normand, M. Haïssaguerre. • Model and by Aquiprint. graphics : F. Garcia, E. Gaillacq • Photo Credits : Liryc - Richard Noury - Gautier Dufau - Production du désert - THE Marie Astrid Jamois - Grilled Cheese - Maitetxu Etchevarria. LIRYC THEY ARE DONORS BEAT ABBOTT, ANCRE, ASSOCIATION PAUL ET PHILIPPE PERROT, MARK & LAURA BAILEY, BIOSENCE WEBSTER, BOSTON SCIENTIFIC, BERNARD MAGREZ, MEDTRONIC, RUBIS.