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Personalized Therapies for Atrial Fibrillation. A Translational Approach

Periodic Reporting for period 2 - PersonalizeAF (Personalized Therapies for Atrial Fibrillation. A Translational Approach)

Reporting period: 2022-02-01 to 2024-03-31

Atrial Fibrillation (AF) is the most common cardiac arrhythmia affecting more than 6 million Europeans with a cost exceeding 1% of the EU health care system budget (13.5 billion annually). New treatment strategies and the progress achieved in research on AF mechanisms and substrate evaluation methods to date have not been commensurate with an equivalent development of the knowledge and technologies required to individually characterize each patient in search of the most efficient therapy.
PersonalizeAF addresses this challenge by delivering an innovative multinational, multi-sectorial, and multidisciplinary research and training programme in new technologies and novel strategies for individualized characterization of AF substrate to and increase treatments’ efficiency.
From the research point of view, PersonalizeAF will integrate data and knowledge from in-vitro, in silico, ex vivo and in vivo animal and human models to: 1) generate an individual description of the state of the atrial muscle identifying the disease mechanisms and characteristics; 2) understanding the potential effect that different therapies have on different atrial substrates; and 3) combining this information to generate a specific profile of the patient and the best therapy for each patient.
With this purpose, PersonalizeAF partnership aggregates relevant scientific staff from the academic and clinical world with highly specialised biomedical companies which will be involved in a high-level personalised training programme that will train a new generation of highly skilled professionals and guarantee ESRs and future PhD students outstanding Career Opportunities in the biomedical engineering, cardiology services and medical devices sectors.
In the first two years of the PersonalizeAF project, 15 ESRs have been recruited and moving forward in their interdisciplinary projects, following their personal Career Development Plans. The different consortium bodies are periodically meeting, including the monitoring processes of the Supervisory Board of the Network. 4 consortium meetings have been celebrated fully online, where the beneficiaries, Partner Organizations, Advisor Board and ESRs have cooperated to pursue the PersonalizeAF objectives. One of these meetings had the participation of another MSCA project, giving an added value to the researchers. Also, 3 Network-wide Training Activities, including 16 workshops have been organized successfully, in which ESRs and external attendees were involved. Scientific and non-scientific Work Packages are moving forward despite of the sanitary situation since all the members of the project have worked thoroughly to adapt to this unprecedented situation. 16 Deliverables have been submitted to the reporting platform and 2 Milestones were achieved so far. The ESRs have started performing their planned secondments in other organizations. Currently, the consortium is preparing the first on-site meeting in Bordeaux, that will happen in July 2022 and will give the opportunity to meet in person after two years of online communication and collaborations. The ESRs have shown a really productive research production, since 29 dissemination actions were submitted by them (16 were approved), counting conference posters, conference papers and journal papers. The website of the project (www.personalizeaf.net) is online and has great engagement receiving more than 1000 visits per month, and several communication actions are being taken: 3 newsletters launched, daily twitter activity (https://twitter.com/PersonalizeAF) and LinkedIn, periodic blogposts and videoblogs (https://www.youtube.com/channel/UCjNg9EOWPACvu9OMwMWB0aA) .
PersonalizeAF will focus on the development of medical technologies for atrial characterization in order to improve the sensitivity and specificity of atrial biomarkers. This will be achieved by developing new diagnostic tools to support the design of the best patient-specific treatment. This will help to gain insight into the sub-classification of AF patients, as well as the relationship of these disease sub-phenotypes with the treatment outcome. With these expectations, new knowledge, new skills and new approaches are required to first address the complex medical and technological issue of AF patients management, and therefore to train new professionals in the academic, medical and industrial sectors with these skills.

The need for a new generation of researchers is growing and consequently also for institutions that will be able to set the future AF research and educational agenda. PersonalizeAF takes up this challenge and targets to deliver an innovative multinational, multi-sectorial, and multidisciplinary research and training programme in cardiac genetics, cardiac ion channels, stem cells, signal and image processing, computer modelling and patient management with the focus to investigate AF mechanisms with a translational-oriented approach, develop more effective therapies aiming at terminating the disease mechanisms, and finally personalize AF treatments.

To open the field of AF personalization management, PersonalizeAF will implement a variety of technologies addressing these problems:
1) Characterization technologies to describe the patient-specific mechanisms that intervene in cardiac arrhythmia and assess the conditions behind its development. We aim to develop a novel genetic and transcriptomic profiling workbench, able to identify the specific determinant beyond AF apparition and progression. PersonalizeAF also intends to construct novel technologies for tissue description, in terms of fibrosis extent, based on both intracardiac measurements by impedance catheters and non-invasive measures through MRI analysis. We will also characterize the atrial mechanic degradation involved in the AF progression by novel echocardiographic markers, as well as by mathematical simulations. PersonalizeAF will also characterize the individual electric manifestation of the cardiac arrhythmia in each patient both by intracardiac analysis through electric catheters and by non-invasive electrical mapping through electrocardiographic imaging. The information obtained from these technologies will be integrated, making use of artificial intelligence techniques, to generate a specific profile of the patient.
2) Technologies for the assessment of the effect of each therapy option for each disease sub-phenotype. Nowadays, the lack of sub-phenotype disease division prevents a patient-specific classification of the therapy and its success based on characterization of the disease. To achieve it, PersonalizeAF will develop novel technologies for AF therapy characterization and monitoring and the associated technology to identify atrial-specific characteristics that will allow a patient-efficient treatment selection and application. On top of this technological development, PersonalizeAF will test these potential individualized therapies in patient-specific simulations based on the patient disease phenotype, in order to confirm the therapy assignment.
3) Decision support systems for individualized best therapy selection. Once the individualized AF markers for each patient have been obtained, as well as the therapies classified according to their degree of success in each disease sub-phenotype, a high-level analysis is necessary in order to first identify the sub-group of AF which each patient belongs to, as well as to assign the best therapy.
PersonalizeAF Methodology