Periodic Reporting for period 2 - MY-ATRIA (MultidisciplinarY training network for ATrial fibRillation monItoring, treAtment and progression) Reporting period: 2019-11-01 to 2022-04-30 Summary of the context and overall objectives of the project Cardiovascular diseases are the leading cause of death accounting for 30% of deaths worldwide, according to the World Health Organization. Among these diseases, the incidence and prevalence of pathologies related to atrial diseases, particularly atrial fibrillation (AF) and interatrial block, are today reaching pandemic proportions. Despite the high incidence of AF, the ability to treat AF is not improving, at least as assessed by age-adjusted mortality rate post-diagnosis. To improve diagnosis and therapy, a multi-disciplinary approach is needed and to develop it, MY-ATRIA put together a multisectorial consortium, to include technological, clinical and industrial knowledge. MY-ATRIA will address the challenging problems related to detecting atrial arrhythmias with novel device technology as well as to better understanding atrial disease development and response to treatment. The consortium includes 6 academic and 2 industrial Beneficiaries and 5 clinical and 4 industrial Partners to provide scientific support, secondments and training. A new figure of modern professional researchers in AF field will be trained with multidisciplinary competencies, able to transfer advances in basic science to market and clinics. From a scientific point of view, the objectives are: 1. Understanding atrial arrhythmia mechanisms using 3D simulations2. Creating a set of new tools to characterize the progression of AF, and to detect and monitor AF for screening purposes3. Studying the effects of treatment (pharmacological cardioversion and ablation) Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far MY‐ATRIA activities have dealt with the training of ESR and development of their research. These activities focused on three main lines: i) Training‐by‐doing as part of research activities of WP2, WP3 and WP4); ii) Secondment periods and joint‐research activities; iii) Network‐wide training and events. Despite the COVID-19 outbreak which has delayed or postponed some of the planned activities, MY-ATRIA was able to run all the scheduled events (even if some were converted in on-line events or rescheduled to allow in-person participations) and to reach all the training objectives. Concerning the research activities, MY-ATRIA researchers were very productive and advanced the knowledge on AF mechanisms and progression (see “Progress beyond the state-of-the art” sections). Their research generated results which deserved publication on scientific journals or presentation at international conferences. The scientific production consists of 20 journal papers, 22 articles in international conference proceeding and 2 articles in national conference. A fairly balance ratio between journal and conference contributions was maintained (45% journals, 55% conferences) and shows that dissemination activities was differentiated to maximize potential impacts. Quality of the scientific results is also demonstrated by a few scientific awards obtained by the ESR (best poster awards).Concerning the training part, during the second reporting period three Network‐wide events were organized as planned: a) The Winter School in Milano, Italy (January 2021,remote); b) ESR’s day in Milano, Italy (January 2021,remote) c) The Final Workshop in Karlsruhe, Germany (September 2021, in person). Also, an additional ESR’s day in Valencia, Spain (January 2022, remote) was organized in cooperation with the PersonalizedAF MSCA ITN Consortium (grant agreement No.860974). This event gave the ESRs the opportunity to exchange experience within two consortia which shared a common interest in the area of Atrial Fibrillation. This event was important to create a link and professional interchange among two large research networks.Secondment periods and joint‐research activities were highly impacted by the outbreak of the COVID‐19 pandemic, but several actions have been set in place to mitigate this problem (postponements of secondments, enrolment of new partners and remote secondment execution). Globally, the ESR had, on average, secondment experience for a duration of 4.05+/-2.35 months. In support to the research/training activities, the communication/dissemination tasks were constantly running during the period and resulted in: i) two newsletters, ii) the update of the website to spread information of MY‐ATRIA activities and iii) the presentation of preliminary results in Scientific Conferences. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) MY-ATRIA aims to address the challenging problems related to detecting atrial arrhythmias with novel device technology as well as to understanding the influence of atrial geometries, anatomical substrates and remodelling processes in atrial disease development and response to treatment. MY-ATRIA contributes to three main areas: 1) basic knowledge on atrial functioning (WP2), 2) screening and monitoring of atrial dysfunction (WP3), and 3) patient treatment (WP4)Area 1, Basic research: Research is related to the improvement of the state of the art on AF mechanisms, by combining computer models to real data (endocavitary or surface recordings). Significant progresses have been obtained in: i) the compression of interatrial conduction defects and cellular heterogeneity on the electrical behaviour of the atria (ESR1); ii) the assessment of three gain‐of‐function mutations (KCNH2 T895M, KCNH2 T436M, and KCNE3‐V17M) related to episodes of AF using simulations at multi‐scale levels (ESR2); ii) the development of ECG, Body Surface Map (BSM) and machine learning‐based tools to support physicians in diagnoses, ablation planning, and complication prediction for patients with AF and atrial flutter (ESR3) and iv) in developing integrated approach comprising of electrograms signals, 3D meshes and the novel complex networks methods, to support physicians in personalized planning of the therapy (ESR4). Area 2, Monitoring, progression, and risk stratification: The research focuses on AF detection and monitoring of progression using specialised everyday sensors and new devices. Significant progresses have been attained in: i) the association between ischemic events and BAF episodes and the design of a clinical study for large Holter data collection (ESR5); ii) the reliability of AF screening by the combination of signal processing methods for reducing false AF detection (CNN was trained to detect transient noise and low-quality signals) with novel wet electrode for ECG recordings (ESR6); iii) in the analysis of relationship between AF and autonomic nervous system by novel markers of autonomic reactivity in AF (ESR 7); iv) in developing ad-hoc methods for analysis of single lead subcutaneous device and improving its clinical utility (ESR8); v) in developing novel ECG processing technics for the detection of different atrial tachyarrhythmia (ESR9).Area 3, Treatment: The research seeks to clarify which therapy is more appropriate for each single patient, based on the characteristics of the patient’s atria and electrical activity of the heart, using a combined computational and real data approach. Advancements in this area involved: i) computer models were leveraged to uncover the hidden AF mechanisms and tailored virtual hearts were used to foresee the optimal treatment (ESR10); ii) the feasibility to locate parasympathetic innervation regions in human atria directly from the analysis of electrograms (EGMs) (ESR11) and iii) an improved characterization of AF dynamics for guiding catheter ablation by the analysis of multi‐site EGMs.