Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time but continue to increase in diameter before they eventually rupture. Left untreated, the patients’ prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures can result in paraplegia from spinal cord ischaemia or even death, particularly for aneurysms extending from the thoracic to the abdominal aorta and thus involving many segmental arteries to the spinal cord, i.e. thoracoabdominal aortic aneurysms of Crawford type II. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10 to 20%. However, it has been found that the deliberate occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord does not increase rates of permanent paraplegia. A therapeutic option, ‘minimally invasive segmental artery coil embolization’ has been devised which proceeds in a ‘staged’ way to occlude groups of arteries under highly controlled conditions after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.

Sudden cardiac arrest (SCA) causes ~20% of all deaths in Europe. SCA is lethal within minutes if left untreated and survival rates are presently only 5-20%. Therefore, there is a large medical need to improve SCA prevention and treatment. Designing effective individualized prevention and treatment strategies requires knowledge on genetic and environmental risk factors. So far, these efforts have been hampered by the lack of sufficiently large study cohorts of SCA patients with detailed information. Obtaining SCA patient samples is challenging as the condition happens suddenly and unexpectedly. In this project, leading European scientific teams which have created large relevant population cohorts, mostly dedicated to SCA research, join forces to fully exploit available data towards improving SCA management. This will be done by: - Building an unique and growing database of >100.000 (DNA) samples including >20.000 SCA patient samples, by combining existing European databases and infrastructures. - Identifying risk factors (inherited, acquired, environmental) and first-response treatment strategies that may explain the differences in SCA occurrence and survival between European countries - Collaborating with professional networks, such as the European Heart Rhythm Association, and European Resuscitation Council, to translate the outcomes into changes in clinical practice and influencing European health policies on SCA management.

Depression is a common and serious comorbidity of cardiovascular disease (CVD) affecting one in three patients, among which women earlier and more frequently. Depression increases the risk for CVD development, acute events and mortality by >2 fold, independently of traditional risk factors, and constitutes an enormous socioeconomic burden in terms of morbidity, mortality and healthcare costs. Still, the patients at risk, disease trajectories and causative mechanisms involved remain unknown. TO_AITION addresses the hypothesis that immune-metabolic dysregulation, occurring as a result of genetic, lifestyle and environmental risk factors ‘training’ innate immunity, drives low grade systemic inflammation leading to the development of CVD-depression comorbidity. It integrates basic (cell models, immune-metabolic mechanisms, myeloid cell reprogramming), preclinical (animal models, CRISPR genome editing) and clinical (longitudinal cohorts with comprehensive existing data) research, in order to characterise immune-metabolic mechanisms driving CVD-depression comorbidity. Both hypothesis and data-driven strategies will be employed to address causality, focusing on genetic, epigenetic, transcriptional, metabolic and other disturbances leading to the development of comorbidity. Drug-drug interactions and their effects on causative mechanisms and disease trajectories will also be determined. Pathways identified will be evaluated in cell-based and animal models to prove their causal role and obtain mechanistic insight. Finally, new risk models will be developed, and relevant regulatory, cost-effectiveness and feasibility issues addressed. Effective patient-oriented awareness actions, dissemination, exploitation and management activities are also provisioned. TO_AITION will therefore rationally change our current understanding of the causative mechanisms driving CVD-depression comorbidity, unravelling patients’ complexity and improving their diagnosis, monitoring and management.

euCanSHare will develop the first centralised, secure and sustainable platform for enhanced cross-border data sharing and multi-cohort personalised medicine research in cardiology. At its heart, the platform will contain the most comprehensive cardiovascular data catalogue ever assembled, which will facilitate data discoverability and exploitation in full alignment with the FAIR principles. The project will implement the interoperability of currently fragmented yet mature IT solutions developed by the consortium members for generating a comprehensive multi-functionality platform. It will also integrate major cardiovascular data sources from Europe and Canada, including the renowned MORGAM, BiomarCaRE and CAHHM initiatives. euCanSHare’s legal framework will be built through detailed ethical and legal interoperability analysis, while investigating innovative solutions for promoting responsible Open Science based on the emerging blockchain technology. Initially populated with 35 European and Canadian cohorts (corresponding to about one million records), the platform will provide extensive functionalities, including for data deposition, data harmonisation and quality control, which will support the integration of new cohorts beyond the duration of the project, thus ensuring its scalability. Moreover, sustainability will be targeted by leveraging through our multi-disciplinary partners the most established data infrastructures, namely ELIXIR, EGA, BBMRI and euro-BioImaging in Europe, as well as Maelstrom from Canada. The unique features of the platform will be demonstrated and adjusted through several use cases, including for biomarker validation, knowledge discovery, cardiovascular risk assessment, public health research and industry-driven studies. Furthermore, intensive outreach campaigns and hands-on workshops will be organised to attract a range of stakeholders, data providers and end-users from the academic, public health and industrial sectors.

Healthcare is the fasted growing EU27 expenditure. Personalised medicine, comprising tailored approaches for prevention, diagnosis, monitoring and treatment is essential to reduce the burden of disease and improve the quality of life. Integration of multiple data types (multimodal data) into artificial intelligence models is required for the development of accurate and personalised interventions. This is particularly true for the inclusion of genomic data, which is information-rich and individual-specific, and more routinely available as the cost of sequencing continues to fall. Multimodal data integration is complex due to privacy & governance requirements, the presence of multiple standards, distinct data formats, and underlying data complexity and volume. NextGen tools will remove barriers in data integration several cardiovascular use cases. NextGen deliverables will include tooling for multimodal data integration and research portability, extension of secure federated analytics to genomic computation, more effective federated learning over distributed infrastructures, more effective and accessible tools for genomic data analysis; improved clinical efficiency of variant prioritisation; scalable genomic data curation; and improved data discoverability and data management. A comprehensive gap analysis of the existing landscape, factoring ongoing initiatives will ensure NextGen deliverables are forward-looking and complementary. NextGen embedded governance framework and robust regulatory processes will ensure secure multi-jurisdictional multiomic multimodal data access aligned with initiatives including “1+ Million Genomes” and the European Health Data Space. Several real-world pilots will demonstrate the effectiveness of NextGen tools and will be integrated in the NextGen Pathfinder network of five collaborating clinical sites as a self-contained data ecosystem and comprehensive proof of concept.