Cardiovascular diseases remain the main cause of mortality worldwide; in particular, heart failure (HF) poses complex challenges in clinical practice, as it is associated with a significant variability in aetiologies, manifestations and risks, as well as in its progression and trajectories over time. Clinical risks of HF can vary from reduced cardiac function and regular hospitalisations, all the way to cardiac events and mortality. There is a need for a personalised medicine approach to tailor the care models (i.e. lifestyle changes, medications, interventions) to each HF patient’s risk profile and hence optimise the clinical outcomes. Artificial intelligence (AI) solutions trained from multi-source cardiovascular data have the potential to dissect the precise characteristics of each patient and predict their likely trajectories at an early stage. However, existing AI methods remain a far distance from clinical transfer and adoption due to a common and key limitation: their trustworthiness and acceptance by cardiologists and patients alike have not been achieved. AI4HF will develop the first trustworthy AI solutions for personalised risk assessment and management of HF patients. The project will build on a unique set of big data repositories, trustworthy AI methods, computational tools and clinical results from major EU-funded projects in cardiology. To test robustness, fairness, transparency, usability and transferability, the validation with take place in eight clinical centres in both high- and low-to-middle-income countries in the EU and internationally. AI4HF will develop a comprehensive and standardised methodological framework for trustworthy and ethical AI development and evaluation based on the FUTURE-AI guidelines developed by the consortium members. AI4HF will be implemented through continuous multi-stakeholder engagement, taking into account clinical needs and patient preferences, as well as socio-ethical and regulatory perspectives.

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 death (SCD) is a major public health problem accounting for ~20% of all deaths in Europe with an estimated yearly incidence of ~350-700,000, often in patients with previous myocardial infarction (MI). In SCD, the heart suddenly and unexpectedly stops beating. If untreated, the patient dies within minutes, but SCD can be successfully prevented by an implantable cardioverter-defibrillator (ICD). The ICD is highly effective, but is associated with potentially severe complications and high healthcare costs. Based on historical evidence, guidelines recommend prophylactic ICD implantation in post-MI patients with left ventricular ejection fraction (LVEF)≤35% to prevent SCD. However, only a minority of these patients will ever need the device. In addition, in absolute numbers the majority of SCD cases occurs in patients with LVEF>35% who are currently not considered for prophylactic ICD. Due to the inherent risks and considerable health care expenditures, a personalised treatment approach for ICD implantation is urgently required. Using state-of-the-art methods and large clinical datasets from established international cohorts and registries across different European geographies, PROFID will develop a clinical decision support tool (risk score) to predict the individual SCD risk and identify those post-MI patients that will optimally benefit from an ICD. Two parallel randomised clinical trials will validate implementation of the risk score to determine ICD implantation, while health economic analyses will assess its economic impact on health care systems. A software tool for clinical use of the risk score will be implemented, and a pilot run in 3 European regions with participation of insurance companies and authorities. The unique composition of the consortium with key opinion leaders, patient organisations, large hospital chains, payers, policy makers and state authorities across Europe, will ensure implementation into routine clinical practice.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a prevalence of 1.5-2% in European populations. By being a major cause of stroke, dementia, heart failure, and premature death, AF is a major threat to healthy ageing. Despite increasing knowledge on the diverse mechanisms that cause the AF substrate in individual patients, current strategies for prevention and therapy of AF remain largely unguided by mechanistic insights. As a result - with the exception of anticoagulation for the prevention of AF-related stroke – treatment of AF has thus far failed to improve patients’ outcome. The CATCH ME consortium will bridge the present disconnect between our understanding of the molecular and electrophysiological mechanisms of AF and the current unstructured approach to its prevention and treatment. The consortium combines clinical, molecular, ECG engineering, and biostatistical expertise, and has access to large sets of human biological material (atrial tissue and bloods samples) and carefully phenotyped patient populations. Together, we will identify and integrate the main drivers of prevalent and incident AF in patients, and validate new ECG- and blood based markers in well-characterized cohorts. The results of these investigations will provide a quantitative estimate of the prevalence and impact of new and established risk factors for AF in Europe and uncover potential new targets and strategies for the prevention and treatment of this arrhythmia. We will integrate these factors into a new clinical classification of AF that will be externally validated in two large patient cohorts, including response to current treatment strategies, and AF-related complications. In summary, CATCH ME will 1. identify major AF-related modifiers of health in the elderly in Europe, 2. develop clinical tools that have the potential of transforming the management of AF in individual patients, and 3. inform future personalized strategies to prevent and treat AF in Europe.

CORE–MD will translate expert scientific and clinical evidence on study designs for evaluating high-risk medical devices into advice for EU regulators, to achieve an appropriate balance between innovation, safety, and effectiveness. A unique collaboration between medical associations, regulatory agencies, notified bodies, academic institutions, patients’ groups, and health technology assessment agencies, will systematically review methodologies for the clinical investigation of high-risk medical devices (Work Package 1), recommend how new trial designs can contribute (Work Package 2), and advise on methods for aggregating real-world data from medical device registries with experience from clinical practice (Work Package 3). Multidisciplinary workshops will propose a hierarchy of levels of evidence from clinical investigations; educational and training objectives for all stakeholders, to build expertise in regulatory science in Europe; and an ethics charter for medical device innovation (Work Package 4). Industry participation will be invited. Specific CORE–MD tasks will advise on optimal statistical methods, the utility of patient-reported outcomes, the conduct of registry trials, clinical criteria for evaluating artificial intelligence as a medical device, and how to evaluate medical devices used in children. The essential principles of medical device trials will be considered jointly with the Good Clinical Trials Collaborative. Links between CORE–MD partners will catalyse sustainable networks for research. The consortium is led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, and involves all 33 specialist medical associations that are members of the Biomedical Alliance in Europe. Final recommendations will be submitted to the Working Group on Clinical Investigation and Evaluation of the European Commission to be considered when developing EU guidance or common specifications.