TARGET: A Major European Project Aiming to Advance the Personalised Management of Atrial Fibrillation-Related Stroke via the Development of Health Virtual Twins Technology and Artificial Intelligence

Atrial fibrillation (AF) is the most prevalent heart arrhythmia globally, resulting in severe complications, substantial financial costs, and significant resource use(1). AF frequently goes unnoticed until the patient presents with AF-related complications (e.g. stroke, heart failure, dementia and hospitalisations), particularly with brief episodes of AF that spontaneously revert to sinus rhythm. In Europe, stroke (a major complication of AF) is a leading cause of death and the top cause of disability. The pathophysiology of AF-related stroke (AFRS) involves severe neurological deficits which considerably worsens prognosis. While risk factors for poor stroke outcomes are known, current AF prediction models have limitations and fail to account for dynamic changes in risk profiles (2,3). In addition, the importance of various stroke risk factors in AF may have changed over the years, for example, sex differences in AFRS risk(4,5). This has had implications for stroke risk stratification, concerning the use of the well-validated CHA2DS2-VASc score or a non-sex version (CHA2DS2-VA)(6–8). Nevertheless, recognising the residual cardiovascular risks associated with AF despite anticoagulation, the management of this condition has moved towards a more holistic or integrated care approach, which has been associated with better clinical outcomes(9,10). This has led to such an approach recommended in contemporary guidelines(11–14). Stroke prevention is central to AF management (15). Indeed, oral anticoagulant treatment in AFRS presents a dilemma: early initiation may increase haemorrhagic transformation risk, while delays can lead to recurrent ischemic strokes. Post-stroke rehabilitation, crucial for reducing risks and improving outcomes, lacks consensus on effective protocols, particularly personalised approaches based on functional outcomes in AFRS patients. This uncertainty can result in the exclusion of patients who would benefit from rehabilitation or the inefficient use of healthcare resources on those unlikely to help. Given this background, the European Union, through the Horizon Europe research programme, has funded the "Health Virtual Twins for the Personalised Management of Stroke Related to Atrial Fibrillation” (TARGET) project (grant agreement no. 101136244). TARGET’s consortium involves nineteen partners including universities, hospitals, companies and a charity. The project kicked-started in January 2024 under the scientific leadership of Prof Sandra Ortega-Martorell (Principal Investigator, Liverpool John Moores University, LJMU), the methodological leadership in AI and virtual twins of Prof Ivan Olier (LJMU), the clinical leadership in AF and stroke of Prof Gregory Lip (University of Liverpool), and the coordination of Prof Mattias Ohlsson (Lund University).