[IMpACT] Integrative Modeling of Autonomic dysfunction and Cardiac arrhyThmogenesis
Ente: EC
Scadenza: 2029-08-31
Importo max: 193.643 EUR
Paese: EU
Descrizione
Autonomic dysfunction (AD) occurs when the autonomic nervous system (ANS) fails to properly regulate cardiac function, increasing cardiovascular risk. AD is typically characterized by an imbalance between sympathetic and parasympathetic activity and increased heterogeneity in the intrinsic cardiac nervous system (ICANS). These factors collectively disrupt electrical conduction and excitation–contraction coupling. This project hypothesizes that AD, when exacerbated by structural remodelling as in heart failure (HF), creates a substrate highly favorable for the development of atrial and ventricular arrhythmias. A mechanistic understanding of how AD shapes arrhythmia risk at the whole-heart level is still lacking.
IMpACT addresses this gap by developing a next-generation four-chamber (4C) electromechanical heart model with detailed ICANS representation. Building on an established 4C electromechanical model of a healthy heart, it will integrate autonomic effects on the sinoatrial node, atrioventricular node, and myocardium. The model will be calibrated and validated against literature data and clinical data from patients undergoing cardioneuroablation. Model variants will be created for healthy and structurally remodelled hearts to investigate how distinct AD patterns and pathological substrates affect cardiac rhythm and contraction.
This novel approach addresses significant gaps in current research, as no existing models integrate autonomic nervous system effects on both electrophysiology and electromechanical behavior across all cardiac regions. IMpACT will provide mechanistic insights into proarrhythmic pathways, quantify the impact of different AD scenarios on conduction and contractility, and assess arrhythmic vulnerability across substrates of varying complexity. Ultimately, this approach will deliver a powerful tool to guide personalized risk stratification and support the development of safer, targeted therapies for patients with complex cardiac conditions.
Settori: Horizon Europe Topics
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