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Integrative Modeling of Autonomic dysfunction and Cardiac arrhyThmogenesis

Project description

Computational modelling of cardiac arrhythmias

The autonomic nervous system (ANS) regulates heart rate and rhythm, and its dysfunction is a key driver of cardiac arrhythmias. An imbalance between the sympathetic and parasympathetic branches of this system, particularly in the context of heart failure, may lead to abnormal electrical activity. However, it remains poorly understood how ANS dysfunction shapes arrhythmia risk across the whole heart. With the support of the Marie Skłodowska-Curie Actions programme, the IMpACT project aims to develop a detailed four-chamber computational heart model that integrates ANS effects on cardiac electrophysiology and mechanics. The model will be validated against clinical data to quantify how different patterns of ANS dysfunction promote arrhythmias, providing a powerful tool for personalised risk stratification and targeted therapy development.

Objective

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

POLITECNICO DI MILANO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 193 643,28
Address
PIAZZA LEONARDO DA VINCI 32
20133 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Higher or Secondary Education Establishments
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Total cost

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Partners (2)