Project description
Enhancing prediction of arrhythmogenesis in cardiac diseases
Structural remodelling in cardiac diseases can disrupt electrical conduction and trigger arrhythmias. Current predictive models often fail to accurately assess arrhythmia risk due to incomplete data. The ERC-funded HeartCORE project will investigate how cardiac remodelling, including non-myocyte reorganisation, contributes to conduction disturbances and arrhythmogenesis in two contexts: interstitial fibrosis in congenital hypertrophic cardiomyopathy and localised scarring following myocardial infarction. Using an animal model that closely mimics human cardiac electrophysiology, the project aims to establish the relationship between structural changes and electrophysiological dysfunction. It will analyse Langendorff-perfused rabbit hearts to characterise conduction and repolarisation properties with a dual-wavelength panoramic optical mapping system. Furthermore, it will integrate whole-heart mesoscopic reconstructions with high-resolution immunohistochemistry images to build a computational model of cardiac electrical activity.
Objective
Remodelling processes associated with genetic and non-genetic cardiac diseases can cause electrical conduction disturbances and arrhythmias. Current models used to predict functional alterations due to structural remodelling fail to accurately assess arrhythmogenic risk, mainly because they do not draw upon comprehensive functional and structural data and are typically based on low-resolution and non-integrated information. Here, I present HeartCORE, an interdisciplinary approach designed to establish a mechanistic relationship between electrophysiological dysfunction and structural alterations in an animal model that mimics human cardiac electrophysiology. Langendorff-perfused rabbit hearts will first be electrically characterized in terms of conduction, repolarization properties, and arrhythmogenicity using a dual-wavelength panoramic optical mapping system that includes the transmural dimension. The hearts will then be transformed into well-preserved, fully transparent organs and imaged with a high-throughput light sheet mesoscope to reconstruct cardiac muscle organization and collagen deposits with micrometric resolution. Selected high-resolution immunohistochemistry images will be integrated with the structural data of each organ to develop a computational model of cardiac electrical activity and explore the possibility of reproducing in silico experimentally observed electrical behaviour. This methodology will be applied to investigate the impact of cardiac remodelling (including non-myocyte reorganization) on conduction disturbances and arrhythmogenesis in two distinct scenarios: generalized interstitial fibrosis in congenital hypertrophic cardiomyopathy and localized scarring in acquired myocardial infarction. HeartCORE aims to create a unifying model that integrates functional and structural data, enabling a comprehensive investigation of the morphological causes leading to electrical alterations and enhancing predictive concepts in arrhythmogenesis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-ADG
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00185 Roma
Italy
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