HCR.20.009 – Electropathology-based personalized diagnosis and therapy of atrial fibrillation: a circular research approach covering cell, signal and patient

Route: Health care research, sickness prevention and treatment

Cluster question: 104 How do we develop minimally invasive techniques and interventions for diagnosis, prognosis, and treatment?

Atrial fibrillation (AF) is a common, progressive cardiac arrhythmia caused by environmental and genetic factors. It affects millions of people in the EU and has a tremendous societal and economic impact. Importantly, current treatment modalities for AF are only moderately effective. This is due to the lack of mechanism-based therapies and reliable diagnostic tools to detect and stage AF. Our interdisciplinary team discovered that AF onset and progression is rooted in electropathology, defined as electrical conduction disorders caused by structural damage of atrial tissue. The severity of electropathology determines the stage of AF and poor response to treatment. Therefore, electropathology may be exploited to identify root causes of AF, design novel mechanism-based personalized therapies and develop non-invasive diagnostics.
To exploit this new concept, the following sub-questions are formulated. 1) What are the molecular key modulators that drive electropathology and represent these modulators druggable targets and biomarkers in AF? Can established model systems serve to develop ‘Cardiac-Arrhythmia-on-a-Chip’ technology to detect electropathology from cardiomyocytes to whole organs? 2) How to develop model systems to mathematically describe electrical conduction disorders and translate non-invasive measurements to high-resolution outcomes? 3) Which advanced signal processing algorithms are required to design non-invasive devices to determine electropathology and thus AF stage? 4) Given new understanding of key modulators of electropathology can we detect the root causes of AF and identify early AF? 5) How to create optimal patient participation in AF studies? Hereto, the AF-innovation-platform serves to disseminate research findings, study patients’ willingness to test novel therapies, diagnostic tools and co-creation of studies.
This transdisciplinary circular research project fuses knowledge on molecular and electrical root causes of AF from cell to patient.

Keywords

Arrhythmia, cardiac arrhythmia on a chip, co-creation with patients, diagnostics, electropathology, Participatory Action Research, Personalized medicine

Other organisations

AFIP, Cytocypher, Erasmus Medical Center (EMC), PraxaSense, Saxion Enschede, Technische Universiteit Delft (TUD), UMCG

Submitter

Organisation Amsterdam UMC, Vumc
Name Prof. dr. B.J.J.M. (Bianca) Brundel
E-mail b.brundel@amsterdamumc.nl
Website http://physiologyamsterdam.org/team/brundel/