Project Title: Empowering the heart to terminate its own rhythm disorders 

Project number: 04510012110051

Project leader: Tim De Coster 

Funding: ZonMW Off Road grant 2021 

Starting date: 01/12/2022

End date: 29/02/2024

About the project:

Heart rhythm disorders, or cardiac arrhythmias, sometimes stop spontaneously, while others persist and require medical intervention. Why these different outcomes occur is still poorly understood.

My project focused on atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Using a computational “digital twin” of a human heart cell model, I aimed to uncover the mechanisms that determine whether an arrhythmia persists or terminates spontaneously. These findings were then be tested in cell cultures.

Ultimately, my goal is to harness and strengthen the heart’s natural anti-arrhythmic mechanisms. This could provide the basis for new treatments that encourage arrhythmias to terminate on their own, reducing the need for further medical intervention.

Results:

Scientific outcomes

The mechanisms underlying spontaneous arrhythmia termination proved more complex than originally anticipated, and not all initial objectives could be achieved within the project. Nevertheless, the work provided new insights into how interactions between cardiac cells influence the initiation, persistence, and termination of abnormal electrical activity. Experimental and computational approaches revealed previously unrecognized collective behaviour in cardiac tissue, including conditions that can promote the termination of oscillatory activity. These findings provide new directions for investigating how the heart’s own dynamics might be exploited to control arrhythmias.

Scientific publications 

My project contributed to two scientific publications:

• Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics: 
  An experimental and computational investigation into collective electrical activity in cardiac tissue and the mechanisms that can enable oscillatory activity to start or stop.
• (Cardiac) complexity needs interaction:
  An editorial highlighting recent progress in understanding the interactions between electrical, mechanical, and biochemical processes in the heart, as well as the importance of interdisciplinary research.

Science outreach

I published two articles on the Dutch educational platform Natuurkunde.nl:

• Hartspiercellen: motortjes van je hart: introducing the biophysics of cardiac cells and showing how concepts from physics and mathematics help us understand the heart.
• Hartslag en hartritmestoornissen:
  explaining how electrical excitation waves regulate heart rhythm and how disturbances in these waves can result in arrhythmias.

Conference organisation

I co-organised a minisymposium on Nonliner Waves in Cardiac Tissue at an international conference on waves, bringing together researchers working on wave dynamics and related phenomena. The meeting facilitated exchange between different disciplines and provided new perspectives.

Follow-up funding

The challenges encountered during the project also identified areas where additional expertise and interdisciplinary collaboration could advance the research. This resulted in a €10,000 Kiem grant from Leiden University to establish a new collaboration and further develop this research direction.