Topology for understanding the paired nature of cardiac arrhythmia

Objetivo

This proposal aims to revolutionize the understanding and treatment of cardiac arrhythmias by introducing a topological perspective, a completely novel approach in the field, offering a transformative opportunity to advance both the understanding and treatment of life-threatening arrhythmias. Reentries, where the heart's electrical signal follows an abnormal circular path, are central to arrhythmias. Current ablation strategies aim to scar tissue to disrupt these circuits.

I challenge the prevailing belief that reentries exist as isolated phenomena, showing instead that they are interconnected. By applying the index theorem for phase singularities, I demonstrate that reentries occur in pairs: a clockwise loop (index -1) is always accompanied by a counterclockwise loop (index +1), ensuring the sum of indices is zero. Crucially, incomplete reentry loops, often dismissed as irrelevant, also carry a non-zero index and must be targeted to effectively terminate arrhythmias.

The project focuses on three major arrhythmias: atrial tachycardia (AT), ventricular tachycardia (VT), and atrial fibrillation (AF). For AT, we build on substantial computational and clinical evidence showing paired reentry circuits around critical boundaries (CBs). We aim to expand this framework to bi-atrial ATs, a previously uncharted territory. For VT, the ventricles' thickness adds 3D complexity; we hypothesize the index theorem remains valid, with reentry loops and CBs transforming into 3D structures. Using simulations, pig experiments, and clinical analyses, we will identify these 3D CBs and develop precise ablation strategies. For AF, persistent irregular reentries challenge the limits of the index theorem. Through simulations and high-density human recordings, we will determine whether CBs remain relevant as ablation targets.

All findings will be integrated into an open-source software package, ensuring reproducibility and accessibility for the broader research community.