From cells to maps: studying arrhythmia mechanisms using network theory

Nele Vandersickel

Core Team

Nele Vandersickel

Nele Vandersickel

Sander Hendrickx

Robin Van den Abeele

Arthur Bezerra

Bjorn Verstraeten

Arstanbek Okenov

Timur Nezlobinskii

Eike Wülfers

Sebastiaan Lootens

Mattias Duytschaever

Sebastiaan Knecht

Armin Luik

Annika Haas

Main Clinical collaborations

Nele Vandersickel

From the cell to the arrhythmia

Nele Vandersickel

Anatomical reentry

Functional reentry = rotors

Focal sources

Many different cell models: atrial

Nele Vandersickel

Simulations done by OpenCARP

Notice the big differences!

Many different cell models: ventricle models

Nele Vandersickel

Simulations done by OpenCARP

Notice the big differences!

Tracking rotational activity

Nele Vandersickel

Most used method: phase mapping

Shors et al, IEEE, 1996,
Gray et al, Nature, 1998,
Bray et al, IEEE, 2002,
Umapathy et al, Circ A&E, 2010
Kuklik et al, TBME, 2014

-Pi

Pi

Problems with phase mapping (Kuklik et al, 2017, IEEE Trans Biomed Eng.)
 

  • Frequent false positive PS detection due to chance
  • Phase mapping ignores fractionation and double potentials
  • Ignores conduction block
  • Presents waves coming from opposite directions are seen as transient rotation.

Tracking rotational activity

Most used method: phase mapping

Most used method: phase mapping

Most used method: phase mapping

Nele Vandersickel

Phase mapping is a very local method!

Tracking rotational activity

New alternative method: directed graph mapping

Network theory is very popular in science and technology...

Search algorithm

Brain

Facebook

Nele Vandersickel

Rotating electrical waves are just the cycles in our network!

Tracking rotational activity

Alternative method: directed graph mapping

Nele Vandersickel

Is a global method!

Tracking focal activity

Alternative method: directed graph mapping

Can also track focal sources!

Nele Vandersickel

New version almost ready open source/source available with some restrictions for commercial use

You can create your own pipeline!

www.dgmapping.com

Directed graph mapping: mature software package

Nele Vandersickel

We also added different implementations of phase mapping

Spatial organization of datapoints is not required!

Computational data

  • any subset

Input

  1. Coordinates of the measuring electrodes
  2. Local Activation Times or full signal

Experimental data

  • needle data
  • socket data
  • grid data
  • ...

Clinical data

  • CARTO
  • RHTYHMIA
  • Basket Catheter
  • ECGI data

DGM: a software package to analyze reentry automatically

Nele Vandersickel

DGM: a software package to analyze reentry automatically

Nele Vandersickel

DGM: a software package to analyze reentry automatically

Nele Vandersickel

Extended toolkit for visualization

DGM: a software package to analyze reentry automatically

Nele Vandersickel

Study 1: tracking core of rotors in simulations of different models

Nele Vandersickel

Study 1: tracking core of rotors in simulations of different models

Nele Vandersickel

Ongoing study

Study 2: analysis of Torsade de Pointes in the experimental CAVB dog model

Episodes are focal or reentry?

Nele Vandersickel

Chronic CAVB block

Dofetilide challenge

Study 2: analysis of Torsade de Pointes in the experimental CAVB dog model

DGM      lab

Vandersickel et al, JACC: EP 2017

  • Non-terminating episodes have many more reentries than terminating episode
  • Focal sources have preferred locations

Nele Vandersickel

Van den Abeele et al, Frontier in Physiology 2023

Study 3: analysis of VF in optical mapping data in rats

We found a new network method in addition to cycle search, which can find rotational activity:

 

Helmholtz decomposition of graphs

Nele Vandersickel

Experiment performed by lab of Fu Siong, Imperial College Londen

Ongoing study

Study 4: analysis of VT in clinical data

DGM can analyze mapping data in VT

Hawson et al., JACC EP, 2023

Nele Vandersickel

Why do often slower ATs arise after ablation of the reentry? (can be up to 1/3 cases...)

Anterior

Posterior

Reentry at the roof

Slower AT at the MV

Anterior

Posterior

Roof ablation

Study 5: solving AT

Nele Vandersickel

MV

LPV

RPV

Text

Study 5: solving AT- Anatomy of the left atrium: 3 natural boundaries: topology!

Nele Vandersickel

600 different simulations: 2 holes, 3 holes and 4 holes

All possible virtual ablation lines

Study 5: solving AT- Simulation on spheres with 3 natural boundaries: topology

Nele Vandersickel

3 Patterns

Complete rotation

Incomplete rotation

Parallel activation

Good entrainment

Bad entrainment

Bad entrainment

Study 5: solving AT- Simulation on spheres with 3 natural boundaries

Nele Vandersickel

Incomplete rotation becomes complete rotation, resulting in a slower AT

100% of simulations!

Study 5: solving AT- Simple ablation strategy

Nele Vandersickel

Study 5: solving AT- Index theorem > 20 years old

Nele Vandersickel

Reentries come in pairs of 2: clockwise and counterclockwise

Complete rotation

Parallel activation

Incomplete rotation

Critical Boundary

Critical Boundary

Non-Critical Boundary

CB: Santucci et al. JACC EP 2023

Study 5: solving AT- Index theorem > 20 years old

Nele Vandersickel

CB:

CB:

NCB: 0

Incomplete rotation becomes complete rotation, resulting in a slower AT

Loops come in pairs of 2: currently second loop is always missed

Study 5: solving AT- Index theorem > 20 years old

Nele Vandersickel

Study 5: solving AT- Scar creates additional holes

MV

LPV

RPV

131 MRAT cases

Study 5: solving AT- Clinical cases

Nele Vandersickel

20 detailed cases with slowing after ablation

Study 5: solving AT- We explain why ablation gives slower ATs!

Nele Vandersickel

Study 5: solving AT- Current classification can be replaced

Macro reentry

Localized reentry

Micro reentry

Focal

Rotor

Around anatomic obstacle, like valve or vessels.

Around non conducting area > 2-1.5cm, e.g. scar or functional block

  • Atypical Flutter    (LA involving valves or vessels)

  • Atypical Flutter   (RA involving valves or vessels)​

  • Typical Flutter (clockwise and counter clockwise)

  • WPW

  • Atypical Flutter    (LA with scar or previous ablation lines with gaps)​

  • AVNRT    (considering slow  and fast pathway)

Around non conducting area < 1cm, e.g. scar or functional block

  • Atypical Flutter    (LA with scar​)

  • Atypical Flutter   (RA crista terminalis region)

  • Ectopic AT

Spiral activation pattern with no scar in the core.

Focal activation from  one single spot with centrifugal activation pattern

CL tends to be longer >350ms due to larger path

CL range varies and CL can shift around 20-40 ms during arrhythmia due to slight path variations

CL tends to be shorter due to short path, whole CL is covered by signals found in a small area like e.g. 4cm2 often a combination of double potentials in the „middle“ and very long fractionated signals surrounding

CL often not presented completely in one chamber

Focal activation patterns could also hint to epicardial entries – look for potential conducting structure like vein of Marshall, Bachmann´s etc. and exits that would fit a macro reentry with epicardial parts

We think non-existent in AT, especially as a stable configuration leading to a stable AT.

Maybe something close to a spiral pattern can exist in AF

  • AF

All of this is replaced by our simple classification!

Study 5: solving AT- Current classification can be replaced

Macro reentry

Localized reentry

Micro reentry

Focal

Rotor

Around anatomic obstacle, like valve or vessels.

Around non conducting area > 2-1.5cm, e.g. scar or functional block

  • Atypical Flutter    (LA involving valves or vessels)

  • Atypical Flutter   (RA involving valves or vessels)​

  • Typical Flutter (clockwise and counter clockwise)

  • WPW

  • Atypical Flutter    (LA with scar or previous ablation lines with gaps)​

  • AVNRT    (considering slow  and fast pathway)

Around non conducting area < 1cm, e.g. scar or functional block

  • Atypical Flutter    (LA with scar​)

  • Atypical Flutter   (RA crista terminalis region)

  • Ectopic AT

Spiral activation pattern with no scar in the core.

Focal activation from  one single spot with centrifugal activation pattern

CL tends to be longer >350ms due to larger path

CL range varies and CL can shift around 20-40 ms during arrhythmia due to slight path variations

CL tends to be shorter due to short path, whole CL is covered by signals found in a small area like e.g. 4cm2 often a combination of double potentials in the „middle“ and very long fractionated signals surrounding

CL often not presented completely in one chamber

Focal activation patterns could also hint to epicardial entries – look for potential conducting structure like vein of Marshall, Bachmann´s etc. and exits that would fit a macro reentry with epicardial parts

We think non-existent in AT, especially as a stable configuration leading to a stable AT.

Maybe something close to a spiral pattern can exist in AF

  • AF

2nd Submitted paper

Atrial topology for a unified understanding of typical and atypical flutter

Mattias Duytschaever, Robin Van Den Abeele ... Annika Haas, Armin Luik, ... Sander Hendrickx, Nele Vandersickel

Study 5: solving AT- European Heart Journal

Nele Vandersickel

Study 5: solving AT- Live case!

Study 5: solving AT- Live case!

www.dgmapping.com

Study 5: DGM can compute the critical boundaries automatically!

Nele Vandersickel

www.dgmapping.com

Study 5: DGM can compute the critical boundaries automatically!

Nele Vandersickel

Working on the final step: automatization scar detection

Take home message

DGM: diagnostic tool based on network theory

www.dgmapping.com

CB:

CB:

NCB: 0

Incomplete rotation becomes complete rotation, resulting in a slower AT

Able to change ablation therapy in AT!

Can be applied to many different datasets!

  • Needle data of Torsade de Pointes in dogs
  • Optical mapping
  • Simulated datasets
  • Clinical datasets

Nele Vandersickel

Working group

By Nele Vandersickel

Working group

  • 73