Completing my thesis at IADI/Biosense Webster has been a fantastic journey and there are many people that I am very grateful to.

First, I would like to thank my research supervisors, Freddy Odille and Christian De Chillou, for choosing me as their PhD student. Without them I would never have ended up spending so much time exploring the fascinating world of electrophysiology.

I am grateful to Christian De Chillou who had the initial idea of me doing a PhD. Together with Jacques Felblinger, they made sure it became a reality. I am grateful to Freddy Odille for the considerable time and effort helping me through the projects' hiccups, the writing of papers and finally the completion of this thesis.

I am grateful to the management team in Biosense France for their support in this project. This was a first for the team and thank you for your time and energy in making sure I had the best possible conditions for this project. Special thanks to Thibault Pugeat, Loic Masson, Anthony Ouvrard, Deborah Zaffuto, Matthieu Taufour and Wislane Ambri. Thank you for your trust and continued belief in this project.

I'm grateful to the entire Nancy Electrophysiology Unit for spending their precious time in their busy schedules to help me understand and take into account the numerous aspects of the world of electrophysiology: Isabelle, Jean-Marc, Alberto, Néfissa, Charles, Jerome, Arnaud, Pierre Yves, Damien, Fabien, Céline, Catherine, Laurence, Delphine, Myriam, Annick. Special thanks to my co-authors for their extra time in testing and assessing the novel methods developed. I couldn't finish without thanking Isa, your continuous support, your patience and your love.

5

Summary

Since the beginning of the 1990s and the use of radiofrequency to ablate cardiac arrhythmias, electrophysiologists treat increasing complex rhythm disorders. 3D mapping systems enable catheter locations to be known with high precision and therefore are very important tools for electrophysiology.

Identifying zones of interest remains long and involves many steps based on indirect analyses of the heart's properties.

The main objective of the thesis is to develop new tools to locate the critical isthmus in post infarct ventricular tachycardia. The clear identification of the circuit components of the ventricular tachycardia enables the development of an ablation strategy to treat the patient. The studied methods do not require a 12-lead electrocardiogram (ECG) of the ventricular tachycardia and therefore have the advantage of being able to be used even if the tachycardia cannot be initiated during the procedure.

A major area of research is the development of an algorithm that automatically extracts the relevant data obtained during pace mapping. This facilitates the display of multi-parametric maps highlighting potential reentry circuits.

Another area of research is the development of a graph-based method to study the variations of the electrical properties of the ventricle. The paced points are considered as vertices of a graph. Each edge is given a weight and finding the path between two vertices of minimum weight allows the analysis of potential reentry circuits.

Abstract

Depuis le début des années 1990 et l'utilisation de l'énergie de radiofréquence pour l'ablation par voie endocavitaire des troubles du rythme rapide, les rythmologues interventionnels prennent en charge des troubles du rythme de plus en plus complexe. Des systèmes de cartographie 3D permettent une représentation précise dans l'espace du positionnement du cathéter et constituent donc un outil très important pour le rythmologue interventionnel. L'identification des zones d'intérêts reste néanmoins longue et sujet à des nombreuses étapes reposant sur des analyses indirectes des propriétés électriques du coeur.

L'objectif principal de la thèse est le développement de nouveaux outils afin de localiser l'isthme critique des tachycardies ventriculaires après infarctus du myocarde. L'identification précise des composantes du circuit de la tachycardie ventriculaire permet la mise en place d'une stratégie d'ablation pour traiter le patient. Les méthodes étudiées ne nécessitent pas un électrocardiogramme (ECG) à 12 dérivations de la tachycardie ventriculaire et présentent donc l'avantage de pouvoir être utilisées même en cas d'échec de déclenchement de la tachycardie pendant la procédure.

Un axe majeur de recherche est le développement d'un algorithme qui permet d'extraire de façon automatique les données pertinentes obtenus lors de la topo-stimulation. Cela permet de faciliter l'affichage des cartes multi paramétriques mettant en avant les circuits de réentrée.

Un autre axe de recherche est l'étude des variations des propriétés électriques du ventricule sous forme de graphe. Les points de stimulations sont considérés comme l'ensemble des sommets du graphe. Chaque arrête est associé à un poids et trouver le chemin entre deux sommets de poids minimum permet d'analyser les circuits de réentrée possibles.

Introduction

After myocardial injury, the disruption in blood supply to the heart infarction can modify the electrical pathways and lead to the formation of re-entrant circuits. These circuits possess an entrance, core and exit and can result in regular and fast heart rates, episodes that are named ventricular tachycardia (VT).

Electrophysiology is the study of the electrical functioning and the electrical properties of the heart. This can be done by equipping catheters with electrodes to record the electrical data of the heart. The catheters can be used in conjunction with mapping systems to create precise electro-anatomical 3D maps.

The The reference-less pace mapping is a novel method based solely on the analysis of the electrocardiogram (ECG) data obtained during pace-mapping. This approach does not require a reference VT recording of the tachycardia and is particularly useful when the tachycardia cannot be induced. An increasing number of procedures are done with remote magnetic navigation and the quality of the ECG signal collected in the modifying magnetic field setting was studied with a new acquisition device. A multi-parameter electrogram automatic calculator was developed to determine the likelihood that a given site is located at a VT isthmus entrance, a key component of the circuit. Automatic detection was developed because pace mapping analysis is currently limited because of the time-consuming steps that the interventional cardiologist needs to do to visualize the information of interest. A method to automatically extract the key information and facilitate the use of pace-mapping data was developed. A graph-based method GRAAPH (Graph-based Reconstruction of Arrhythmic Activations by Pacing the Heart) was implemented to take full advantage of all the available information obtained by pace mapping. The connections between each pacing site during pace-mapping was analyzed to generate a suggested activation pattern of the VT circuit.

The main contributions are that the reference-less pace mapping accurately identifies the same target zones as conventional pace mapping as well as additional zones that may cause other VT circuits. The automatic processing reduced the need for manual annotations and facilitated the visualization of the multi-parametric maps identifying the location of the entrance, core and exit of the VT circuit. The GRAAPH method successfully highlights possible activation patterns without the need of the reference VT. These three techniques highlight the electrical connections of the ventricle and could provide further insights to help the physician determine the most effective ablation strategy.

Part 1: Ventricular tachycardia and catheter ablation

Electrical activity of the heart

Cells in the normal human heart possess excitatory properties. Indeed, the electrical activity of the heart is responsible for its beating properties. Ions passing through the transmembrane ion channels of the heart cells generate action potentials, then leading to tissue contraction. The ventricle is a fiber-wound of interconnecting muscle fibers [1]. The orientation of fibers varies and its structure is characterized by a smooth transition of fiber angle from endocardium to epicardium.

A first common diagnostic tool for having a quick overview of the electrical activity of the heart is the analysis of the electrocardiogram: electrodes placed on the skin record the electrical variation over time of the cardiac muscle.

A normal electrocardiogram is composed of a P wave, representing the depolarization of the upper part of the heart, the atria, then a QRS wave representing the depolarization of the ventricles, the lower part of the heart followed by a T wave, representing the repolarization of the ventricles (figure 1).

Ventricular tachycardia

A disruption in blood supply to the heart can lead to infarction, scarring and death of areas of tissue of the cardiac muscle. After myocardial injury, the myocardium can be divided into three areas, the necrotic zone, the peripheral intermediate scar zone and the healthy zone. Patients having had an infarction are likely to have modified electrical pathways that can lead to the formation of re-entrant circuits. These circuits can result in regular and fast heart rates, episodes that are named ventricular tachycardia (VT).

One method for stratifying this risk is by measuring the duration of the QRS wave. The longer it is, the higher the risk of having a cardiovascular related death [2], [3].

Electrophysiology

Electrophysiology is the study of the electrical properties of the heart. A common practice of this field is to insert a catheter containing multiple electrodes into the heart to record its electrical activity.

Electrophysiologists puncture the femoral vein and then insert catheters through this vein to the heart.

The catheters possess a handle that enable the electrophysiologist to move the tip of the catheter to the desired location inside the heart. The catheter can be connected to a radiofrequency generator, enabling the creation of ablation lesions. The unipolar and bipolar signals recorded from the electrodes on the catheter, can be visualized in real time on a recording system. Moving the catheter and recording the corresponding signal (e.g. activation mapping, see section 7) during tachycardia is a useful tool to facilitate the identification of the circuit [4]. The catheters also allow pacing from the electrodes, thus exciting the nearby tissue. Pacing from one site and recording from surrounding sites is also useful to analyze how electricity propagates in the heart [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. Currently, several multielectrode catheters are available such as the flower shape 5 spline catheter, with 4 electrodes on each spline, the PENTARAY TM catheter (Biosense Webster Inc., Diamond Bar, USA). This catheter can be used in conjunction with the CARTO® mapping system that enables the creation of precise electro-anatomical 3D maps. Indeed, Biosense Webster's catheters can be equipped with a small magnetic sensor enabling the location of the catheter to be known at all times. This location, as well as the recorded electrical data is processed to be visualized on 3D maps. A 3D mapping system facilitates the detailed analysis of the electrical properties of the heart and helps direct delivery of ablation lesions.

Impulse propagation

Cardiac excitation involves generation of the action potential (AP) as shown in figure 2 and is the result of the interactions between the membrane ionic currents and the ionic milieu of the cell [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF].

Figure 2.

Action potential of a cell over time [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF].

For a single cell under space-clamp conditions, the transmembrane potential 𝑉 𝑚 can be determined by the total transmembrane ionic current 𝐼 𝑖𝑜𝑛 and the membrane capacitance 𝐶 𝑚 :

𝑑𝑉 𝑚 𝑑𝑡 = -1 𝐶 𝑚 ⁄ * 𝐼 𝑖𝑜𝑛 (1)
The movement of ions across the membrane occurs via voltage-gated ion channels, pumps and exchanges.

Once the cell's activation threshold is reached, the fast inward sodium current 𝐼 𝑁𝐴 depolarizes the membrane and generates the fast AP rise. When the 𝑉 𝑚 reaches -25 mV, the inward L-type calcium current 𝐼 𝐶𝑎(𝐿) is responsible for the AP plateau and reduces the repolarizing action of outward delayed potassium currents 𝐼 𝐾 . L-type calcium channels slowly inactivate and the potassium current 𝐼 𝐾 increases during the plateau leading to the repolarization of the membrane towards its resting potential.

If we now consider cells to be part of a continuous chain, current flows from an individual cell to its neighboring cells through intercellular gap junctions. In a linear cell chain, the AP propagation follows:

𝐶 𝑚 * 𝜕𝑉 𝑚 𝜕𝑡 + 𝐼 𝑖𝑜𝑛 = 𝑎 2𝑟 𝑖 ⁄ * 𝜕 2 𝑉 𝑚 𝜕𝑥 2 (2)
With 𝑎 the fiber radius, 𝑟 𝑖 the axial resistance per unit length. Under space-clamp conditions, 𝜕 2 𝑉 𝑚 𝜕𝑥 2 is null and so 𝑒𝑞𝑢𝑎𝑡𝑖𝑜𝑛 (2) reduces back to 𝑒𝑞𝑢𝑎𝑡𝑖𝑜𝑛 (1). In this multicellular model, the 𝐼 𝑖𝑜𝑛 charge of a given cell is now divided between discharging the membrane capacitance and also depolarizing the membrane of neighboring cells. The resistance 𝑟 𝑖 is not a constant and varies depending of the electrical coupling of the different cells. For example cardiac fiber orientation has an impact with a more rapid conduction in the direction parallel to the myocardial fiber axis than in the transverse direction [START_REF] Sano | Directional difference of conduction velocity in the cardiac ventricular syncytium studied by microelectrodes[END_REF]. Moreover, different layers of connective tissue lead to variations in resistance.

Myocardial infarction

Myocardial infraction and the subsequent block of oxidative metabolism and the fall in adenosine triphosphate/adenosine diphosphate (ATP/ADP) have many effects on ion concentrations channels and carriers [START_REF] Carmeliet | Cardiac ionic currents and acute ischemia: from channels to arrhythmias[END_REF]. For example, external potassium and internal sodium concentrations are increased whereas both internal and external pH becomes more acid. Some myocardial cells die while others survive because they continue to receive some blood supply. When the necrotic myocardial cells are replaced by fibrous tissue, the surviving cells in the subendocardium can be trapped in the scar [START_REF] Fenoglio | Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates[END_REF]. Histologically, five dominant patterns can be defined: 1) contiguous areas of viable myocardium, 2) small confluent areas of fibrosis surrounded by viable myocardium, 3) confluent areas of fibrosis containing only strands of viable cardiomyocytes, 4) confluent areas of fibrosis containing solitary viable cardiomyocytes, and 5) transmural confluent fibrosis [START_REF] Wijnmaalen | Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate[END_REF]. Preparations from infarcted canine hearts have shown that as time passes, fibrosis increases, muscle fibers in the border zone are separated by increasing amounts of connective tissue and can change directions [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF].

For the surviving cells, each ionic current change has its own time course of remodeling and can continue to vary several years after the onset of the infract [START_REF] Baba | Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia[END_REF]. The remodeling can also be consequences of the continuous changes during infarct healing such as increased wall stress, hypertension and medication [START_REF] Wijnmaalen | Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate[END_REF].

These changes can lead to a reduced membrane excitability and a prolonged effective refractory period [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] Kleber | Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart[END_REF], [START_REF] Potse | The role of extracellular potassium transport in computer models of the ischemic zone[END_REF]. Tension and an increase in volume due to osmotic changes lead to cell stretching [START_REF] Carmeliet | Cardiac ionic currents and acute ischemia: from channels to arrhythmias[END_REF]. Stretching causes opening of stretch-sensitive channels that lead to enhanced inward and outward currents. This can lead to the shortening of the plateau of the action potential. In the myocardium associated with healed canine infarcts, each myocyte is connected to fewer cells. A great reduction (of up to 75%) in side-to-side cell interconnections has been found as well as a decreased number of gap junctions [START_REF] Luke | Remodeling of ventricular conduction pathways in healed canine infarct border zones[END_REF].

After infraction, the distribution of the nerve fibers in the ventricles is also altered. The necrotic myocardium is associated with denervation, whereas the peripheries of myocardial scar and perivascular regions are richly innervated [START_REF] Cao | Relationship between regional cardiac hyperinnervation and ventricular arrhythmia[END_REF], [START_REF] Ajijola | Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context[END_REF]. Sympathetic nerve activation have effects on a series of electrophysiological properties such as automaticity, refractoriness, and conduction velocity of myocardial cells [START_REF] Ajijola | Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context[END_REF]- [START_REF] Opthof | Interaction of sympathetic and parasympathetic nervous system on ventricular refractoriness assessed by local fibrillation intervals in the canine heart[END_REF].

The duration of the coronary artery occlusion is also proportionally correlated to the size and transmural extent of the myocardial scar [START_REF] Piers | Early reperfusion therapy affects inducibility, cycle length, and occurrence of ventricular tachycardia late after myocardial infarction[END_REF]. Early reperfusion results in interstitial fibrosis of the inner third of the wall extending toward the midmyocardium, whereas late reperfusion or permanent occlusion results in more uniform transmural necrosis [START_REF] Wijnmaalen | Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate[END_REF], [START_REF] Miyazaki | Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart[END_REF], [START_REF] Matsuda | Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis[END_REF].

These combined effects result in changes in action potential, cell coupling and structure that can eventually lead to the development of VT substrate and occurrences of arrhythmias [START_REF] Peters | Myocardial architecture and ventricular arrhythmogenesis[END_REF], [START_REF] Cao | Nerve sprouting and sudden cardiac death[END_REF].

Abnormal electrical circuits a. Slow conduction

One of the main consequences of ischemia is slowed conduction. This decrease in conduction velocity can be due to reduced cell excitability, decrease in cell-to-cell coupling and tissue structure.

i. Due to reduced cell excitability

After ischemia, the reduced availability of sodium channels lead to a decrease in the fast inward sodium current 𝐼 𝑁𝐴 , reducing excitability and conduction velocities between cells [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF]. When the sodium channel availability falls below 11%, the generated depolarizing charge is no longer sufficient to depolarize the membrane above the excitation threshold and the overall conduction ceases, a conduction block has been created. Simulations have determined that the lowest conduction velocity prior to failure is 17 cm/s, a third of the velocity (54 cm/s) at full membrane excitability [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF].

ii. Due to reduced cell-to-cell coupling

After ischemia, changes in the average conductance of gap junctions due to progressive interstitial fibrosis reduces cell-to-cell coupling [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF], [START_REF] Luke | Remodeling of ventricular conduction pathways in healed canine infarct border zones[END_REF]. Conduction velocity then decreases with increasing coupling resistance. Slowing of conduction is direction dependent and mainly occurs in a direction transverse rather than longitudinal to fiber orientation [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF], [START_REF] Pogwizd | Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart[END_REF], [START_REF] Dillon | Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts[END_REF]. The characteristic histological pattern in zones of slow conduction is of parallel muscle fibers oriented transversely to the activation wave front.

Lower conduction velocities can be sustained with reduced intercellular coupling compared to reduced cell excitability [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF]. The lower the coupling, the slower the conduction but also the higher the conduction safety. Low coupling leads to very slow, robust, and discontinuous conductions. Indeed, as coupling is reduced, there is greater confinement of the depolarizing current to the remaining coupled and depolarized cells. As a result, individual cells depolarize with a high margin of safety, but much slower.

iii. Due to tissue structure

Reduced conduction velocities can also be caused by the complex structures of viable myocardium [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF]. Side-to-side electrical coupling among fibers can be absent over several millimeters, only interconnections further away can transfer the activation to neighboring bundles [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF]. Long conduction times are due to increased path lengths and zig-zagging patterns of conduction.

b. Unidirectional block

Another consequence of ischemia is unidirectional block, a particular type of block that stops the conducting wave in one direction but does not if the propagation comes from the opposite direction. The blocking properties depend on the direction of the conducting wave.

i. Asymmetry of excitability

The electric asymmetry of the cardiac AP can lead to unidirectional block. Indeed, if local cardiac excitation interacts with the repolarization phase of a preceding wave, the development of a unidirectional block is possible. The AP can propagate incrementally in the retrograde direction but block in the antegrade direction. The incremental AP response in the retrograde direction reflects the residual voltage due to the underlying progressive recovery from inactivation of sodium channels whereas in the antegrade direction the current can be not sufficient to conduct [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF].

ii. Tissue structure

The tissue structure can also lead to unidirectional block. After ischemia, small areas of dense scars are interspersed within areas of preserved voltages [START_REF] Wijnmaalen | Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate[END_REF]. Each patch has different conducting properties that can lead to slow, unidirectional, bidirectional or non conducting zones. During premature stimulation, unidirectional conduction block can occur in a certain direction but not in all directions because of the gradual conducting properties of the region [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF], [START_REF] Ciaccio | Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping[END_REF]. That conduction block is considered as functional, not anatomic, if it is only present at the short activation coupling intervals of premature stimulation and ventricular tachycardia but not at the longer cycle lengths of normal sinus rhythm [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF].

Moreover, block can occur when the conducting wave exits a narrow path. After crossing a narrow path the propagating wave becomes curved. A decrease in the width of the path leads to a decrease in the radius of the curved wavefront. Beyond a critical curvature, unidirectional block will arise [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF].

c. Reentry mechanisms

Many factors influence the conduction of electrical impulses and excitation waves can be slowed as well as impacted by a unidirectional block. When possible, the propagating wave will rotate around these zones, and reenter the site of original unidirectional block. As shown in figure 3, if sufficient time for recovery of excitability has elapsed, the merged impulse can cross the unidirectional block line from the opposite side to reenter the previously excited region and thus a repetitive cycle can be initiated. This is facilitated when the initial unidirectional block area is bounded laterally by arcs of non-conducting zones, either functional or anatomical [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF], [START_REF] Downar | Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms[END_REF]. non-conducting zone (in green) that is in turn surrounded by healthy myocardium (in white). The color-coded arrows represent the propagation o of the conducting wave (the wave is first located by the red arrows, then orange, yellow, green, grey and purple). In A) the wave is blocked in the abnormal conducting zone but continues to propagate around the non-conducting zone to then reenter the abnormal area from the opposite side. In B) the impulse crosses the unidirectional block line from the opposite side and repetitive cycle is initiated [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF].

This mechanism is called reentry. For maintaining reentrant activation, the circuit length must be long enough to enable tissue in each part of the circuit to restore its excitability sufficiently to respond to the next impulse. The higher the velocity, the larger the circuit. Although slow conduction is not a prerequisite for reentry, it reduces the minimal length of reentrant circuits and therefore enhances the likelihood that a circuit can be contained within an area of myocardial scar [START_REF] De Bakker | Slow conduction in the infarcted human heart. 'Zigzag' course of activation[END_REF]. The central common pathway of conductive myocardial tissue is called the isthmus or diastolic pathway. The isthmus of the reentrant circuit, is bounded laterally by nonconductive tissue. This nonconductive tissue can either be zones of block, scar area, or an anatomic obstacle such as the mitral valve [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF], [START_REF] Ciaccio | Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping[END_REF], [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. In the majority of cases, the barriers consist of zones of block, characterized by continuous lines of double potentials [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. When the mitral valve is involved, the isthmus is always activated parallel to the mitral annulus in either direction [START_REF] Wilber | Catheter ablation of the mitral isthmus for ventricular tachycardia associated with inferior infarction[END_REF].

The reentrant circuit is mostly likely to be endocardial, but can also be mid-myocardial, intramural, subepicardial or transmural [START_REF] Ciaccio | Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping[END_REF], [START_REF] Kaltenbrunner | Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized?[END_REF], [START_REF] Baker | Ventricular tachycardia in the infarcted, Langendorff-perfused human heart: Role of the arrangement of surviving cardiac fibers[END_REF]. In some rare cases, the circuit is biventricular [START_REF] Krafchek | Cryoablation of arrhythmias from the interventricular septum: initial experience with a new biventricular approach[END_REF]. In the majority of patients, a given isthmus is associated with a single VT morphology [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. Extensive sheet of surviving myocardial fibers with multiple entry and exit points allow for different reentrant paths at different times, all in the same heart [START_REF] Downar | Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms[END_REF]. Multiple entrances and exits from the slowly conducting tissue allow for a variety of reentry circuit configurations to form [START_REF] Downar | Endocardial mapping of ventricular tachycardia in the intact human heart. II. Evidence for multiuse reentry in a functional sheet of surviving myocardium[END_REF]. For example, in [START_REF] De Bakker | Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation[END_REF], five tachycardias with different QRS morphologies were initiated in the same patient during intraoperative mapping. An area of slow conduction that is a bystander relative to one tachycardia circuit can participate in another circuit [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF].

On average, isthmi were 31 mm long and 16 mm wide [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF].

An isthmus that the depolarization wavefront must cross to perpetuate the tachycardia is defined as the critical VT isthmus [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. Critical isthmi always correspond to a slow conduction zone, with 57% to 81% of the VT total cycle length being recorded in the critical isthmus. Conduction velocity in the critical isthmi ranged from 6.9 to 19.5 cm/s and is not linked to isthmus width [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. The same critical isthmus can be shared by multiple tachycardias. Up to 4 different VT morphologies have been reported to share the same critical isthmus [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF].

This "figure of eight" reentry mechanism seems to be the most common pattern [4]. In [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF], 76% of VTs exhibited a double-loop figure-8 reentrant circuit. The onset and the stability of a given reentrant circuit is determined by a combination of cell excitability, coupling and tissue structure influencing the overall conducting properties of the circuit [START_REF] Baba | Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia[END_REF]. There is often a long delay between infarction and the occurrence of VT [START_REF] Janse | Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction[END_REF], [START_REF] Sacher | Ventricular tachycardia ablation: evolution of patients and procedures over 8 years[END_REF]. This suggests an important role for continued late remodeling and changes in the electrophysiological properties of surviving myocardial cells occurring long after myocardial infarction [START_REF] Moss | Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator[END_REF].

The reperfusion strategy also has an impact. Reperfused patients have smaller areas of dense scar but larger areas of scar border zone [START_REF] Wijnmaalen | Early Reperfusion During Acute Myocardial Infarction Affects Ventricular Tachycardia Characteristics and the Chronic Electroanatomic and Histological Substrate[END_REF]. This patchy pattern characterized by small areas of dense scar and thicker border zones may result in shorter isthmus length, faster conduction, and therefore shorter VT cycle length. More aggressive reperfusion strategies for acute myocardial infarction reduce the number of infarct survivors that eventually require ablation [START_REF] Sacher | Ventricular tachycardia ablation: evolution of patients and procedures over 8 years[END_REF].

Myocardial remodeling results in enhanced arrhythmogenicity with reentry being responsible for a number of clinically important chronic tachyarrhythmias [START_REF] Kléber | Basic mechanisms of cardiac impulse propagation and associated arrhythmias[END_REF], [START_REF] Janse | Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction[END_REF], [START_REF] Peters | Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia[END_REF].

Identification of the VT circuit a. Surgery

Despite antiarrhythmic drug and pacemaker therapy 40% of patients continue to have recurrent tachycardia episodes [START_REF] Miller | Subendocardial resection for ventricular tachycardia: predictors of surgical success[END_REF]. This initially led to the development of a surgery-based method of treatment, subendocardial resection, which removes a 1 to 2 mm thick sheet of endocardium [START_REF] Miller | Subendocardial resection for ventricular tachycardia: predictors of surgical success[END_REF]. This technique with the removal of between 2 and 40 cm² of subendocardial tissue had success rates approaching 90% in terms of VT elimination [START_REF] Stevenson | Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction[END_REF], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. However, some areas were particularly challenging to cure [START_REF] Miller | Subendocardial resection for ventricular tachycardia: predictors of surgical success[END_REF]. In the inferior free wall, the endocardium is particularly trabeculated and the proximity of the mitral valve further hindered surgery. Moreover, disparate sites of origin of ventricular tachycardia further increased failure rates of surgery. The mortality rate above 5% limited the use of surgery to a few patients [START_REF] Miller | Subendocardial resection for ventricular tachycardia: predictors of surgical success[END_REF], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

b. Catheters

Although the surface electrocardiogram enables a quick overview of the overall electrical activity of the heart, electrophysiologic guided mapping with catheters was developed to analyze in more detail the activation wave fronts that are involved in ischemic ventricular tachycardia [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF].

Catheters are long tubes containing multiple electrodes that are inserted into the heart to record its electrical activity. They are generally 7 or 8 Fr wide and possess a handle to help guide the recording electrodes to the desired position. Catheters can be deflectable, unidirectionally or bidirectionally.

Electrodes come in multiple shapes, size and spacing. Figure 4 is an example of a flower shape 5 spline catheter, the PENTARAY TM catheter (Biosense Webster Inc., Diamond Bar, USA). The catheter can also provide temperature and impedance monitoring, particularly useful during energy delivery by radiofrequency.

Radiofrequency directly transfers electromagnetic energy into thermal energy to the tissue by resistive heating. Durable lesions will form when the tissue temperature exceeds 50°C with irreversible loss of cellular depolarization. Radiofrequency also delivers energy to the tissue by conductive heating, with deeper tissue layers destroyed by passive heat transfer [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF]. An increase in ablation power will lead to an increase in lesion size due to both the increase in the source temperature and the increase in diameter of the heat source. However, the tissue temperatures must remain below 100°C to prevent intramyocardial steam from forming and dissecting tissue for release.

These "steam pops," can result in cardiac perforation and tamponade [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF].

The size of an RF lesion depends on a great number of factors. On top of power and duration of energy delivery, catheter stability, lesion contiguity and continuity, contact, electrode-tissue orientation, cooling from the surrounding blood pool and anatomic wall thickness all influence lesion formation [START_REF] Stevenson | Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction[END_REF], [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF].

For example, lesions are larger with the electrode in parallel position than in perpendicular position [START_REF] González-Suárez | Computational modeling of open-irrigated electrodes for radiofrequency cardiac ablation including blood motion-saline flow interaction[END_REF].

Monitoring tip-electrode temperature can help maximize power delivery. For example, in the "temperature-control" mode, the output of the radiofrequency generator is adjusted to keep the electrode temperature below a target value. Using a very large ablation electrode (8 mm in length) leads to a greater volume of direct resistive heating and a greater convective cooling of the electrode by the blood. However, a large ablation electrode has reduced mobility and flexibility as well as a lower resolution of recordings [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF].

i. Irrigated

Additionally, the electrode can be irrigated with saline for convective cooling to maintain a low electrode temperature [START_REF] González-Suárez | Computational modeling of open-irrigated electrodes for radiofrequency cardiac ablation including blood motion-saline flow interaction[END_REF]. This can prevent the electrode-tissue temperature reaching 100°C and developing coagulum [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF], [START_REF] González-Suárez | Computational modeling of open-irrigated electrodes for radiofrequency cardiac ablation including blood motion-saline flow interaction[END_REF], [START_REF] Nakagawa | Inverse relationship between electrode size and lesion size during radiofrequency ablation with active electrode cooling[END_REF].

As convective cooling from the bloodstream is no longer required, an irrigated electrode is capable of delivering more energy at sites of low blood flow, such as ventricular trabecular crevasses [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF].

Moreover, the additional energy delivered increases the depth of direct resistive heating and therefore the diameter of the effective source. With an irrigated catheter, the highest temperatures occur 3 to 4 mm below the tissue surface, producing deeper and larger lesions without increasing the diameter of the endocardial surface of the lesion [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF].

Irrigating an electrode enables the reduction in electrode size while maintaining a sufficient lesions size. A smaller irrigated electrode also has the benefit of being more flexible and enabling higher-resolution electrogram resolutions [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF], [START_REF] Nakagawa | Inverse relationship between electrode size and lesion size during radiofrequency ablation with active electrode cooling[END_REF].

Electrode temperature or electrode-tissue interface temperature do not reflect the temperature of the underlying tissue and therefore cannot be used to predict lesion size [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF]. This greatly limits the value of electrode temperature monitoring as irrigated catheter tip temperatures are a poor indicator of lesion formation [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF].

ii. Half-normal saline

Saline has an ionic charge and conducts electrical current with lower impedance than blood or tissue.

Radiofrequency current therefore preferentially disperses to the saline cloud in contact with the ablation electrode created with irrigation. Half-normal saline is an irrigant that has the particularity of possessing a lower ionic irrigation and thus a higher electrical impedance and therefore enables radiofrequency to preferentially be focused to the targeted cardiac tissue [START_REF] Nguyen | Radiofrequency ablation using an open irrigated electrode cooled with halfnormal saline[END_REF], [START_REF] Nguyen | Prospective multicenter experience with cooled radiofrequency ablation using high impedance irrigant to target deep myocardial substrate refractory to standard ablation[END_REF]. This method of decreasing the irrigant ionic concentration leads to deeper ablation lesions [START_REF] Nguyen | Radiofrequency ablation using an open irrigated electrode cooled with halfnormal saline[END_REF], [START_REF] Nguyen | Prospective multicenter experience with cooled radiofrequency ablation using high impedance irrigant to target deep myocardial substrate refractory to standard ablation[END_REF]. This may be a useful strategy to improve radiofrequency current delivery for myocardial circuits, especially arrhythmogenic cardiac tissue refractory to standard ablation [START_REF] Nguyen | Radiofrequency ablation using an open irrigated electrode cooled with halfnormal saline[END_REF]. Moreover, the use of higher-impedance fluid also has advantages for the pericardial space. Half-normal saline may further protect parietal pericardium by acting as insulation and may also obviate the need for the continuous evacuation of fluid [START_REF] Nguyen | Prospective multicenter experience with cooled radiofrequency ablation using high impedance irrigant to target deep myocardial substrate refractory to standard ablation[END_REF]. However, pushing the reasoning further was not successful as using an irrigant with absolutely no ionic components does result in even larger lesions but with a much higher steam pop rate [START_REF] Nguyen | Radiofrequency ablation using an open irrigated electrode cooled with halfnormal saline[END_REF].

c. 3D system

Initially, electrophysiological catheters were navigated and localized in the heart with the use of multiple 2D fluoroscopy x-ray planes. A major limitation of fluoroscopy is its inability to accurately link local electrograms to their spatial position and orientation [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF]. It is not possible to accurately associate (tag) a specific spatial position in the heart with its specific electrogram. Moreover, the position of a catheter cannot be accurately determined in respect to a site that has already been mapped [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF].

The CARTO® system (Biosense Webster Inc., Diamond Bar, USA) enables the generation of 3D electroanatomical maps [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF]. The entire heart can be reconstructed in real time with color-coded electrophysiological information projected on the electroanatomical map. A miniature passive magnetic field sensor is located at the tip of the catheter. As shown in figure 5, an external ultralow (5 * 10 -6 to 5 * 10 -5 T) magnetic field emitter (locator pad) is located beneath the operating table. It contains three coils with each coil generating a magnetic field that decays as a function of distance. The signals received by the sensor located in the catheter measure the strength of the magnetic field, thus enabling the distance from each coil to be precisely determined. These distances determine the radii of theoretical spheres around each coil. The intersection of the three spheres determines the location and orientation of the sensor in six degrees of freedom (x, y, z, roll, pitch, and yaw) [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF]. This mapping method enables the determination of the location of catheters with high precision (mean relative distance error of 0.73±0.03 mm) and good reproducibility (standard deviation of 0.74±0.05 mm).

The high spatial resolution (<1 mm) enables the construction of very detailed electroanatomical maps. The location of the catheter can be determined with reference to any previously created electroanatomical map, further helping the selection of the best target site for ablation [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF].

i. X-ray exposure

The use of a 3D system reduces x-ray exposure to both the staff and the patient [START_REF] Gepstein | A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results[END_REF]. This is important as cardiovascular imaging and intervention represent nearly 40% of medical radiation exposure to the US population [START_REF] Fazel | Approaches to enhancing radiation safety in cardiovascular imaging: a scientific statement from the American Heart Association[END_REF].

There are two main biological effects of radiation. A deterministic effect provoking predictable changes in tissue when the radiation exceeds a specific threshold and a stochastic effect, linked to the potential for future harm. For any given radiation exposure, the cancer risk is higher in females than in males and differs among individuals [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF]. The cancer risk is three to four times higher in children than in adults [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF]. Children are at a higher risk than adults because they have more rapidly dividing cells and a greater life expectancy.

The decrease in radiation exposure is especially important in children [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF], [START_REF] Von Bergen | Nonfluoroscopic and radiation-limited ablation of ventricular arrhythmias in children and young adults: a case series[END_REF]. The medical staff are also impacted even if they wear radioprotection. Cardiologists have a typical cumulative lifetime attributable risk on the order of magnitude of 1 cancer per 100 [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF], [START_REF] Venneri | Cancer risk from professional exposure in staff working in cardiac catheterization laboratory: insights from the National Research Council's Biological Effects of Ionizing Radiation VII Report[END_REF]. They therefore need to make every effort to give 'the right imaging exam, with the right dose, to the right patient' by implementing the ALARA (as low as reasonably achievable) principle [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF].

ii. Integration of fluoroscopy images

The CARTOUNIVU TM Module (Biosense Webster Inc., Diamond Bar, USA) enables the integration of previously acquired fluoroscopy images and cine loops into the current 3D electroanatomical maps [START_REF] Reents | Catheter ablation of ventricular arrhythmias using a fluoroscopy image integration module[END_REF].

Using CARTOUNIVU TM can lead to an operator independent reduction 52% reduction in fluoroscopy time and 63% in radiation dosage for VT ablation procedures [START_REF] Reents | Catheter ablation of ventricular arrhythmias using a fluoroscopy image integration module[END_REF].

A near-zero fluoroscopy procedure can be achieved in up to half of the VT ablation procedures [START_REF] Cano | Safety and feasibility of a minimally fluoroscopic approach for ventricular tachycardia ablation in patients with structural heart disease: influence of the ventricular tachycardia substrate[END_REF]. The percentage is particularly high in ischemic patients with endocardial ablation [START_REF] Cano | Safety and feasibility of a minimally fluoroscopic approach for ventricular tachycardia ablation in patients with structural heart disease: influence of the ventricular tachycardia substrate[END_REF]. For epicardial mapping, CARTOUNIVU TM is particularly useful to visualize the coronary arteries within the epicardial voltage map, helping the development of safer ablation strategies [START_REF] Cano | Safety and feasibility of a minimally fluoroscopic approach for ventricular tachycardia ablation in patients with structural heart disease: influence of the ventricular tachycardia substrate[END_REF].

d. Remote magnetic navigation

In addition to 3D mapping systems, another important method is remote magnetic navigation. Instead of directing the catheter with the catheter's handle, the orientation of the tip of the catheter is controlled by modifying a magnetic field (0.08-0.1 Tesla) generated by two permanent magnets [START_REF] Skoda | Catheter ablation of ischemic ventricular tachycardia with remote magnetic navigation: STOP-VT multicenter trial[END_REF]. The catheter possesses small magnets that are drawn by the desired magnetic field vector. The catheter deflects to align parallel to the magnetic field [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Faddis | Novel, magnetically guided catheter for endocardial mapping and radiofrequency catheter ablation[END_REF], [START_REF] Jin | Acute and long term outcomes of catheter ablation using remote magnetic navigation for the treatment of electrical storm in patients with severe ischemic heart failure[END_REF]. Figure 6 shows the electrophysiology room in Nancy equipped with such a system, the Niobe® system (Stereotaxis Inc., St. Louis, USA). The main advantage of this technique is the increased catheter movement and the ability to steer the flexible distal portion of the catheter in any direction. In contrast to manually controlled catheters that deflect in a single plane, the tip of the magnetic catheter can be deflected toward any direction in 3D space [START_REF] Qian | Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia[END_REF]. This is particularly valuable for complex situations and unknown cardiac anatomies [START_REF] Akca | Outcomes of repeat catheter ablation using magnetic navigation or conventional ablation[END_REF]. The force applied by the catheter with this technique is modest but stability is high [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Faddis | Novel, magnetically guided catheter for endocardial mapping and radiofrequency catheter ablation[END_REF], [START_REF] Proietti | Remote magnetic with open-irrigated catheter vs. manual navigation for ablation of atrial fibrillation: a systematic review and meta-analysis[END_REF]. Finally, the electrophysiologist is usually located in the next door room and can take off his radioprotection equipment. This reduces physical stress and radiation exposure for the operator [START_REF] Biase | MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population[END_REF].

Remote magnetic navigation is safe and is an alternative approach to manually performed ablation in the treatment of ischemic tachycardias with clinical outcomes being at least equivalent to manual ablation [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Proietti | Remote magnetic with open-irrigated catheter vs. manual navigation for ablation of atrial fibrillation: a systematic review and meta-analysis[END_REF], [START_REF] Jin | Acute and long term outcomes of catheter ablation using remote magnetic navigation for the treatment of electrical storm in patients with severe ischemic heart failure[END_REF], [START_REF] Qian | Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia[END_REF].

e. Contact catheters

A major improvement in catheters' design was the added possibility to measure the contact applied between the tip of the catheter and the tissue. This has increased the quality of mapping, lesions as well as ablation safety.

In THERMOCOOL SMARTTOUCH® catheters, (Biosense Webster Inc., Diamond Bar, USA), the ablation tip electrode is connected to the rest of the shaft by a small spring. The movement of the spring is detected.

The distal portion of the spring is connected to a transmitter coil that emits a reference signal that is then detected by location sensor coils located in the proximal portion of the spring. Once the movement is determined, the associated force is deduced based on the spring characteristics [START_REF] Ikeda | Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size[END_REF], [START_REF] Perna | Assessment of catheter tip contact force resulting in cardiac perforation in swine atria using force sensing technology[END_REF]. In bench testing, the resolution of the contact measurements was less than 1 gram [START_REF] Ikeda | Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size[END_REF]. This technology is integrated to the CARTO® system enabling force measurements to be visualized directly in real time during mapping and ablating [START_REF] Martinek | Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation[END_REF]. Moreover, on top of the quantity of force applied, the orientation of the contact can also be visualized with a 3D vector [START_REF] Martinek | Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation[END_REF].

i. Mapping

During catheter mapping, electrogram characteristics are collected and analyzed. Poor contact can lead to misinterpreted data. Indeed, an area might be wrongly identified as a low-voltage zone because of lack of contact. Collecting data with a catheter having a minimum forces of 9 grams can reduce misinterpretations [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Mizuno | Contact force monitoring for cardiac mapping in patients with ventricular tachycardia[END_REF]. Moreover, contact force catheters can lead to a decrease in radiation use [START_REF] Martinek | Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation[END_REF].

As we have previously discussed, this is beneficial for the patient as well as the medical team.

ii. Ablation efficacy

Before contact catheters, electrophysiologists could not directly measure contact force. They relied on fluoroscopy, tactile feedback, electrogram amplitude, impedance and temperature drop to estimate contact [START_REF] Ikeda | Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size[END_REF]. However, these measures have been shown to be inaccurate with up to 22% of radiofrequency applications in the ventricle using such estimates not resulting in any lesion formation [START_REF] Sacher | Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment[END_REF],

[66], [START_REF] Perna | Assessment of catheter tip contact force resulting in cardiac perforation in swine atria using force sensing technology[END_REF].

Indeed, pure tactile feedback can be influenced by contact, torque and deflection of the catheter shaft.

An impression of contact on the distal part of the catheter might be in fact due to contact somewhere else along the catheter. The tactile feedback can also be influenced by the presence of a sheath [START_REF] Martinek | Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation[END_REF]. Concerning the impedance drop during ablation, the major limitation is that this measure is only available during radiofrequency applications. It cannot be used to position the catheter before the application [START_REF] Ikeda | Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size[END_REF].

Moreover, the impedance drop does not predict the magnitude of the contact force [START_REF] Ikeda | Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size[END_REF]. A decrease in electrogram amplitude is not able to predict lesion size. This may be due to the fact that the electrode can continue to record the electrical activity outside the lesion thus limiting the use electrogram reduction [START_REF] Sacher | Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment[END_REF].

As we have previously seen, irrigation can alter electrode temperature [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Nakagawa | Comparison of in vivo tissue temperature profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus temperature control in a canine thigh muscle preparation[END_REF]. Irrigated catheter tip temperature monitoring is therefore a poor indicator of contact. Directly measuring contact force therefore decreases the number of radiofrequency applications that do not lead to any lesions, avoiding ablations that do not have sufficient contact and can lead to reduced overall procedure times [START_REF] Sacher | Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment[END_REF], [START_REF] Martinek | Clinical impact of an open-irrigated radiofrequency catheter with direct force measurement on atrial fibrillation ablation[END_REF].

iii. Ablation safety

It is possible to perforate cardiac tissue with a contact force as low as 77 grams and ablation can lead to a decrease the perforating force of 23% [START_REF] Perna | Assessment of catheter tip contact force resulting in cardiac perforation in swine atria using force sensing technology[END_REF]. Being able to measure the contact force can help the physician to safely navigate the catheter in the heart. Moreover, the visualization of the direction of the force applied can increase safety. Indeed, during epicardial ablation, if the force is not applied towards the myocardium and towards the lung, the radiofrequency applications may result in pulmonary lesions [START_REF] Sacher | Endocardial versus epicardial ventricular radiofrequency ablation: utility of in vivo contact force assessment[END_REF]. Without force vector information, up to 50% of the lesions could be towards the wrong direction [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF], [START_REF] Jesel | Characterization of contact force during endocardial and epicardial ventricular mapping[END_REF].

iv. Metrics beyond contact

Contact force alone is not sufficient to guarantee high quality lesions [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF]. On top of absolute contact force quantity, a combination of factors influence lesion formation including radiofrequency power and time, orientation between the catheter and tissue, catheter stability, constant force and energy delivered during ablation. Moreover, lesion continuity with small interlesion distances improve ablation lines. Wall thickness also has an important impact on transmural lesions. All these parameters need to be taken into account to deliver optimal lesions [START_REF] Ariyarathna | Role of contact force sensing in catheter ablation of cardiac arrhythmias: evolution or history repeating itself?[END_REF].

f. Multielectrode mapping

Another major evolution in catheters' design is multielectrode catheters. Understanding the electrical propagation of the heart depends on the ability for the electrophysiologists to create accurate maps of this electrical activity [START_REF] Stinnett-Donnelly | Effects of electrode size and spacing on the resolution of intracardiac electrograms[END_REF]. The electrograms collected by the electrodes on the catheter are distanceweighted averages of the activity of an area of heart tissue located underneath each electrode. Bipolar electrograms correspond to the difference between the signals collected by two electrodes and thus limits the far-field electrical contribution to the collected bipolar signal. The spatial resolution is increased as the distance between the electrode and the analyzed tissue is decreased, further highlighting the importance of tissue contact [START_REF] Stinnett-Donnelly | Effects of electrode size and spacing on the resolution of intracardiac electrograms[END_REF]. Regarding the electrode design, the resolution of the electrogram is increased the smaller the electrode width and the interelectrode spacing.

Conventional catheters possess a 3.5 mm tip electrode as well as a more proximal 1 mm electrode. The center-to-center spacing between the two electrodes is 3.25 mm. The bipolar signals collected are estimated to correspond to an area of tissue that can represent up to 2.4 cm 2 [START_REF] Acosta | Multielectrode vs. point-by-point mapping for ventricular tachycardia substrate ablation: a randomized study[END_REF].

Multielectrode catheters have been developed to increase mapping resolution [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. They have a higher number of electrodes (10 or above) with smaller electrode size and closer center-to-center interelectrode distance enabling each signal collected to correspond to the electrical activity of a smaller tissue area [START_REF] Stinnett-Donnelly | Effects of electrode size and spacing on the resolution of intracardiac electrograms[END_REF], [START_REF] Acosta | Multielectrode vs. point-by-point mapping for ventricular tachycardia substrate ablation: a randomized study[END_REF]. Smaller electrodes have an increased electrogram resolution. Each electrode records the electrical activity of a smaller portion of the tissue. The overlap of the bipolar electrogram between the two unipolar signals is therefore smaller, leading to an overall larger bipolar electrogram [START_REF] Leshem | High-resolution mapping of ventricular scar: evaluation of a novel integrated multielectrode mapping and ablation catheter[END_REF]. This electrode configuration enables the recording of lower amplitude signals [START_REF] Downar | Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms[END_REF]. This can be particularly useful in areas with low voltage and scar, facilitating the identification of small preserved myocardial bundles. These structures could otherwise remain invisible with conventional catheters [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. Multielectrode catheters enable the recording of distinct diastolic activity and have been found to have sufficient sensitivity to map the heterogeneous and complex post myocardial scar structures [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF], [START_REF] Della Bella | Multielectrode contact mapping to assess scar modification in post-myocardial infarction ventricular tachycardia patients[END_REF]. Moreover, the increased substrate definition due to the reduced far field participating of the neighboring healthy tissue can lead to larger low voltage areas [START_REF] Berte | Impact of electrode type on mapping of scar-related VT[END_REF].

Another advantage of the smaller electrodes of multielectrode catheters is the lowered pacing threshold.

The increased electric current density of smaller electrodes can achieve capture of lower-voltage tissue than conventional catheters [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. This can be particularly useful for pace mapping, an important technique to identify ablation targets that will be developed in depth later.

Furthermore, the increased number of electrodes leads to more data points being collected at each beat, resulting in increased mapping density and speed [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. This has been shown to shorten the overall duration of mapping as the electrophysiologist often terminates the mapping phase as soon as the density of points is sufficient to understand the circuit [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. The increase number of data collected at each beat is particularly useful during the mapping of ventricular tachycardias that can only be sustained for a short period of time [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. High-density mapping has been defined as over 25 points acquired per cm 2 and can allow precise characterization of patchy fibrotic areas by limiting potential errors due to interpolation between points [4], [START_REF] Della Bella | Multielectrode contact mapping to assess scar modification in post-myocardial infarction ventricular tachycardia patients[END_REF]. Overall, the use of multielectrode catheters has a positive impact and can lead to increased patient outcomes and lower VT recurrence rates [START_REF] Yamashita | Impact of new technologies and approaches for post-myocardial infarction ventricular tachycardia ablation during long-term follow-up[END_REF].

ORION TM

An example of such a multipolar catheter currently used in clinical practice is the INTELLAMAP ORION TM 64-electrode catheter (Boston Scientific Inc., Cambridge, USA). It is an 8F minibasket catheter with 8 splines, each containing 8 electrodes. Each electrode has an area of 0.4 mm 2 and a center to center interelectrode spacing of 2.5 mm [4]. During each beat, an average of 2 splines are in contact with the myocardium enabling the catheter to acquire on average 12 electrograms [4]. The remaining 6 splines are facing the blood pool. Although mechanical ectopy can occur while moving the catheter inside the chamber, the number of data points that can be acquired is significant (up to 148 per cm 2 ) [4], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

However, it's design is ill suited for mapping papillary muscles or the epicardium [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

g. Microelectrode mapping

Recent catheter developments have looked into incorporating microelectrodes on an ablation catheter to take advantage of the increased mapping resolution and pacing capabilities. Microelectrodes enable the detection of smaller channels of surviving myocardial bundles and when incorporated on an ablation catheter can further improve the positioning of the catheter for radiofrequency delivery [START_REF] Leshem | High-resolution mapping of ventricular scar: evaluation of a novel integrated multielectrode mapping and ablation catheter[END_REF]. Furthermore, microelectrodes facilitate pacing with capture in low-voltage areas and the lower pacing thresholds reduce the impact of noise and artifacts [START_REF] Leshem | High-resolution mapping of ventricular scar: evaluation of a novel integrated multielectrode mapping and ablation catheter[END_REF].

The latest ablation catheter, the QDOT MICRO® (Biosense Webster Inc., Diamond Bar, USA) has 3 microelectrodes embedded along the circumference of the distal electrode. Each electrode measures 0.086 mm 2 with a center to center interelectrode spacing of 1.5 mm. The innovative design of the microelectrodes located at the circumference of the distal electrode facilitate the recording of bipolar electrograms in a parallel orientation to the chamber wall. The two microelectrodes are more spatially and temporally distant from one another in a parallel than in a perpendicular configuration. This feature further improves electrogram resolution by reducing the cancelling effect between the two electrodes, leading to an overall larger bipolar electrogram amplitude. The QDOT MICRO® microelectrodes size, spacing as well as design enhance the detection of surviving myocardial bundles [START_REF] Leshem | High-resolution mapping of ventricular scar: evaluation of a novel integrated multielectrode mapping and ablation catheter[END_REF].

h. Automated mapping

The development of novel catheters with its ever-increasing number of electrograms recorded has led to the fact that manual annotation by the electrophysiological team of all the electrograms is timeconsuming, tedious and no longer feasible [START_REF] Haddad | Novel algorithmic methods in mapping of atrial and ventricular tachycardia[END_REF]. Another limit of manual annotation is that presumption and bias can lead to misconceptions [START_REF] Haddad | Novel algorithmic methods in mapping of atrial and ventricular tachycardia[END_REF]. Algorithms, directly implemented in the navigation system, have been developed to automatically detect and annotate the collected points. They are based on user-defined acceptance criteria with each point passing through a series of preassigned filters [START_REF] Nair | New Mapping Technologies[END_REF], [START_REF] Luther | Automated activation and pace-mapping to guide ablation within the outflow tract[END_REF]. For example a tissue proximity indicator can be defined to only mark points that are in close proximity to surface tissue [START_REF] Luther | Automated activation and pace-mapping to guide ablation within the outflow tract[END_REF]. The multiple point collection filters and the large selection of parameters limit erroneous point acquisition. Once acquired, the annotation of the point has also been automatized. Algorithms that use a combination of the maximum negative slope in the unipolar signal as well as the corresponding bipolar signal are the most used to determine the local activation time. Manual correction is rarely needed with operator intervention representing as little as 0.17% of the total accepted electrograms [START_REF] Nakagawa | Rapid high resolution electroanatomical mapping: evaluation of a new system in a canine atrial linear lesion model[END_REF]. The latest versions of navigation systems offer fast and fully-automatic acquisition with accurate annotation that help to better localize the tachycardia circuit [START_REF] Luther | Automated activation and pace-mapping to guide ablation within the outflow tract[END_REF], [START_REF] Bun | Ultra-high-definition mapping of atrial arrhythmias[END_REF].

i. Signal analysis in sinus rhythm

The mapping, catheter and software capabilities were developed to best analyze the electrophysiological data available. Bundles of surviving myocytes within heterogeneous scar and areas of block are key components of the tachycardia substrate and the analysis of abnormal electrographic findings identified during sinus rhythm may help to identify isthmuses during VT [START_REF] Anter | Infarct-related ventricular tachycardia: redefining the electrophysiological substrate of the isthmus during sinus rhythm[END_REF]. By predicting from sinus rhythm analysis the location at which a reentrant circuit is most likely to form, targeted ablation can then be performed to prevent the tachycardia [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF]. The following section will evaluate the use of voltage, scar, fragmented and double potential sinus rhythm mapping to help identify reentrant circuits.

i. Bipolar voltage

Bipolar voltage is a measure of amplitude (usually in mV) of the peak-to-peak deflection.

The mean left ventricle (LV) bipolar electrogram amplitude recorded with a 4 mm tip and a 2 mm-ring electrode separated by 1 mm mapping catheter and filtered at 10-400 Hz was 4.8 mV with 95% of normal LV endocardial electrograms with a peak-to-peak amplitude above 1.55 mV [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Marchlinski | Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy[END_REF]. The infarct zone presents electrograms with lower bipolar amplitudes (1.26 mV) and longer duration (74.26 ms) compared to electrograms recorded from the rest of the ventricle [START_REF] Callans | Electroanatomic left ventricular mapping in the porcine model of healed anterior myocardial infarction: correlation with intracardiac echocardiography and pathological analysis[END_REF]. Figure 7 is an example of a left ventricle bipolar map. The lower limit is set at 0.50 mV, all areas under this value are in red. The upper limit is set at 1.50 mV, all areas above this value are in purple.

The analysis of electrographic amplitude depends on multiple factors and therefore must be interpreted with caution.

Bipolar voltage is a not an absolute measure of the underlying tissue but rather a metric to quantify conduction between 2 electrodes of a given catheter design and technology. Electrode size, interelectrode spacing and filtering all influence voltage measurements [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. Bipolar recordings reduce far-field interferences and this effect is maximized as interelectrode distance is decreased [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. Electrogram amplitude not only depends on catheter design but also on relative wavefront orientations. The orientation of the activation wavefront relative to the two electrodes and the orientation of the activation wavefront relative to myocardial fiber orientation both influence voltage measurements [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF], [START_REF] Berte | Impact of electrode type on mapping of scar-related VT[END_REF], [START_REF] Tung | Directional influences of ventricular activation on myocardial scar characterization: voltage mapping with multiple wavefronts during ventricular tachycardia ablation[END_REF], [START_REF] Cassidy | Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms[END_REF]. For example, voltage measurements in the septal area can be more difficult to determine because of the complex nature of the conduction system [START_REF] Tung | Directional influences of ventricular activation on myocardial scar characterization: voltage mapping with multiple wavefronts during ventricular tachycardia ablation[END_REF]. Multielectrode catheters enable the collection of more data points with a greater variability of the angle between the activation wavefront and the two electrodes and may be less subjective [START_REF] Tschabrunn | Highresolution mapping of ventricular scar: comparison between single and multielectrode catheters[END_REF]. ii. Scar While keeping these voltage limitations in mind, bipolar voltage <0.5 mV has been used to define "dense scar" zones [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Marchlinski | Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. Low voltage does not equal electrically silent nonconductive zones.

These voltage defined regions can overestimate the area of scar by still containing viable myocytes [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. The total low-voltage area can be large reaching over 200 cm 2 hindering complete encirclement with catheter ablation [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. Mapping with smaller electrodes and lower interelectrode distances has helped by identifying healthy sharp and high-voltage signals in areas previously considered as "dense scar" when mapped using standard mapping catheters with larger electrodes [4], [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF].

Voltage mapping can also underestimate the area of scar as contrast-enhanced magnetic resonance imaging has shown that surviving myocardium as little as 2 mm can produce a bipolar electrogram amplitude above 1.5 mV, preventing the identification of the local scar due to a higher far-field signal [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF], [START_REF] Dickfeld | MRI-Guided ventricular tachycardia ablation: integration of late gadoliniumenhanced 3D scar in patients with implantable cardioverter-defibrillators[END_REF], [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF]. This is particularly true in the case of non transmural scar, where viable myocardium overlying the subendocardial scar generate high-voltage signals [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF].

Voltage amplitude alone should not be used to define nonconductive barriers and pacing maneuvers to define the lack of electrical excitability can be used to provide additional information. Pacing stimulus from the pacing electrode directly attempts to depolarize the neighboring tissue. Local capture suggests the presence of viable myocardium and can limit voltage based scar regions overestimations [4], [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF].

However pacing does not help to identify small scar areas. These areas may still create important conduction block, but can escape both voltage and pacing based detection [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. Up to 17% of isthmuses can include areas with normal voltage amplitude [START_REF] Anter | Infarct-related ventricular tachycardia: redefining the electrophysiological substrate of the isthmus during sinus rhythm[END_REF]. Moreover, up to 15% of ablation sites were outside the bipolar low voltage area [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF], [START_REF] Verma | Relationship between successful ablation sites and the scar border zone defined by substrate mapping for ventricular tachycardia post-myocardial infarction[END_REF]. VT termination by ablation outside the low voltage area has also been reported [START_REF] Tung | Directional influences of ventricular activation on myocardial scar characterization: voltage mapping with multiple wavefronts during ventricular tachycardia ablation[END_REF], [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF].

Using different voltage scar definitions can help highlight areas of higher voltage "channels", regions of relatively preserved voltage within denser scar areas [START_REF]Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition[END_REF], [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF]. These sites may serve as the protected VT isthmus but with only 30% of channels containing a clinical VT isthmus, many are not critical to the VT circuit [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF]. This low specificity highlights the fact that the majority of channels are "bystanders", hindering the use of voltage based channel identification to guide ablation [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF].

The limitations of using bipolar voltage alone to identify reentrant circuits has led to the development of other metrics especially regarding the analyses of abnormal electrogram characteristics.

iii. Double potential Double-potential electrograms are defined by at least 2 separate ventricular bipolar potentials with peaks separated by an isoelectric interval. The minimum length of the interval varies from 30 ms [4] to 50 ms [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF].

Split electrograms frequently show opposite unipolar electrogram polarity. This difference in vector orientation indicates the presence of a first wave propagating in a given direction and a second wave propagating in another direction [4]. Double potentials can represent desynchronized activation sequences of multiple wave fronts and can account for 5% of total mapped sites [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF].

A VT isthmus is defined as a conductive myocardial tissue delineated by nonconductive tissue. In addition to an anatomical obstacle or a scar area, a line of double potentials can also represent this nonconductive tissue [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF].

In 31 out of 33 VTs, at least one isthmus boundary was represented by a double potential line. A mean of 1.8 zones of block per patient was identified by a continuous 32 mm line of double potentials [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. Double potentials represent desynchronized activation of tissue and further help to identify reentrant circuits. These split electrograms are recorded at fewer sites and in fewer patients than the fractionated electrograms that we will now look into [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF].

iv. Fragmented signals

Electrograms that are the most abnormal are defined as fractionated. They consist of multiple highfrequency components with low amplitudes and long durations (figure 8). Unfortunately the lack of a standardized definition limits comparisons between studies. Most authors agree that fractionated electrograms are composed of multiple components (5 or above in [4]) crossing the isoelectric baseline with an amplitude less than 0.5 mv and duration longer than 50 ms (reaches 133 ms as in [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF]) [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Josephson | Fractionated electrical activity and continuous electrical activity: fact or artifact?[END_REF].

An amplitude to duration ratio below 0.005 V/s has also been used to further characterize fractionated electrograms [START_REF] Josephson | Fractionated electrical activity and continuous electrical activity: fact or artifact?[END_REF], [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF] while others have looked into a fractionation index defined by number of peaks/width of local electrogram [START_REF] Bogun | Analysis during sinus rhythm of critical sites in reentry circuits of postinfarction ventricular tachycardia[END_REF].

Quantitative characterization is limited by the fact that electrogram amplitude and width vary depending on multiple factors such as electrode design and wavefront orientation. Electrode size has a direct effect on electrogram complexity. Fractionated electrograms recorded by an electrode with a larger diameter are associated with smaller amplitude [START_REF] Jacquemet | Genesis of complex fractionated atrial electrograms in zones of slow conduction: a computer model of microfibrosis[END_REF]. Wavefront direction in relation to the recording dipole will also impact signal amplitude [START_REF] Cassidy | Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms[END_REF]. Changes in wavefront activation or catheter orientation lead to changes in signal amplitude and complexity [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. Electrogram morphology may also change because of artifacts induced by electrode movement and filter settings [START_REF] Josephson | Fractionated electrical activity and continuous electrical activity: fact or artifact?[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF].

Fractionated electrograms are caused by surviving myocardial cells that have been uncoupled and electrically isolated by intervening fibrous tissue. The slow and desynchronized depolarization is responsible for the high-frequency multicomponent long duration electrogram [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF]. The multiple components reflect the depolarization of different surviving muscle bundles at different times [START_REF] Josephson | Fractionated electrical activity and continuous electrical activity: fact or artifact?[END_REF]. The electrical wavefront travelling perpendicular to the fiber long axis activate the muscle bundles across highresistance intercellular connections resulting in conduction delay and multiple components being recorded [START_REF] Fenoglio | Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF], [START_REF] Jacquemet | Genesis of complex fractionated atrial electrograms in zones of slow conduction: a computer model of microfibrosis[END_REF], [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF]. The fiber axis variations prevent a consistent wavefront direction that maximizes the detection of fragmented signals in a given ventricle to be identified [START_REF] Tung | Directional influences of ventricular activation on myocardial scar characterization: voltage mapping with multiple wavefronts during ventricular tachycardia ablation[END_REF]. More severe micro fibrosis can lead to reduce transverse conduction and an increased number of electrogram deflections [START_REF] Jacquemet | Genesis of complex fractionated atrial electrograms in zones of slow conduction: a computer model of microfibrosis[END_REF]. Fractionated electrograms also increase with time because of growing connective tissue during infarct healing [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF]. Increased spatial resolution helps to determine the different bundles responsible for fractionated electrograms [START_REF] Stinnett-Donnelly | Effects of electrode size and spacing on the resolution of intracardiac electrograms[END_REF].

Patients with ventricular tachycardia have more numerous and longer fractionated electrograms [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF]. Fractionated sites may represent non uniform anisotropic conduction and help delineate regions where reentry occurs [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Gardner | Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts[END_REF]. Fractionated electrograms that persist regardless of different electrical activation sequences are even more likely to be associated with reentry circuit isthmuses [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF]. The electrogram duration is longer in the reentry circuit but fractionation is most common (up to 69%) outside of the circuit [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF]. Fractionated activity can even occur without the presence of reentrant circuits [START_REF] Josephson | Fractionated electrical activity and continuous electrical activity: fact or artifact?[END_REF], [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF]. This low specificity prevents the use of fractionation sites identified in sinus rhythm as targets for ablation [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF]. Late potentials can either be isolated potentials or continuous fragmented activity. Very late potentials describe potentials that occur at least 100 ms after the QRS [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF], [START_REF] Haqqani | Fundamental differences in electrophysiologic and electroanatomic substrate between ischemic cardiomyopathy patients with and without clinical ventricular tachycardia[END_REF]. Late potentials are found in most post infarct VT ablation patients, with a rate ranging from 66% [START_REF] Silberbauer | Noninducibility and late potential abolition: a novel combined prognostic procedural end point for catheter ablation of postinfarction ventricular tachycardia[END_REF] to 88% [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF]. The average area containing late potentials for each patient is 22.2 cm 2 [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF]. Patients without late potentials seem to have smaller and less-dense scars [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF], [START_REF] Haqqani | Fundamental differences in electrophysiologic and electroanatomic substrate between ischemic cardiomyopathy patients with and without clinical ventricular tachycardia[END_REF], [START_REF] Tsiachris | Electroanatomical voltage and morphology characteristics in postinfarction patients undergoing ventricular tachycardia ablation: pragmatic approach favoring late potentials abolition[END_REF]. Moreover, very late potentials are usually clustered in 1 or 2 regions [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF].

Local abnormal ventricular activity (LAVA) are any sharp high-frequency potentials distinct from the farfield ventricular electrogram. These potentials can be high or low amplitude and occur at any time before, during, or after the QRS [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF], [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF]. LAVAs can be hidden in the QRS far-field signal making their identification challenging [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF]. Different pacing maneuvers can be used to help identification. Pacing at a fixed rate from the right ventricle (RV) apex changes the direction of the electrical wavefront and can help to identify otherwise undetected local activity [START_REF] Verma | Relationship between successful ablation sites and the scar border zone defined by substrate mapping for ventricular tachycardia post-myocardial infarction[END_REF], [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF], [START_REF]Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease[END_REF]. Moreover, the addition of a single coupled extra stimulus with a low coupling interval has been used to exhibit the decremental conduction properties of LAVAs and facilitate their identification from far-field ventricular electrograms [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF], [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF], [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF]. Local ectopic activity can similarly be used to help identification [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF]. LAVAs are found in 96% of ischemic patients and occupy an average area of 39 cm 2 [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF].

Decrement-evoked potential (DEEP) mapping technique consists of annotating the latest sharp, near-field component of the bipolar signals during the pacing train and on the first extra stimulus. If the delay between the two is over 10 ms, the site is categorized as DEEP [START_REF] Jackson | Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation[END_REF], [START_REF] Porta-Sánchez | Multicenter study of ischemic ventricular tachycardia ablation with decrement-evoked potential (DEEP) mapping with extra stimulus[END_REF]. Double or triple extra stimulus can also be similarly used to highlight these zones of slow conduction and functional block [START_REF] Acosta | Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures[END_REF]. DEEP display areas with decremental conduction that can be hidden during sinus rhythm. DEEP sites can allow the time for blocked regions to recover excitability and then initiate reentry [START_REF] Jackson | Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation[END_REF]. DEEPs are more specifically associated with VT circuits and are localized more frequently in the diastolic pathway of the VT than late potentials [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF], [START_REF] Jackson | Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation[END_REF], [START_REF] Porta-Sánchez | Multicenter study of ischemic ventricular tachycardia ablation with decrement-evoked potential (DEEP) mapping with extra stimulus[END_REF].

In addition to endocardial mapping, epicardial mapping has also been used for late potential or LAVA mapping [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF], [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF], [START_REF] Reddy | Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction[END_REF]. Compared to the endocardium, the pericardium has the advantage of possessing less obstacles to catheter movement, making it easier to reach a particular area. However, adequate contact can be more challenging to achieve increasing the risk of falsely identifying low voltage values [START_REF] Reddy | Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction[END_REF]. The onset of local epicardial electrograms is further delayed due to additional transmural conduction facilitating their identification [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF]. During combined endocardial-epicardial mapping, the scar borders of the two areas are close [START_REF] Reddy | Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction[END_REF]. Moreover, patients without any endocardial substrate can be explored with epicardial mapping. Overall, endocardial LAVAs were present in 90% patients whereas epicardial LAVAs were present in 81% patients [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF].

Color-coded activation delay maps of late potentials have been used to highlight the localization of late potentials [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF]. This representation facilitates the identification of conduction channels [START_REF] Berruezo | Scar dechanneling: new method for scar-related left ventricular tachycardia substrate ablation[END_REF]. This technique can be easily coupled with previously described voltage map analysis and seem to increase the specificity of predicting a clinical channel [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF], [START_REF]Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease[END_REF]. Moreover, very late potentials seem to be more specific but less sensitive in predicting critical conducting channels [START_REF] Bogun | Analysis during sinus rhythm of critical sites in reentry circuits of postinfarction ventricular tachycardia[END_REF], [START_REF]Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease[END_REF]- [START_REF] Haqqani | Fundamental differences in electrophysiologic and electroanatomic substrate between ischemic cardiomyopathy patients with and without clinical ventricular tachycardia[END_REF]. Late, LAVA and DEEP potentials have been used as a guide for targeting ablation in numerous studies [START_REF] De Riva | Targeting the hidden substrate unmasked by right ventricular extrastimulation improves ventricular tachycardia ablation outcome after myocardial infarction[END_REF], [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF], [START_REF] Brunckhorst | Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction[END_REF]- [START_REF] Bogun | Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia[END_REF],

[109], [START_REF] Jais | Elimination of local abnormal ventricular activities clinical perspective: a new end point for substrate modification in patients with scar-related ventricular tachycardia[END_REF], [START_REF] Jackson | Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation[END_REF], [START_REF] Miller | Effect of subendocardial resection on sinus rhythm endocardial electrogram abnormalities[END_REF]. Conceptually this enables to address all actual as well as potential circuits while keeping the advantage of a more selective intervention than the complete encircling of the scar [START_REF] Della Bella | Multielectrode contact mapping to assess scar modification in post-myocardial infarction ventricular tachycardia patients[END_REF], [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF].

However, some patients still have clinical isthmus circuits that are not linked to the identified channels [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF].

For example, late potentials can only be recorded in as little as 30% of isthmus sites [START_REF] Anter | Infarct-related ventricular tachycardia: redefining the electrophysiological substrate of the isthmus during sinus rhythm[END_REF], [START_REF] Cassidy | Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms[END_REF]. Late potential sites being not specific to the clinical VT, this strategy can still result in an extensive ablation, especially in patients with large myocardial infarctions [START_REF] Marchlinski | Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy[END_REF], [START_REF] Mountantonakis | Relationship between voltage map 'channels' and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia[END_REF]. Late potential ablation has been shown to limit VT inducibility, with late potential abolition having a positive predictive value of 75%, negative predictive value of 90.4%, sensitivity of 60.0%, and specificity of 95.0% for arrhythmia recurrence [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF]. Overall, there is currently no consensus about the best sinus rhythm signal morphology to target during ablation [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF], [START_REF] Miller | Effect of subendocardial resection on sinus rhythm endocardial electrogram abnormalities[END_REF].

vi. Activation gradients

On top of localizing low-voltage regions, electrically unexcitable scar and abnormal electrogram components, activation gradients during sinus rhythm have been used to further identify abnormal conduction properties [START_REF] Anter | Infarct-related ventricular tachycardia: redefining the electrophysiological substrate of the isthmus during sinus rhythm[END_REF], [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF]. The electrical propagation is expected to be slowed at the isthmus location during sinus rhythm, causing delayed activation between closely located points [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF]. Areas with the most significant activation gradients during sinus rhythm can therefore represent zones that are vulnerable for conduction slowing or block during re-entry. These critical zones can be combined with other sinus rhythm techniques to reach a sensitivity of 83.8% and specificity of 89.2% in estimating the isthmus location [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF]. This suggests that activation gradients during sinus rhythm can be used as an additional tool to better understand and characterize the location of the reentrant circuit and improve reentrant VT ablation accuracy in post-infarct patients [START_REF] Anter | Infarct-related ventricular tachycardia: redefining the electrophysiological substrate of the isthmus during sinus rhythm[END_REF], [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF].

vii. Limitations of sinus map

The main limitation of all the substrate-based mapping techniques is that an isthmus during ventricular tachycardia is not always present during sinus rhythm [4]. Lines of block may be at least partially functional and therefore remain undetectable during sinus rhythm [START_REF] Ciaccio | Relationship between sinus rhythm activation and the reentrant ventricular tachycardia isthmus[END_REF]. The conditions required for re-entrant circuits to occur tend to depend on functional rather than fixed abnormalities [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. Furthermore, electrogram characteristics are influenced by wavefront activation and catheter orientation [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. This explains why neither the type, duration, nor timing of electrograms recorded during sinus rhythm are completely reliable in localizing the reentry circuit and may in fact represent characteristics unrelated to the reentrant activity [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Waxman | Significance of fragmented ventricular electrograms observed using intracardiac recording techniques in man[END_REF]. For example, late electrograms during sinus rhythm can represent slow conduction into dead end pathways [START_REF] Cassidy | Catheter mapping during sinus rhythm: relation of local electrogram duration to ventricular tachycardia cycle length[END_REF]. Artifacts resulting from catheter movement or filter settings can also hinder analysis [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Waxman | Significance of fragmented ventricular electrograms observed using intracardiac recording techniques in man[END_REF]. The different sinus rhythm mapping techniques lack in standardization mostly in regard quantitative description of signal characteristics and filter settings leading to difficulty in comparing results [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF], [START_REF] Waxman | Significance of fragmented ventricular electrograms observed using intracardiac recording techniques in man[END_REF]. The confusion also hinders the use of sinus rhythm mapping. Finally, the ablation of all sinus-rhythm identified targets can lead to ablating large areas, representing up to one-third of the surface of the left ventricle [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF]. Overall, sinus rhythm based mapping techniques need to be interpreted with caution when used to define the mechanisms of ventricular tachyarrhythmia in post infarct patients [START_REF] Picano | The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology[END_REF], [START_REF] Waxman | Significance of fragmented ventricular electrograms observed using intracardiac recording techniques in man[END_REF].

j. Activation mapping during tachycardia i. Definition

Mapping the activation pattern during tachycardia is a widespread technique to localize the reentry circuit.

Activation mapping consists of sampling the local electrical activity during tachycardia from different sites [START_REF] Miller | Pattern of endocardial activation during sustained ventricular tachycardia[END_REF]. The unipolar and bipolar signals are recorded and the relative timing between the sites is determined [4]. The display of the different timings on 3D mapping systems allow patterns of activation to be identified [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Miller | Pattern of endocardial activation during sustained ventricular tachycardia[END_REF]. Figure 10 shows an example of an activation map during VT. The color coding (red-yellow-green-blue-purple) enables the quick identification of the activation sequence.

ii. Induction

Most patients are not in tachycardia when the electrophysiology study starts. A programmed electrical stimulation is used to induce the ventricular tachycardia. An external stimulator is connected to the catheter and delivers 2 ms pulses at a 600 ms basic cycle length followed by an extra stimulus pulse with a shorter coupling. If the stimulation fails to induce the VT, the coupling of the extra stimulus is gradually reduced. Up to 3 extra stimuli can be added and a basic cycle length of 400 ms can be used to try to induce VT. The sensitivity of programmed stimulation rises and the specificity drops as the number of extra stimuli is increased [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF], [START_REF] Brugada | Results of a ventricular stimulation protocol using a maximum of 4 premature stimuli in patients without documented or suspected ventricular arrhythmias[END_REF]. If the VT cannot be induced, the catheter is moved and the programmed ECG Intracardiac signals stimulation is started again at another location [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF], [START_REF] Marchlinski | Long-term success of irrigated radiofrequency catheter ablation of sustained ventricular tachycardia: post-approval THERMOCOOL VT trial[END_REF]. The stimulation protocol often starts via the catheter positioned at the right ventricular apex before moving to the right ventricular outflow tract or the left ventricle. Induction of a VT is highly dependent on the stimulation protocol and lacks in reproducibility [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF], [START_REF] Rosenbaum | Immediate reproducibility of electrically induced sustained monomorphic ventricular tachycardia before and during antiarrhythmic therapy[END_REF]. The induced tachycardia is considered sustained if it lasts more than 30 seconds or results in loss of consciousness [START_REF] Miller | Subendocardial resection for ventricular tachycardia: predictors of surgical success[END_REF]. Recordings of previous VTs help determine the clinical relevance of the induced tachycardia [START_REF] Marchlinski | Long-term success of irrigated radiofrequency catheter ablation of sustained ventricular tachycardia: post-approval THERMOCOOL VT trial[END_REF]. The mean number of VTs induced in a patient varies between 2.4 and 3 [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF], [START_REF] Tanner | Catheter ablation of recurrent scar-related ventricular tachycardia using electroanatomical mapping and irrigated ablation technology: results of the prospective multicenter Euro-VT-study[END_REF], [START_REF] Stevenson | Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial[END_REF]. General anesthesia limits the ease of inducing VTs [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF].

iii. Reference and annotation

The timings of the signals of the different catheter locations are all compared to the same electrical reference. The electrical reference is chosen as a morphologically stable and regular electrogram. The electrogram can either be endocardial (from a fix catheter) or a surface lead. If a surface QRS is selected, a sharp and easily identifiable feature is selected (maximum). The window of interest is often centered on the reference with a width equal to the VT cycle length minus 20 ms [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. For each pair of electrode, the local activation time is determined by taking into account both unipolar and bipolar signals. Automatic annotation algorithms are based on selecting the timing of the largest rapid deflection of the unipolar signal corresponding to a bipolar signal above a certain threshold. The time interval to the electrical reference is then calculated and is used if the value can be reproduced on at least two consecutive beats [START_REF] Miller | Pattern of endocardial activation during sustained ventricular tachycardia[END_REF].

iv. Activation

After the catheter has been positioned all over the cavity, the overall activation pattern can be analyzed.

The critical isthmus corresponds to a slow conducting zone and represents a large proportion, between 57% and 81%, of the total VT cycle length [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. The conduction velocity is slowed both at the isthmus entrance (0.28 m/s) and isthmus exit (0.40 m/s) [4]. The curved wave front propagation in these two areas can also explain the slowed propagation. Indeed, conduction speed is greatly influenced by fiber orientation. Conduction that is perpendicular to the fiber direction can be reduced up to 10 times [4]. The onset of the QRS complex occurs when the impulse exits the scar and activates the large mass of healthy myocardium [4], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Miller | Pattern of endocardial activation during sustained ventricular tachycardia[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. It is important to carefully interpret the activation map in order to understand the circuit. For example, diastolic potentials can also be present outside the isthmus location, adding complexity to the analysis [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. Furthermore, the complete circuit is not always entirely localized on the left ventricular endocardium and some tachycardias have subepicardial or intramural components [START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF], [START_REF] Kaltenbrunner | Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized?[END_REF]. These usually exhibit a gap in the activation sequence as part of the circuit is concealed on the endocardial map [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. In these cases, epicardial mapping may help to further understand the circuit by mapping these hidden features [START_REF] Baker | Ventricular tachycardia in the infarcted, Langendorff-perfused human heart: Role of the arrangement of surviving cardiac fibers[END_REF]. After detailed review, an activation map enables the distinct identification of the entrance, isthmus, and exit sites of the circuit.

Activation mapping during VT is very valuable to identify isthmuses for patients with hemodynamically stable monomorphic tachycardia [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Josephson | Recurrent sustained ventricular tachycardia. 1. Mechanisms[END_REF]. It can localize in detail reentry circuits and isthmuses formed by either fixed or functional lines of conduction block [4], [START_REF] Josephson | Substrate mapping for ventricular tachycardia: assumptions and misconceptions[END_REF]. Activation mapping is a valuable mapping strategy.

v. Limitations of activation map

Failure to induce tachycardia is the main limitation of activation mapping during tachycardia [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF]. At least 20% of the time patients have no inducible clinical tachycardia [START_REF]Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease[END_REF], [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF], [START_REF] Josephson | Recurrent sustained ventricular tachycardia. 1. Mechanisms[END_REF]. Even when induced, the VT can be unstable and factors such as hemodynamic collapse, changing morphology and termination of tachycardia during mapping greatly limit the utility of activation mapping [START_REF] Kienzle | Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia[END_REF], [START_REF] Cassidy | The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia[END_REF], [START_REF] Jackson | Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation[END_REF], [START_REF] Soejima | Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping[END_REF]. Mapping during VT can be performed in only between 30% and 40% of cases [START_REF] Tung | Directional influences of ventricular activation on myocardial scar characterization: voltage mapping with multiple wavefronts during ventricular tachycardia ablation[END_REF], [START_REF] Tung | Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: an International VT Ablation Center Collaborative Group study[END_REF]. Even when the targeted VT is stable, inability to delineate the entirety of the circuit (intramural components) can further limit activation mapping [START_REF] Segal | Long-term results after ablation of infarct-related ventricular tachycardia[END_REF]. Mapping only during VT does not able to determine whether the conduction blocks are anatomical or functional [START_REF] De Chillou | Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction[END_REF]. To reduce the impact of these limitations, activation mapping is often coupled with other techniques such as substrate, entrainment, or pace mapping [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

k. Entrainment mapping i. Definition

Entrainment involves applying during tachycardia, via the mapping catheter, an electrical stimulus with sufficient strength to capture. This stimulus produces the continuous resetting of the reentry circuit and can help determine the pacing site location relative to the tachycardia circuit [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. If the stimulus is applied at a site in the circuit and during the excitable gap after the preceding wavefront but before the next wavefront, the pacing stimulus will capture the underlying myocardium. The stimulated orthodromic wavefront will travel in the same direction as the tachycardia wavefronts and will propagate through the circuit, resetting the tachycardia [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. If a train of several stimuli is applied with an appropriate strength and rate, the reentry circuit is continuously reset. If the pacing site is outside the circuit, the stimulated wavefront propagates through a portion of the myocardium before reaching the reentry circuit. Then, the stimulated wavefront enters the circuit and resets the tachycardia [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. Through the analysis of the measured postpacing intervals, the QRS morphology and the recorded electrograms, the entrainment technique can be used to help identify the critical sites of the arrhythmia circuit. Entrainment mapping is useful for understanding the different components of VT circuit [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF], [START_REF] Tung | Recognition of farfield electrograms during entrainment mapping of ventricular tachycardia[END_REF].

ii. Postpacing interval

The postpacing interval (PPI), measured between the start of the last captured stimulus and the first local potential of the pacing electrode represents the conduction time from the pacing site to the circuit, through the reentry circuit and then back to the pacing site. When pacing does not alter conduction velocity nor the propagation pathway, this delay, especially when subtracted by the circuit cycle length, can be used as an indication of the proximity of the pacing site to the reentry circuit [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF]. Indeed, if the pacing site is located in the reentry circuit, the postpacing interval represents the delay for one revolution through the reentry circuit and will be equal to the tachycardia cycle length (TCL). If the pacing site is outside the circuit, the postpacing interval will be greater than the cycle length and the difference will represent the conduction time from the pacing site to and back from the circuit [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. A postpacing interval within 30 ms of the tachycardia cycle length is used to determine close proximity to the reentry circuit [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF].

iii. QRS morphology

The morphology of the QRS complex during entrainment also provides useful information on the proximity of the pacing site to the reentry circuit [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. When the pacing site is located outside the reentry circuit, the paced QRS complex is due to the fusion of wavefronts propagating directly away from the pacing site with those emerging from the tachycardia circuit. This is called classic entrainment [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. When the pacing site is within a protected region in the reentry circuit or a bystander site that is connected with the isthmus, pacing during tachycardia will not change the QRS morphology. This is called concealed entrainment or entrainment with concealed fusion [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. The analysis of the QRS morphology helps determine whether a pacing site is located outside the circuit.

iv. S-QRS interval

The stimulus-QRS (S-QRS) interval, measured between the start of the captured stimulus and the beginning of the QRS complex, can provide further information regarding the location of the pacing site. Entrainment with concealed fusion indicates that the pacing site is either in the common pathway of the reentry circuit or in a bystander site. If the site is located in the common pathway, the stimulus-QRS interval is equal to the electrogram-QRS interval during VT [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF]. A difference in stimulus-QRS and electrogram-QRS of 30 ms has been used to distinguish bystander sites from common pathway sites [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

During entrainment with concealed fusion, the S-QRS interval represents the conduction time from the pacing site to the reentry circuit exit. For pacing sites that are in the circuit, this indicates the distance from the pacing site to the reentry circuit exit [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF], [START_REF] Bogun | Response to pacing at sites of isolated diastolic potentials during ventricular tachycardia in patients with previous myocardial infarction[END_REF]. The location of the pacing site within the critical zone is determined by its S-QRS/VT cycle length ratio. An exit site is defined as a stimulus-QRS/VT CL ratio below 0.3, the common pathway and entry sites have a stimulus-QRS/VT CL ratio between 0.3 and 0.7, and the inner loop sites have a stimulus-QRS/VT CL ratio above 0.7 [4], [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF], [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

v. Limitations of entrainment

Entrainment mapping has numerous limitations, the main one being failure to induce hemodynamically well tolerated tachycardia stable enough to allow pacing [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. This can represent half of scar based reentrant VTs [START_REF] Dixit | Mapping for ventricular tachycardia[END_REF].

Moreover, several aspects can limit interval comparisons. The technique is only valid if pacing does not alter conduction velocities and conduction paths in the reentry circuit [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. Indeed, if the conduction velocity slows or the length of the reentry path increases, the postpacing interval will be prolonged, and entrainment produced by pacing at such a reentry circuit site would then have a postpacing interval longer than the tachycardia cycle length, further complicating the analysis [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. Pacing rates only slightly faster than the tachycardia cycle length are used in clinical practice to limit these negative effects [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF]. The timing of the local signal needed for postpacing interval measurements can also be difficult to determine.

The presence of far-field potentials and low-amplitude fractionated electrograms can complicate interval measurements [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF], [START_REF] Tung | Recognition of farfield electrograms during entrainment mapping of ventricular tachycardia[END_REF]. During high stimulus pacing, part of the circuit can be captured that does 54 not correspond to the to the area producing the local electrogram, rendering the post pacing interval difficult to analyze [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF].

Entrainment mapping can overestimate the size of the isthmus by up to 50% [4]. The technique has been found to exaggerate the exit area of the isthmus with concealed QRS fusion combined with PPI-TCL below 30 ms occurring beyond the distal curvature of the isthmus [4]. After taking into account these limitations, entrainment mapping remains an important technique to improve our understanding of ventricular reentry circuits and its critical components [4], [START_REF] Stevenson | Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction[END_REF], [START_REF] Ciaccio | Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm[END_REF], [START_REF] Stevenson | Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping[END_REF], [START_REF] Tung | Recognition of farfield electrograms during entrainment mapping of ventricular tachycardia[END_REF].

l. Pace Mapping i. Definition

Pace mapping consists of stimulating the myocardium and analyzing the induced ECG signal, the 12-lead morphology and the S-QRS interval. The conduction delay and QRS configuration reflects the pacing site location and electrical properties [START_REF] Soejima | Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping[END_REF], [START_REF] Stevenson | Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars[END_REF]. It is important to take into account waveform amplitude as well as QRS morphology when comparing two signals [START_REF] Dixit | Mapping for ventricular tachycardia[END_REF], [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF]. This comparison is quantified with a dedicated software [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF]. A commonly used metric is the correlation calculation 𝐶𝑂𝑅𝑅 as shown in 𝑒𝑞𝑢𝑎𝑡𝑖𝑜𝑛 (3) between vectors 𝑋 and 𝑌, each composed of 12 leads 𝑋 𝑖 and 𝑌 𝑖 [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF]. The software is designed to find the best possible match by sliding the two signals over each other and then selecting the position that provides the highest score. The maximum correlation score is 1 and represents a perfect match whereas the minimum possible is -1 and represents the worst possible match for example in case of similar amplitude but with opposite polarity [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. Initially, the two waveforms were only compared visually by human interpretation but an objective quantitative approach was developed to provide a metric reducing operator bias and subjectivity especially by enabling the quantification of subtle amplitude or precordial lead transition differences between two ECG patterns [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF], [START_REF] Moak | Ablation of the vanishing PVC, facilitated by quantitative morphology-matching software[END_REF]. Before the use of correlation scores, visual comparisons could lead to the conclusion that pacing over an area up to 4 cm2 produced similar QRS patterns [START_REF] Brunckhorst | Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction[END_REF]. Subtle changes can now be precisely quantified and more recent studies have shown that correlation values decrease with distance, even when pacing sites are separated by just a few mms [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF], [START_REF] Green | Resolution of pace mapping stimulus site separation using body surface potentials[END_REF].

𝐶𝑂𝑅𝑅 = ∑ (𝑋 𝑖 -𝑋 ̅) 12 𝑖=1 ×(𝑌 𝑖 -𝑌 ̅) ∑ (𝑋 𝑖 -𝑋 ̅) 2 12 𝑖=1 ×∑ (𝑌 𝑖 -𝑌 ̅) 2 12 𝑖=1 (3)
The PASO TM Module (Biosense Webster Inc., Diamond Bar, USA) enables the visualization of 3D pace maps, the correlation value of the paced signal with the tachycardia QRS being associated via a color code to the 3D localization of each pacing site. This technique of generating color coded maps of correlation values between the paced signal and the tachycardia is widely used when the targeted arrhythmia is hemodynamically unstable, preventing activation or entrainment techniques. Standard pace mapping only requires one QRS complex of the tachycardia [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF].

ii. Pacing parameters

Pacing is generally performed by bipolar rather than unipolar pacing [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. The advantage of bipolar pacing is smaller stimulus artifacts simplifying the analysis of the early portion of the QRS complex [START_REF] Kadish | A comparison of QRS complexes resulting from unipolar and bipolar pacing: Implications for pace-mapping[END_REF].

The drawback of bipolar pacing is the potential and unmeasurable shift of the effective site of stimulation away from the catheter tip and towards the proximal electrode as the activation at the anode may coexist or merge with the distal cathodal excitation [START_REF] Kadish | A comparison of QRS complexes resulting from unipolar and bipolar pacing: Implications for pace-mapping[END_REF]. This shift can modify the effective area of impulse and thus slightly change the paced QRS morphology [START_REF] Brunckhorst | Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction[END_REF]. The shift is increased as the pacing current and interelectrode spacing increases but remains minor when the interelectrode distance is 5 mm [START_REF] Kadish | A comparison of QRS complexes resulting from unipolar and bipolar pacing: Implications for pace-mapping[END_REF].

The pacing parameters generally used are 10 mA with a 2 ms pulse width at a pacing cycle length similar to that of the clinical VT [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF], [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. Pacing thresholds depends on the underlying tissue as they increase in scar areas and decrease in healthy myocardial tissue. To avoid capture over a too large area, some studies involve checking the pacing threshold at each site to then set the stimulus strength either slightly greater or at twice the threshold [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF], [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. This increases accuracy and may better simulate a point source but at the cost of time-consuming less practical pacing maneuvers for each pacing point.

Some studies pace at strong current strengths depolarizing large areas to better simulate a propagating wave front emerging from an exit site [START_REF] Kadish | Differences in QRS configuration during unipolar pacing from adjacent sites: implications for the spatial resolution of pace-mapping[END_REF], [START_REF] Tung | Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia[END_REF]. Overall, major current dependent differences are uncommon [START_REF] Kadish | A comparison of QRS complexes resulting from unipolar and bipolar pacing: Implications for pace-mapping[END_REF]. The pacing rate has an influence on the QRS morphology and pacing at a rate close to the tachycardia is desirable [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF]Effect of coupling interval and pacing cycle length on morphology of paced ventricular complexes: implications for pace mapping[END_REF]. If the pacing cycle length differs by more than 80 ms, the accuracy of the pace map will be reduced as the QRS morphology can be rate dependent [START_REF] Gerstenfeld | Quantitative comparison of spontaneous and paced 12-lead electrocardiogram during right ventricular outflow tract ventricular tachycardia[END_REF].

iii. Identifying the VT circuit

When a site inside a defined isthmus is paced, the wavefront propagates along the protected channel and follows at least two directions, the orthodromic and antidromic direction of the VT. If the pacing site is located near the exit, the orthodromic wave leaves the channel first and depolarizes the region close to the exit area of the isthmus, resulting in a similar QRS morphology to the VT. If the pacing site is located near the entrance, the antidromic wave leaves the channel first, producing a very different QRS morphology [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Bogun | Response to pacing at sites of isolated diastolic potentials during ventricular tachycardia in patients with previous myocardial infarction[END_REF], [START_REF] Stevenson | Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars[END_REF], [START_REF] Josephson | Ventricular activation during ventricular endocardial pacing. II. Role of pace-mapping to localize origin of ventricular tachycardia[END_REF], [START_REF] Brunckhorst | Identification of the ventricular tachycardia isthmus after infarction by pace mapping[END_REF].

Pace-mapping is very helpful in identifying the critical sites of the isthmus [START_REF] Cronin | HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias[END_REF], [START_REF] Bogun | Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia[END_REF], [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. The high correlation sites, with an average correlation score of 89%, best matching the VT morphology are located in the exit zone of the isthmus whereas the neighboring sites with much lower correlation values, with an average of 39%, are located in the entrance zone (figure 11) [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. The speed of change in correlation values provides further information on the VT isthmus location. A gradual change is seen when moving from the exit zone to the outer exit zone along the direction of the tachycardia circuit. The abrupt change from good to poor values further helps in determining the isthmus orientation by defining the transition from the exit to the entrance zone [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. This abrupt change cannot be seen during concealed entrainment maneuvers during VT. Indeed, regardless of the pacing position along the isthmus, the activation will propagate in the orthodromic direction leading to a similar QRS morphology to the VT. In the antidromic direction, the wave collides with the orthodromic wavefront of the previous cycle. The propagation does not take the shortest path to the healthy myocardium but will reach the myocardium at the exit zone of the tachycardia [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF], [START_REF] Brunckhorst | Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction[END_REF]. This is consistent with the fact that the S-QRS interval during pacing in sinus rhythm is shorter than during VT [START_REF] Bogun | Response to pacing at sites of isolated diastolic potentials during ventricular tachycardia in patients with previous myocardial infarction[END_REF].

A suggested workflow to determine the VT isthmus through pacemapping is to first identify the sites with the highest correlation values corresponding to the isthmus exit. Then neighboring sites (10-15 mm) are paced to find the low correlation zone corresponding to the isthmus entrance [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. A voltage map and all the information it contains can further guide the pacing strategy. The exit site is likely to be located in a border zone between low and high amplitude points [START_REF] Bogun | Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia[END_REF], [START_REF] Vergara | Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation[END_REF]. Isolated and very late potentials with long electrogram durations are more likely to be located in the isthmus [START_REF] Nakahara | Characterization of the arrhythmogenic substrate in ischemic and nonischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia[END_REF], [START_REF] Bogun | Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia[END_REF], [START_REF] Bogun | Response to pacing at sites of isolated diastolic potentials during ventricular tachycardia in patients with previous myocardial infarction[END_REF].

Pace mapping in sinus rhythm also provides a measure of slow conduction, determined by the interval between the stimulus and the QRS complex, the S-QRS interval. Pacing sites with long S-QRS values slowly conduct to healthy myocardium and can be located in a potential isthmus or adjacent to regions of conduction block [START_REF] Stevenson | Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars[END_REF], [START_REF] Brunckhorst | Identification of the ventricular tachycardia isthmus after infarction by pace mapping[END_REF]. S-QRS intervals above 40 ms are associated with critical sites and have been used to help identify reentry circuits [START_REF] Soejima | Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping[END_REF]. The reentry circuit exit zone, close to the infract border, will exhibit low S-QRS intervals [START_REF] Brunckhorst | Identification of the ventricular tachycardia isthmus after infarction by pace mapping[END_REF].

Pacing also enables the identification of unexcitable scar that creates conduction block, a critical component for reentry circuit. The lack of capture with a high stimulus strength (20 mA) and a large virtual electrode radius marks the zone as unexcitable [START_REF] Soejima | Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation[END_REF]. Pacing provides complementary information to electrogram amplitude in defining likely conduction block areas, potentially facilitating the identification of reentry circuits.

Pacing provides valuable information to identify the VT isthmus, facilitating targeted ablation [START_REF] Marchlinski | Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy[END_REF], [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF].

RF lesions can be deployed to transect the isthmus, interrupting a critical portion of the reentrant circuit [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. One the ablation has been performed, pacing maneuvers can be used to confirm the block. If the exit zone has been successfully ablated, pacing form a neighboring site within the isthmus after ablation will exhibit a very different QRS morphology and a longer SQR interval compared to before ablation [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF], [START_REF] Tilz | Electrical isolation of a substrate after myocardial infarction: a novel ablation strategy for unmappable ventricular tachycardias-feasibility and clinical outcome[END_REF]. If a second ablation line along the entrance zone is also made, both lines can be checked by making sure that the stimulation pacing from a site between the entrance and the exit does not reach healthy myocardium.

iv. Limitations of pace mapping

One limitation of interpreting pacing information is when multiple different QRS morphologies are produced during the same pacing drive. The multiple morphologies complicate the analysis of the activation pattern from the site. A single study in 2012 reported that multiple QRS morphologies in a given pacing site were observed in 57% of patients [START_REF] Tung | Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia[END_REF]. This high percentage not reported in other studies might be in part due to the intermittent contact at the tip of the catheter, leading to intermittent capture.

The study was done before the introduction of contact catheters. Another challenge to pacing maneuvers is to fully understand the electrical properties of the analyzed myocardium to then unmask potential VT circuit mechanisms. Pacing from a point source may not mimic a broad wavefront of a reentrant tachycardia [START_REF] Brunckhorst | Identification of the ventricular tachycardia isthmus after infarction by pace mapping[END_REF]. For example, functional blocks present during tachycardia need to be also identified 59 during pacemapping in sinus rhythm. The differences between the two mechanisms need further study.

Moreover, it is difficult to estimate the virtual pacing electrode of a given pacing site, complicating the differentiation between near and far myocardial capture [START_REF] Tung | Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia[END_REF]. Pace mapping technique is currently time consuming but future multielectrode catheter designs will facilitate and accelerate the creation of pace maps [START_REF] Chillou | Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm[END_REF]. A final limitation that has been reported is the induction of the tachycardia itself during pacing maneuvers [START_REF] Josephson | Ventricular activation during ventricular endocardial pacing. II. Role of pace-mapping to localize origin of ventricular tachycardia[END_REF]. This is not an issue as an activation map can then be created to further understand the arrhythmia. The initiation of the tachycardia is most frequent when pacing close to the exit zone, the late and slowed conduction along the isthmus facilitating VT induction [START_REF] Tung | Functional pace-mapping responses for identification of targets for catheter ablation of scar-mediated ventricular tachycardia[END_REF].

Part 2: Novel reference-less pace-mapping methods for identifying VT circuits Ischemia modifies the conduction of electrical impulses in the ventricle and can create the necessary conditions for reentry tachycardia. The onset and the stability of a given reentrant circuit is determined by the overall conducting properties of the circuit. Signal analysis in sinus rhythm, activation, entrainment and pace mapping have been developed to identify the tachycardia circuit but are considerably hindered when the tachycardia cannot be induced. The following section will look into novel methods to take the most advantage of the available information to identify the critical components of VT circuit mechanisms.

These methods are reference-less mapping, improving signal quality, analyzing isthmus entrance characteristics, automating the workflow and graph-based reconstruction of activation patterns.

1) Correlation gradient mapping

In current clinical practice, the conventional pace mapping technique consists of stimulating the myocardium and comparing the 12-lead morphology of the induced ECG signal with a reference VT recording. The main challenge of the conventional technique is that a reference VT recording is required.

Moreover, this technique highlights the circuit of the VT recording. Additional secondary circuits may occur that also warrant study. The following paper studies a novel reference-less pace-mapping method based solely on the analysis of the ECG data obtained during pace-mapping [START_REF] Odille | Catheter treatment of ventricular tachycardia: a reference-less pace-mapping method to identify ablation targets[END_REF]. A local correlation map is defined by analyzing pairwise correlations between the paced QRS signals from a network of neighboring pacing sites. This reference-less method is proposed in order to quantify local changes in activation pathways. The electrical properties of the electric influx between two points does not depend on the selected reference VT recording. Abnormal points are identified by high correlation gradient values.

My main contribution to the paper was the acquisition of all the relevant pacing information into the CARTO® system. The current version of the CARTO® software only includes the correlation map so for each procedure I helped the cardiologist to "mentally" reconstruct the correlation gradient map. I was also responsible for anonymizing and exporting the data from the CARTO® to the in-house SMARTIS software, and provided support for interpreting all the exported CARTO® data (vendor-generated meshes, catheter positions, ECG data in sinus rhythm and pace-mapping, ablation data etc.). The work described later in this manuscript aimed at improving and extending the SMARTIS software, and the results of this first study were used as input data for the last two chapters in particular.

2) Improving ECG signal quality during remote magnetic navigation

In remote magnetic navigation, the orientation of the tip of the catheter is controlled by moving two magnets that in turn modify the magnetic field [START_REF] Skoda | Catheter ablation of ischemic ventricular tachycardia with remote magnetic navigation: STOP-VT multicenter trial[END_REF]. According to Faraday's law of induction, Ф(𝐵) the flux of the magnetic field will also induce an electromotive force Ɛ in the various cables around the patient. Imaging) and this study is a result of its adaption to the electrophysiology setting [START_REF] Reis | Reconstruction of the 12-lead ECG using a novel MR-compatible ECG sensor network[END_REF]. I highlighted the importance of using the correlation coefficient metric. I also designed the study protocol, especially regarding the simultaneous acquisition with the new and conventional setup, the selection of the different motion patterns and different arrhythmias. The acquisition and data export with the CARTO® system was also my contribution to this work.

The new acquisition device studied here improves the quality of the ECG signal collected in the magnetic navigation setting. This could help optimize workflow, result in higher density maps and reduce procedure times.

3) Isthmus entrance calculator based on electrogram characteristics

Multiple electrogram characteristics have been found to be associated with re-entry circuits. However, the analysis of any parameter alone is insufficient to completely define the VT isthmus location. The following paper studies the value of 10 different electrogram characteristics in identifying a VT isthmus entrance [START_REF] Battaglia | An efficient algorithm based on electrograms characteristics to identify ventricular tachycardia isthmus entrance in post-infarct patients[END_REF]. The studied parameters were bipolar and unipolar voltage, time from QRS onset to electrogram onset, time from electrogram offset to QRS offset, electrogram duration, number of positive peaks, S-QRS interval as well as the presence of fragmentation, double potentials and late potentials. All the parameters can be collected in the absence of an induced VT.

My contribution to the paper was in acquiring all the different electrogram characteristics into the CARTO® system and precisely defining all the components of the isthmus. Once the left ventricular 3D map was entirely reconstructed, I helped defining the critical isthmus by drawing onto the map the lateral boundaries, entrance and exit channels as well as the mid-isthmus line. Isthmus dimensions were also measured. The isthmus definition played a critical role in the segmentation of the PM points as all the points were analyzed according to the VT isthmus entrance location.

Logistic regression analysis showed that bipolar voltage, number of electrogram positive peaks, and S-QRS interval were independently associated with VT isthmus entrance location. A multi-parameter electrogram evaluation is a promising approach to localize a VT isthmus entrance. Based upon these results, a webbased graphical user interface was developed and implemented in an automatic calculator to quickly determine the likelihood that a given site is located at a VT isthmus entrance. The calculator is accessible at the following link: VT Isthmus Entrance Calculator (figure 12). Automatic processing during pace-mapping reduces the need for manual annotations and has the potential of quickly extracting all the relevant information. These parameters are interconnected and influence the formation of VT circuits. For example, the analysis of correlation gradient maps enables the identification of the core zones of potential VT circuits. We wish to further take advantage of all the available information and will describe in this section a graph-based method to combine multiple parameters in order to visualize the detailed pathway of the underlying reentrant circuit. The connections between each pacing site during pace-mapping are analyzed to generate a suggested activation pattern of the VT circuit. This new method led to the filing of a U.S. provisional patent, Computer assisted electrophysiological intervention for reentrant circuit identification, application number 63179054.

b. Technical background

Graphs are widely used to mathematically model interconnected objects [START_REF] Wilson | Introduction to graph theory[END_REF]. We will briefly present the main mathematical definitions used in graph theory. A graph 𝐺 is composed of elements called vertices if pacing sites 𝑖 and 𝑗 are adjacent pairs. Each edge 𝑒 can be assigned a number, or weight 𝑤(𝑒). Solving the shortest path problem consists in finding the path with a minimum total weight between two connected vertices. Dijkstra algorithm is a commonly used algorithm to solve shortest path problems [START_REF] Dijkstra | A note on two problems in connexion with graphs[END_REF].

It relies on the fact that if node 𝑣 𝑦 is on the shortest path between 𝑣 𝑥 and 𝑣 𝑧 , knowing the shortest path between 𝑣 𝑥 and 𝑣 𝑧 , implies knowing the shortest between 𝑣 𝑥 and 𝑣 𝑦 . The minimal path from 𝑣 𝑥 to all the other nodes is constructed by starting with adjacent nodes and then investigating edges that are further away and determining whether they give rise to a shorter path.

c. Graph-based modeling of VT circuits

Pacing sites can be studied as vertices of a simple directed graph. A distance threshold between vertices can be used to define whether any two vertices are connected. Information found in the data collected from pace-mapping is then extracted. The model is based on defining for each pair of adjacent vertices the ease for an electrical influx to go from one point to another. During tachycardia, the electrical influx will preferentially propagate along the path that provides the least resistance. Solving the shortest path could indicate the most likely pathway from one pacing site to all the other pacing sites. Once the most likely pathway is determined, an estimation of the delay along the calculated shortest path is used to generate a pseudo-activation map.

d. Implementation

Two patients referred for post-infarct VT catheter ablation were retrospectively analyzed with GRAAPH.

During the procedure, both activation and pace mapping had been performed to identify the VT isthmus.

Anonymized data was exported from the CARTO® workstation and then processed using the in-house GRAAPH software written in MATLAB language (The Mathworks, Natick, USA), version R2020a.

The GRAAPH method begins by analyzing the locations and ECG morphologies of the pace-mapping sites.

Reference-less correlation gradient values of neighboring pacing sites were calculated by semiautomatic analysis as previously described in [START_REF] Odille | Catheter treatment of ventricular tachycardia: a reference-less pace-mapping method to identify ablation targets[END_REF], [START_REF] Hoyland | A paced-ECG detector and delineator for automatic multi-parametric catheter mapping of ventricular tachycardia[END_REF]. A graph is generated using the pacing sites as vertices.

Pairs of pacing sites with a high correlation gradient were then identified as a being part of a core zone of a reentrant circuit. Two adjacent pacing sites were considered to be connected, forming an edge of the graph, if they were separated by a distance below 40 mm and the reference-less correlation gradient between them was below 2%/mm. An example of such a graph is shown figure 13. A weight was calculated and applied to each edge to represent the ease for electricity to go from one point to another. The weight of the edge between pacing sites i and j was determined as a combination of ∆𝑠𝑄𝑅𝑆 (𝑖,𝑗) (absolute difference in S-QRS delay between site 𝑖 and site 𝑗) and 𝐶𝐺 (𝑖,𝑗) (correlation gradient between site 𝑖 and site 𝑗) by the following equation:

𝑊 (𝑖,𝑗) = 𝛼 * ∆𝑠𝑄𝑅𝑆 (𝑖,𝑗) + 𝛽 * 𝐶𝐺 (𝑖,𝑗) + 𝛾 * ∆𝑠𝑄𝑅𝑆 (𝑖,𝑗) * 𝐶𝐺 (𝑖,𝑗)

𝛼, 𝛽, 𝛾 can be modified to change the weight applied to the edges. Then, for a given 𝛼, 𝛽, 𝛾, a shortest path based on Dijkstra's algorithm was calculated from each of the pacing sites of the core zone 𝑃𝑀 𝑐𝑜𝑟𝑒 to all of the other pacing sites.

Each pacing site 𝑖 was then given a pseudo-activation delay, 𝐷𝑒𝑙𝑎𝑦 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖), estimated by the sum of ∆𝑠𝑄𝑅𝑆 absolute differences along the shortest path 𝑆𝑃 (𝑃𝑀 𝑐𝑜𝑟𝑒 ,𝑖) = {𝑗 1 , … , 𝑗 𝑁 } (an ordered set of vertices), according to the following:

𝐷𝑒𝑙𝑎𝑦 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖) = ∑ ∆𝑠𝑄𝑅𝑆 (𝑗 𝑛 ,𝑗 𝑛+1 ) 𝑛=𝑁-1 𝑛=1 (6)

e. Results

The GRAAPH method can enable quick identification of areas of interest and the pseudo activation map is similar to the activation pattern. Figure 15 The Lin's coefficient was optimized by tuning the parameters 𝛼, 𝛽, 𝛾 using a grid search. The best combination resulting in the highest similitude between the pseudo activation and the activation map was not only patient dependent but also changed depending on which initial pacing site of the core zone was selected. The Lin's coefficient varied between 0.5 and 0.76.

f. Discussion and conclusion

A novel method has been proposed that highlights possible activation patterns without the need of the reference VT. GRAAPH generates a map, the pseudo-activation map, which provides an indication of the direction of the underlying reentrant circuit. The pseudo-delay given to each point, determined by the sum of ∆𝑠𝑄𝑅𝑆 absolute differences gives an indication of the activation sequence.

Additional work could be done to improve the current method by looking into better estimating the activation delay during tachycardia. This could be achieved by taking into account sinus rhythm activation delays and studying its implications on tachycardia activation values.

Further research on a larger number of patients is needed to try to determine the best weight formula that needs to be applied to the edges. Applying machine learning techniques might further improve the method. The objective would be to determine a weight formula independent of the initial pacing site of the patient that generates a pseudo activation map the most similar to the activation pattern of the circuit as possible.

The GRAAPH method could be particularly interesting in patients with multiple high correlation gradient zones. The method would therefore generate multiple pseudo activation maps providing the physician with an overview of the suggested activation patterns of the different VT circuits. The analysis of the pseudo-activation maps highlighting the electrical propagation pattern of the ventricle could provide further insights to help the physician determine the most effective ablation strategy.

Conclusion

The future of electrophysiology will likely be marked by the use of catheters with an increased number of electrodes and a decrease in electrode size. More information will be detected by this ever-growing array of sensors enabling maps of higher density to be created. This new information collected will need to be coupled with new automatic algorithms to quickly pinpoint the electrophysiologist towards the information of interest. To further increase their performance, these algorithms will not only take into account electroanatomic data but also incorporate information from different modalities. For example, magnetic resonance imaging could provide valuable insights about transmural scar depth as well as fiber orientation. In particular, the analysis of scar geometry could help determine the direction of a reentrant circuit.

Moreover, with the ageing population, the number of patients will increase, and techniques that treat patients faster and cheaper will be favored to limit the cost of healthcare. For example, robotic systems are not currently widely used as their development is limited by financial and speed considerations. The demand for faster and cheaper systems has already started and will likely gain momentum in the near future.

This thesis presented several novel approaches for identifying VT circuits. The studied methods are particularly useful in the event that the tachycardia is not inducible during the electrophysiology study.

Special attention was given to automatically extract the key information and facilitate its visualization. The easier it is to visualize the data, the easier it is to then identify the links between the key parameters.

A long term goal of a post-infarct VT electrophysiology study is to be able to determine whether a given ventricle that has never sustained a tachycardia has the substrate to sustain one. If it is the case, targeted catheter ablation could be delivered to prevent the patient from sustaining any tachycardia. This approach focused on treating before the first life threatening event would significantly change how patients are treated today. This solution could also reduce the burden of healthcare by for example limiting the number of costly defibrillator implementations.

The use of more complex mathematical tools such as artificial intelligence might be needed to identify new patterns. Machine learning could be interesting to use because of the complexity of the data that needs to be taken into account. The development of such techniques needs to be done in a language that physicians can understand. This is the key for widespread adoption.

Résumé

Après une lésion du myocarde, la perturbation de l'apport sanguin peut modifier les voies électriques et

I

  'd like to thank my family and friends for making sure I keep a balance and enjoy what I do, absolutely key for long-term success.

FiguresPart 2 : 1 ) 3 ) 12 Figures List Figure 1 .

 21312List1 Figures List ................................................................................................................................................... Abbreviations/Symbols ............................................................................................................................... Introduction ................................................................................................................................................. Publication list ............................................................................................................................................. Part 1: Ventricular tachycardia and catheter ablation ................................................................................ 1. Electrical activity of the heart ......................................................................................................... 2. Ventricular tachycardia ................................................................................................................... 3. Electrophysiology ............................................................................................................................ 4. Impulse propagation ....................................................................................................................... 5. Myocardial infarction ...................................................................................................................... 6. Abnormal electrical circuits ............................................................................................................. a. Slow conduction .......................................................................................................................... b. Unidirectional block..................................................................................................................... c. Reentry mechanisms ................................................................................................................... 7. Identification of the VT circuit ......................................................................................................... a. Surgery ......................................................................................................................................... b. Catheters ..................................................................................................................................... c. 3D system .................................................................................................................................... d. Remote magnetic navigation ...................................................................................................... e. Contact catheters ........................................................................................................................ f. Multielectrode mapping .............................................................................................................. g. Microelectrode mapping ............................................................................................................. h. Automated mapping.................................................................................................................... i. Signal analysis in sinus rhythm .................................................................................................... j. Activation mapping during tachycardia ...................................................................................... k. Entrainment mapping ..................................................................................................................

Figure 2 .

 2 Figure 2. Action potential of a cell over time. .............................................................................................

Figure 3 .

 3 Figure 3. Structure of the reentrant circuit mechanism. ............................................................................

Figure

  Figure 4. PENTARAY TM catheter. .................................................................................................................

Figure 11 .

 11 Figure 11. Pace-mapping helps identify the isthmus. .................................................................................

Figure 12 .

 12 Figure 12. Screenshot of the ventricular tachycardia isthmus entrance calculator. .................................

Figure 13 .

 13 Figure 13. Graph using the pacing sites as vertices. .................................................................................

Figure 14 .

 14 Figure 14. Pseudo activation map for patient 1 and pacing site 40. .........................................................

Figure 15 .

 15 Figure 15. The calculated pseudo activation values and opposite activation values for pacing site 42. .

Figure 16 .

 16 Figure 16. Pseudo-activation map (A) and the opposite activation map (B) for patient 1 and pacing site 42. Pseudo-activation map (C) and the activation map (D) for patient 2 and pacing site 74. ..................

  field of catheter ablation has progressed with the development of new tools to best analyze the electrophysiological data available. Activation mapping is the sampling of the local electrical activity during tachycardia from different sites of the ventricle and the most direct technique to identify the activation pattern of the tachycardia. Unfortunately, failure to induce tachycardia is common and other indirect methods are needed, such as pace mapping. Pace mapping consists of stimulating the myocardium and analyzing the induced signal. This signal reflects the pacing site location and electrical properties. Bundles of surviving myocytes within heterogeneous scar and areas of block are key components of the tachycardia substrate and the analysis of abnormal electrographic findings have increased our understanding of ventricular arrhythmias. Once the reentry circuit is clearly identified, catheter ablation is used to treat the tachycardia. This thesis by publication at the Diagnosis and Interventional Adaptive Imaging (IADI) unit focused on improving the identification of reentry tachycardia with pace mapping by exploring 5 axes: a referenceless method, electrocardiogram signal quality, isthmus entrance calculator, automating the workflow and a graph-based reconstruction of activation patterns.

Figure 1 .

 1 Figure 1. P, QRS and T wave representing the activation of the heart.

Figure 3 .

 3 Figure 3. Structure of the reentrant circuit mechanism. The abnormal conducting zone (in blue) is surrounded bynon-conducting zone (in green) that is in turn surrounded by healthy myocardium (in white). The color-coded arrows represent the propagation o of the conducting wave (the wave is first located by the red arrows, then orange, yellow, green, grey and purple). In A) the wave is blocked in the abnormal conducting zone but continues to propagate around the non-conducting zone to then reenter the abnormal area from the opposite side. In B) the impulse crosses the unidirectional block line from the opposite side and repetitive cycle is initiated[START_REF] Ciaccio | Formation of reentrant circuits in the mid-myocardial infarct border zone[END_REF].

Figure 4 .

 4 Figure 4. PENTARAY TM catheter (Biosense Webster Inc., Diamond Bar).

Figure 5 .

 5 Figure 5. The CARTO® system. Three coils C1, C2, C3 each generate a magnetic field that decays as a function of distance. The signals received by the sensor S located in the catheter enables the distance D1, D2, D3 from each coil to be determined. These distances determine the radii of theoretical spheres around each coil. The intersection of the three spheres determines the location and orientation of the sensor in six degrees of freedom (x, y, z, roll, pitch, and yaw)[46].

Figure 6 .

 6 Figure 6. Electrophysiology room in Nancy equipped with the remote magnetic navigation Niobe® system (Stereotaxis Inc., St. Louis, USA). The two permanent magnets are located on both sides of the table.

Figure 7 .

 7 Figure 7. Bipolar map of a left ventricle (Biosense Webster Inc., Diamond Bar).

Figure 8 .

 8 Figure 8. Fractionated signal (Biosense Webster Inc., Diamond Bar).

  v. Late potentials, LAVA and DEEP Late potentials are defined as low voltage (<1.5 mV) local ventricular potentials occurring at least 20 ms after the end of the surface QRS[103]-[109]. An example is shown figure 9.

Figure 9 .

 9 Figure 9. Late potential (Biosense Webster Inc., Diamond Bar).

Figure 10 .

 10 Figure 10. Activation map in tachycardia (Biosense Webster Inc., Diamond Bar).

Figure 11 .

 11 Figure 11. Pace-mapping helps identify the isthmus. High correlation sites are marked in red and are located in the exit zone. Neighboring sites with much lower correlation are located in the entrance zone (Biosense Webster Inc., Diamond Bar).

  This force Ɛ can induce noise in the 12-lead ECG cables. The induced noise coupled with the presence of the high-pass acquisition filter can render the monitoring of the ECG challenging for up to 10 seconds after each magnet movement[START_REF] Reis | Electrocardiogram Acquisition During Remote Magnetic Catheter Navigation[END_REF]. The pacemapping technique previously described relies on precise comparisons of ECG signals and such artifacts can hinder the physician's ability to analyze pacemapping data. Moreover, any movement induced noise in the acquisition circuit will be amplified because of the magnetic field, further hindering precise ECG comparisons. Possible causes of such movements can be the patient trembling or neighboring devices such as the pump. The following paper studies and tests a novel acquisition device based on optical transmission to limit the magnetic correlated distortions on the ECG.My contribution to the paper was in highlighting the clinical and technical implications of this new device on pacemapping procedures. The original concept was first developed for MRI (Magnetic Resonance

Figure 12 .

 12 Figure12. Screenshot of the ventricular tachycardia isthmus entrance calculator predicting whether a pacing site is likely to be in the VT isthmus entrance. A pacing site with a bipolar voltage of 0.35 mV, an S-QRS interval of 120 ms and 1 positive deflection is likely to be in the VT isthmus entrance VT Isthmus Entrance Calculator[START_REF] Battaglia | An efficient algorithm based on electrograms characteristics to identify ventricular tachycardia isthmus entrance in post-infarct patients[END_REF].

  𝑉(𝐺) = {𝑣 1 , 𝑣 2, 𝑣 3 … } (or nodes) and a set of pairs of elements called edges 𝐸(𝐺) = {𝑒 1 = {𝑣 1 , 𝑣 2, }, 𝑒 2 = {𝑣 2 , 𝑣 3, }, … }. In our study, the pacing sites are the nodes of the graph and the links between adjacent pairs of pacing sites are the edges. Simple directed graphs are graphs with no loops and with edges that are ordered pairs of distinct vertices. If we have 𝑛 pacing sites, the corresponding graph can be represented by an 𝑛 × 𝑛 adjacency matrix 𝐴 = (𝑎 𝑖𝑗 ), with 𝑎 𝑖𝑗 = 0 if pacing sites 𝑖 and 𝑗 are not connected and 𝑎 𝑖𝑗 = 1

Figure 13 .

 13 Figure 13. Graph using the pacing sites as vertices.

  These values were called the pseudo-activation values and were projected on the ventricle. The resulting map was called the pseudo-activation map. An example of a pseudo-activation map from the first procedure with 𝑃𝑀 𝑐𝑜𝑟𝑒 = 40 and weight 𝑊 = ∆𝑠𝑄𝑅𝑆 (𝛼 = 1, 𝛽 = 0, 𝛾 = 0) can be seen figure 14.

Figure 14 .

 14 Figure 14. Pseudo activation map for patient 1 and pacing site 40 (Biosense Webster Inc., Diamond Bar).

  represents the calculated pseudo-activation values and activation values from the first procedure with pacing site 42 using the weight 𝑊 = ∆𝑠𝑄𝑅𝑆. When comparing both methods, the mean was 5.92 ms; the standard deviation 30.43 ms; the median 8.4 ms; the mean absolute error 23.27 ms, Lin's coefficient 0.67 and Spearman's 0.40. Figure16shows the visual representation of the corresponding pseudo-activation map (A) and an opposite activation map (B) for patient 1, pacing site 42 as well as the pseudo-activation map (C) and activation map (D) for patient 2, pacing site 74. Regarding patient 1, the pacing site 42 is located at the entrance of the reentrant circuit and was correctly identified as being part of a core zone of the circuit. The pacing site 42 is located at the entrance of the reentrant circuit and the resulting pseudo-activation map has an opposite activation pattern to the activation map. Patient 2 only had a limited activation map but the tachycardia circuit could still be clearly identified. Pacing site 74 is located at the exit site of the reentrant circuit and was correctly identified as being part of a core zone of the circuit. In both patients, the pseudo-activation map and the activation map are similar and both maps enable quick identification of areas of interest and show the overall activation pattern of a reentrant circuit.

Figure 15 .

 15 Figure 15. The calculated pseudo activation values and opposite activation values for pacing site 42.

Figure 16 .Figure 16 .

 1616 Figure 16. Pseudo-activation map (A) and the opposite activation map (B) for patient 1 and pacing site 42. Pseudoactivation map (C) and the activation map (D) for patient 2 and pacing site 74 (Biosense Webster, Diamond Bar, CA).

  conduire à la formation de circuits réentrants. Ces circuits possèdent une entrée, une partie centrale et une sortie et peuvent entraîner des rythmes cardiaques réguliers et rapides, épisodes qui sont nommés tachycardie ventriculaire (TV). L'électrophysiologie est l'étude du fonctionnement électrique et des propriétés électriques du coeur. Des cathéters munis d'électrodes permettent l'enregistrement des données électriques du coeur. Les cathéters peuvent être utilisés en conjonction avec des systèmes de cartographie pour créer des cartes 3D électro-anatomiques précises.Le domaine de l'ablation par cathéter a progressé grâce au développement de nouveaux outils permettant d'analyser en détail les données électrophysiologiques disponibles. La carte d'activation repose sur l'analyse des temps d'activation locale pendant la tachycardie des différents sites du ventricule. Cette technique est la plus directe pour identifier le schéma d'activation de la tachycardie. Malheureusement, l'échec de l'induction de la tachycardie est fréquent et d'autres méthodes indirectes sont nécessaires, comme la technique de pace-mapping. Le pace-mapping consiste à stimuler le myocarde et à analyser le signal induit. Ce signal reflète l'emplacement du site de stimulation et ses propriétés électriques. Les faisceaux de myocytes survivants au sein d'une cicatrice hétérogène et les zones de bloc sont des éléments clés du substrat de la tachycardie et l'analyse des zones électriques anormaux a permis d'améliorer notre compréhension des arythmies ventriculaires. Une fois que le circuit de réentrée est clairement identifié, l'ablation par cathéter est utilisée pour traiter la tachycardie. L'ischémie modifie la conduction des impulsions électriques dans le ventricule et peut créer les conditions nécessaires à la formation d'une tachycardie par réentrée. Le déclenchement et la stabilité d'un circuit réentrant donné sont déterminés par les propriétés conductrices globales du circuit. L'analyse du signal en rythme sinusal, l'activation, l'entraînement et le pace-mapping ont été développés pour identifier le circuit de tachycardie mais ces techniques sont considérablement limitées lorsque la tachycardie ne peut être induite. Ce travail s'intéresse aux nouvelles méthodes permettant de tirer le meilleur parti des informations disponibles pour identifier les composants critiques des mécanismes du circuit de la TV en explorant 5 axes : le pace-mapping sans référence, l'amélioration de la qualité du signal, l'analyse des caractéristiques de l'entrée de l'isthme, l'automatisation des calculs et la reconstruction graphique des schémas d'activation.Un calculateur automatique d'électrogrammes multiparamétriques a été mis au point pour déterminer la probabilité qu'un site donné soit situé à l'entrée d'un isthme de TV, une localisation clé du circuit.On a constaté que de multiples caractéristiques de l'électrogramme sont associées aux circuits de réentrée. Cependant, l'analyse d'un seul paramètre est insuffisante pour définir complètement la localisation de l'isthme de TV. Nous avons étudié 10 caractéristiques d'électrogramme différentes pour identifier une entrée d'isthme de TV. Les paramètres étudiés sont l'amplitude bipolaire et unipolaire, le temps entre le début du QRS et le début de l'électrogramme, le temps entre le début de l'électrogramme et le début du QRS, la durée de l'électrogramme, le nombre de pics positifs, l'intervalle S-QRS ainsi que la présence de fragmentation, de potentiels doubles et de potentiels tardifs. Tous ces paramètres peuvent être recueillis en l'absence de TV induite.L'analyse de régression logistique a montré que l'amplitude bipolaire, le nombre de pics positifs de l'électrogramme et l'intervalle S-QRS étaient indépendamment associés à la localisation de l'entrée de l'isthme TV. Une évaluation multiparamétrique de l'électrogramme est une approche prometteuse pour localiser l'entrée d'un isthme TV. Sur la base de ces résultats, une interface utilisateur graphique a été développée et mise en oeuvre dans un calculateur automatique pour déterminer rapidement la probabilité qu'un site donné soit situé à l'entrée d'un isthme de TV. 123 La détection automatique a été développée car l'analyse des points de pace-map est actuellement limitée en raison des étapes fastidieuses que le cardiologue interventionnel doit effectuer pour visualiser les informations importantes. Le traitement automatique a réduit le besoin d'annotations manuelles et a facilité la visualisation des cartes multiparamétriques identifiant l'emplacement de l'entrée, du coeur et de la sortie du circuit TV. L'analyse des données recueillies pendant le rythme sinusal et le pace-mapping permet l'étude détaillée des caractéristiques électriques d'un ventricule donné. Cette analyse est actuellement limitée en raison des étapes fastidieuses que le cardiologue interventionnel doit effectuer pour visualiser les informations d'intérêt. L'absence de techniques de détection déjà implémentées entrave l'utilisation des données de pace-mapping. Nous présentons une nouvelle méthode pour extraire automatiquement les informations clés. Des critères d'ondelettes, de temps et d'énergie sont utilisés pour détecter les pics de stimulation et les battements rythmés, ainsi que pour délimiter le début et le sommet d'un QRS. L'objectif global est de fournir au médecin un outil logiciel permettant de visualiser rapidement les cartes les plus pertinentes (amplitude, gradient de corrélation et intervalle S-QRS) pour identifier les circuits potentiels de TV. Le traitement automatique a réduit le besoin d'annotations manuelles et a facilité la visualisation des cartes pertinentes. L'analyse conjointe des cartes multiparamétriques permet d'identifier l'emplacement de l'entrée, du coeur et de la sortie du circuit de TV. Une fois le circuit identifié, les cibles d'ablation peuvent être déterminées afin d'éliminer les zones critiques à conduction lente.L'avenir de l'électrophysiologie sera probablement marqué par l'utilisation de cathéters comportant un nombre accru d'électrodes plus petites. Davantage d'informations seront détectées par un réseau toujours plus grand de capteurs, ce qui permettra de créer des cartes de plus grande densité. Ces nouvelles informations collectées devront être couplées à de nouveaux algorithmes automatiques pour orienter rapidement l'électrophysiologiste vers l'information qui l'intéresse. Pour accroître encore leurs performances, ces algorithmes ne prendront pas seulement en compte les données électroanatomiques mais intégreront également des informations provenant de différentes modalités. Par exemple, l'imagerie par résonance magnétique pourrait fournir des informations précieuses sur la profondeur de la cicatrice transmurale ainsi que sur l'orientation des fibres. En particulier, l'analyse de la géométrie de la cicatrice pourrait aider à déterminer la direction d'un circuit réentrant. Par ailleurs, avec le vieillissement de la population, le nombre de patients va augmenter, et les techniques permettant de traiter les patients plus rapidement et à moindre coût seront privilégiées pour limiter le coût des soins de santé. Par exemple, les systèmes robotiques ne sont actuellement pas très utilisés car leur développement est limité par des considérations financières et de rapidité. La demande de systèmes plus rapides et moins chers a déjà commencé et va probablement s'amplifier dans un avenir proche. Cette thèse a présenté plusieurs nouvelles approches pour identifier les circuits de TV. Les méthodes étudiées sont particulièrement utiles dans le cas où la tachycardie n'est pas inductible pendant l'étude électrophysiologique. Une attention particulière a été accordée à l'extraction automatique des informations clés et à la facilitation de leur visualisation. Plus il est facile de visualiser les données, plus il est facile d'identifier ensuite les liens entre les paramètres clés. Un objectif à long terme d'une étude électrophysiologique de la TV post-infarctus est de pouvoir déterminer si un ventricule donné qui n'a jamais soutenu une tachycardie a le substrat pour en soutenir une. Si c'est le cas, une ablation ciblée par cathéter pourrait être pratiquée pour empêcher le patient de subir une tachycardie. Cette approche axée sur le traitement avant le premier événement mettant en danger la vie du patient modifierait considérablement la façon dont les patients sont traités aujourd'hui. Cette solution pourrait également réduire la charge des soins de santé en limitant par exemple le grand nombre d'implémentations coûteuses de défibrillateurs. L'utilisation d'outils mathématiques plus complexes tels que l'intelligence artificielle pourrait être nécessaire pour identifier de nouveaux modèles. L'apprentissage automatique pourrait être intéressant à utiliser en raison de la complexité des données à prendre en compte. Le développement de ces techniques doit se faire dans un langage que les médecins peuvent comprendre. C'est la clé d'une adoption généralisée.

  4. PENTARAY TM catheter. ................................................................................................................. The CARTO® system. .................................................................................................................... Electrophysiology room in Nancy................................................................................................. Bipolar map of a left ventricle. .....................................................................................................

	Figure 5. Figure 6. Figure 7.

Figure 8. Fractionated signal. ......................................................................................................................

Figure 9. Late potential. ..............................................................................................................................

Figure 10. Activation map in tachycardia. ...................................................................................................

Le pace-mapping sans référence est une nouvelle méthode basée uniquement sur l'analyse des données de l'électrocardiogramme (ECG) obtenues pendant le pace-mapping. Cette approche ne nécessite pas d'enregistrement de la TV de référence et est particulièrement utile lorsque la tachycardie ne peut être induite. Le pace-mapping sans référence identifie avec précision les mêmes zones cibles que la cartographie de rythme conventionnelle ainsi que des zones supplémentaires qui peuvent être à l'origine d'autres circuits de TV.Dans la pratique clinique actuelle, la technique conventionnelle du pace-mapping consiste à stimuler le myocarde et à comparer la morphologie des 12 dérivations du signal ECG induit avec un enregistrement de la TV de référence. La principale difficulté de la technique conventionnelle réside dans le fait qu'un enregistrement de la TV de référence est nécessaire. De plus, cette technique met en évidence le circuit de l'enregistrement de TV. D'autres circuits secondaires peuvent apparaître et méritent également d'être étudiés. Nous avons étudié une nouvelle méthode du pace-mapping sans référence, basée uniquement sur l'analyse des données ECG obtenues pendant la technique de pace-mapping. Une carte de corrélation locale est définie en analysant les corrélations par paires entre les signaux QRS stimulés provenant de sites de stimulation voisins. Cette méthode sans référence est proposée afin de quantifier les changements locaux dans les voies d'activation. Les propriétés électriques de l'influx électrique entre deux points ne dépendent pas de l'enregistrement de TV de référence sélectionné. Les points anormaux sont identifiés par des valeurs de gradient de corrélation élevées.La méthode conventionnelle et la méthode sans référence ont été évaluées rétrospectivement sur 24 procédures d'ablation de TV. La technique de pace-mapping sans référence peut identifier avec précision les mêmes zones cibles que la technique de pace-mapping conventionnelle, ainsi que des zones supplémentaires pouvant être à l'origine d'autres circuits de TV. Le passage abrupt de bonnes à mauvaises valeurs aide également à déterminer l'orientation de l'isthme en définissant la transition entre la zone de sortie et la zone d'entrée. La méthode sans référence peut être utilisée en plus de la méthode conventionnelle, et est particulièrement utile pour traiter les patients chez qui une TV ne peut pas être induit pendant l'intervention.

Acknowledgements

20

The conventional and reference-less method was evaluated retrospectively in 24 VT ablation procedures.

The reference-less pace-mapping can accurately identify the same target zones as conventional pacemapping, plus additional zones that may cause other VT circuits. The abrupt change from good to poor values also helps in determining the isthmus orientation by defining the transition from the exit to the entrance zone. The reference-less method can be used in addition to the conventional method, and is especially useful to treat patients in whom VT cannot be induced during the intervention.

4) Paced-ECG detector and delineator for automatic multi-parametric mapping

The analysis of data collected during sinus rhythm and pacemapping enables the detailed study of the electrical characteristics of a given ventricle. This analysis is currently limited because of the timeconsuming steps that the interventional cardiologist needs to do to visualize the information of interest.

The lack of already implemented detection techniques hinder the use of pace-mapping data. The following paper presents a novel method to automatically extract the key information. Wavelet, time and energy criteria are used to detect pacing spikes and paced beats as well as to delineate the onset and peak of a QRS. The overall goal is to provide the physician with a software tool to rapidly visualize the most relevant maps (voltage, correlation gradient and S-QRS interval) to identify potential VT circuits.

My contribution to the paper was the design, implementation and validation of the signal processing methods. I also developed the in-house software in order to validate the automated detection tool, and I extracted the relevant metrics to evaluate the detection performance. The detector and delineator performed well and the maps using the physician and the algorithm inputs looked very similar. The automatic processing reduced the need for manual annotations and facilitated the visualization of the relevant maps. The joint analysis of the multi-parametric maps helps identify the location of the entrance, core and exit of the VT circuit. Once the circuit is identified, ablation targets can be determined in order to eliminate the critical slow-conducting zones.

108

The pseudo-activation map was finally compared to the activation pattern of the tachycardia. When the starting point was located in the exit zone of the reentrant circuit, the pseudo activation map was compared to the activation map. When the starting point was located in the entrance zone of the reentrant circuit, the pseudo activation map had an opposite activation pattern and was compared to the opposite activation map. The tachycardia being a circuit, the local activation time 𝐿𝐴𝑇 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖) of each pacing site 𝑖 of the tachycardia can be defined modulo the cycle length. For a given pacing site of an identified core zone, 𝑃𝑀 𝑐𝑜𝑟𝑒 site, an activation time, 𝐿𝐴𝑇 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑃𝑀 𝑐𝑜𝑟𝑒 ) of 0 was used. Additionally, only positive values for 𝐿𝐴𝑇 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖) were used. The local activation values were thus between 0 and the value of the cycle length. The opposite activation time 𝐿𝐴𝑇 𝑂𝑝𝑝𝑜𝑠𝑖𝑡𝑒𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖) was determined by giving the opposite activation time𝐿𝐴𝑇 𝑂𝑝𝑝𝑜𝑠𝑖𝑡𝑒𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑃𝑀 𝑐𝑜𝑟𝑒 ) the value of 0 and to affect to all the other points the value of 𝐶𝑦𝑐𝑙𝑒 𝐿𝑒𝑛𝑔𝑡ℎ -𝐿𝐴𝑇 𝑃𝑀 𝑐𝑜𝑟𝑒 (𝑖). The local opposite activation values thus varied between 0 and the value of the cycle length and represented the opposite activation pattern of the tachycardia.

The pseudo-activation maps, activation maps, and opposite activation maps were integrated into the CARTO® system for visualization. The agreement between pseudo-activation maps, activation maps, and opposite activation maps was assessed by correlation analysis (mean, standard deviation, median, mean absolute error and both Spearman's and Lin's definitions). Des recherches supplémentaires sur un plus grand nombre de patients sont nécessaires pour essayer de déterminer la meilleure formule de pondération qui doit être appliquée aux bords. L'application de techniques d'apprentissage automatique pourrait encore améliorer la méthode. L'objectif serait de déterminer une formule de pondération indépendante du site de stimulation initial du patient qui génère une carte de pseudo-activation la plus similaire possible au schéma d'activation du circuit.

La méthode GRAAPH pourrait être particulièrement intéressante chez les patients présentant de multiples zones à gradient de corrélation élevé. La méthode génèrerait donc plusieurs cartes de pseudo-activation fournissant au médecin un aperçu des schémas d'activation suggérés des différents circuits de TV.

L'analyse des cartes de pseudo-activation mettant en évidence le schéma de propagation électrique du ventricule pourrait fournir des informations supplémentaires pour aider le médecin à déterminer la stratégie d'ablation la plus efficace.

Title:

Computer assisted electrophysiological intervention treating complex ventricular arrhythmias

Summary:

Since the beginning of the 1990s and the use of radiofrequency to ablate cardiac arrhythmias, electrophysiologists treat increasing complex rhythm disorders. 3D mapping systems enable catheter locations to be known with high precision and therefore are very important tools for electrophysiology.

Identifying zones of interest remains long and involves many steps based on indirect analyses of the heart's properties.

The main objective of the thesis is to develop new tools to locate the critical isthmus in post infarct ventricular tachycardia. The clear identification of the circuit components of the ventricular tachycardia enables the development of an ablation strategy to treat the patient. The studied methods do not require a 12-lead electrocardiogram of the ventricular tachycardia and therefore have the advantage of being able to be used even if the tachycardia cannot be initiated during the procedure.

A major area of research is the development of an algorithm that automatically extracts the relevant data obtained during pace mapping. This facilitates the display of multi-parametric maps highlighting potential reentry circuits.

Another area of research is the development of a graph-based method to study the variations of the electrical properties of the ventricle. The paced points are considered as vertices of a graph. Each edge is given a weight and finding the path between two vertices of minimum weight allows the analysis of potential reentry circuits.

Keywords:

Cardiac electrophysiology; Electrocardiography; Radiofrequency catheter ablation