Graph-based Reconstruction of Arrhythmic Activations by Pacing the Heart (GRAAPH) 

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Due to reduced cell excitability

After ischemia, the reduced availability of sodium channels lead to a decrease in the fast inward sodium current 𝐼𝑁𝐴, reducing excitability and conduction velocities between cells[6]. 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[6].

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[6], [11], [15]. 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[6], [11], [26], [27]. 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[6]. 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.

Integration of fluoroscopy images

The CARTOUNIVUTM Module (Biosense Webster Inc., Diamond Bar, USA) enables the integration of previously acquired fluoroscopy images and cine loops into the current 3D electroanatomical maps[57]. Using CARTOUNIVUTM can lead to an operator independent reduction 52% reduction in fluoroscopy time and 63% in radiation dosage for VT ablation procedures[57].
A near-zero fluoroscopy procedure can be achieved in up to half of the VT ablation procedures[58]. The percentage is particularly high in ischemic patients with endocardial ablation[58]. For epicardial mapping, CARTOUNIVUTM is particularly useful to visualize the coronary arteries within the epicardial voltage map, helping the development of safer ablation strategies[58].

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[59]. The catheter possesses small magnets that are drawn by the desired magnetic field vector. The catheter deflects to align parallel to the magnetic field[45], [60], [65]. Figure 6 shows the electrophysiology room in Nancy equipped with such a system, the Niobe® system (Stereotaxis Inc., St. Louis, USA).

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[72]. The electrograms collected by the electrodes on the catheter are distance-weighted 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[72]. 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 cm2[73].
Multielectrode catheters have been developed to increase mapping resolution[74]. 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[72], [73]. 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[75]. This electrode configuration enables the recording of lower amplitude signals[30]. 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[74]. 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[45], [74], [76]. Moreover, the increased substrate definition due to the reduced far field participating of the neighboring healthy tissue can lead to larger low voltage areas[77].
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[45], [74]. 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[74]. 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[31]. 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[45]. High-density mapping has been defined as over 25 points acquired per cm2 and can allow precise characterization of patchy fibrotic areas by limiting potential errors due to interpolation between points[4], [76]. Overall, the use of multielectrode catheters has a positive impact and can lead to increased patient outcomes and lower VT recurrence rates[78].

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[84]. 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[85]. The following section will evaluate the use of voltage, scar, fragmented and double potential sinus rhythm mapping to help identify reentrant circuits.

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[45], [86]. 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[87]. 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[5]. Bipolar recordings reduce far-field interferences and this effect is maximized as interelectrode distance is decreased[74]. 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[5], [77], [88], [89]. For example, voltage measurements in the septal area can be more difficult to determine because of the complex nature of the conduction system[88]. 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[74].

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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[117]. The conditions required for re-entrant circuits to occur tend to depend on functional rather than fixed abnormalities[5]. Furthermore, electrogram characteristics are influenced by wavefront activation and catheter orientation[5]. 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[97], [118]. For example, late electrograms during sinus rhythm can represent slow conduction into dead end pathways[119]. Artifacts resulting from catheter movement or filter settings can also hinder analysis[97], [118]. 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[99], [118]. 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[97]. 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[54], [118].

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[59]. 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. Ɛ=−𝑑Ф(𝐵)𝑑𝑡 (4).
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[149]. 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 Imaging) and this study is a result of its adaption to the electrophysiology setting[150]. 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.

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.

Table of contents :

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
l. Pace Mapping
1) Correlation gradient mapping
2) Improving ECG signal quality during remote magnetic navigation
3) Isthmus entrance calculator based on electrogram characteristics
4) Paced-ECG detector and delineator for automatic multi-parametric mapping
5) Graph-based Reconstruction of Arrhythmic Activations by Pacing the Heart (GRAAPH) 
a. Introduction
b. Technical background
c. Graph-based modeling of VT circuits
d. Implementation
e. Results
f. Discussion and conclusion
Bibliography .


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