Computer-Assisted Electroanatomical Guidance for Cardiac Electrophysiology Procedures

Cardiac arrhythmias are serious life-threatening episodes affecting both the aging population and younger patients with pre-existing heart conditions. One of the most effective therapeutic procedures is the minimally-invasive catheter-driven endovascular electrophysiology study, whereby electrical potentials and activation patterns in the affected cardiac chambers are measured and subsequent ablation of arrhythmogenic tissue is performed. Despite emerging technologies such as electroanatomical mapping and remote intraoperative navigation systems for improved catheter manipulation and stability, successful ablation of arrhythmias is still highly-dependent on the operator’s skills and experience. This thesis proposes a framework towards standardisation in the electroanatomical mapping and ablation planning by merging knowledge transfer from previous cases and patient-specific data. In particular, contributions towards four different procedural aspects were made: optimal electroanatomical mapping, arrhythmia path computation, catheter tip stability analysis, and ablation simulation and optimisation. In order to improve the intraoperative electroanatomical map, anatomical areas of high mapping interest were proposed, as learned from previous electrophysiology studies. Subsequently, the arrhythmic wave propagation on the endocardial surface and potential ablation points were computed. The ablation planning is further enhanced, firstly by the analysis of the catheter tip stability and the probability of slippage at sparse locations on the endocardium and, secondly, by the simulation of the ablation result from the computation of convolutional matrices which model mathematically the ablation process. The methods proposed by this thesis were validated on data from patients with complex congenital heart disease, who present unusual cardiac anatomy and consequently atypical arrhythmias. The proposed methods also build a generic framework for computer guidance of electrophysiology, with results showing complementary information that can be easily integrated into the clinical workflow.Open Acces

Ablation of Cardiac Tissue with Nanosecond Pulsed Electric Fields: Experiments and Numerical Simulations

Cardiac ablation for the treatment of cardiac arrhythmia is usually performed by heating tissue with radio-frequency (RF) electrical currents to create conduction-blocking lesions in order to stop the propagation of electrical waves. Problems associated with RF ablation are recurrence of arrhythmias after successful treatments, tissue loss beyond the targeted tissue, long duration of the ablation procedure, and thermal side effects including thrombus formation that may lead to stroke. Here, we propose a new, non-thermal ablation method using nanosecond pulsed electric fields (nsPEFs) with better-controlled ablation volume, shorter procedure time, and no thermal side effects. We demonstrate that we can create non-conductive transmural lesions using different electrode configurations. We also develop a numerical model of nsPEF ablation, which allows us to estimate the critical electric field which leads in cardiac tissue and helps to provide a guideline for clinical tissue ablation. Our experimental model is a Langendorff-perfused rabbit heart. The heart is placed in a life-support system, and optical mapping is performed to study its electrical activity. We further developed the capability to apply short sequences of nanosecond pulses to tissue through pairs of customized electrodes. In order to characterize the 3D geometry of an ablated volume, we have adopted propidium iodide and TTC staining in conjunction with tissue sectioning. Our results obtained by optical mapping data and PI/TTC stained tissue show that fully transmural lesions can be obtained faster and with better control over the ablated volume than in conventional (RF) ablation, in the absence of thermal side effects. In order to aid nsPEF ablation planning, we used the COMSOL finite element software to create a model of the electric field distribution in cardiac tissue, which has a complex anisotropic architecture, for different electrode configurations. The experimental and numerical results are consistent and suggest a critical electric field strength of 3kV/cm for the death of cardiac tissue. This threshold obtained by the numerical model can function as a guideline for future clinical nsPEF treatment of atrial fibrillation. In summary, we have developed nsPEF ablation for the treatment of cardiac arrhythmia to provide better control over the ablated volume than conventional (RF) ablation, to reduce procedure time, and to avoid thermal side effects. Our ultimate goal is to bring this technology to the clinical practice

The first human experience of a contact force sensing catheter for epicardial ablation of ventricular tachycardia

Contact force (CF) is one of the major determinants for sufficient lesion formation. CF-guided procedures are associated with enhanced lesion formation and procedural success.We report our initial experience in epicardial ventricular tachycardia (VT) ablation with a force-sensing catheter using a new approach with an angioplasty balloon. Two patients with arrhythmogenic right ventricular cardiomyopathy who underwent prior unsuccessful endocardial ablation were treated with epicardial VTablation. CF data were used to titrate force, power and ablation time

Principles of Electroanatomic Mapping

Electrophysiologic testing and radiofrequency ablation have evolved as curative measures for a variety of rhythm disturbances. As experience in this field has grown, ablation is progressively being used to address more complex rhythm disturbances. Paralleling this trend are technological advancements to facilitate these efforts, including electroanatomic mapping (EAM). At present, several different EAM systems utilizing various technologies are available to facilitate mapping and ablation. Use of these systems has been shown to reduce fluoroscopic exposure and radiation dose, with less significant effects on procedural duration and success rates. Among the data provided by EAM are chamber reconstruction, tagging of important anatomic landmarks and ablation lesions, display of diagnostic and mapping catheters without using fluoroscopy, activation mapping, and voltage (or scar) mapping. Several EAM systems have specialized features, such as enhanced ability to map non-sustained or hemodynamically unstable arrhythmias, ability to display diagnostic as well as mapping catheter positions, and wide compatibility with a variety of catheters. Each EAM system has its strengths and weaknesses, and the system chosen must depend upon what data is required for procedural success (activation mapping, substrate mapping, cardiac geometry), the anticipated arrhythmia, the compatibility of the system with adjunctive tools (i.e. diagnostic and ablation catheters), and the operator's familiarity with the selected system. While EAM can offer significant assistance during an EP procedure, their incorrect or inappropriate application can substantially hamper mapping efforts and procedural success, and should not replace careful interpretation of data and strict adherence to electrophysiologic principles

Circle Method for Robust Estimation of Local Conduction Velocity High-Density Maps From Optical Mapping Data: Characterization of Radiofrequency Ablation Sites

Conduction velocity (CV) slowing is associated with atrial fibrillation (AF) and reentrant ventricular tachycardia (VT). Clinical electroanatomical mapping systems used to localize AF or VT sources as ablation targets remain limited by the number of measuring electrodes and signal processing methods to generate high-density local activation time (LAT) and CV maps of heterogeneous atrial or trabeculated ventricular endocardium. The morphology and amplitude of bipolar electrograms depend on the direction of propagating electrical wavefront, making identification of low-amplitude signal sources commonly associated with fibrotic area difficulty. In comparison, unipolar electrograms are not sensitive to wavefront direction, but measurements are susceptible to distal activity. This study proposes a method for local CV calculation from optical mapping measurements, termed the circle method (CM). The local CV is obtained as a weighted sum of CV values calculated along different chords spanning a circle of predefined radius centered at a CV measurement location. As a distinct maximum in LAT differences is along the chord normal to the propagating wavefront, the method is adaptive to the propagating wavefront direction changes, suitable for electrical conductivity characterization of heterogeneous myocardium. In numerical simulations, CM was validated characterizing modeled ablated areas as zones of distinct CV slowing. Experimentally, CM was used to characterize lesions created by radiofrequency ablation (RFA) on isolated hearts of rats, guinea pig, and explanted human hearts. To infer the depth of RFA-created lesions, excitation light bands of different penetration depths were used, and a beat-to-beat CV difference analysis was performed to identify CV alternans. Despite being limited to laboratory research, studies based on CM with optical mapping may lead to new translational insights into better-guided ablation therapies

Contact and Noncontact Mapping Systems in the Electrophysiology Laboratory

The most important step for the operator to perform a successful radiofrequency ablation procedure for the treatment of cardiac tachyarrhythmias is to accurately identify the origin of and localize the arrhythmia focus and to determine the sequence of electrical activity. Intracardiac mapping techniques came a long distance from single catheter recordings to three dimensional voltage and morphology reconstructing systems. The aim of this review is to summarize the benefits and disadvantages of the existing cardiac mapping systems

Development and validation of an algorithm to predict the success of the ablation of macroreentrant atrial tachycardia.

Ablation of macroreentrant atrial tachycardia (MRAT) is challenging because of complex anatomy and multiple reentrant loops. In order to define an effective ablation strategy, 3-dimensional electroanatomic mapping proved very useful. To identify predictors of ablation procedure failure may be helpful for patients treatment. In the first part of our study we analyzed into details the electroanatomical features of the reentry circuit in MRAT and we compared the characteristics of successfully versus unsuccessfully consecutive treated patients undegoing electroanatomic mapping and ablation of MRAT in order to identify variables predicting the ablation outcome. Ablation was linearly placed at the mid-diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure. We demonstrated a significant difference as to the electroanatomic mapping characteristics: successfully treated cases showed a narrower target isthmus with a slower conduction velocity across the isthmus itself. In the second part of our research, we analyzed the relation between the strongest predictors of procedure outcome identified in part I (MDI width and conduction velocity across the MDI) and the chance of success of the ablation procedure. In order to analyze this relation and to predict the difficulty of the ablation procedure, we developed an algorithm and we validated prospectively the accuracy of the developed model in a second patient series

High Resolution Multi-parametric Diagnostics and Therapy of Atrial Fibrillation: Chasing Arrhythmia Vulnerabilities in the Spatial Domain

After a century of research, atrial fibrillation (AF) remains a challenging disease to study and exceptionally resilient to treatment. Unfortunately, AF is becoming a massive burden on the health care system with an increasing population of susceptible elderly patients and expensive unreliable treatment options. Pharmacological therapies continue to be disappointingly ineffective or are hampered by side effects due to the ubiquitous nature of ion channel targets throughout the body. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, ablation procedures can be complex, leading to varying levels of recurrence, and have a number of serious risks. The high recurrence rate could be due to the difficulty of accurately predicting where to draw the ablation lines in order to target the pathophysiology that initiates and maintains the arrhythmia or an inability to distinguish sub-populations of patients who would respond well to such treatments. There are electrical cardioversion options but there is not a practical implanted deployment of this strategy. Under the current bioelectric therapy paradigm there is a trade-off between efficacy and the pain and risk of myocardial damage, all of which are positively correlated with shock strength. Contrary to ventricular fibrillation, pain becomes a significant concern for electrical defibrillation of AF due to the fact that a patient is conscious when experiencing the arrhythmia. Limiting the risk of myocardial injury is key for both forms of fibrillation. In this project we aim to address the limitations of current electrotherapy by diverging from traditional single shock protocols. We seek to further clarify the dynamics of arrhythmia drivers in space and to target therapy in both the temporal and spatial domain; ultimately culminating in the design of physiologically guided applied energy protocols. In an effort to provide further characterization of the organization of AF, we used transillumination optical mapping to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acutely induced episodes of AF. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms, with a demonstrated range of discordance between the epicardial and endocardial dynamic propagation patterns. After confirming the presence of epi-endo dyssynchrony in multiple animal models, we further investigated the anatomical structure to look for regional trends in transmural fiber orientation that could help explain the spectrum of observed patterns. Simultaneously, we designed and optimized a multi-stage, multi-path defibrillation paradigm that can be tailored to individual AF frequency content in the spatial and temporal domain. These studies continue to drive down the defibrillation threshold of electrotherapies in an attempt to achieve a pain-free AF defibrillation solution. Finally, we designed and characterized a novel platform of stretchable electronics that provide instrumented membranes across the epicardial surface or implanted within the transmural wall to provide physiological feedback during electrotherapy beyond just the electrical state of the tissue. By combining a spatial analysis of the arrhythmia drivers, the energy delivered and the resulting damage, we hope to enhance the biophysical understanding of AF electrical cardioversion and xiii design an ideal targeted energy delivery protocol to improve upon all limitations of current electrotherapy

Development and validation of an algorithm to predict the success of the ablation of macroreentrant atrial tachycardia.

Ablation of macroreentrant atrial tachycardia (MRAT) is challenging because of complex anatomy and multiple reentrant loops. In order to define an effective ablation strategy, 3-dimensional electroanatomic mapping proved very useful. To identify predictors of ablation procedure failure may be helpful for patients treatment. In the first part of our study we analyzed into details the electroanatomical features of the reentry circuit in MRAT and we compared the characteristics of successfully versus unsuccessfully consecutive treated patients undegoing electroanatomic mapping and ablation of MRAT in order to identify variables predicting the ablation outcome. Ablation was linearly placed at the mid-diastolic isthmus (MDI) to achieve arrhythmia interruption and conduction block. Variables were analyzed for predictors of both procedural failure and cumulative failure. We demonstrated a significant difference as to the electroanatomic mapping characteristics: successfully treated cases showed a narrower target isthmus with a slower conduction velocity across the isthmus itself. In the second part of our research, we analyzed the relation between the strongest predictors of procedure outcome identified in part I (MDI width and conduction velocity across the MDI) and the chance of success of the ablation procedure. In order to analyze this relation and to predict the difficulty of the ablation procedure, we developed an algorithm and we validated prospectively the accuracy of the developed model in a second patient series