Contributions To The Methodology Of Electrocardiographic Imaging (ECGI) And Application Of ECGI To Study Mechanisms Of Atrial Arrhythmia, Post Myocardial Infarction Electrophysiological Substrate, And Ventricular Tachycardia In Patients

ABSTRACT OF THE DISSERTATION Contributions to the Methodology of Electrocardiographic Imaging: ECGI) and Application of ECGI to Study Mechanisms of Atrial Arrhythmia, Post Myocardial Infarction Electrophysiological Substrate, and Ventricular Tachycardia in Patients by Yong Wang Doctor of Philosophy in Biomedical Engineering Washington University in St. Louis, 2009 Professor Yoram Rudy, Chair Electrocardiographic Imaging: ECGI) is a noninvasive imaging modality for cardiac electrophysiology and arrhythmia. ECGI reconstructs epicardial potentials, electrograms and isochrones from body-surface electrocardiograms combined with heart-torso geometry from computed tomography: CT). The application of a new meshless method, the Method of Fundamental Solutions: MFS) is introduced to ECGI with the following major advantages: 1. Elimination of meshing and manual mesh optimization processes, thereby enhancing automation and speeding the ECGI procedure. 2. Elimination of mesh-induced artifacts. 3. Simpler implementation. These properties of MFS enhance the practical application of ECGI as a clinical diagnostic tool. The current ECGI mode of operation is offline with generation of epicardial potential maps delayed to data acquisition. A real time ECGI procedure is proposed, by which the epicardial potentials can be reconstructed while the body surface potential data are acquired: \u3c 1msec/frame) during a clinical procedure. This development enables real-time monitoring, diagnosis, and interactive guidance of intervention for arrhythmia therapy. ECGI is applied to map noninvasively the electrophysiological substrate in eight post-MI patients during sinus rhythm: SR). Contrast-enhanced MRI: ceMRI) is conducted to determine anatomical scar. ECGI imaged regions of electrical scar corresponded closely in location, extent, and morphology to the anatomical scars. In three patients, late diastolic potentials are imaged in the scar epicardial border zone during SR. Scar-related ventricular tachycardia: VT) in two patients are imaged, showing the VT activation sequence in relation to the abnormal electrophysiological substrate. ECGI imaging the substrate in a beat-by-beat fashion could potentially help in noninvasive risk stratification for post-MI arrhythmias and facilitate substrate-based catheter ablation of these arrhythmias. ECGI is applied to eleven consecutive patients referred for VT catheter ablation procedure. ECGI is performed either before: 8 patients) or during: 3 patients) the ablation procedure. Blinded ECGI and invasive electrophysiology: EP) study results are compared. Over a wide range of VT types and locations, ECGI results are consistent with EP data regarding localization of the arrhythmia origin: including myocardial depth) and mechanism: focal, reentrant, fascicular). ECGI also provides mechanistic electrophysiological insights, relating arrhythmia patterns to the myocardial substrate. The study shows ECGI has unique potential clinical advantages, especially for hemodynamically intolerant VT or VT that is difficult to induce. Because it provides local cardiac information, ECGI may aid in better understanding of mechanisms of ventricular arrhythmia. Further prospective trials of ECGI with clinical endpoints are warranted. Many mechanisms for the initiation and perpetuation of atrial fibrillation: AF) have been demonstrated over the last several decades. The tools to study these mechanisms in humans have limitations, the most common being invasiveness of a mapping procedure. In this paper, we present simultaneous noninvasive biatrial epicardial activation sequences of AF in humans, obtained using the Electrocardiographic Imaging: ECGI) system, and analyzed in terms of mechanisms and complexity of activation patterns. We performed ECGI in 36 patients with a diagnosis of AF. To determine ECGI atrial accuracy, atrial pacing from different sites was performed in six patients: 37 pacing events), and ECGI was compared to registered CARTO images. Then, ECGI was performed on all 36 patients during AF and ECGI epicardial maps were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients: 97% procedural success). The spatial accuracy in determining initiation sites as simulated by atrial pacing was ~ 6mm. ECGI imaged many activation patterns of AF, most commonly multiple wavelets: 92%), with pulmonary vein: 69%) and non-pulmonary vein: 62%) trigger sites. Rotor activity was seen rarely: 15%). AF complexity increased with longer clinical history of AF, though the degree of complexity of nonparoxysmal AF varied and overlapped. ECGI offers a way to identify unique epicardial activation patterns of AF in a patient-specific manner. The results are consistent with contemporary animal models of AF mechanisms and highlight the coexistence of a variety of mechanisms among patients

Functional Mapping of Three-Dimensional Electrical Activation in Ventricles

University of Minnesota Ph.D. dissertation. 2010. Major: Biomedical Engineering. Advisor: Bin He. 1 computer file (PDF); 139 pages.Ventricular arrhythmias account for nearly 400,000 deaths per year in the United States alone. Electrical mapping of the ventricular activation could facilitate the diagnosis and treatment of arrhythmias, e.g. guiding catheter ablation. To date, both direct mapping and non-contact mapping techniques have been routinely used in electrophysiology labs for obtaining the electrical activity on the endocardial surface. Non-invasive functional mapping methods are also developed to estimate the electrical activity on the epicardium or on both epicardium and endocardium from the body surface measurements. Though successful, the results using above methods are all limited on the surface of the heart and thus cannot directly characterize the cardiac events originating within the myocardial wall. Our group's goal is to develop a functional mapping method to estimate the three-dimensional cardiac electrical activity from either non-invasive body surface potential maps or minimally-invasive intracavitary potential maps, by solving the so-called "inverse problem". Hence the information under the surface of the heart could be revealed to better characterize the cardiac activation. In the present thesis study, the previously developed three-dimensional cardiac electrical imaging (3DCEI) approach has been further investigated. Its function is expanded for not only estimating the global activation sequence but also reconstructing the potential at any myocardial site throughout the ventricle. New algorithms under the 3DCEI scheme are also explored for more powerful mapping capability. The performance of the enhanced 3DCEI approach is rigorously evaluated in both control and diseased swine models when the clinical settings are mimicked. The promising results validate the feasibility of estimating detailed three-dimensional cardiac activation by using the 3DCEI approach, and suggest that 3DCEI has great potential of guiding the clinical management of cardiac arrhythmias in a more efficient way

Validation and Opportunities of Electrocardiographic Imaging: From Technical chievements to Clinical Applications

[EN] Electrocardiographic imaging (ECGI) reconstructs the electrical activity of the heart from a dense array of body-surface electrocardiograms and a patient-specific heart-torso geometry. Depending on how it is formulated, ECGI allows the reconstruction of the activation and recovery sequence of the heart, the origin of premature beats or tachycardia, the anchors/hotspots of re-entrant arrhythmias and other electrophysiological quantities of interest. Importantly, these quantities are directly and non-invasively reconstructed in a digitized model of the patient's three-dimensional heart, which has led to clinical interest in ECGI's ability to personalize diagnosis and guide therapy. Despite considerable development over the last decades, validation of ECGI is challenging. Firstly, results depend considerably on implementation choices, which are necessary to deal with ECGI's ill-posed character. Secondly, it is challenging to obtain (invasive) ground truth data of high quality. In this review, we discuss the current status of ECGI validation as well as the major challenges remaining for complete adoption of ECGI in clinical practice. Specifically, showing clinical benefit is essential for the adoption of ECGI. Such benefit may lie in patient outcome improvement, workflow improvement, or cost reduction. Future studies should focus on these aspects to achieve broad adoption of ECGI, but only after the technical challenges have been solved for that specific application/pathology. We propose 'best' practices for technical validation and highlight collaborative efforts recently organized in this field. Continued interaction between engineers, basic scientists, and physicians remains essential to find a hybrid between technical achievements, pathological mechanisms insights, and clinical benefit, to evolve this powerful technique toward a useful role in clinical practice.This study received financial support from the Hein Wellens Fonds, the Cardiovascular Research and Training Institute (CVRTI), the Nora Eccles Treadwell Foundation, the National Institute of General Medical Sciences of the National Institutes of Health (P41GM103545), the National Institutes of Health (NIH HL080093), the French government as part of the Investments of the Future program managed by the National Research Agency (ANR-10-IAHU-04), from the VEGA Grant Agency in Slovakia (2/0071/16), from the Slovak Research and Development Agency (APVV-14-0875), the Fondo Europeo de Desarrollo Regional (FEDER), the Instituto de Salud Carlos III (PI17/01106) and from Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana (AICO/2018/267) and NIH grant (HL125998) and National Science Foundation (ACI-1350374).Cluitmans, M.; Brooks, D.; Macleod, RS.; Dossel, O.; Guillem Sánchez, MS.; Van Dam, P.; Svehlikova, J.... 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Non-invasive localization of atrial ectopic beats by using simulated body surface P-wave integral maps

Non-invasive localization of continuous atrial ectopic beats remains a cornerstone for the treatment of atrial arrhythmias. The lack of accurate tools to guide electrophysiologists leads to an increase in the recurrence rate of ablation procedures. Existing approaches are based on the analysis of the P-waves main characteristics and the forward body surface potential maps (BSPMs) or on the inverse estimation of the electric activity of the heart from those BSPMs. These methods have not provided an efficient and systematic tool to localize ectopic triggers. In this work, we propose the use of machine learning techniques to spatially cluster and classify ectopic atrial foci into clearly differentiated atrial regions by using the body surface P-wave integral map (BSPiM) as a biomarker. Our simulated results show that ectopic foci with similar BSPiM naturally cluster into differentiated non-intersected atrial regions and that new patterns could be correctly classified with an accuracy of 97% when considering 2 clusters and 96% for 4 clusters. Our results also suggest that an increase in the number of clusters is feasible at the cost of decreasing accuracy.This work was partially supported by The "Programa Prometeu" from Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana (www.edu.gva.es/fio/index_es.asp) Award Number: PROMETEU/2016/088 to JS; The "Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016" from the Ministerio de Economia, Industria y Competitividad of Spain, Agencia Estatal de Investigacion (www.mineco.gob.es) and the European Commission (European Regional Development Funds - ERDF -FEDER) (ec.europa.eu/regional_policy/es/funding/erdf/) Award Number: DPI2016-75799-R to JS and The "Programa Estatal de Investigacion, Desarrollo e Innovacion Orientado a los Retos de la Sociedad" from the Ministerio de Economia y Competitividad of Spain, Agencia Estatal de Investigacion (www.mineco.gob.es) and the European Commission (European Regional Development Funds - ERDF -FEDER) (ec.europa.eu/regional_policy/es/funding/erdf/) Award Number: TIN2014-59932-JIN to AFA and RS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ferrer Albero, A.; Godoy, EJ.; Lozano, M.; Martínez Mateu, L.; Alonso Atienza, F.; Saiz Rodríguez, FJ.; Sebastián Aguilar, R. (2017). Non-invasive localization of atrial ectopic beats by using simulated body surface P-wave integral maps. PLoS ONE. 12(7):1-23. https://doi.org/10.1371/journal.pone.0181263S12312

The relationship of myocardial contraction and electrical excitation—the correlation between scintigraphic phase image analysis and electrophysiologic mapping

Phase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation. We sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both. In 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites. In each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups. A noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences

On the efficiency and accuracy of the single equivalent moving dipole method to identify sites of cardiac electrical activation

We have proposed an algorithm to guide radiofrequency catheter ablation procedures. This algorithm employs the single equivalent moving dipole (SEMD) to model cardiac electrical activity. The aim of this study is to investigate the optimal time instant during the cardiac cycle as well as the number of beats needed to accurately estimate the location of a pacing site. We have evaluated this algorithm by pacing the ventricular epicardial surface and inversely estimating the locations of pacing electrodes from the recorded body surface potentials. Two pacing electrode arrays were sutured on the right and left ventricular epicardial surfaces in swine. The hearts were paced by the electrodes sequentially at multiple rates (120–220 bpm), and body surface ECG signals from 64 leads were recorded for the SEMD estimation. We evaluated the combined error of the estimated interelectrode distance and SEMD direction at each time instant during the cardiac cycle, and found the error was minimum when the normalized root mean square (RMS[subscript n]) value of body surface ECG signals reached 15 % of its maximum value. The beat-to-beat variation of the SEMD locations was significantly reduced (p < 0.001) when estimated at 15 % RMS[subscript n] compared to the earliest activation time (EAT). In addition, the 5–95 % interval of the estimated interelectrode distance error decreased exponentially as the number of beats used to estimate a median beat increased. When the number of beats was 4 or larger, the 5–95 % interval was smaller than 3.5 mm (the diameter of a commonly used catheter). In conclusion, the optimal time for the SEMD estimation is at 15 % of RMS[subscript n], and at that time instant a median beat estimated from 4 beats is associated with a beat-to-beat variability of the SEMD location that is appropriate for catheter ablation procedures.National Institutes of Health (U.S.) (grant 1RO1HL103961

Electrophysiology

The outstanding evolution of recording techniques paved the way for better understanding of electrophysiological phenomena within the human organs, including the cardiovascular, ophthalmologic and neural systems. In the field of cardiac electrophysiology, the development of more and more sophisticated recording and mapping techniques made it possible to elucidate the mechanism of various cardiac arrhythmias. This has even led to the evolution of techniques to ablate and cure most complex cardiac arrhythmias. Nevertheless, there is still a long way ahead and this book can be considered a valuable addition to the current knowledge in subjects related to bioelectricity from plants to the human heart

Non-Invasive Electrocardiographic Imaging of Ventricular Activities: Data-Driven and Model-Based Approaches

Die vorliegende Arbeit beleuchtet ausgewählte Aspekte der Vorwärtsmodellierung, so zum Beispiel die Simulation von Elektro- und Magnetokardiogrammen im Falle einer elektrisch stillen Ischämie sowie die Anpassung der elektrischen Potentiale unter Variation der Leitfähigkeiten. Besonderer Fokus liegt auf der Entwicklung neuer Regularisierungsalgorithmen sowie der Anwendung und Bewertung aktuell verwendeter Methoden in realistischen in silico bzw. klinischen Studien