Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the leading cause of ischemic stroke and is the most commonly observed arrhythmia in clinical cardiology. Catheter ablation of AF, in which specific regions of cardiac anatomy associated with AF are intenionally injured to create scar tissue, has been honed over the last 15 years to become a relatively common and safe treatment option. However, the success of these anatomically driven ablation strategies, particularly in hearts that have been exposed to AF for extended periods, remains poor. AF induces changes in the electrical and structural properties of the cardiac tissue that further promotes the permanence of AF. In a process known as electroanatomical (EAM) mapping, clinicians record time signals known as electrograms (EGMs) from the heart and the locations of the recording sites to create geometric representations, or maps, of the electrophysiological properties of the heart. Analysis of the maps and the individual EGM morphologies can indicate regions of abnormal tissue, or substrates that facilitate arrhythmogenesis and AF perpetuation. Despite this progress, limitations in the control of devices currently used for EAM acquisition and reliance on suboptimal metrics of tissue viability appear to be hindering the potential of treatment guided by substrate mapping. In this research, we used computational models of cardiac excitation to evaluate param- eters of EAM that affect the performance of substrate mapping. These models, which have been validated with experimental and clinical studies, have yielded new insights into the limitations of current mapping systems, but more importantly, they guided us to develop new systems and metrics for robust substrate mapping. We report here on the progress in these simulation studies and on novel measurement approaches that have the potential to improve the robustness and precision of EAM in patients with arrhythmias. Appropriate detection of proarrhythmic substrates promises to improve ablation of AF beyond rudimentary destruction of anatomical targets to directed targeting of complicit tissues. Targeted treatment of AF sustaining tissues, based on the substrate mapping approaches described in this dissertation, has the potential to improve upon the efficacy of current AF treatment options

Decoding atrial fibrillation:Personalized identification and quantification of electropathology

Electrophysiological mapping-guided ablation strategies targeting atrial fibrillation (AF) have improved considerably over the past few years. However, it remains a major challenge to design effective strategies for particularly persistent AF. This can be partially explained by the inadequate understanding of the mechanisms and electropathological substrate underlying AF. Progression of AF is accompanied by structural and electrical remodeling, resulting in complex electrical conduction disorders, which is defined as electropathology. The severity of electropathology thus defines the stage of AF and is a major determinant of the effectiveness of AF therapy. In this thesis, features of electrophysiological properties of atrial tissue have been explored, developed and quantified during normal sinus rhythm, programmed electrical stimulation and AF. In addition, inter- and intra-individual variation in these quantified parameters has been examined in patients with and without prior episodes of AF. The most suitable objective parameters will aid in the identification of patients at risk for early onset or progression of AF. Part I of this thesis focusses on quantified electrogram features related to electropathology. In part II, abnormalities in wavefront propagation due to heterogeneous conduction properties were explored. Part III focusses on identification of post-operative AF and the relation with electropathology. In part IV of this thesis, some clinical implications of high-resolution mapping during cardiac surgery and application of quantified electrophysiological features are discussed

Multichannel Intracardiac Electrogram Analysis to Estimate the Depolarisation Wavefront Propagation: Supporting Diagnostics and Treatment of Atrial Fibrillation

Kardiale Arrhythmien sind Störungen des Herzrhythmus, welche von unregelmäßigem Herzschlag kommen. Vorhofflimmern ist die am weitesten verbreitete Herzrhythmusstörung und ist mit zunehmendem Alter weiter verbreitet. Thromboembolische Ereignisse und Störungen der Hämodynamik können als Begleiterscheinungen von Vorhofflimmern (AFib) auftreten und eine signifikant gesteigerte Morbidität und Mortalität zur Folge haben. Die Be- handlung von AFib erfolgt mit Medikamenten und zudem mit Hilfe der Katheterablation. Im Zuge der Ablation versuchen Ärzte die Bereiche arrhythmogenen Substrats zu lokalisieren. Danach werden kleine Ablationsnarben im Herzgewebe erzeugt, welche die Ausbreitung abnormaler elektrischer Erregungen im Herzen unterdrücken sollen. Die Erfolgsraten dieser Prozedur erreichen bis zu 70% nach zwei oder drei Ablationen. Im Zuge diese Arbeiten wurden die Regionen arrhythmogenen Substrats lokalisiert, und die Details der Erregungsausbreitung über dieses Substrat wurden bestimmt. Im Verlauf dieser Arbeit wurden klinische Daten, experimentelle Daten und Simulationen für die Analyse genutzt. Simulationen wurden genutzt um die lokale Aktivierungszeit (LAT) auf klinischen Anatomien zu bestimmen. Experimentelle Daten wurden mit Hilfe eines Elektrodenpatches von einem Hund herzen erfasst. Klinische Daten wurden mit Hilfe eines elektroanatomischen Mappingsystems im Rahmen klinischer Routineuntersuchungen aufgezeichnet. Die aufgezeichneten Daten wurden einer Vorverarbeitung unterzogen um messtechnische und geometrische Artefakte wie das ventrikuläre Fernfeld (VFF) oder hoch- und niederfrequentes Rauschen zu unterdrücken. Eine Vielzahl von Merkmalen wurden aus den vorbearbeiteten Daten gewonnen. Dies waren die Bestimmung des Stimulationsprokotolls, die Abschätzung der Dauer der fraktionierten Aktivität, die Korrelation der Morphologie, Spitzen-zu-Spitzen Amplitude, Bestimmung der QRS Komplexe, lokale Aktivierungszeit, die Bestimmung einer stabilen Katheterposition und die Markierung der Region des arrhythmogenen Substrats. Die Methode zur Bestimmung von Richtung und Geschwindigkeit der Erregungsausbreitung wurde bestimmt. Ein grafisches Nutzerinterface (GUI) wurde entwickelt zur Bestimmung der Ausbreitungsgeschwindigkeit und darauf basierender regionaler Analyse. Simulierte Daten wurden genutzt um die Leistungsfähigkeit der entwickelten Algorithmen zu beurteilen. Zur Simulation der LAT auf klinischen Anatomien wurde die fast marching Methode (FaMaS) genutzt. In diesen Simulationen war die goldene Wahrheit für eine Beurteilung der Parameterabschätzung bekannt. Ein umsichtiger und erfolgreicher Versuch wurde unternommen, um Muster und Geschwindig- keit der Erregungsausbreitung auf dem Vorhof zu bestimmen. Dies wurde auf Basis der LAT Zeit und stabiler Katheterpositionen durchgeführt. Interessante Regionen wurden zudem als wahrscheinliche Regionen eines arrhythmogenen Substrats im linken Vorhof markiert. Dies wurde auf Grundlage mehr als eines Merkmals und visueller Beurteilung deren Verteilung im Vorhof durchgeführt. Für die stimulierten Daten wurde die Aktivität der S1 und S2 Erregung verglichen um Änderungen in der Erregungsausbreitung abzuschätzen. Die Auswertung der experimentellen Daten wurde in Kooperation mit internationalen Part- nern aus den USA durchgeführt. Für verschiedene Szenarien wurden dabei Richtung und Muster der Erregungsausbreitung abgeschätzt. Die zeitliche und räumliche Informationen der vorgeschlagenen Method war dabei genau kontrolliert. Mit den Auswertemethoden aus dieser Arbeit können die wahrscheinliche Region des arrhythmogenen Substrats und der Verlauf der Erregungsausbreitung auf dem Vorhof für Vorhofflimmern und Vorhofflattern bestimmt werden. Diese können dem behandelnden Arzt bei der Planung der Ablationstherapie und erfolgreicher Durchführung helfen

A novel simplified approach to radiofrequency catheter ablation of idiopathic ventricular outflow tract premature ventricular contractions : from substrate analysis to results

Summary: Premature ventricular contractions (PVCs) are a common finding in the general population. The most common site of PVCs, in patients without structural heart disease, is the right ventricular outflow tract (RVOT) and the left ventricular outflow tract (LVOT). The prognosis associated with frequent PVCs depends on the presence of structural heart disease, so that idiopathic PVCs have been considered benign. Recently however, evidence has emerged that a small percentage of those patients may present with polymorphic ventricular tachycardia or ventricular fibrillation or evolve to left ventricular dysfunction. Catheter ablation is indicated for frequent symptomatic PVCs refractory to medical therapy or in case of patient’s preference. Currently, catheter ablation is based on activation mapping, confirmed by pace mapping match of at least 11/12 ECG leads between the paced beat and the PVC morphology. The acute success rate ranges from 78% to 100% according to the series, and to the location of the PVCs. Remote magnetic navigation presents as a good option for PVC ablation offering a high success rate with better safety profile. Intraprocedural low PVC burden occurs in up to 30% to 48% of cases, resulting in either, cancelation of the ablation procedure in up to 11% of patients, or reduction of the success rate from 85% to 56% when ablation is attempted with pace mapping only. Recently non-invasive mapping systems based on the electrocardiogram analysis (ECGI) have been developed. These systems are capable of mapping an arrhythmia with just one beat, instead of the usual point by point acquisition, being especially useful in the case of rare arrhythmias. EGGI also constitutes a valuable noninvasive tool for studying the mechanisms of arrhythmias. With this system we were able to demonstrate the presence of an electrophysiological substrate in the RVOT of patients with PVCs and apparently normal hearts. It has been accepted for many years that in patients with idiopathic PVCs from the outflow tracts, the RVOT displays normal electroanatomical mapping features and electrophysiological properties. However, we have demonstrated that there is a substrate for idiopathic PVCs in the form of low voltage areas (LVAs) that are not detected by usual image methods including cardiac magnetic resonance (CMR). We described for the first time, the association between the presence of ST-segment elevation in V1-V2 at the 2nd intercostal space (ICS) with LVAs across the RVOT and have proposed it as a non-invasive electrocardiographic marker of LVAs. We also identified the presence of abnormal potentials in intracardiac electrograms at the ablation site during diastole, after the T wave of the surface ECG that became presystolic during the PVC and were called diastolic potentials (DPs). In Chapter V we describe in detail the study that validated those findings and evaluated the feasibility and efficacy of a proposed simplified substrate approach, for catheter ablation in patients with low intraprocedural PVC burden, defined as less than 2 PVCs/min in the first 5 minutes of the procedure. It consists of fast mapping of the RVOT in sinus rhythm looking for LVAs and DPs, identifying the area, and finally performing a restricted activation map of the PVCs at that area. Briefly, it was a prospective single-arm clinical trial at two centers and three groups were studied: a) patients with low intraprocedural PVC burden that underwent ablation with the novel simplified approach method (study group); b) patients with low intraprocedural PVC burden that underwent ablation using the standard activation mapping method between 2016 and 2018 (historical group); and c) patients without PVCs, subjected to catheter ablation of supraventricular tachycardias that agreed to have a voltage map of the RVOT in sinus rhythm performed (validation group). The calculated sample size was 38 patients in each group. The exclusion criteria were as follows: known structural heart disease, history of sustained ventricular arrhythmias, inability to perform CMR, previous ablation and standard 12-Lead ECG with evidence of conduction or electrical disease or abnormal QRS morphology were excluded. Patients in the study and validation groups, had an ECG performed at the 2nd ICS and the RVOT mapped in sinus rhythm to assess the presence of ST-segment elevation, and LVAS and DPs, respectively. The results were compared between both groups. The study group and the historical group were compared regarding the efficacy of the new simplified ablation method in terms of abolishment of the PVCs and improvement of procedure speed and success rate. When available, ECGI was performed in the study group to evaluate the accuracy of the method to identify the site of origin of the PVCs. The ECGI was performed with two systems, the Amycard (EP Solutions SA, Switzerland) and the VIVO (Catheter Precision, NJ USA). The prevalence of LVAs and DPs was significantly higher in the study group in comparison with the validation group, respectively, 71% vs 11%, p<0.0001 and 87% vs 8%, p<0.0001. The ST-segment elevation was a good predictor of LVAS with a sensitivity of 87%, specificity of 96%, positive predictor value of 93% and negative predictor value of 91%. The novel simplified approach abolished the PVCs in 90% of the patients as opposed to 47% of patients in the historical group, p<0.0001. Only 74% patients underwent ablation in the historical group versus 100% in the study group. In patients that underwent ablation, the procedure time was significantly lower in the study group when comparing to the historical group, 130 (100-164) vs 183 (160-203) min, p<0.0001 and the success rate was significantly higher, 90% vs 64%, p=0.013. The recurrence rate in patients with a successful ablation after a median follow-up time of 1060 (574-1807) days, was not significantly different between both groups, Log-Rank=0.125 ECGI before ablation was performed in 17 patients in the study group. In 6 patients the ECGI was performed just with the Amycard system, in two just with the VIVO system and in 9 patients both systems were used. We found a good agreement between the ECGI and the invasive mapping, with the predicted site of origin being in the same or contiguous segment of the ablation site in 14/15 patients (93%) with the Amycard system and in 100% of patients with the VIVO system. When both systems were used simultaneously, the agreement between them was 8/9 (90%). So, in conclusion, the proposed approach partially based on substrate mapping including searching for LVAs and DPs, proved to be feasible, faster, and more efficient than the previous approach based exclusively on activation mapping. ST-segment elevation at the 2nd ICS proved to be a good predictor of LVAs. ECGI was a valuable tool to noninvasively predict the site of origin the arrhythmia

Eteisten sähkösignaali normaalin rytmin aikana terveen sydämen eteisvärinäkohtauksia saavilla

Atrial fibrillation (AF) is the most common tachyarrhythmia and is associated with substantial morbidity, increased mortality and cost. The treatment modalities of AF have increased, but results are still far from optimal. More individualized therapy may be beneficial. Aiming for this calls improved diagnostics. Aim of this study was to find non-invasive parameters obtained during sinus rhythm reflecting electrophysiological patterns related to propensity to AF and particularly to AF occurring without any associated heart disease, lone AF. Overall 240 subjects were enrolled, 136 patients with paroxysmal lone AF and 104 controls (mean age 45 years, 75% males). Signal measurements were performed by non-invasive magnetocardiography (MCG) and by invasive electroanatomic mapping (EAM). High-pass filtering techniques and a new method based on a surface gradient technique were adapted to analyze atrial MCG signal. The EAM was used to elucidate atrial activation in patients and as a reference for MCG. The results showed that MCG mapping is an accurate method to detect atrial electrophysiologic properties. In lone paroxysmal AF, duration of the atrial depolarization complex was marginally prolonged. The difference was more obvious in women and was also related to interatrial conduction patterns. In the focal type of AF (75%), the root mean square (RMS) amplitudes of the atrial signal were normal, but in AF without demonstrable triggers the late atrial RMS amplitudes were reduced. In addition, the atrial characteristics tended to remain similar even when examined several years after the first AF episodes. The intra-atrial recordings confirmed the occurrence of three distinct sites of electrical connection from right to left atrium (LA): the Bachmann bundle (BB), the margin of the fossa ovalis (FO), and the coronary sinus ostial area (CS). The propagation of atrial signal could also be evaluated non-invasively. Three MCG atrial wave types were identified, each of which represented a distinct interatrial activation pattern. In conclusion, in paroxysmal lone AF, active focal triggers are common, atrial depolarization is slightly prolonged, but with a normal amplitude, and the arrhythmia does not necessarily lead to electrical or mechanical dysfunction of the atria. In women the prolongation of atrial depolarization is more obvious. This may be related to gender differences in presentation of AF. A significant minority of patients with lone AF lack frequent focal triggers, and in them, the late atrial signal amplitude is reduced, possibly signifying a wider degenerative process in the LA. In lone AF, natural impulse propagation to LA during sinus rhythm goes through one or more of the principal pathways described. The BB is the most common route, but in one-third, the earliest LA activation occurs outside the BB. Susceptibility to paroxysmal lone AF is associated with propagation of the atrial signal via the margin of the FO or via multiple pathways. When conduction occurs via the BB, it is related with prolonged atrial activation. Thus, altered and alternative conduction pathways may contribute to pathogenesis of lone AF. There is growing evidence of variability in genesis of AF also within lone paroxysmal AF. Present study suggests that this variation may be reflected in cardiac signal pattern. Recognizing the distinct signal profiles may assist in understanding the pathogenesis of AF and identifying subgroups for patient-tailored therapy.Eteisvärinä on yleisin hoitoa vaativa rytmihäiriö ja siihen liittyy merkittävää sairastuvuutta, lisääntynyttä kuolleisuutta ja kustannuksia. Eteisvärinän hoitovaihtoehdot ovat lisääntyneet, mutta hoidon tulokset ovat huonosti ennakoitavissa eivätkä hoidot edelleenkään tehoa hyvin. Tässä tutkimuksessa selvitettiin eteisvärinän ilmentymän ja sähköfysiologisten piirteiden yhteyttä rakenteellisesti terveen sydämen kohtauksellisessa eteisvärinässä. Tavoitteena oli löytää kajoamattomasti mitattavia muuttujia, joita voitaisiin käyttää eteisvärinäsairauden kliinisten alaryhmien sähköfysiologisten piirteiden, kohtauksiin johtavien tekijöiden ja taudinkuvan tunnistamiseen. Tutkittavana oli 136 potilasta ja 104 tervettä koehenkilöä. Pääasiallisina menetelminä käytettiin kajoamatonta magnetokardiografiaa (MKG) ja sydämen sisäistä elektroanatomista kartoitusta. MKG mittaa sydämen sähköisen aktivaation aiheuttamia magneettikenttiä kehon pinnalta ja sen etuna sydänsähkökäyrään (EKG) verrattuna on mm. suurempi herkkyys kehon pinnan suuntaisille virroille. Pääosa käytetyistä signaalianalyysimenetelmistä kehitettiin tutkimuksen puitteissa. Tutkimuksessa osoitettiin ensimmäistä kertaa eroa eteissignaalin hienorakenteessa rakenteellisesti terveen sydämen eteisvärinän kliinisten alamuotojen välillä. Potilailla, joilla eteisvärinän alku liittyi eteislisälyöntisyyteen, ns. paikallisalkuinen eteisvärinä, normaalin rytmin aikainen eteissignaali oli lievästi pidentynyt, mutta sen korkeus oli normaali. Potilailla, joilla ei todettu lisälyöntisyyttä, eteissignaalin kesto oli normaali, mutta signaalin loppuosa oli madaltunut. Löydös viittaa siihen, että ei-paikallisalkuisessa eteisvärinässä eteiskudos saattaa olla alttiimpi eteisvärinälle kuin paikallisalkuisessa eteisvärinässä, jossa pääasiallinen rytmihäiriömekanismi olisi lisälyöntisyys. Tutkimuksessa todettiin myös, että naisilla eteisten aktivaatiosignaali oli potilailla selvästi pidempi kuin terveillä, mutta miehillä vastaava ero oli marginaalinen. Tämä saattaa liittyä sukupuolten väliseen eroon eteisvärinän ilmaantumisessa. Sydämensisäisissä kartoituksissa normaalirytmin aikaista signaalin johtumista oikeasta eteisestä vasempaan tutkittiin suurimmassa julkaistussa potilassarjassa. Tulokset vahvistivat aiempia käsityksiä johtumisreiteistä, mutta toivat esiin myös huomattavan määrän potilaita, joilla johtuminen tapahtui rinnakkaisesti useita reittejä pitkin. Tämä saattaa olla merkityksellistä näiden potilaiden rytmihäiriöalttiudessa. Tutkimus osoitti myös, että eteisten välisiä johtumistapoja voidaan tunnistaa kajoamattomasti MKG:lla. Pintamittaukset laajemmassa potilasaineistosta ja terveillä tukivat sydämen sisäisistä mittauksista saatua käsitystä että nimenomaan useita reittejä pitkin tapahtuva johtuminen voi olla eteisvärinälle altistava tekijä. Tutkimus antaa uutta tietoa rakenteellisesti terveen sydämen eteisvärinän piirteistä, vahvistaa käsitystä eteisvärinän syntymekanismien moninaisuudesta ja osoittaa että näitä mekanismeja voidaan mahdollisesti tunnistaa myös pintamittausmenetelmillä. Kehitetyt MKG menetelmät ovat lupaavia tekniikoita eteisvärinätaudin alamuotojen tunnistamisessa tutkimusta ja myös kliinistä taudinmääritystä varten. Parantunut taudinmääritys voi auttaa kohdentamaan eri hoitotapoja tehokkaammin niistä hyötyville potilaille

A Computational Based Approach for Non-invasive Localization of Atrial ectopic foci

Las arritmias auriculares son las arritmias cardı́acas más comunes, afectan a seis millones de personas en Europa e imponen una enorme carga sanitaria en la sociedad. Las nuevas tecnologı́as médicas están ayudando a los electrofisiólogos a adaptar el tratamiento a cada paciente de diferentes maneras. Por ejemplo, la resonancia magnética (MRI) permite evaluar la distribución espacial de la fibrosis auricular; los mapas electroanatómicos (EAM) permiten obtener una caracterización eléctrica de los tejidos en tiempo real; Las imágenes electrocardiográficas (ECGI) permiten estudiar la actividad eléctrica cardı́aca de forma no invasiva; y la ablación por radiofrecuencia (RFA), permite eliminar el tejido patológico en el corazón que desencadena o mantiene una arritmia. A pesar del acceso a tecnologı́as avanzadas y de la existencia de guı́as clı́nicas bien desarrolladas para el tratamiento de las arritmias auriculares, las tasas de éxito del tratamiento a largo plazo siguen siendo bajas, debido a la complejidad de la enfermedad. Por lo tanto, existe una necesidad imperiosa de mejorar los resultados clı́nicos en beneficio de los pacientes y el sistema de salud. Se podrı́an emplear modelos biofı́sicos detallados de las aurı́culas y el torso para integrar todos los datos del paciente en un solo modelo 3D de referencia capaz de reproducir los complejos patrones de activación eléctrica observados en experimentos y la clı́nica. Sin embargo, existen algunas limitaciones relacionadas con la dificultad de construir tales modelos para cada paciente o realizar un número considerable de simulaciones para planificar la terapia óptima de RFA. Teniendo en cuenta todas esas limitaciones, proponemos utilizar modelos biofı́sicos detallados y simulaciones como una herramienta para entrenar sistemas de aprendizaje automático, para lo cual dispondrı́amos de todos los datos y variables del problema, que serı́an imposibles de obtener en un entorno clı́nico real. Por lo tanto, podemos realizar cientos de simulaciones electrofisiológicas, considerando una variedad de escenarios y patologı́as comunes, y entrenar un sistema que deberı́a ser capaz de reconocerlos a partir de un conjunto limitado de datos no invasivos del paciente, como un electrocardiograma (ECG), o mapa de potencial de superficie corporal (BSPM).Abstract Atrial arrhythmias are the most common cardiac arrhythmia, affecting six million people in Europe and imposing a huge healthcare bur- den on society. New technologies are helping electrophysiologists to tailor the treatment to each patient in different ways. For instance, magnetic resonance imaging (MRI) allows to assess the spatial distribution of atrial fibrosis; electro-anatomical maps (EAM) permit to obtain an electrical char- acterization of tissue in real-time; electrocardiographic imaging (ECGI) al- lows to study cardiac electrical activity non-invasively; and radiofrequency ablation (RFA), allows to eliminate pathological tissue in the heart that is triggering or sustaining an arrhythmia. Despite the access to advanced technologies and well-developed clinical guidelines for the management of atrial arrhythmia, long-term treatment success rates remain low, due to the complexity of the disease. Therefore, there is a compelling need to improve clinical outcomes for the benefit of patients and the healthcare system. Detailed biophysical models of the atria and torso could be employed to integrate all the patient data into a single reference 3D model able to re- produce the complex electrical activation patterns observed in experiments and clinics. However, there are some limitations related to the difficulty of building such models for each patient, or performing a substantial number of simulations to plan the optimal RFA therapy. Considering all those lim- itations, we propose to use detailed biophysical models and simulations as a tool to train machine learning systems, for which we have all the ground- truth data which would be impossible to obtain in a real clinical setting. Therefore, we can perform hundreds of electrophysiology simulations, con- sidering a variety of common scenarios and pathologies, and train a system that should be able to recognize them from a limited set of non-invasive pa- tient data, such as an electrocardiogram (ECG), or a body surface potential map (BSPM)

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

Mapping of Atrial Fibrillation: Back to the Drawing Board

New high-resolution mapping approach for mapping of atrial fibrillation in patients during cardiac surgery and the discovery of asynchronous activation of the endocardial and epicardial layers of the atria during atrial fibrillation