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

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations

Background: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. Methods: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. Results: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. Conclusion: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's

The year in cardiology: arrhythmias and pacing.

During this last year, there has been much progress with regard to anticoagulant and ablation therapy for atrial fibrillation (AF). Apart from recently issued European Society of Cardiology Guidelines for the management of patients with supraventricular arrhythmias, there has been little progress in research in this field. Ventricular arrhythmias and device therapy have seen modest progress

Integrated Cardiac Electromechanics: Modeling and Personalization

Cardiac disease remains the leading cause of morbidity and mortality in the world. A variety of heart diagnosis techniques have been developed during the last century, and generally fall into two groups. The first group evaluates the electrical function of the heart using electrophysiological data such as electrocardiogram (ECG), while the second group aims to assess the mechanical function of the heart through medical imaging data. Nevertheless, the heart is an integrated electromechanical organ, where its cyclic pumping arises from the synergy of its electrical and mechanical function which requires first to be electrically excited in order to contract. At the same time, cardiac electrical function experiences feedback from mechanical contraction. This inter-dependent relationship determines that neither electrical function nor mechanical function alone can completely reflect the pathophysiological conditions of the heart. The aim of this thesis is working towards building an integrated framework for heart diagnosis through evaluation of electrical and mechanical functions simultaneously. The basic rational is to obtain quantitative interpretation of a subject-specific heart system by combining an electromechanical heart model and individual clinical measurements of the heart. To this end, we first develop a biologically-inspired mathematical model of the heart that provides a general, macroscopic description of cardiac electromechanics. The intrinsic electromechanical coupling arises from both excitation-induced contraction and deformation-induced mechano-electrical feedback. Then, as a first step towards a fully electromechanically integrated framework, we develop a model-based approach for investigating the effect of cardiac motion on noninvasive transmural imaging of cardiac electrophysiology. Specifically, we utilize the proposed heart model to obtain updated heart geometry through simulation, and further recover the electrical activities of the heart from body surface potential maps (BSPMs) by solving an optimization problem. Various simulations of the heart have been performed under healthy and abnormal conditions, which demonstrate the physiological plausibility of the proposed integrated electromechanical heart model. What\u27s more, this work presents the effect of cardiac motion to the solution of noninvasive estimation of cardiac electrophysiology and shows the importance of integrating cardiac electrical and mechanical functions for heart diagnosis. This thesis also paves the road for noninvasive evaluation of cardiac electromechanics

Three-dimensional Multiscale Modelling and Simulation of Atria and Torso Electrophysiology

A better understanding of the electrical activity of the heart under physiological and pathological conditions has always been key for clinicians and researchers. Over the last years, the information in the P-wave signals has been extensively analysed to un-cover the mechanisms underlying atrial arrhythmias by localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the P-wave signals or body surface poten-tial maps are still far from being completely understood. Multiscale anatomical and functional models of the heart are a new technological framework that can enable the investigation of the heart as a complex system. This thesis is centred in the construction of a multiscale framework that allows the realistic simulation of atrial and torso electrophysiology and integrates all the anatom-ical and functional descriptions described in the literature. The construction of such model involves the development of heterogeneous cellular and tissue electrophysiolo-gy models fitted to empirical data. It also requires an accurate 3D representation of the atrial anatomy, including tissue fibre arrangement, and preferential conduction axes. This multiscale model aims to reproduce faithfully the activation of the atria under physiological and pathological conditions. We use the model for two main applica-tions. First, to study the relationship between atrial activation and surface signals in sinus rhythm. This study should reveal the best places for recording P-waves signals in the torso, and which are the regions of the atria that make the most significant contri-bution to the body surface potential maps and determine the main P-wave characteris-tics. Second, to spatially cluster and classify ectopic atrial foci into clearly differenti-ated atrial regions by using the body surface P-wave integral map (BSPiM) as a bi-omarker. We develop a machine-learning pipeline trained from simulations obtained from the atria-torso model aiming to validate whether ectopic foci with similar BSPiM naturally cluster into differentiated non-intersected atrial regions, and whether new BSPiM could be correctly classified with high accuracy.En la actualidad, una mejor compresión de la actividad eléctrica del corazón en condi-ciones fisiológicas y patológicas es clave para médicos e investigadores. A lo largo de los últimos años, la información derivada de la onda P se ha utilizado para intentar descubrir los mecanismos subyacentes a las arritmias auriculares mediante la localiza-ción de focos ectópicos y rotores de alta frecuencia. Sin embargo, la relación entre la activación de distintas regiones auriculares y las características tanto de las ondas P como de la distribución de potencial en la superficie del torso está lejos de entenderse completamente. Los modelos cardíacos funcionales y anatómicos son una nueva he-rramienta que puede facilitar la investigación relativa al corazón entendido como sis-tema complejo. La presente tesis se centra en la construcción de un modelo multiescala para la simula-ción realista de la electrofisiología cardíaca tanto a nivel auricular como de torso, integrando toda la información anatómica y funcional disponible en la literatura. La construcción de este modelo implica el desarrollo, en base a datos experimentales, de modelos electrofisiológicos heterogéneos tanto celulares como tisulares. Así mismo, es imprescindible una representación tridimensional precisa de la anatomía auricular, incluyendo la dirección de fibras y los haces de conducción preferentes. Este modelo multiescala busca reproducir fielmente la activación auricular en condiciones fisiológi-cas y patológicas. Su uso se ha centrado fundamentalmente en dos aplicaciones. En primer lugar, estudiar la relación entre la activación auricular en ritmo sinusal y las señales en la superficie del torso. Este estudio busca definir la mejor ubicación para el registro de las ondas P en el torso así como determinar aquellas regiones auriculares que contribuyen fundamentalmente a la formación y distribución de potenciales super-ficiales así como a las características de las ondas P. En segundo lugar, agrupar y cla-sificar espacialmente los focos ectópicos en regiones auriculares claramente diferen-ciables empleando como biomarcador los mapas superficiales de integral de la onda P (BSPiM). Se ha desarrollado para ello una metodología de aprendizaje automático en la que las simulaciones obtenidas con el modelo multiescala aurícula-torso sirven de entrenamiento, permitiendo validar si los focos ectópicos cuyos BSPiMs son similares se agrupan de forma natural en regiones auriculares no intersectadas y si BSPiMs nue-vos podrían ser clasificados prospectivamente con gran precisión.Avui en dia, una millor comprenssió de l'activitat elèctrica del cor en condicions fisio-lògiques i patològiques és clau per a metges i investigadors. Al llarg dels últims anys, la informació derivada de l'ona P s'ha utilitzat per intentar descobrir els mecanismes subjacents a les arítmies auriculars mitjançant la localització de focus ectòpics i rotors d'alta freqüència. No obstant això, la relació entre l'activació de diferents regions auri-culars i les característiques tant de les ones P com de la distribució de potencial en la superfície del tors està lluny d'entendre's completament. Els models cardíacs funcionals i anatòmics són una nova eina que pot facilitar la recerca relativa al cor entès com a sistema complex. La present tesi es centra en la construcció d'un model multiescala per a la simulació realista de la electrofisiologia cardíaca tant a nivell auricular com de tors, integrant tota la informació anatòmica i funcional disponible en la literatura. La construcció d'aquest model implica el desenvolupament, sobre la base de dades experimentals, de models electrofisiològics heterogenis, tant cel·lulars com tissulars. Així mateix, és imprescindible una representació tridimensional precisa de l'anatomia auricular, in-cloent la direcció de fibres i els feixos de conducció preferents. Aquest model multies-cala busca reproduir fidelment l'activació auricular en condicions fisiològiques i pa-tològiques. El seu ús s'ha centrat fonamentalment en dues aplicacions. En primer lloc, estudiar la relació entre l'activació auricular en ritme sinusal i els senyals en la superfí-cie del tors. A més a més, amb aquest estudi també es busca definir la millor ubicació per al registre de les ones P en el tors, així com, determinar aquelles regions auriculars que contribueixen fonamentalment a la formació i distribució de potencials superfi-cials a l'hora que es caracteritzen les ones P. En segon lloc, agrupar i classificar espa-cialment els focus ectòpics en regions auriculars clarament diferenciables emprant com a biomarcador els mapes superficials d'integral de l'ona P (BSPiM). És per això que s'ha desenvolupat una metodologia d'aprenentatge automàtic en la qual les simulacions obtingudes amb el model multiescala aurícula-tors serveixen d'entrenament, la qual cosa permet validar si els focus ectòpics, llurs BSPiMs són similars, s'agrupen de for-ma natural en regions auriculars no intersectades i si BSPiMs nous podrien ser classifi-cats de manera prospectiva amb precisió.Ferrer Albero, A. (2017). Three-dimensional Multiscale Modelling and Simulation of Atria and Torso Electrophysiology [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/88402TESI