Early Results on the Utilisation of ECG-Imaging during Catheter Ablation Procedures for Prediction of Sites of Earliest Activation during Re-entrant Ventricular Tachycardia

Success rate of ventricular tachycardia (VT) ablation remains sub-optimal. Current technology does not allow fast and accurate delineation of the ablation target. Noninvasive panoramic ECG-imaging (ECGI) offers the possibility of studying the interaction between arrhythmogenic substrate and earliest sites of activation during VT to improve ablation strategies. ECGI mapping (CardioInsight, Medtronic) was performed in 5 patients undergoing VT ablation. Ventricular pacing was delivered from the RV and three indices were measured at each ventricular site to map susceptibility to arrhythmia initiation: Re-entry vulnerability index (RVI), local dispersion of AT (∆AT) and local dispersion of repolarization (∆ARI). Regions of high susceptibility were defined as those corresponding to the bottom 5% of RV I and the upper 5% of ∆AT and ∆ARI. Morphologically distinct VTs were analyzed to measure the AT sequence and localize the region of earliest epicardial activation (AT < 5 ms). In total, 20 VTs were analyzed (4.0 ± 1.2 per patient). The minimum distance between the region of high vulnerability and the region of earliest AT during VT was 5.6 ± 8.6 mm for RV I, 6.1 ± 10.8 mm for ∆AT and 12.8 ± 22.4 mm for ∆ARI (P > 0.13 for all pair-wise comparison). The vulnerable region presented at least partial overlap with the region of earliest activation during VT in 50%, 55% and 50% of all VTs for RV I, ∆AT and ∆ARI, respectively. These early data confirm the mechanistic link between markers of arrhythmogenic risk and VT initiation and suggest that ECGI could be potentially used for targeting ablation in non-inducible or hemodynamically non-tolerated VTs

Limitations and Challenges in Mapping Ventricular Tachycardia: New Technologies and Future Directions

Recurrent episodes of ventricular tachycardia in patients with structural heart disease are associated with increased mortality and morbidity, despite the life-saving benefits of implantable cardiac defibrillators. Reducing implantable cardiac defibrillator therapies is important, as recurrent shocks can cause increased myocardial damage and stunning, despite the conversion of ventricular tachycardia/ventricular fibrillation. Catheter ablation has emerged as a potential therapeutic option either for primary or secondary prevention of these arrhythmias, particularly in post-myocardial infarction cases where the substrate is well defined. However, the outcomes of catheter ablation of ventricular tachycardia in structural heart disease remain unsatisfactory in comparison with other electrophysiological procedures. The disappointing efficacy of ventricular tachycardia ablation in structural heart disease is multifactorial. In this review, we discuss the issues surrounding this and examine the limitations of current mapping approaches, as well as newer technologies that might help address them

Non-Invasive Electrocardiographic Mapping of Arrhythmia and Arrhythmogenic substrate in the Human Ventricle.

PhD Theses.The ablation of ventricular tachycardia often involves mapping when the arrhythmia is ongoing. This is often limited by haemodynamic instability. Non-invasive electrocardiographic mapping (ECGI) may aid in the mapping process by allowing expedient localisation. However, insufficient testing of this technology against ground truth data has been conducted. Furthermore, the system could have utility in detection of arrhythmogenic substrate. Current clinical practice uses echocardiography to risk stratify patients for implantation of intracardiac defibrillators (ICDs). Invasive epicardial electrogram data was collected in 8 patients. Activation and repolarisation times were compared to ECGI derived data showing modest correlation. A detailed analysis of ventricular tachycardia sites of origin in the heart was elucidated using validated electrophysiological techniques. These were compared to ECGI derived data in 18 patients, showing better accuracy than the 12 lead ECG with a resolution of ~2.2cm suggesting it may be a useful adjunctive tool in mapping unstable VT. ECGI derived data collected during sinus rhythm was compared to invasive electrogram maps in 16 patients. The capacity of ECGI to localise scar showed modest accuracy. ECGI and Cardiac MRI scans were performed in 21 patients with cardiac amyloidosis. ECGI showed cardiac amyloidosis to be associated with both ventricular conduction and repolarization abnormalities, supporting the hypothesis that arrhythmic mechanisms may be linked to mortality in this condition

Methods for Arrhythmogenic Substrate Identification and Procedural Improvements for Ventricular Arrhythmias.

Ventricular arrhythmias (VA) are a frequent precursor to sudden cardiac death (SCD) in patients with structural heart disease (SHD). Patients with SHD are at risk of recurrent ventricular tachycardia (VT), which generally occurs due to re-entry within and around the presence of an arrhythmogenic scar. Therefore, scarred myocardium forms the necessary substrate for arrhythmogenesis to occur. A scar may occur due to obstructive coronary artery disease, causing ischaemic cardiomyopathy (ICM), or from cardiac injury due to several other causes, including inflammatory, infiltrative, toxin-mediated, or genetic heart disease, termed non-ischaemic cardiomyopathy (NICM). An implantable cardioverting defibrillator (ICD) can abort SCD from recurrent VAs. However, they do not stop VAs from occurring in the first place. Anti-arrhythmic drugs (AADs) may reduce the frequency and burden of VAs but have limited efficacy. Some have a narrow therapeutic window or the potential for multiorgan toxicity and can be poorly tolerated. Catheter ablation (CA) is a class I indication for treating sustained monomorphic VT refractory to AADs. CA reduces VT burden, the number of defibrillator therapies, greater freedom from recurrent ventricular arrhythmia, and improves quality of life. However, recurrences can be experienced in up to 50% of patients with SHD-related VT. Some reasons for the failure of CA include reliable identification of critical components of substrate that can harbour VAs both in sinus rhythm and during ongoing VT using electroanatomic mapping (EAM) and imaging techniques, as well as limitations in assessing intraprocedural endpoints. Further refinement of electroanatomic mapping techniques is required to improve the efficacy of CA. This thesis aims to expand on current techniques for substrate identification and methods to improve the efficacy of VA ablation procedures

The action potential duration and repolarization of the human ventricle and its relation to the body surface ECG

Repolarization dispersion has been associated with increased risk of cardiac arrhythmia in animal studies, but whether it is present in humans and how its manifests on the surface ECG is unknown. This thesis aimed to bridge the gap between our basic cellular and intracardiac understanding of cardiac electrical activity with the surface ECG focusing specifically on cardiac repolarization and the surface ECG. Restitution studies in humans with structurally normal and abnormal hearts were performed, looking at transmural and regional gradients of repolarization. The data were then analysed to assess the association of intracardiac repolarization with the surface T-wave. Finally a novel non-invasive ECG (ECGI) was used to study the electrical substrate in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). In normal human heart restitution studies epicardial APD was shorter than endocardial APD, with smaller differences in the apicobasal orientation. It was found that, local repolarization times in the right and left ventricle occur along the upslope of the body surface T-wave in leads V1-V3 and V5,V6 and Lead-I respectively; and the difference between the end of the upslope in V1 and V6 provides a good representation of right to left dispersion of repolarization. In patients with structurally abnormal hearts myocardial scar, regardless of pathology, resulted in prolonged APD compared to normal healthy tissue diminishing transmural gradients of APD and resulting in localised transmural dispersion of repolarization. Finally ECGI characterised the electrophysiological substrate in ARVC, demonstrating prolonged APD in these patients compared to control patients. ECGI was able to demonstrate the presence of electrophysiological changes before changes were visible on cardiac MRI. In conclusion, this work shows that APD gradients are present in the intact human heart, and can be demonstrated both using contact electrophysiological mapping and on methods that incorporate the body surface ECG

Advances in Electrocardiograms

Electrocardiograms have become one of the most important, and widely used medical tools for diagnosing diseases such as cardiac arrhythmias, conduction disorders, electrolyte imbalances, hypertension, coronary artery disease and myocardial infarction. This book reviews recent advancements in electrocardiography. The four sections of this volume, Cardiac Arrhythmias, Myocardial Infarction, Autonomic Dysregulation and Cardiotoxicology, provide comprehensive reviews of advancements in the clinical applications of electrocardiograms. This book is replete with diagrams, recordings, flow diagrams and algorithms which demonstrate the possible future direction for applying electrocardiography to evaluating the development and progression of cardiac diseases. The chapters in this book describe a number of unique features of electrocardiograms in adult and pediatric patient populations with predilections for cardiac arrhythmias and other electrical abnormalities associated with hypertension, coronary artery disease, myocardial infarction, sleep apnea syndromes, pericarditides, cardiomyopathies and cardiotoxicities, as well as innovative interpretations of electrocardiograms during exercise testing and electrical pacing

MRI-guided non-invasive epicardial mapping in patients with implanted pacing devices

Developing patient-specific 3D heart models to non-invasively localize arrhythmic foci. My research focussed on the application of MRI and complex electrocardiography in patients with MRI conditional pacemaker systems

Cost-effectiveness analysis of radiofrequency ablation versus drugs for the treatment of a trial fibrillation in the South African population

Thesis (PhD)--Stellenbosch University, 2021.ENGLISH SUMMARY : Atrial fibrillation is the most commonly found and sustained arrhythmia. It affects about 1% of the total population and is found in more than one in ten in the elderly. The prevalence is increasing with the aging population. Patients with atrial fibrillation are at an increased risk of heart failure and all-cause mortality, and have a fivefold increased risk of stroke. Atrial fibrillation is associated with debilitating symptoms and an impaired quality of life. The restoration and maintenance of sinus rhythm is favourable and the current guidelines recommend the use of both rate and rhythm control strategies, which involve the prescription of anti-arrhythmic drug therapy. These anti-arrhythmic drugs are frequently ineffective, with large studies showing that atrial fibrillation returns in as many as 85% of patients within one year. These drugs are also associated with adverse events, occasionally serious, which may lead to hospitalisation. Catheter ablation (a minimally invasive procedure), has over the past decade revolutionised the treatment of atrial fibrillation. The 2010 European Society of Cardiology guidelines recommend catheter ablation for paroxysmal atrial fibrillation as a class IIa recommendation with level of evidence “A”. Current literature indicates that patients with atrial fibrillation who undergo pulmonary vein ablation have a significantly lower risk of death, stroke and dementia compared to patients with atrial fibrillation who are not treated with ablation, while stroke and dementia is similar to that of the general population. This study used a decision tree analysis, a Markov model and Monte Carlo simulation to calculate the cost-effectiveness of catheter ablation versus commonly used anti-arrhythmic drugs for the treatment of paroxysmal atrial fibrillation. Input into the model was founded on an extensive literature review, interviews with local electrophysiologists and a sample of real patient data, which examined the costs associated with among others, the length of hospital stay and the cost of the procedure. The model simulated 1 000 patients receiving either pulmonary vein isolation through radiofrequency ablation or anti-arrhythmic drugs and the following variables were measured, QALYs, average cost, incremental costs, average effectiveness, incremental effectiveness, average length of stay in hospital for complications, relative risk of death for radiofrequency catheter ablation versus anti-arrhythmic drugs and also the net monetary benefits. A total of fourteen variables were tested and sensitivity analyses were performed on each. It was found that in all but two cases, pulmonary vein isolation with radiofrequency catheter ablation dominated over anti-arrhythmic drug therapy as being more cost-effective for the management of paroxysmal atrial fibrillation. Finally, it was determined that pulmonary vein isolation with radiofrequency catheter ablation should be considered as a first line therapy for patients with paroxysmal atrial fibrillation in South Africa.AFRIKAANSE OPSOMMING : Atriale fibrillasie is die mees algemene en volgehoue aritmie. Dit raak ongeveer 1% van die bevolking. Onder bejaardes is die voorkoms egter soveel as 10%, wat beteken dat die toestand toeneem in verhouding met die verouderende bevolking. Atriale fibrillasie verhoog ’n pasiënt se risiko vir beroerte vyfvoudig, tesame met hartversaking en alle-oorsake mortaliteit. Die toestand se uitmergelende simptome verlaag ook lewenskwaliteit. Die kanse vir die herstel en instandhouding van sinusritme is positief. Bestaande riglyne beveel dus die gebruik van ritme- of spoed-beheer medikasie aan, wat beteken dat anti-aritmie medikasie voorgeskryf word. Dit is egter dikwels oneffektief en verskeie omvattende studies het bewys dat tot 85% van die pasiënte binne een jaar weer ‘n ritmestoornis ervaar. Hierdie middels word ook dikwels verbind met newe-effekte wat ernstig mag wees en tot hospitalisasie mag lei. Kateterablasie (’n minimaal-ingrypende prosedure) het oor die afgelope dekade die behandeling van atriale fibrillasie onherkenbaar verander. Vir pasiënte wat hoogs simptomaties, of paroksismaal, is ten spyte van optimale terapie, beveel die Europese Vereniging van Kardiologie se 2010 riglyne ablasie aan as ‘n klas IIa aanbeveling. Huidige literatuur dui op ‘n laer koers van sterftes, beroerte en demensie onder atriale fibrillasie pasiënte wat atriale fibrillasie ablasie ondergaan, in vergelyking met pasiënte wat met medikasie behandel word. Eersgenoemde het inteendeel dieselfde risikoprofiel as die algemene bevolking. Hierdie studie gebruik ’n keuse-boom analisemodel en ’n waarskynlikheid-Markov model met Monte Carlo-simulasie om die koste-effektiwiteit van kateterablasie met anti-aritmiese medikasie te vergelyk in die behandeling van pasiënte met paroksismale atriale fibrillasie. Die data wat in die model gebruik word, is gebaseer op ’n uitgebreide literatuurstudie, onderhoude met elektrofisioloë, en ’n steekproef van pasiëntdata, en ondersoek, onder andere, die duur van hopitaalverblyf en die koste verbonde aan die prosedure. Die studie maak gebruik van ’n simulasiemodel waar 1 000 pasiënte óf ablasie óf medikasie ontvang het. Die volgende veranderlikes is gemeet: QALYs, gemiddelde koste, toenemende koste, gemiddelde doeltreffendheid, toenemende doeltreffendheid, gemiddelde hospitaalverblyf tydens komplikasies, die relatiewe riskio van sterfte en monetêre voordele. Veertien veranderlikes is getoets en aan sensitiwiteitsanalises onderwerp. In dertien uit die viertien analises was kateterablasie meer koste-effektief as anti-aritmiese medikasie in die behandeling en bestuur van anti-aritmiese medikasie. Die studie kom dus tot die gevolgtrekking dat kateterablasie oorweeg moet word as voorkeurterapie vir pasiënte met paroksismale atriale fibrillasie in Suid-Afrika.Doctora

Modélisation de l’activité électrique des oreillettes avant et après ablation par cathéter

- Réalisé au centre de recherche de l'hospital du Sacré-Coeur de Montréal. - Programme conjoint entre Université de Montréal et École Polytechnique de Montréal.La fibrillation auriculaire (FA) est la forme d’arythmie la plus fréquente chez les êtres humains. Les mécanismes qui gouvernent l’initiation et les manifestations de cette maladie sont complexes, de nature dynamique, incluant des interactions à travers multiples échelles temporelles et spatiales dans les oreillettes. Ceci conduit très souvent à des manifestations imprévisibles et à des phénomènes qui émergent à l’échelle de l’organe, et qui se reflètent à l’échelle de tout le torse. Pour remédier à ce problème, on peut effectuer une ablation par cathéter, qui consiste à créer sur le tissu auriculaire des lésions linéaires qui bloquent et contraignent la propagation électrique. Parfois, ces lignes se reconnectent quelque temps après l’intervention, ce qui mène à des récidives, nécessitant ainsi une nouvelle intervention. Le but de ce projet est de modéliser un suivi de l’onde P post-opératoire pour détecter de manière non-invasive la reconnexion des lignes d’ablation et ainsi prédire les récidives de fibrillation auriculaire. À l’aide d’un modèle mathématique des oreillettes et du thorax, les ondes P sont simulées avant et après ablation, ainsi qu’après reconnexion de certaines lignes d’ablation. Les résultats montrent que la morphologie et les caractéristiques de l’onde P, ainsi que la carte d’activation sont affectées significativement par l’ablation et les reconnexions subséquentes. Ces différences sont plus facilement détectables lorsque les reconnexions naissent sur la veine pulmonaire inférieure gauche. Les changements sont plus importants pour les électrodes placées sur certaines zones du torse, notamment dans le dos. Ces nouvelles données aident actuellement à la conception d’une étude clinique pour valider l’approche.Atrial fibrillation (AF) is the most common form of arrhythmia in humans. The mechanisms governing the initiation and manifestations of that disease are complex, dynamic in nature, including interactions across multiple spatial and temporal scales in the atria. This often leads to unpredictable manifestations and phenomena that arise at the level of the organ, and are reflected across the entire torso. To remedy that problem, catheter ablation can be carried out, which consists in creating linear lesions which block and force the electrical propagation in the atrial tissue. Sometimes these lines reconnect after the procedure, which leads to atrial fibrillation recurrence, thus requiring a new intervention. The purpose of this work is to model the monitoring of the postoperative P wave to detect non-invasively the reconnection of ablation lines and to predict atrial fibrillation recurrences. Using a mathematical model of the atria and thorax, the P waves are simulated before and after ablation, as well as after reconnection of some ablation lines. The results show that the morphology and the characteristics of the P wave as well as the activation map are significantly affected by the ablation lines and the subsequent reconnections. These differences are more easily detected when reconnections arise on the left inferior pulmonary vein. The changes are most important in electrodes placed in certain areas of the torso, notably in the back. These new data are helping to plan a clinical study to validate the approach