New perspectives in catheter ablation for atrial fibrillation Towards a better treatment to reach better outcomes

The overall aim of the studies presented in this thesis is to elucidate whether there is still room for improvement in the field of catheter ablation for AF either paroxysmal and persistent, and the following chapters will guide the reader in a virtual path that addresses this issue

Endocardial activation mapping of human atrial fibrillation

Successful ablation of arrhythmias depends upon interpretation of the mechanism. However, in persistent atrial fibrillation (AF) ablation is currently directed towards the mechanism that initiates paroxysmal AF. We sought to address the hypothesis that atrial activation patterns during persistent AF may help determine the underlying mechanism. Activation mapping of AF wavefronts is labor intensive and often restricted to short time segments in limited atrial locations. RETRO-Mapping was developed to identify uniform wavefronts that occur during AF, and summate all wavefront vectors on to an orbital plot. Uniform wavefronts were mapped using RETRO-Mapping during sinus rhythm, atrial tachycardia, and atrial fibrillation, and validated against detailed manual analysis of the same wavefronts with conventional isochronal mapping. RETRO-Mapping was found to have comparable accuracy to isochronal mapping. RETRO-Mapping was then used to investigate atrial activation patterns during persistent AF. Atrial activation patterns demonstrated evidence of spatiotemporal stability over long time periods. Orbital plots created at different time points in the same location remained unchanged. Together with this important discovery, both fractionation and bipolar voltage were also demonstrated to express stability over time. Spatiotemporal stability during persistent AF enables sequential mapping as an acceptable technique. This property also allowed the development of a method for displaying sequentially mapped locations on a single map – RETRO-Choropleth Map. These findings go against the multiple wavelet hypothesis with random activation. Having gained insights in to these stable activation patterns, extensive analysis was undertaken to identify the presence of focal activation. Focal activations were identified during persistent AF. RETRO-Mapping was used to show that adjacent activation patterns were not related to focal activations. Lastly, the effect of pulmonary vein isolation (PVI) was studied by mapping atrial activation patterns before and after PVI. RETRO-Mapping showed that PVI leads to increased organisation of AF in most patients, supporting a mechanistic role of the pulmonary veins in persistent AF. In conclusion, a new technique has been developed and validated for automated activation mapping of persistent AF. These techniques could be used to guide additional ablation strategies beyond PVI for patients with persistent AF.Open Acces

The utility of handheld and wearable devices in the diagnosis of cardiac arrhythmias

The aim of this thesis is to highlight the existing body of literature on the utility of wearable and handheld devices in the diagnosis and management of cardiac arrhythmias. Furthermore, the thesis investigates the accuracy and utility of the AliveCor Kardia for the detection of cardiac arrhythmias in a systematic fashion

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

The ganglionated plexus: The upstream triggers of atrial fibrillation

The ganglionated plexuses (GP) are dense epicardial nerves that are implicated in atrial fibrillation (AF). They can be functionally located from the endocardium using high frequency stimulation (HFS) which can locate distinct GP that trigger atrial ectopy/AF (ET-GP) or atrioventricular (AV) dissociating (AVD-GP). Our aim was to map and understand the histological, anatomical and functional properties of the different types of GP and ablate them with or without pulmonary vein isolation (PVI) in patients with AF. We hypothesised that ablating these specific GP sites is feasible, and prevents AF. Firstly, to investigate this, we mapped for AVD-GP and ET-GP using HFS in the left atrium of patients with AF. An automated process was used to merge and transform all patient maps onto one reference left atrial shell. A probability density function was applied at each tested site, including GP and negative HFS response sites, to create a probability distribution atlas of AVD-GP and ET-GP. There were distinct anatomical regions according to each GP sub-type, and ET-GP had preponderance to the PV ostia, roof, and mid-anterior wall. These are the areas that would usually be targeted with circumferential PVI. Therefore, a prospective, randomised, controlled study was performed (GANGLIA-AF) which assessed ET-GP ablation without PVI and PVI alone in patients with paroxysmal AF. Patients were followed-up for 12 months with multiple 48hr Holter monitors. The primary endpoint was any documented atrial arrhythmia >30s, and the secondary endpoints included complications and redo ablations. This showed that there was no statistically significant difference in AF prevention between the two arms, however the GP ablation arm required less ablation on average than the PVI arm. We also performed a smaller pilot study of redo AF ablation patients, assessing for feasibility and safety of GP ablation in addition to redo PVI. The same follow-up and endpoint criteria were used as in the GANGLIA-AF study. Some patients had permanent PVI, and non-PV triggers of AF were identifiable with HFS. We also developed a custom-built high frequency stimulator (Tau-20) that was used to identify ectopy-triggering (ET) sites in Langendorff-perfused porcine hearts. We were able to replicate the HFS responses used in the clinical setting in the porcine atria. Transmural cross-sectional dissections were taken from ET and non-ET sites, and the tissues were stained for parasympathetic and sympathetic nerves using immunohistochemistry methods. This showed that the mean density of nerves was greater in ET sites compare to non-ET sites. The Tau-20 has been successfully trialled in humans in the clinical setting, and with further improvements, it may replace the old Grass S88 stimulator for future GP ablation cases. In conclusion, ET-GP are upstream triggers of AF that can be ablated without PVI to prevent paroxysmal AF. GP ablation can be achieved with less RF energy than PVI implying a more specific technique on mechanistic grounds. The cross-over rate and clinical outcomes for GP ablation needs further improvement but GANGLIA-AF provides evidence that GP ablation may be an alternative or an adjunct technique to PVI. In addition, our ex-vivo evidence of increased nerve density at ET sites may account for the differential functional response of ET-GP stimulation in the clinical setting.Open Acces