Catheter ablation in patients with atrial fibrillation : mapping refinements, outcome prediction and effect on quality of life

PhD ThesisChapter 1 presents a literature review, focused primarily on the pathophysiology and management of atrial fibrillation (AF). Chapter 2 examines correlations between the dominant frequency of AF - calculated using principal component analysis from a modified surface 12-lead ECG (which included posterior leads), a standard 12-lead ECG and intracardiac recordings from both atria. The inclusion of posterior leads did not improve correlation with left atrial activity because of the dominance of lead V1 in both ECG configurations. Chapter 3 explores whether acute and 12-month outcome following catheter ablation for AF can be predicted beforehand from clinical and surface AF waveform parameters. Multivariate risk scores combining these parameters can predict arrhythmia outcome following ablation, and could therefore be used to identify those most likely to benefit from this therapy. Chapter 4 examines the effect of catheter ablation on AF symptoms and quality of life (QoL). AF symptom and QoL scores improved significantly in patients who maintained sinus rhythm after ablation but did not change in those with recurrent AF. AF-specific QoL scales are more responsive to change and correlate better with ablation outcome. Chapter 5 examines inter-atrial frequency gradients in patients with persistent AF using multipolar contact mapping. A right-to-left atrial frequency gradient was found in a quarter of the patients studied, implying that their arrhythmia was being maintained by high frequency sources in the right rather than the left atrium. Chapter 6 examines whether targeting high frequency and highly repetitive complex fractionated atrial electrogram sites, identified using multipolar contact mapping during persistent AF, resulted in arrhythmia termination and maintenance of sinus rhythm long-term. The utility of administering flecainide to distinguish critical from bystander AF sites was also investigated. Flecainide did not help refine ablation targets and 12-month outcome after targeting these sites was not superior to other ablation strategies

CURRENT CHALLENGES IN ATRIAL FIBRILLATION ABLATION

Full version unavailable due to 3rd party copyright restrictions.The ablative management of atrial fibrillation, despite a number of landmark discoveries, remains one of the most challenging fields in interventional electrophysiology. It is generally accepted that successful isolation of the pulmonary veins is a highly effective way of managing paroxysmal forms of AF. However, despite almost a decade of research into alternative lesion patterns, the solution to persistent AF remains beyond our grasp. A variety of strategies have been proposed to target key areas in the atria; these use various complex mapping systems, usually based on tailored lesion sets to try and improve outcomes. None have proven to be the golden bullet. We have investigated the role of a lesion set intended to alter the electrical properties of the posterior wall of the left atrium. Commonly known as the ‘box-set’, this pattern has shown promise in early studies and may provide some key insights into future developments. Surgical ablation using the Epicor system aims to deliver the box-set lesion, outcomes have previously been documented but each series has its limitations. In our series, very late outcomes are reported to show an 80% freedom from AF rate in patients with paroxysmal AF pre-operatively and only 20% in those with long-standing persistent forms. The reason behind this dramatic variation is explored through the invasive electrophysiologal assessment of both successful and unsuccessful cases. We report a clear correlation between the successful isolation of the posterior wall and long-term freedom from AF. Though surgical ablation may be an acceptable approach for some, the ultimate goal is a lesion set that can be delivered purely endocardially. We explore the outcome of one such empirical pattern based on the box-set concept delivered through linear catheter technology and report outcomes broadly similar to alternative patterns

Which patients recur as atrial tachycardia rather than atrial fibrillation after catheter ablation of atrial fibrillation?

INTRODUCTION: The ablation gaps have been known as the main mechanism of recurrence as atrial tachycardia (AT) rather than atrial fibrillation (AF) after AF catheter ablation. However, AF organization due to reduction of critical mass or focal trigger may also be the mechanism of AT recurrence. We sought to find out the main clinical factors of recurrence as AT rather than AF after AF ablation in the absence of antiarrhythmic drug effect. METHODS: We analyzed 521 patients (70.8% men, 64.1% paroxysmal AF) who experienced AT or AF recurrence without antiarrhythmic drug effect during 44.7 ± 25.4 months follow-up. RESULTS: Among 521 patients with recurrence, 42.0% (219 of 521) recurred with AT. The proportion of AT recurrence was not different between the pulmonary vein isolation only group and additional linear ablation group (45.1% vs. 38.1%, p = 0.128). The absence of hypertension (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.29-0.83, p = 0.007), small left atrial (LA) volume index (OR 0.89 per 10 mL/m2, 95% CI 0.79-1.00, p = 0.049), and high mean LA bipolar voltage (OR 2.03 per 1 mV, 95% CI 1.30-3.16, p = 0.002) were independently associated with AT recurrence, whereas additional linear ablation was not. Among 90 patients who underwent repeat ablation procedure, rates of PV reconnection (p = 0.358) and gap in prior linear ablations (p = 0.269) were not significantly different between AT recurrence group and AF recurrence group. CONCLUSION: The degree of LA remodeling is significantly associated with recurrence as AT after AF ablation, irrespective of potential ablation gap in linear lesion.ope

Virtual In-Silico Modeling Guided Catheter Ablation Predicts Effective Linear Ablation Lesion Set for Longstanding Persistent Atrial Fibrillation: Multicenter Prospective Randomized Study

Objective: Radiofrequency catheter ablation for persistent atrial fibrillation (PeAF) still has a substantial recurrence rate. This study aims to investigate whether an AF ablation lesion set chosen using in-silico ablation (V-ABL) is clinically feasible and more effective than an empirically chosen ablation lesion set (Em-ABL) in patients with PeAF. Methods: We prospectively included 108 patients with antiarrhythmic drug-resistant PeAF (77.8% men, age 60.8 ± 9.9 years), and randomly assigned them to the V-ABL (n = 53) and Em-ABL (n = 55) groups. Five different in-silico ablation lesion sets [1 pulmonary vein isolation (PVI), 3 linear ablations, and 1 electrogram-guided ablation] were compared using heart-CT integrated AF modeling. We evaluated the feasibility, safety, and efficacy of V-ABL compared with that of Em-ABL. Results: The pre-procedural computing time for five different ablation strategies was 166 ± 11 min. In the Em-ABL group, the earliest terminating blinded in-silico lesion set matched with the Em-ABL lesion set in 21.8%. V-ABL was not inferior to Em-ABL in terms of procedure time (p = 0.403), ablation time (p = 0.510), and major complication rate (p = 0.900). During 12.6 ± 3.8 months of follow-up, the clinical recurrence rate was 14.0% in the V-ABL group and 18.9% in the Em-ABL group (p = 0.538). In Em-ABL group, clinical recurrence rate was significantly lower after PVI+posterior box+anterior linear ablation, which showed the most frequent termination during in-silico ablation (log-rank p = 0.027). Conclusions: V-ABL was feasible in clinical practice, not inferior to Em-ABL, and predicts the most effective ablation lesion set in patients who underwent PeAF ablation.ope

Markers of Left Atrial Fibrosis in Atrial Fibrillation and Prediction of Successful Rhythm Control Intervention

Introduction Methods to restore atrial fibrillation (AF) to sinus rhythm include catheter ablation and electrical cardioversion. Myocardial fibrosis is associated with recurrence and may be measurable using circulating biomarkers. Other methods include cardiac magnetic resonance (CMR) and electro-anatomical mapping. The aims were: 1) Compare biomarkers in AF patients and controls. 2) Assess biomarker levels at multiple sampling sites. 3) Determine associations between methods of fibrosis quantification. 4) Determine their predictive value for arrhythmia recurrence. Methods 93 AF ablation patients, 79 cardioversion patients, and 40 control patients were enrolled. Enzyme-linked immunosorbent assay was used to determine peripheral serum levels of galectin-3 (gal-3), type I collagen C terminal peptide (ICTP), type III procollagen N terminal peptide (PIIINP), and fibroblast growth factor 23 (FGF-23). Additionally, in ablation patients, levels were measured in the coronary sinus and both atria. 31 ablation patients underwent CMR. Follow up was 12 months. Results ICTP levels were higher in ablation patients than in controls (p=0.007). Peripheral ICTP levels were higher than intracardiac levels (p<0.001), and CS levels were higher than atrial levels (p<0.001). Peripheral gal-3 levels were higher than left atrial levels (p=0.001). FGF-23 was weakly predictive of AF recurrence after cardioversion (HR 1.003 p=0.012). No other biomarkers predicted AF recurrence. Low voltage in the left atrium was the only independent predictor of AF recurrence, mapped in sinus rhythm (HR 4.323 p=0.014) or AF (HR 5.195 p=0.046). LV extracellular volume was associated with LA pressure (beta 0.49, P=0.008) and coronary sinus ICTP (beta 0.75, P<0.001). Conclusion There is no clinically useful predictive effect of the biomarkers in this study. Further research into FGF-23 is warranted. Associations between LV extracellular volume, ICTP and LA pressure may suggest elevated ventricular myocardial turnover of type I collagen in this cohort, and a possible link with atrial pathology

A Mechanistically Guided Approach to Treatment of Multi-Wavelet Reentry: Experiments in a Computational Model of Cardiac Propagation

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States today. However, treatment options remain limited despite the enormous magnitude of both AF prevalence and the associated economic cost. Of those treatment options that are available, ablation-based interventional methods have demonstrated the highest rates of long-term cure. Unfortunately, these methods have substantially lower efficacy in patients with heavier burdens of disease, thus leaving the most affected individuals with the least hope for successful treatment. The focus of this research is to develop a mechanistically guided approach towards the treatment of multi-wavelet reentry (MWR), one of the primary drivers of AF. For this purpose, we use a computational model of electrical propagation in cardiac tissue to simulate both episodes of fibrillatory activity and the ablative treatment thereof. We demonstrate that the probability of forming the reentrant circuits necessary for continuous electrical activity is a function of the shape and size of a tissue as well as its underlying cellular properties. Ablation at tissue sites with high probability of circuit formation more efficiently reduces the overall duration of fibrillatory episodes than ablation at sites with low probability. We then propose and validate in silico a parameter-based metric for predicting the propensity of an individual tissue to support fibrillation, which we term the fibrillogenicity index. Using this metric, we develop an algorithm for prospectively determining optimized, tissue-specific ablation patterns. Finally, we examine the relationship between multi-wavelet reentry and focal drivers, and demonstrate that MWR and fibrillatory conduction exist along a continuum. We examine the complex interplay between functional and structural substrates within fibrillating tissue and define the mechanisms by which they promote the perpetuation of AF. These findings present a novel theoretical framework for understanding treatment of multi-wavelet reentry driven AF and provide a set of testable predictions that can serve to guide the design of future experimental studies aimed at advancing the rational design of patient-specific ablation sets for treating AF

Design and development of optical reflectance spectroscopy and optical coherence tomography catheters for myocardial tissue characterization

Catheter ablation therapy attempts to restore sinus rhythm in arrhythmia patients by producing site-specific tissue modification along regions which cause abnormal electrical activity. This treatment, though widely used, often requires repeat procedures to observe long-term therapeutic benefits. This limitation is driven in part by challenges faced by conventional schemes in validating lesion adequacy at the time of the procedure. Optical techniques are well-suited for the interrogation and characterization of biological tissues. In particular, optical coherence tomography (OCT) relies on coherence gating of singly-scattered light to enable high-resolution structural imaging for tissue diagnostics and procedural guidance. Alternatively, optical reflectance spectroscopy (ORS) is a point measurement technique which makes use of incoherent, multiply-scattered light to probe tissue volumes and derive important data from its optical signature. ORS relies on the fact that light-tissue interactions are regulated by absorption and scattering, which directly relate to the intrinsic tissue biochemistry and cellular organization. In this thesis, we explore the integration of these modalities into ablation catheters for obtaining procedural metrics which could be utilized to guide catheter ablation therapy. We first present the development of an accelerated computational light transport model and its application for guiding ORS catheter design. A custom ORS-integrated ablation catheter is then implemented and tested within porcine specimens in vitro. A model is proposed for real-time estimation of lesion size based on changes in spectral morphology acquired during ablation. We then fabricated custom integrated OCT M-mode RF catheters and present a model for detecting contact status based on deep convolutional neural networks trained on endomyocardial images. Additionally, we demonstrate for the first time, tracking of RF-induced lesion formation employing OCT Doppler micro-velocimetry; this response is shown to be commensurate with the degree of treatment. We further demonstrate for the first time spectroscopic tracking of kinetics related to the heme oxidation cascade during thermal treatment, which are linked to tissue denaturation. The pairing of these modalities into a single RF catheter was also validated for guiding lesion delivery in vitro and within live pigs. Finally, we conclude with a proof-of-concept demonstration of ORS as a mapping tool to guide epicardial ablation in human donor hearts. These results showcase the vast potential of ORS and OCT empowered RF catheters for aiding intraprocedural guidance of catheter ablation procedures which could be utilized alongside current practices