Constitutively active acetylcholine-dependent potassium current increases atrial defibrillation threshold by favoring post-shock re-initiation

Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (I-K,I-ACh -> I-K,I-ACh-c), which is associated with ECV failure. This study investigated the role of I-K,I-ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25-100 V to determine aDFT. Blocking I-K,I-ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate I-K,I-ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. re-initiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by I-K,I-ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after I-K,I-ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies I-K,I-ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness

Frequency Analysis of Atrial Fibrillation From the Surface Electrocardiogram

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy are sufficiently predictable by clinical and echocardiographic parameters. Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface electrocardiogram (ECG) using digital signal processing (filtering, subtraction of averaged QRST complexes, and power spectral analysis) and shows large inter-individual variability. This measurement correlates well with intraatrial cycle length, a parameter which appears to have primary importance in AF domestication and response to therapy. AF with a low fibrillatory rate is more likely to terminate spontaneously, and responds better to antiarrhythmic drugs or cardioversion while high rate AF is more often persistent and refractory to therapy. In conclusion, frequency analysis of AF seems to be useful for non-invasive assessment of electrical remodeling in AF and may subsequently be helpful for guiding AF therapy

High Resolution Multi-parametric Diagnostics and Therapy of Atrial Fibrillation: Chasing Arrhythmia Vulnerabilities in the Spatial Domain

After a century of research, atrial fibrillation (AF) remains a challenging disease to study and exceptionally resilient to treatment. Unfortunately, AF is becoming a massive burden on the health care system with an increasing population of susceptible elderly patients and expensive unreliable treatment options. Pharmacological therapies continue to be disappointingly ineffective or are hampered by side effects due to the ubiquitous nature of ion channel targets throughout the body. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, ablation procedures can be complex, leading to varying levels of recurrence, and have a number of serious risks. The high recurrence rate could be due to the difficulty of accurately predicting where to draw the ablation lines in order to target the pathophysiology that initiates and maintains the arrhythmia or an inability to distinguish sub-populations of patients who would respond well to such treatments. There are electrical cardioversion options but there is not a practical implanted deployment of this strategy. Under the current bioelectric therapy paradigm there is a trade-off between efficacy and the pain and risk of myocardial damage, all of which are positively correlated with shock strength. Contrary to ventricular fibrillation, pain becomes a significant concern for electrical defibrillation of AF due to the fact that a patient is conscious when experiencing the arrhythmia. Limiting the risk of myocardial injury is key for both forms of fibrillation. In this project we aim to address the limitations of current electrotherapy by diverging from traditional single shock protocols. We seek to further clarify the dynamics of arrhythmia drivers in space and to target therapy in both the temporal and spatial domain; ultimately culminating in the design of physiologically guided applied energy protocols. In an effort to provide further characterization of the organization of AF, we used transillumination optical mapping to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acutely induced episodes of AF. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms, with a demonstrated range of discordance between the epicardial and endocardial dynamic propagation patterns. After confirming the presence of epi-endo dyssynchrony in multiple animal models, we further investigated the anatomical structure to look for regional trends in transmural fiber orientation that could help explain the spectrum of observed patterns. Simultaneously, we designed and optimized a multi-stage, multi-path defibrillation paradigm that can be tailored to individual AF frequency content in the spatial and temporal domain. These studies continue to drive down the defibrillation threshold of electrotherapies in an attempt to achieve a pain-free AF defibrillation solution. Finally, we designed and characterized a novel platform of stretchable electronics that provide instrumented membranes across the epicardial surface or implanted within the transmural wall to provide physiological feedback during electrotherapy beyond just the electrical state of the tissue. By combining a spatial analysis of the arrhythmia drivers, the energy delivered and the resulting damage, we hope to enhance the biophysical understanding of AF electrical cardioversion and xiii design an ideal targeted energy delivery protocol to improve upon all limitations of current electrotherapy

Assessment of ventricular repolarization instability and cardiac risk stratification in different pathological and abnormal conditions

Cardiovascular diseases (CVDs) represents the leading cause of mortality worldwide [1,2]. These pathological conditions are mainly characterized by a structurally abnormal heart, that is, a vulnerable substrate, prone to the abnormal generation and/or propagation of the electrical impulse, determining the onset of ventricular arrhythmias, which can result in sudden cardiac death (SCD) [3]. In this context, the assessment of ventricular repolarization from the electrocardiogram (ECG) signal has been shown to provide with valuable information for risk stratification and several electrocardiographic indices have been proposed in the literature [4]. The main objective of this thesis is to propose methodological advances for the assessment of ventricular repolarization instability in pathological and abnormal conditions. These contributions are aimed at improving the prediction of ventricular arrhythmias and, consequently, better identifying SCD risk. In particular, we have addressed this objective by developing robust methodologies for the assessment of T-wave alternans (TWA) and ventricular repolarization instability, in invasive and non-invasive cardiac signals, that have been evaluated in both experimental and clinical conditions. In the first part of the thesis, TWA was simultaneously characterized (prevalence, magnitude, time-course, and alternans waveform) in body-surface ECG and intracardiac electrograms (EGMs) signals during coronary artery occlusion. Signals from both body surface ECG and intracardiac EGMs recorded from 4 different anatomical heart locations (coronary sinus, epicardial space and left and right ventricles) were analyzed following a multilead strategy. Leads were linearly combined using the periodic component analysis (πCA) [5], which maximizes the 2-beat periodicity (TWA periodicity) content present on the available leads. Then the Laplacian Likelihood Ratio method (LLRM) [6] was applied for TWA detection and estimation. A sensitivity study for TWA detection from the 5 different locations of leads was performed, revealing that it is the combination of the ECG leads that better performs. In addition, this multilead approach allowed us to find the optimal combination of intracardiac leads usable for in-vivo monitorization of TWA directly from an implantable device, with a sensitivity comparable to the ECG analysis. These results encourage further research to determine the feasibility of predicting imminent VT/VF episodes by TWA analysis implemented in implantable cardioverter defibrillator’s (ICD) technology.Then, we have studied the potential changes induced by a prolonged exposure to simulated microgravity on ventricular repolarization in structurally normal hearts. It is well known that this environmental condition affects the control of autonomic and cardiovascular systems [7], with a potential increase on cardiac electrical instability. The effects of short- (5 days), mid- (21 days) and long- (60 days) exposure to simulated microgravity on TWA using the head-down bed-rest (HDBR) model [8] were assessed. TWA was evaluated before (PRE), during and after (POST) the immobilization period, by the long-term averaging technique in ambulatory ECG Holter recordings [9]. Additionally, we proposed an adapted short-term averaging approach for shorter, non-stationary ECG signals obtained during two stress manoeuvres (head-up tilt-table and bicycle exercise tests). Both approaches are based on the multilead analysis used in the previous study. The absence of significant changes between PRE and POST-HDBR on TWA indices suggests that a long-term exposure to simulated microgravity is not enough to induce alterations in healthy myocardial substrate up to the point of reflecting electrical instability in terms of TWA on the ECG. Finally, methodological advances were proposed for the assessment of ventricular repolarization instability from the ECG signal in the presence of sporadic (ventricular premature contractions, VPCs) and sustained (atrial fibrillation) rhythm disturbances.On the one hand, a methodological improvement for the estimation of TWA amplitude in ambulatory ECG recordings was proposed, which deals with the possible phase reversal on the alternans sequence induced by the presence of VPCs [10]. The performance of the algorithm was first evaluated using synthetic signals. Then, the effect of the proposed method in the prognostic value of TWA amplitude was assessed in real ambulatory ECG recordings from patients with chronic heart failure (CHF). Finally, circadian TWA changes were evaluated as well as the prognostic value of TWA at different times of the day. A clinical study demonstrated the enhancement in the predictive value of the index of average alternans (IAA) [9] for SCD stratification. In addition, results suggested that alternans activity is modulated by the circadian pattern, preserving its prognostic information when computed just during the morning, which is also the day interval with the highest reported SCD incidence. Thus, suggesting that time of the day should be considered for SCD risk prediction. On the other hand, the high irregularity of the ventricular response in atrial fibrillation (AF) limits the use of the most common ECG-derived markers of repolarization heterogeneity, including TWA, under this clinical condition [11]. A new method for assessing ventricular repolarization changes based on a selective averaging technique was developed and new non-invasive indices of repolarization variation were proposed. The positive impact in the prognostic value of the computed indices was demonstrated in a clinical study, by analyzing ECG Holter recordings from CHF patients with AF. To the best of our knowledge, this is the first study that attempts a non-invasive SCD stratification of patients under AF rhythm by assessing ventricular repolarization instability from the ECG signal. To conclude, the research presented in this thesis sheds some light in the identification of pro-arrhythmic factors, which plays an important role in adopting efficient therapeutic strategies. In particular, the optimal configuration for real-time monitoring of repolarization alternans from intracardiac EGMs, together with the prognostic value of the proposed non-invasive indices of alternans activity and ventricular instability variations in case of AF rhythms demonstrated in two clinical studies, would increase the effectiveness of (ICD) therapy. Finally, the analysis of ECG signals recorded during HDBR experiments in structurally healthy hearts, also provides interesting information on cardiovascular alterations produced in immobilized or bedridden patients.<br /

Incidence and predictors of premature ventricular complexes following catheter ablation for atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and previous studies have focused on the epidemiology, mechanisms and risk factors for this global disease (Ryder and Benjamin 1999). Various studies have examined the mechanism, epidemiology, and risk factors for AF. One of the most common triggers for AF is believed to be premature atrial contractions (PACs) usually arising from the pulmonary veins of the left atrium, but the relationship between AF and premature ventricular complexes (PVCs) is not well understood. Studies investigating the triggers of premature beats in both the atria and ventricles are similar, so it is possible that treatment for one arrhythmia may affect the incidence of another. It is hypothesized that due to commonly shared mechanisms of triggered activity or automaticity between PACs and PVCs, and shared risk factors, that patients with AF undergoing treatment with catheter ablation may be prone to develop PVCs. OBJECTIVE: To investigate the incidence of clinically detected PVCs among patients undergoing catheter ablation for AF, and clinical predictors of PVC development in this cohort of patients. We also aim to evaluate if incident PVC detection is associated with recurrent AF following AF ablation in a cohort of 317 patients receiving treatment at a single academic medical center. METHODS: A total of 375 patients undergoing AF ablation from 2009-2012 were reviewed, and patients that underwent repeat ablations were excluded, yielding 317 patients for analysis. T-tests and Chi-squared analyses were used in univariate analyses to test for significance between characteristics of AF patients who did and did not develop PVCs. Kaplan-Meier analyses and Cox proportional hazards models were used for univariate and multivariate survival analyses, respectively, to assess the risks of incident PVC development. RESULTS: Of 317 patients with AF undergoing pulmonary vein isolation (PVI) ablation, 36.3% developed clinically detectable PVCs following ablation. A history of clinically evident PVC prior to catheter ablation for AF was associated with an 80% increase in risk of incident PVC development (HR=1.83, 95% CI 1.02-3.26, p=0.041). Additionally, a history of prior angioplasty, stent, or percutaneous coronary intervention (PCI) was associated with a 73% decreased risk of incident PVCs (HR=0.27, 95% CI 0.08-0.88, p=0.03). In patients with a history of PVC prior to ablation, or who developed PVCs after ablation, there was no significant difference in the risk of AF recurrence (HR=1.01, 95% CI 0.70-1.46, p=0.96; and HR=1.09, 95% CI 0.78-1.53, p=0.60, respectively). CONCLUSIONS: Over 1 in 3 patients develop clinically detected PVCs following catheter ablation. Predictors of incident PVC development include a history of PVC, whereas a history of angioplasty, stent, or PCI was associated with less incident PVC development. Furthermore, there was no significant association between both a history of PVC or incident PVC and risk of recurrent AF following ablation

Atrial fibrillation detection by heart rate variability in Poincare plot

© 2009 Park et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies

[ES] Las arritmias cardíacas son un problema importante para los sistemas de salud en el mundo desarrollado debido a su alta incidencia y prevalencia a medida que la población envejece. La fibrilación auricular (FA) y la fibrilación ventricular (FV) se encuentran entre las arritmias más complejas observadas en la práctica clínica. Las consecuencias clínicas de tales alteraciones arrítmicas incluyen el desarrollo de eventos cardioembólicos complejos en la FA, y repercusiones dramáticas debido a procesos fibrilatorios sostenidos que amenazan la vida infringiendo daño neurológico tras paro cardíaco por FV, y que pueden provocar la muerte súbita cardíaca (MSC). Sin embargo, a pesar de los avances tecnológicos de las últimas décadas, sus mecanismos intrínsecos se comprenden de forma incompleta y, hasta la fecha, las estrategias terapéuticas carecen de una base mecanicista suficiente y poseen bajas tasas de éxito. Entre los mecanismos implicados en la inducción y perpetuación de arritmias cardíacas, como la FA, se cree que las dinámicas de las fuentes focales y reentrantes de alta frecuencia, en sus diferentes modalidades, son las fuentes primarias que mantienen la arritmia. Sin embargo, se sabe poco sobre los atractores, así como, de la dinámica espacio-temporal de tales fuentes fibrilatorias primarias, específicamente, las fuentes focales o rotacionales dominantes que mantienen la arritmia. Por ello, se ha desarrollado una plataforma computacional, para comprender los factores (activos, pasivos y estructurales) determinantes, y moduladores de dicha dinámica. Esto ha permitido establecer un marco para comprender la compleja dinámica de los rotores con énfasis en sus propiedades deterministas para desarrollar herramientas basadas en los mecanismos para ayuda diagnóstica y terapéutica. Comprender los procesos fibrilatorios es clave para desarrollar marcadores y herramientas fisiológica- y clínicamente relevantes para la ayuda de diagnóstico temprano. Específicamente, las propiedades espectrales y de tiempo-frecuencia de los procesos fibrilatorios han demostrado resaltar el comportamiento determinista principal de los mecanismos intrínsecos subyacentes a las arritmias y el impacto de tales eventos arrítmicos. Esto es especialmente relevante para determinar el pronóstico temprano de los supervivientes comatosos después de un paro cardíaco debido a fibrilación ventricular (FV). Las técnicas de mapeo electrofisiológico, el mapeo eléctrico y óptico cardíaco, han demostrado ser recursos muy valiosos para dar forma a nuevas hipótesis y desarrollar nuevos enfoques mecanicistas y estrategias terapéuticas mejoradas. Esta tecnología permite además el trabajo multidisciplinar entre clínicos y bioingenieros, para el desarrollo y validación de dispositivos y metodologías para identificar biomarcadores multi-dominio que permitan rastrear con precisión la dinámica de las arritmias identificando fuentes dominantes y atractores con alta precisión para ser dianas de estrategias terapeúticas innovadoras. Es por ello que uno de los objetivos fundamentales ha sido la implantación y validación de nuevos sistemas de mapeo en distintas configuraciones que sirvan de plataforma de desarrollo de nuevas estrategias terapeúticas. Aunque el mapeo panorámico es el método principal y más completo para rastrear simultáneamente biomarcadores electrofisiológicos, su adopción por la comunidad científica es limitada principalmente debido al coste elevado de la tecnología. Aprovechando los avances tecnológicos recientes, nos hemos enfocado en desarrollar, y validar, sistemas de mapeo óptico de alta resolución para registro panorámico cardíaco, utilizando modelos clínicamente relevantes para la investigación básica y la bioingeniería.[CA] Les arítmies cardíaques són un problema important per als sistemes de salut del món desenvolupat a causa de la seva alta incidència i prevalença a mesura que la població envelleix. La fibril·lació auricular (FA) i la fibril·lació ventricular (FV), es troben entre les arítmies més complexes observades a la pràctica clínica. Les conseqüències clíniques d'aquests trastorns arítmics inclouen el desenvolupament d'esdeveniments cardioembòlics complexos en FA i repercussions dramàtiques a causa de processos fibril·latoris sostinguts que posen en perill la vida amb danys neurològics posteriors a la FV, que condueixen a una aturada cardíaca i a la mort cardíaca sobtada (SCD). Tanmateix, malgrat els avanços tecnològics de les darreres dècades, els seus mecanismes intrínsecs s'entenen de forma incompleta i, fins a la data, les estratègies terapèutiques no tenen una base mecanicista suficient i tenen baixes taxes d'èxit. La majoria dels avenços en el desenvolupament de biomarcadors òptims i noves estratègies terapèutiques en aquest camp provenen de tècniques valuoses en la investigació de mecanismes d'arítmia. Entre els mecanismes implicats en la inducció i perpetuació de les arítmies cardíaques, es creu que les fonts primàries subjacents a l'arítmia són les fonts focals reingressants d'alta freqüència dinàmica i AF, en les seves diferents modalitats. Tot i això, se sap poc sobre els atractors i la dinàmica espaciotemporal d'aquestes fonts primàries fibril·ladores, específicament les fonts rotacionals o focals dominants que mantenen l'arítmia. Per tant, s'ha desenvolupat una plataforma computacional per entendre determinants actius, passius, estructurals i moduladors d'aquestes dinàmiques. Això va permetre establir un marc per entendre la complexa dinàmica multidomini dels rotors amb ènfasi en les seves propietats deterministes per desenvolupar enfocaments mecanicistes per a l'ajuda i la teràpia diagnòstiques. La comprensió dels processos fibril·latoris és clau per desenvolupar puntuacions i eines rellevants fisiològicament i clínicament per ajudar al diagnòstic precoç. Concretament, les propietats espectrals i de temps-freqüència dels processos fibril·latoris han demostrat destacar un comportament determinista important dels mecanismes intrínsecs subjacents a les arítmies i l'impacte d'aquests esdeveniments arítmics. Mitjançant coneixements previs, processament de senyals, tècniques d'aprenentatge automàtic i anàlisi de dades, es va desenvolupar una puntuació de risc mecanicista a la aturada cardíaca per FV. Les tècniques de cartografia òptica cardíaca i electrofisiològica han demostrat ser recursos inestimables per donar forma a noves hipòtesis i desenvolupar nous enfocaments mecanicistes i estratègies terapèutiques. Aquesta tecnologia ha permès durant molts anys provar noves estratègies terapèutiques farmacològiques o ablatives i desenvolupar mètodes multidominis per fer un seguiment precís de la dinàmica d'arrímies que identifica fonts i atractors dominants. Tot i que el mapatge panoràmic és el mètode principal per al seguiment simultani de paràmetres electrofisiològics, la seva adopció per part de la comunitat multidisciplinària d'investigació cardiovascular està limitada principalment pel cost de la tecnologia. Aprofitant els avenços tecnològics recents, ens centrem en el desenvolupament i la validació de sistemes de mapes òptics de baix cost per a imatges panoràmiques mitjançant models clínicament rellevants per a la investigació bàsica i la bioenginyeria.[EN] Cardiac arrhythmias are a major problem for health systems in the developed world due to their high incidence and prevalence as the population ages. Atrial fibrillation (AF) and ventricular fibrillation (VF), are amongst the most complex arrhythmias seen in the clinical practice. Clinical consequences of such arrhythmic disturbances include developing complex cardio-embolic events in AF, and dramatic repercussions due to sustained life-threatening fibrillatory processes with subsequent neurological damage under VF, leading to cardiac arrest and sudden cardiac death (SCD). However, despite the technological advances in the last decades, their intrinsic mechanisms are incompletely understood, and, to date, therapeutic strategies lack of sufficient mechanistic basis and have low success rates. Most of the progress for developing optimal biomarkers and novel therapeutic strategies in this field has come from valuable techniques in the research of arrhythmia mechanisms. Amongst the mechanisms involved in the induction and perpetuation of cardiac arrhythmias such AF, dynamic high-frequency re-entrant and focal sources, in its different modalities, are thought to be the primary sources underlying the arrhythmia. However, little is known about the attractors and spatiotemporal dynamics of such fibrillatory primary sources, specifically dominant rotational or focal sources maintaining the arrhythmia. Therefore, a computational platform for understanding active, passive and structural determinants, and modulators of such dynamics was developed. This allowed stablishing a framework for understanding the complex multidomain dynamics of rotors with enphasis in their deterministic properties to develop mechanistic approaches for diagnostic aid and therapy. Understanding fibrillatory processes is key to develop physiologically and clinically relevant scores and tools for early diagnostic aid. Specifically, spectral and time-frequency properties of fibrillatory processes have shown to highlight major deterministic behaviour of intrinsic mechanisms underlying the arrhythmias and the impact of such arrhythmic events. Using prior knowledge, signal processing, machine learning techniques and data analytics, we aimed at developing a reliable mechanistic risk-score for comatose survivors of cardiac arrest due to VF. Cardiac optical mapping and electrophysiological mapping techniques have shown to be unvaluable resources to shape new hypotheses and develop novel mechanistic approaches and therapeutic strategies. This technology has allowed for many years testing new pharmacological or ablative therapeutic strategies, and developing multidomain methods to accurately track arrhymia dynamics identigying dominant sources and attractors. Even though, panoramic mapping is the primary method for simultaneously tracking electrophysiological parameters, its adoption by the multidisciplinary cardiovascular research community is limited mainly due to the cost of the technology. Taking advantage of recent technological advances, we focus on developing and validating low-cost optical mapping systems for panoramic imaging using clinically relevant models for basic research and bioengineering.Calvo Saiz, CJ. (2022). Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182329TESI

A novel wavelet-based filtering strategy to remove powerline interference from electrocardiograms with atrial fibrillation

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/1361-6579/aae8b1[EN] Objective: The electrocardiogram (ECG) is currently the most widely used recording to diagnose cardiac disorders, including the most common supraventricular arrhythmia, such as atrial fibrillation (AF). However, different types of electrical disturbances, in which power-line interference (PLI) is a major problem, can mask and distort the original ECG morphology. This is a significant issue in the context of AF, because accurate characterization of fibrillatory waves (f-waves) is unavoidably required to improve current knowledge about its mechanisms. This work introduces a new algorithm able to reduce high levels of PLI and preserve, simultaneously, the original ECG morphology. Approach: The method is based on stationary wavelet transform shrinking and makes use of a new thresholding function designed to work successfully in a wide variety of scenarios. In fact, it has been validated in a general context with 48 ECG recordings obtained from pathological and non-pathological conditions, as well as in the particular context of AF, where 380 synthesized and 20 long-term real ECG recordings were analyzed. Main results: In both situations, the algorithm has reported a notably better performance than common methods designed for the same purpose. Moreover, its effectiveness has proven to be optimal for dealing with ECG recordings affected by AF, sincef-waves remained almost intact after removing very high levels of noise. Significance: The proposed algorithm may facilitate a reliable characterization of thef-waves, preventing them from not being masked by the PLI nor distorted by an unsuitable filtering applied to ECG recordings with AF.Research supported by grants DPI2017-83952-C3 MINECO/AEI/FEDER, UE and SBPLY/17/180501/000411 from Junta de Comunidades de Castilla-La Mancha.García, M.; Martínez, M.; Ródenas, J.; Rieta, JJ.; Alcaraz, R. (2018). A novel wavelet-based filtering strategy to remove powerline interference from electrocardiograms with atrial fibrillation. Physiological Measurement. 39(11):1-15. https://doi.org/10.1088/1361-6579/aae8b1S115391

Atrial fibrosis identification with unipolar electrogram eigenvalue distribution analysis in multi-electrode arrays

Atrial fbrosis plays a key role in the initiation and progression of atrial fbrillation (AF). Atrial fbrosis is typically identifed by a peak-to-peak amplitude of bipolar electrograms (b-EGMs) lower than 0.5 mV, which may be considered as ablation targets. Nevertheless, this approach disregards signal spatiotemporal information and b-EGM sensitivity to catheter orientation. To overcome these limitations, we propose the dominant-to-remaining eigenvalue dominance ratio (EIGDR) of unipolar electrograms (u-EGMs) within neighbor electrode cliques as a waveform dispersion measure, hypothesizing that it is correlated with the presence of fbrosis. A simulated 2D tissue with a fbrosis patch was used for validation. We computed EIGDR maps from both original and time-aligned u-EGMs, denoted as R and RA, respectively, also mapping the gain in eigenvalue concentration obtained by the alignment, ΔRA. The performance of each map in detecting fbrosis was evaluated in scenarios including noise and variable electrode-tissue distance. Best results were achieved by RA, reaching 94% detection accuracy, versus the 86% of b-EGMs voltage maps. The proposed strategy was also tested in real u-EGMs from fbrotic and non-fbrotic areas over 3D electroanatomical maps, supporting the ability of the EIGDRs as fbrosis markers, encouraging further studies to confrm their translation to clinical settings

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