Validating left atrial fractionation and low-voltage substrate during atrial fibrillation and sinus rhythm-A high-density mapping study in persistent atrial fibrillation

Altres ajuts: Deutsche Herzstiftung (German Heart Foundation).Background: Low-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR. Materials and methods: Thirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high-density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined. Results: PFPs displayed low voltages both during AF (median 0.30 mV (Q1-Q3: 0.20-0.50 mV) and SR (median 0.35 mV (Q1-Q3: 0.20-0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1-Q3: 51-76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA 80%) fractionation concordance in AF and SR. Conclusion: Substrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF

Spatial Characterization and Estimation of Intracardiac Propagation Patterns During Atrial Fibrillation

This doctoral thesis is in the field of biomedical signal processing with focus on methods for the analysis of atrial fibrillation (AF). Paper I of the present thesis addresses the challenge of extracting spatial properties of AF from body surface signals. Different parameters are extracted to estimate the preferred direction of atrial activation and the complexity of the atrial activation pattern. In addition, the relation of the spatial properties to AF organization, which is quantified by AF frequency, is evaluated. While no significant correlation between the preferred direction of atrial activation and AF frequency could be observed, the complexity of the atrial activation pattern was found to increase with AF frequency. The remaining three papers deal with the analysis of the propagation of the electrical activity in the atria during AF based on intracardiac signals. In Paper II, a time-domain method to quantify propagation patterns along a linear catheter based on the detected atrial activation times is developed. Taking aspects on intra-atrial signal organization into account, the detected activation times are combined into wavefronts, and parameters related to the consistency of the wavefronts over time and the activation order along the catheter are extracted. Furthermore, the potential relationship of the extracted parameters to established measures from body surface signals is investigated. While the degree of wavefront consistency was not reflected by the applied body surface measures, AF frequency could distinguish between recordings with different degrees of intra-atrial signal organization. This supports the role of AF frequency as an organization measure of AF. In Paper III, a novel method to analyze intracardiac propagation patterns based on causality analysis in the frequency domain is introduced. In particular, the approach is based on the partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The potential of the method is illustrated with simulation scenarios based on a detailed ionic model of the human atrial cell as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. For simulated data, the PDC is correctly reflecting the direction of coupling and thus the propagation between all recording sites. For real data, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of ablation. However, spurious couplings over long distances can be observed when analyzing real data comprised by a large number of simultaneously recorded signals, which gives room for further improvement of the method. The derivation of the PDC is entirely based on the fit of a multivariate autoregressive (MVAR) model, commonly estimated by the least-squares (LS) method. In Paper IV, the adaptive group least absolute selection and shrinkage operator (LASSO) is introduced in order to avoid overfitting of the MVAR model and to incorporate prior information such as sparsity of the solution. The sparsity can be motivated by the observation that direct couplings over longer distances are likely to be zero during AF; an information which has been further incorporated by proposing distance-adaptive group LASSO. In simulations, adaptive and distance-adaptive group LASSO are found to be superior to LS estimation in terms of both detection and estimation accuracy. In addition, the results of both simulations and real data analysis indicate that further improvements can be achieved when the distance between the recording sites is known or can be estimated. This further promotes the PDC as a method for analysis of AF propagation patterns, which may contribute to a better understanding of AF mechanisms as well as improved AF treatment

Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an in-silico modeling study

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.ope

Automated algorithm-driven methods of localising drivers of persistent atrial fibrillation using atrial fibrillation cycle length and atrial fibrillation voltage

The assessment of atrial fibrillation cycle length has played a role in the development of atrial fibrillation ablation by pulmonary vein isolation (PVI) and has also been used to assess response to ablation. Areas of rapid rotational activity in the left atrium have been implied to act as drivers of persistent atrial fibrillation and several methods have been developed to identify these potential drivers. Unprocessed atrial fibrillation electrograms show large variation in cycle length and signal amplitude. Current methods of localising driver regions rely on complex pattern recognition and subjective assessment of operators. The main hypotheses of this thesis were as follows: 1) a technique can be developed to ascertain a clinically relevant, dominant cycle length for any AF segment, 2) the automated technique, can be used to map rapid and regular activity in the left atrium, 3) a patient-tailored definition of rapid activity and low AF voltage, calculated based on patient-specific parameters is feasible; 4) paired with automated low voltage substrate analysis, dominant cycle length analysis is able to provide a framework for localising drivers of AF that is objective, transparent and requires no complex pattern recognition of subjective judgement. To test the hypotheses, a technique was developed based on manual annotation of real-world AF electrograms that was able to ascertain cycle length independent of missing segments or variable cycle length or signal amplitude. Following this, an automated algorithm was validated to determine dominant cycle length. In the following chapter, the nature of AF cycle length was investigated by investigating the patterns of rapid activity with extended AF segments and the concept of patient-tailored definitions of rapid activity was introduced. In the subsequent analysis, the effect of PVI was examined on AF voltage and the AF cycle length, focusing on rapid and regular areas and low voltage zones, and their changes. The last chapter utilised the accumulated information to test the sensitivity and specificity of a percentile-based, patient-tailored approach to low AF voltage and to present an objective, automated method of localising rapid and regular areas within low voltage zones within the left atrium. In summary, it is feasible to assess and locate rapid and regular areas, and localise low voltage zones in persistent AF with a completely automated algorithm, and patient-tailored definitions of low voltage rapid AF activity are a preferable alternative to absolute cut offs.Open Acces

Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the leading cause of ischemic stroke and is the most commonly observed arrhythmia in clinical cardiology. Catheter ablation of AF, in which specific regions of cardiac anatomy associated with AF are intenionally injured to create scar tissue, has been honed over the last 15 years to become a relatively common and safe treatment option. However, the success of these anatomically driven ablation strategies, particularly in hearts that have been exposed to AF for extended periods, remains poor. AF induces changes in the electrical and structural properties of the cardiac tissue that further promotes the permanence of AF. In a process known as electroanatomical (EAM) mapping, clinicians record time signals known as electrograms (EGMs) from the heart and the locations of the recording sites to create geometric representations, or maps, of the electrophysiological properties of the heart. Analysis of the maps and the individual EGM morphologies can indicate regions of abnormal tissue, or substrates that facilitate arrhythmogenesis and AF perpetuation. Despite this progress, limitations in the control of devices currently used for EAM acquisition and reliance on suboptimal metrics of tissue viability appear to be hindering the potential of treatment guided by substrate mapping. In this research, we used computational models of cardiac excitation to evaluate param- eters of EAM that affect the performance of substrate mapping. These models, which have been validated with experimental and clinical studies, have yielded new insights into the limitations of current mapping systems, but more importantly, they guided us to develop new systems and metrics for robust substrate mapping. We report here on the progress in these simulation studies and on novel measurement approaches that have the potential to improve the robustness and precision of EAM in patients with arrhythmias. Appropriate detection of proarrhythmic substrates promises to improve ablation of AF beyond rudimentary destruction of anatomical targets to directed targeting of complicit tissues. Targeted treatment of AF sustaining tissues, based on the substrate mapping approaches described in this dissertation, has the potential to improve upon the efficacy of current AF treatment options

Characterization of Cardiac Electrogram Signals During Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia in United States. The most popular treatment for AF is a percutaneous procedure called catheter ablation. Current AF ablation procedures unfortunately have a poor success rate, primarily because the mechanisms involved in AF are incompletely understood even today. Intra-atrial electrograms have previously been shown to provide information on the mechanisms of AF. This thesis focuses on two such mechanisms – AF-sustaining sites known as sustained rotational activities (RotAs), and atrial tissue with unique electrical properties known as myocardial scars. Catheter ablation procedures today construct the 3D electroanatomic map of the left atrium (LA) by maneuvering a conventional Multipolar Diagnostic Catheter (MPDC) along the LA endocardial surface. These procedures are limited to pulmonary vein isolation and other linear ablation performed on various regions of the left atrium (such as roof and mitral isthmus) where the regions are decided based on the atrial anatomy. However, it remains unclear how to utilize the information provided by the MPDC to analyze and characterize the RotAs and scars. Previous electrogram characterization studies mainly use a single bipole rather than MPDCs to characterize the electrograms based on features such as cycle length or dominant frequency from the time or frequency domain. In this thesis we developed novel techniques for investigating the above mentioned mechanisms using signal analysis, mathematical modeling, numerical simulation and clinical experiments, all utilizing MPDC recordings. First, the variations in the total conduction delay (TCD) from MPDC electrograms as the MPDC moves towards a RotA source was investigated. Second, the maximum peak-to-peak amplitudes of MPDC electrograms recorded during AF and NSR were analyzed. This thesis provides insights into methods of characterization of cardiac electrograms and the findings of this thesis could address the current challenges in AF ablation

Characterizing Atrial Fibrillation Substrate by Electrogram and Restitution Analysis

Vorhofflimmern ist die häufigste supraventrikuläre Arrhythmie in der klinischen Praxis. Es gibt Hinweise darauf, dass pathologisches Vorhofsubstrat (Fibrose) eine zentrale mechanistische Rolle bei der Aufrechterhaltung von Vorhofflimmern spielt. Die Behandlung von Vorhofflimmern erfolgt durch Ablation des fibrotischen Substrats. Der Nachweis eines solchen Substrats ist jedoch eine ungelöste Herausforderung, was durch die mangelnden positiven klinischen Ablationsergebnisse ersichtlich wird. Daher ist das Hauptthema dieser Arbeit die Charakterisierung des atrialen Substrats. Die Bestimmung von Signalmerkmalen an Stellen mit fibrotischem Substrat erleichtert die Erkennung und anschließende Ablation solcher Areale in Zukunft. Darüber hinaus kann das Verständnis der Art und Weise, wie diese Areale das Vorhofflimmern aufrechterhalten, die positiven Ergebnisse von Ablationseingriffen verbessern. Schließlich kann Restitutionsinformation ein weiteres Instrument zur Substratcharakterisierung sein, das bei der Unterscheidung zwischen pathologischen und nicht-pathologischen Arealen helfen und somit das Ablationsergebnis weiter verbessert. In dieser Arbeit werden zwei Ansätze zur Substratcharakterisierung vorgestellt: Zunächst wurde eine Charakterisierung des Substrats mit Hilfe des intraatrialen Elektrogramms vorgenommen. Dazu wurde eine Auswahl spezifischer Merkmale des Elektrogramms an Positionen evaluiert, die eine Terminierung von Vorhofflimmern nach Ablation zur Folge hatten. Die Studie beinhaltete 21 Patienten, bei denen eine Ablation nach Pulmonalvenenisolation das klinisch persistierende Vorhofflimmern beendete. Der klinisch vorgeschlagene Grenzwert der Spannungsamplitude von <0:5 mV wurde genutzt, um die Positionen der Ablation zu definieren. Die Bereiche, in denen das Vorhofflimmern erfolgreich terminiert wurde, wiesen ausgeprägte Elektrogramm-Muster auf. Diese waren gekennzeichnet durch kurze lokale Zykluslängen, die fraktionierte Potentiale und Niederspannungspotentiale enthielten. Gleichzeitig zeigten sie eine lokale Konsistenz und deckten einen Großteil der lokalen Vorhofflimmer-Zykluslänge ab. Die meisten dieser Bereiche wiesen auch im Sinusrhythmus pathologisch verzögerte atriale Spätpotentiale und fraktionierte Elektrogramme auf. Im zweiten Teil der Arbeit wurden Restitutionsdaten der lokalen Amplitude und der lokalen Leitungsgeschwindigkeit (CV) erfasst und genutzt, um daraus Informationen über das zugrunde liegende Substrat abzuleiten. Die Daten zur Restitution wurden von 22 Patienten mit Vorhofflimmern aus zwei Kliniken unter Verwendung eines S1S2-Protokolls mit Stimulationsintervallen von 180 ms bis 500 ms gewonnen. Um Restitutionsdaten der Patientengruppe zu erhalten, musste ein automatisierter Algorithmus entwickelt werden, der in der Lage ist, große Mengen an Stimulationsprotokolldaten zu lesen, zu segmentieren und auszuwerten. Dieser Algorithmus wurde in der vorliegenden Arbeit entwickelt und CVAR-Seg genannt. Der CVAR-Seg Algorithmus bietet eine rauschresistente Signalsegmentierung, die mit extremen Rauschpegeln getestet wurde, die weit über dem erwarteten klinischen Pegel lagen. CVAR-Seg wurde unter einer Open-Source-Lizenz für die Allgemeinheit bereitgestellt. Es ermöglicht aufgrund seines modularen Aufbaus den einfachen Austausch einzelner Verfahrensschritte durch alternative Methoden entsprechend den Bedürfnissen des Anwenders. Darüber hinaus wurde im Rahmen dieser Studie eine neuartige Methode, die sogenannte inverse Doppelellipsenmethode, zur Bestimmung der lokalen CV etabliert. Diese Methode schätzt die CV, die Faserorientierung und den Anisotropiefaktor bei beliebiger Elektrodenanordnung. In Simulationen reproduzierte die Doppelellipsenmethode die vorherrschende CV, Faserorientierung und Anisotropie genauer und robuster als die aktuell gängigste Methode. Zusätzlich erwies sich diese Methode als echtzeittauglich und könnte daher in klinischen Elektrophysiologiesystemen eingesetzt werden. Die Doppelellipsenmethode würde durch die lokalisierte Vermessung des Vorhofsubstrats ermöglichen während eines Kartierungsverfahrens gleichzeitig eine CV-Karte, eine Anisotropieverhältniskarte und eine Faserkarte zu erstellen. Die Restitutionsinformationen der Patientenkohorte wurden mit der CVARSeg-Pipeline und der inversen Doppelellipsenmethode ausgewertet, um Amplituden- und CV-Restitutionskurven zu erhalten. Zur Anpassung der Restitutionskurven wurde eine monoexponentielle Funktion verwendet. Die Parameter der angepassten Funktion, die die Restitutionskurven abbilden, wurden verwendet, um Unterschiede in den Restitutionseigenschaften zwischen pathologischem und nicht-pathologischem Substrat zu erkennen. Das Ergebnis zeigte, dass klinisch definierte pathologische Bereiche durch eine reduzierte Amplitudenasymptote und einen steilen Kurvenabfall bei erhöhter Stimulationsrate gekennzeichnet waren. CV-Kurven zeigten eine reduzierte Asymptote und eine große Variation im Parameter der den Kurvenabfall beschreibt. Darüber hinaus wurden die Restitutionsunterschiede innerhalb des Vorhofs an der posterioren und anterioren Wand verglichen, da die Literatur keine eindeutigen Ergebnisse lieferte. In dieser Arbeit wurde nachgewiesen, dass die posteriore Vorhofwand Amplituden- und CV-Restitutionskurven mit höherer Asymptote und moderaterer Krümmung verglichen mit der anterioren Vorhofwand aufweist. Um über den empirisch beschriebenen manuellen Schwellenwert hinauszugehen, wurde der Parameterraum, der von den Anpassungsparametern der Amplituden- und CV-Restitutionskurven aufgespannt wird, nach natürlich vorkommenden Clustern durchsucht. Obgleich Cluster vorhanden waren, deutete ihre unzureichende Trennung auf einen kontinuierlichen, sich mit dem Schweregrad der Substratpathologie verändernden Verlauf der Amplituden- und CV-Kurven hin. Schließlich wurde eine einfachere und schnellere Methode zur Erfassung von Restitutionsdaten vorgestellt, die einen vergleichbaren Informationsgehalt auf der Grundlage der maximalen Steigung anstelle einer vollständigen Restitutionskurve liefert. In dieser Arbeit werden zwei neue Methoden vorgestellt, der CVAR-Seg-Algorithmus und die inverse Doppelellipsenmethode, die eine Auswertung von S1S2 Stimulationsprotokollen und die Bestimmung der lokalen Leitungsgeschwindigkeit beschleunigen und verbessern. Darüber hinaus werden in dieser Arbeit Merkmale von pathologischem Gewebe definiert, die zur Identifizierung von Arrhythmiequellen beitragen. Somit trägt diese Arbeit dazu bei, die Therapie von Vorhofflimmern in Zukunft zu verbessern

CVAR-Seg: An Automated Signal Segmentation Pipeline for Conduction Velocity and Amplitude Restitution

Background: Rate-varying S1S2 stimulation protocols can be used for restitution studies to characterize atrial substrate, ionic remodeling, and atrial fibrillation risk. Clinical restitution studies with numerous patients create large amounts of these data. Thus, an automated pipeline to evaluate clinically acquired S1S2 stimulation protocol data necessitates consistent, robust, reproducible, and precise evaluation of local activation times, electrogram amplitude, and conduction velocity. Here, we present the CVAR-Seg pipeline, developed focusing on three challenges: (i) No previous knowledge of the stimulation parameters is available, thus, arbitrary protocols are supported. (ii) The pipeline remains robust under different noise conditions. (iii) The pipeline supports segmentation of atrial activities in close temporal proximity to the stimulation artifact, which is challenging due to larger amplitude and slope of the stimulus compared to the atrial activity. Methods and Results: The S1 basic cycle length was estimated by time interval detection. Stimulation time windows were segmented by detecting synchronous peaks in different channels surpassing an amplitude threshold and identifying time intervals between detected stimuli. Elimination of the stimulation artifact by a matched filter allowed detection of local activation times in temporal proximity. A non-linear signal energy operator was used to segment periods of atrial activity. Geodesic and Euclidean inter electrode distances allowed approximation of conduction velocity. The automatic segmentation performance of the CVAR-Seg pipeline was evaluated on 37 synthetic datasets with decreasing signal-to-noise ratios. Noise was modeled by reconstructing the frequency spectrum of clinical noise. The pipeline retained a median local activation time error below a single sample (1 ms) for signal-to-noise ratios as low as 0 dB representing a high clinical noise level. As a proof of concept, the pipeline was tested on a CARTO case of a paroxysmal atrial fibrillation patient and yielded plausible restitution curves for conduction speed and amplitude. Conclusion: The proposed openly available CVAR-Seg pipeline promises fast, fully automated, robust, and accurate evaluations of atrial signals even with low signal-to-noise ratios. This is achieved by solving the proximity problem of stimulation and atrial activity to enable standardized evaluation without introducing human bias for large data sets

Characterization of the Substrate Modification in Patients Undergoing Catheter Ablation of Atrial Fibrillation

Tesis por compendio[ES] La fibrilación auricular (FA) es la arritmia cardíaca más común. A pesar de la gran popularidad de la ablación con catéter (AC) como tratamiento principal, todavía hay margen de mejora. Aunque las venas pulmonares (VPs) son los principales focos de FA, muchos sitios pueden contribuir a su propagación, formando el sustrato de la FA (SFA). El mapeo preciso del SFA y el registro de la modificación del SFA, como marcador positivo después de AC, son fundamentales. Los electrocardiogramas (ECG) y los electrogramas (EGM) se reclutan para este propósito. Los EGM se utilizan para detectar candidatos de AC como áreas que provocan o perpetúan la FA. Por lo tanto, el análisis de EGM es una parte indispensable de AC. Con la capacidad de observar las aurículas globalmente, la principal aplicación de los ECG es evaluar la modificación del SFA analizando las ondas f o P. A pesar del extenso análisis de cualquiera de los tipos de registro, existen algunas brechas. La AC no-VP aumenta el tiempo en quirófano, provocando mayores riesgos y costos. En cuanto al análisis de la modificación del SFA, se utilizan varios umbrales para definir una onda P prolongada. El principal objetivo de la presente Tesis es contribuir al esfuerzo de análisis de SFA y de modificación de SFA. Para ello, la presente Tesis se desarrolló bajo dos hipótesis principales. Que la calidad de la información extraída durante el SFA y el análisis de modificación del SFA se puede mejorar mediante la introducción de pasos innovadores. Además, la combinación de análisis de ECG y EGM puede aumentar la resolución del mapeo y revelar nueva información sobre los mecanismos de FA. Para cumplir con el objetivo principal, el análisis se divide en 4 partes, conformando los 4 capítulos del Compendio de articulos. En primer lugar, se reclutó la dimensión de correlación de grano grueso (DCGG). DCGG localizó de manera confiable EGM complejos y la clasificación por tipos de FA arrojó una precisión del 84 %. Luego, se adoptó un análisis alternativo de la onda P, estudiando por separado su primera y su segunda parte, correspondientes a la aurícula derecha (AD) e izquierda (AI). Los resultados indicaron LA como la principal fuente de modificación del SFA y subrayaron la importancia de estudiar partes integrales de ECG. Los hallazgos de este estudio también sugieren la implementación de partes integrales de ondas P como un posible alivio de las discrepancias en los umbrales de ondas P para definir el tejido fibrótico. Posteriormente, se estudió el efecto diferente del aislamiento de la VP izquierda (AVPI) y derecha (AVPD) sobre la modificación del SFA. AVPI fue la parte crítica, siendo la fuente exclusiva de acortamiento de onda P. El análisis de los registros durante la AC también permitió una observación más cercana de las fluctuaciones de la variabilidad de la frecuencia cardíaca (VFC) a lo largo del procedimiento de CA, lo que reveló información sobre el efecto de la energía de radiofrecuencia (RF) en el tejido auricular. La última parte se centró en el seno coronario (SC), una estructura fundamental en el mapeo de FA para aumentar la resolución de la información. Se definieron los canales más y menos robustos durante el ritmo sinusal (RS) y se investigó la utilidad de SC en la evaluación de la modificación del SFA. Aunque CS no proporcionó una imagen global de la alteración del SFA, pudo registrar con mayor sensibilidad las fluctuaciones en la respuesta auricular durante la AC. Los hallazgos presentados en esta Tesis Doctoral ofrecen una perspectiva alternativa sobre la modificación del SFA y contribuyen al esfuerzo general sobre el mapeo de FA y la evaluación del sustrato posterior a la CAAC, abriendo futuras líneas de investigación hacia una resolución más alta y un mapeo más eficiente de los mecanismos desencadenantes de la FA.[CA] La fibril·lació auricular (FA) és l'arítmia cardíaca més comú. Tot i la gran popularitat de l'ablació amb catèter (AC) com a tractament principal, encara hi ha marge de millora. Tot i que les venes pulmonars (VPs) són els principals focus de FA, molts llocs poden contribuir a la seva propagació, formant el substrat de la FA (SFA). El mapatge precís de l'SFA i el registre de la modificació de l'SFA, com a marcador positiu després d'AC, són fonamentals. Els electrocardiogrames (ECG) i els electrogrames (EGM) es recluten per a aquest propòsit. Els EGM es fan servir per detectar candidats d'AC com a àrees que provoquen o perpetuen la FA. Per tant, lanàlisi dEGM és una part indispensable dAC. Amb la capacitat d'observar les aurícules globalment, la principal aplicació dels ECG és avaluar la modificació de l'SFA analitzant les ones f o P. Tot i l'extensa anàlisi de qualsevol dels tipus de registre, hi ha algunes bretxes. L'AC no-VP augmenta el temps a quiròfan, provocant majors riscos i costos. Pel que fa a l'anàlisi de la modificació de l'SFA, s'utilitzen diversos llindars per definir una ona P perllongada. L'objectiu principal d'aquesta Tesi és contribuir a l'esforç d'anàlisi de SFA i de modificació de SFA. Per això, aquesta Tesi es va desenvolupar sota dues hipòtesis principals. Que la qualitat de la informació extreta durant el SFA i lanàlisi de modificació de lSFA es pot millorar mitjançant la introducció de passos innovadors. A més, la combinació d'anàlisi d'ECG i EGM pot augmentar la resolució del mapatge i revelar informació nova sobre els mecanismes de FA. Per complir amb l'objectiu principal, l'anàlisi es divideix en 4 parts i es conforma els 4 capítols del Compendi d'articles. En primer lloc, es va reclutar la dimensió de correlació de gra gruixut (DCGG). DCGG va localitzar de manera fiable EGM complexos i la classificació per tipus de FA va donar una precisió del 84%. Després, es va adoptar una anàlisi alternativa de l'ona P, estudiant per separat la primera i la segona part corresponents a l'aurícula dreta (AD) i esquerra (AI). Els resultats van indicar LA com la font principal de modificació de l'SFA i van subratllar la importància d'estudiar parts integrals d'ECG. Les troballes d'aquest estudi també suggereixen la implementació de parts integrals d'ones P com a possible alleugeriment de les discrepàncies als llindars d'ones P per definir el teixit fibròtic. Posteriorment, es va estudiar l'efecte diferent de l'aïllament de la VP esquerra (AVPI) i la dreta (AVPD) sobre la modificació de l'SFA. AVPI va ser la part crítica, sent la font exclusiva d'escurçament d'ona P. L'anàlisi dels registres durant l'AC també va permetre una observació més propera de les fluctuacions de la variabilitat de la freqüència cardíaca (VFC) al llarg del procediment de CA , cosa que va revelar informació sobre l'efecte de l'energia de radiofreqüència (RF) en el teixit auricular. L'última part es va centrar al si coronari (SC), una estructura fonamental al mapeig de FA per augmentar la resolució de la informació. Es van definir els canals més i menys robustos durant el ritme sinusal (RS) i es va investigar la utilitat de SC a l'avaluació de la modificació de l'SFA. Tot i que CS no va proporcionar una imatge global de l'alteració de l'SFA, va poder registrar amb més sensibilitat les fluctuacions a la resposta auricular durant l'AC. Les troballes presentades en aquesta Tesi Doctoral ofereixen una perspectiva alternativa sobre la modificació de l'SFA i contribueixen a l'esforç general sobre el mapeig de FA i l'avaluació del substrat posterior a la CAAC, obrint futures línies de recerca cap a una resolució més alta i un mapeig més eficient dels mecanismes desencadenants de la FA.[EN] Atrial fibrillation (AF) is the commonest cardiac arrhythmia. Despite the high popularity of catheter ablation (CA) as the main treatment, there is still room for improvement. Time spent in AF affects the AF confrontation and evolution, with 1,15% of paroxysmal AF patients progressing to persistent annually. Therefore, from diagnosis to follow-up, every aspect that contributes to the AF confrontation is of utmost importance. Although pulmonary veins (PVs) are the main AF foci, many sites may contribute to the AF propagation, by triggering or sustaining the AF, forming the AF substrate. Precise AF substrate mapping and recording of the AF substrate modification, as a positive marker after CA sessions, are critical. Electrocardiograms (ECGs) and electrograms (EGMs) are vastly recruited for this purpose. EGMs are used to detect candidate CA targets as areas that provoke or perpetuate AF. Hence, EGMs analysis is an indispensable part of the CA procedure. With the ability to observe the atria globally, ECGs' main application is to assess the AF substrate modification by analyzing f- or P-waves from recordings before and after CA. Despite the extensive analysis on either recording types, some gaps exist. Non-PV CA increases the time in operation room, provoking higher risks and costs. Furthermore, whether non-PV CA is beneficial is under dispute. As for the AF substrate modification analysis, various thresholds are used to define a prolonged P-wave, related with poor CA prognostics. The main objective of the present Thesis is to contribute to the effort of AF substrate and AF substrate modification analysis. For this purpose, the present Thesis was developed under two main hypotheses. That the information quality extracted during AF substrate and AF substrate modification analysis can be improved by introducing innovative steps. Also, that combining ECG and EGM analysis can augment the mapping resolution and reveal new information regarding AF mechanisms. To accomplish the main objective, the analysis is split in 4 parts, forming the 4 chapters of the Compendium of publications. Firstly, coarse-grained correlation dimension (CGCD) was recruited. CGCD reliably localized highly complex EGMs and classification by AF types yielded 84% accuracy. Then, an alternative P-wave analysis was suggested, studying separately the first and second P-wave parts, corresponding to the right (RA) and left (LA) atrium. The findings indicated LA as the main AF substrate modification source and underlined the importance of studying integral ECG parts. The findings of this study additionally suggest the implementation of integral P-wave parts as a possible alleviation for the discrepancies in P-wave thresholds to define fibrotic tissue. Afterwards, the different effect of left (LPVI) and right pulmonary vein isolation (RPVI) on the AF substrate modification was studied. LPVI was the critical part, being the exclusive source of P-wave shortening. Analysis of recordings during CA also allowed a closer observation of the heart rate variability (HRV) fluctuations throughout the CA procedure, revealing information on the effect of radiofrequency (RF) energy on the atrial tissue. The last part was focused on coronary sinus (CS), a fundamental structure in AF mapping to increase the information resolution. The most and least robust channels during sinus rhythm (SR) were defined and the utility of CS in AF substrate modification evaluation was investigated. Although CS did not provide a global picture of the AF substrate alteration, it was able to record with higher sensitivity the fluctuations in the atrial response during the application of RF energy. The findings presented in this Doctoral Thesis offer an alternative perspective on the AF substrate modification and contribute to the overall effort on AF mapping and post-CA substrate evaluation, opening future lines of research towards a higher resolution and more efficient mapping of the AF drivers.Vraka, A. (2022). Characterization of the Substrate Modification in Patients Undergoing Catheter Ablation of Atrial Fibrillation [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/191410Compendi