Background: Obstructive sleep apnea (OSA) has been associated with atrial enlargement in response to high arterial and pulmonary pressures and increased sympathetic tone. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; its impact on atrial electrical remodeling has not been investigated however. Signal-averaged p-wave (SAPW) is a non-invasive quantitative method to determine p-wave duration, an accepted marker for atrial electrical remodeling. The objective was to determine whether CPAP induces reverse atrial electrical remodeling in patients with severe OSA. Methods: Prospective study in consecutive patients attending the Sleep Clinic at Kingston General Hospital. All patients underwent full polysomnography. OSA-negative and severe OSA were defined as apnea-hypopnea index (AHI) < 5 events/hour and AHI ≥ 30 events/hour, respectively. In severe OSA patients, SAPW was determined pre- and post-intervention with CPAP for 4 - 6 weeks. In OSA-negative controls, SAPW was recorded at baseline and 4 - 6 weeks thereafter without any intervention. Results: A total of 19 severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum O2 saturation were 41.4 ± 10.1 events/hour and 80.5 ± 6.5% in severe OSA patients and 2.8 ± 1.2 events/hour and 91.4 ± 2.1% in controls. Baseline BMI was different between severe OSA patients and controls (34.3 ± 5.4 vs 26.6 ± 4.6 kg/m2; p < 0.001). At baseline, severe OSA patients had a greater SAPW duration than controls (131.9 ± 10.4 vs 122.8 ± 10.5 ms; p = 0.02). After CPAP intervention, there was a significant reduction of SAPW duration in severe OSA (131.9 ± 10.4 to 126.2 ± 8.8 ms; p < 0.001). In controls, SAPW duration did not change within 4 - 6 weeks. Conclusion: CPAP induced reverse atrial electrical remodeling in patients with severe OSA as represented by a significant reduction in SAPW duration. / Thesis (Master, Physiology) -- Queen's University, 2011-07-29 12:53:09.134

No description available.

A gordura epicárdica é biologicamente ativa e sua espessura nos obesos é aumentada. A repercussão da gordura epicárdica sobre o remodelamento cardíaco ainda não está completamente elucidada. No presente estudo, foi avaliada a gordura epicárdica e sua influência no remodelamento cardíaco de obesos mórbidos, antes e após a cirurgia bariátrica. Métodos: No Hospital das Clínicas da Universidade de São Paulo, foram recrutados de forma prospectiva 20 obesos mórbidos sem outras comorbidades e 20 controles. Os participantes realizaram avaliação clínica e laboratorial, medida da duração da onda P no ECG e ecocardiograma transtorácico. O grupo de obesos repetiu essa avaliação 12 meses após a cirurgia bariátrica. A medida da gordura epicárdica foi feita pelo ecocardiograma. Para comparar as variáveis contínuas, foram utilizados os testes t de Student (não pareado e pareado), de Mann-Whitney ou de Wilcoxson. Para definir correlação entre as variáveis lineares, foi utilizado o coeficiente de correlação de Pearson. Para definir a associação entre variáveis categóricas, foi usado o teste exato de Fisher. Para avaliar a associação entre variáveis dependentes e independentes, foi realizada uma análise de regressão múltipla. Os dados foram examinados no software R. Um valor de p abaixo de 0,05 foi considerado significativo. Resultados: No préoperatório, foram observados níveis elevados de proteína C reativa, uma maior duração da onda P, da massa ventricular e do diâmetro do átrio esquerdo nos obesos em relação aos controles (p < 0,05). Uma menor fração de ejeção do ventrículo esquerdo foi observada no grupo de obesos (p < 0,05). A gordura epicárdica foi maior nos obesos (p < 0,01). Uma correlação positiva foi encontrada entre a gordura epicárdica, a duração da onda P (r=0,70; p < 0,01), o diâmetro do átrio esquerdo (r=0,67; p < 0,01) e a massa ventricular (r=0,58; p < 0,01). Uma correlação inversa foi observada entre a gordura epicárdica e a fração de ejeção do ventrículo esquerdo (r=- 0,52; p < 0,01). Na análise de regressão múltipla, a gordura epicárdica permaneceu correlacionada com a duração da onda P, o diâmetro do átrio esquerdo e a fração de ejeção do ventrículo esquerdo (p < 0,05). Em 60% dos obesos, foi identificada alguma alteração na geometria ventricular. Uma associação entre a espessura da gordura epicárdica maior ou igual a 3,7 mm e a presença de remodelamento ventricular geométrico foi demonstrada (p=0,03). No pós-operatório, observou-se uma redução do índice de massa corporal, da proteína C reativa e da gordura epicárdica (p < 0,01). Uma redução da duração da onda P e um aumento da fração de ejeção do ventrículo esquerdo também foram observados (p < 0,01). Na análise de regressão múltipla esses achados permaneceram correlacionados à redução da gordura epicárdica (p < 0,05), independente da variação do índice de massa corporal e da proteína C reativa. Conclusões: Em obesos mórbidos sem outras comorbidades, a gordura epicárdica foi associada a um aumento da duração da onda P, do diâmetro do átrio esquerdo e da massa ventricular, além de uma menor fração de ejeção do ventrículo esquerdo. A espessura da gordura epicárdica igual ou acima de 3,7 mm foi associada a alterações do remodelamento ventricular. A redução da gordura epicárdica após a cirurgia bariátrica foi associada com a redução da duração da onda P e o aumento da fração de ejeção do ventrículo esquerdo, independente da variação do índice de massa corporal e da proteína C reativa / Epicardial fat is biologically active and its thickness is increased in obese subjects. The effects of epicardial fat on cardiac remodeling are still not fully understood. In the present study we evaluated epicardial fat and its influence on cardiac remodeling of morbidly obese, before and after bariatric surgery. Methods: We prospectively recruited 20 morbid obese subjects without other comorbidities and 20 control subjects at Hospital das Clínicas, Universidade de São Paulo. Participants underwent clinical and laboratory assessment, measure of P-wave duration on ECG and transthoracic echocardiogram. The obese group repeated this evaluation 12 months after the bariatric surgery. To compare continuous variables, we used t Student test (paired and nonpaired), Mann-Whitney and Wilcoxson tests. To define the correlation between linear variables we used Pearson correlation coefficient. To define the association between categorical variables we used Fisher exact test. A multiple regression analysis was performed to assess the association between dependent and independent variables. Data were analyzed by software R. A p value below 0.05 was considered statistically significant. Results: Preoperatively, we observed high levels of C-reactive protein, longer P-wave duration, larger ventricular mass and left atrial diameter in obese subjects compared to the controls (p < 0.05). Lower left ventricle ejection fraction was observed in the obese group (p < 0.05). Epicardial fat was higher among obese subjects (p < 0.01). A positive correlation was found between epicardial fat and P-wave duration (r=0.70; p < 0.01), left atrial diameter (r=0.67; p < 0.01), and ventricular mass (r=0.58; p < 0.01). An inverse correlation was observed between epicardial fat and left ventricle ejection fraction (r=-0.52; p < 0.01). In the multiple regression analysis, epicardial fat remained correlated with P-wave duration, left atrial diameter and left ventricle ejection fraction (p < 0.05). In 60% of the obese subjects, there was some abnormality in ventricular geometry. We showed association between thickness of epicardial fat equal to or higher than 3.7 mm and presence of geometric ventricular remodeling (p=0.03). Postoperatively, we observed reduction in body mass index, C-reactive protein and epicardial fat (p < 0.01). Reduction in P-wave duration and an increase in left ventricle ejection fraction were also observed (p < 0.01). In the multiple regression analysis, these findings were correlated with reduction in epicardial fat (p < 0.05), regardless of the variation in body mass index and C-reactive protein. Conclusion: In morbid obese subjects without other comorbidities, epicardial fat was associated with increase in P-wave duration, left atrial diameter and ventricular mass, in addition to smaller left ventricle ejection fraction. Epicardial fat thickness equal to or greater than 3.7 mm was associated with abnormalities in ventricular remodeling. Reduction of epicardial fat after bariatric surgery was associated with reduction of P-wave duration and increase in left ventricle ejection fraction, regardless of the variation in body mass index and C-reactive protein

A gordura epicárdica é biologicamente ativa e sua espessura nos obesos é aumentada. A repercussão da gordura epicárdica sobre o remodelamento cardíaco ainda não está completamente elucidada. No presente estudo, foi avaliada a gordura epicárdica e sua influência no remodelamento cardíaco de obesos mórbidos, antes e após a cirurgia bariátrica. Métodos: No Hospital das Clínicas da Universidade de São Paulo, foram recrutados de forma prospectiva 20 obesos mórbidos sem outras comorbidades e 20 controles. Os participantes realizaram avaliação clínica e laboratorial, medida da duração da onda P no ECG e ecocardiograma transtorácico. O grupo de obesos repetiu essa avaliação 12 meses após a cirurgia bariátrica. A medida da gordura epicárdica foi feita pelo ecocardiograma. Para comparar as variáveis contínuas, foram utilizados os testes t de Student (não pareado e pareado), de Mann-Whitney ou de Wilcoxson. Para definir correlação entre as variáveis lineares, foi utilizado o coeficiente de correlação de Pearson. Para definir a associação entre variáveis categóricas, foi usado o teste exato de Fisher. Para avaliar a associação entre variáveis dependentes e independentes, foi realizada uma análise de regressão múltipla. Os dados foram examinados no software R. Um valor de p abaixo de 0,05 foi considerado significativo. Resultados: No préoperatório, foram observados níveis elevados de proteína C reativa, uma maior duração da onda P, da massa ventricular e do diâmetro do átrio esquerdo nos obesos em relação aos controles (p < 0,05). Uma menor fração de ejeção do ventrículo esquerdo foi observada no grupo de obesos (p < 0,05). A gordura epicárdica foi maior nos obesos (p < 0,01). Uma correlação positiva foi encontrada entre a gordura epicárdica, a duração da onda P (r=0,70; p < 0,01), o diâmetro do átrio esquerdo (r=0,67; p < 0,01) e a massa ventricular (r=0,58; p < 0,01). Uma correlação inversa foi observada entre a gordura epicárdica e a fração de ejeção do ventrículo esquerdo (r=- 0,52; p < 0,01). Na análise de regressão múltipla, a gordura epicárdica permaneceu correlacionada com a duração da onda P, o diâmetro do átrio esquerdo e a fração de ejeção do ventrículo esquerdo (p < 0,05). Em 60% dos obesos, foi identificada alguma alteração na geometria ventricular. Uma associação entre a espessura da gordura epicárdica maior ou igual a 3,7 mm e a presença de remodelamento ventricular geométrico foi demonstrada (p=0,03). No pós-operatório, observou-se uma redução do índice de massa corporal, da proteína C reativa e da gordura epicárdica (p < 0,01). Uma redução da duração da onda P e um aumento da fração de ejeção do ventrículo esquerdo também foram observados (p < 0,01). Na análise de regressão múltipla esses achados permaneceram correlacionados à redução da gordura epicárdica (p < 0,05), independente da variação do índice de massa corporal e da proteína C reativa. Conclusões: Em obesos mórbidos sem outras comorbidades, a gordura epicárdica foi associada a um aumento da duração da onda P, do diâmetro do átrio esquerdo e da massa ventricular, além de uma menor fração de ejeção do ventrículo esquerdo. A espessura da gordura epicárdica igual ou acima de 3,7 mm foi associada a alterações do remodelamento ventricular. A redução da gordura epicárdica após a cirurgia bariátrica foi associada com a redução da duração da onda P e o aumento da fração de ejeção do ventrículo esquerdo, independente da variação do índice de massa corporal e da proteína C reativa / Epicardial fat is biologically active and its thickness is increased in obese subjects. The effects of epicardial fat on cardiac remodeling are still not fully understood. In the present study we evaluated epicardial fat and its influence on cardiac remodeling of morbidly obese, before and after bariatric surgery. Methods: We prospectively recruited 20 morbid obese subjects without other comorbidities and 20 control subjects at Hospital das Clínicas, Universidade de São Paulo. Participants underwent clinical and laboratory assessment, measure of P-wave duration on ECG and transthoracic echocardiogram. The obese group repeated this evaluation 12 months after the bariatric surgery. To compare continuous variables, we used t Student test (paired and nonpaired), Mann-Whitney and Wilcoxson tests. To define the correlation between linear variables we used Pearson correlation coefficient. To define the association between categorical variables we used Fisher exact test. A multiple regression analysis was performed to assess the association between dependent and independent variables. Data were analyzed by software R. A p value below 0.05 was considered statistically significant. Results: Preoperatively, we observed high levels of C-reactive protein, longer P-wave duration, larger ventricular mass and left atrial diameter in obese subjects compared to the controls (p < 0.05). Lower left ventricle ejection fraction was observed in the obese group (p < 0.05). Epicardial fat was higher among obese subjects (p < 0.01). A positive correlation was found between epicardial fat and P-wave duration (r=0.70; p < 0.01), left atrial diameter (r=0.67; p < 0.01), and ventricular mass (r=0.58; p < 0.01). An inverse correlation was observed between epicardial fat and left ventricle ejection fraction (r=-0.52; p < 0.01). In the multiple regression analysis, epicardial fat remained correlated with P-wave duration, left atrial diameter and left ventricle ejection fraction (p < 0.05). In 60% of the obese subjects, there was some abnormality in ventricular geometry. We showed association between thickness of epicardial fat equal to or higher than 3.7 mm and presence of geometric ventricular remodeling (p=0.03). Postoperatively, we observed reduction in body mass index, C-reactive protein and epicardial fat (p < 0.01). Reduction in P-wave duration and an increase in left ventricle ejection fraction were also observed (p < 0.01). In the multiple regression analysis, these findings were correlated with reduction in epicardial fat (p < 0.05), regardless of the variation in body mass index and C-reactive protein. Conclusion: In morbid obese subjects without other comorbidities, epicardial fat was associated with increase in P-wave duration, left atrial diameter and ventricular mass, in addition to smaller left ventricle ejection fraction. Epicardial fat thickness equal to or greater than 3.7 mm was associated with abnormalities in ventricular remodeling. Reduction of epicardial fat after bariatric surgery was associated with reduction of P-wave duration and increase in left ventricle ejection fraction, regardless of the variation in body mass index and C-reactive protein

No description available.

Rationnel et objectif - La fibrillation atriale (FA) est la pathologie rythmique supra-ventriculaire la plus fréquemment diagnostiquée. Le remodelage atrial, qu’il soit électrique ou structurel, conduit à la mise en place et au développement de la cardiomyopathie atriale. La cardiomyopathie atriale est responsable de différentes complications : d’une part mécaniques conduisant à l’augmentation du risque thrombo-embolique et de l’insuffisance cardiaque, d’autre part électriques conduisant à différentes arythmies atriales dont la FA. L’objectif du présent travail est de caractériser les déterminants du remodelage atrial et de leur effet pro-arythmique à l’étage supra-ventriculaire dans la FA. Principaux résultats – Le premier axe de recherche a permis d’objectiver le remodelage induit par le flutter atrial (FLA) chronique à l’aide d’un modèle chronique canin. Le FLA est à l’origine d’un remodelage atrial électrique avec une augmentation de la vulnérabilité à développer de la FA et une diminution des périodes réfractaires effectives (PRE). Cependant, le FLA n’induit pas de remodelage structurel avec notamment l’absence d’augmentation de la durée de FA, de diminution des vitesses de conduction et d’augmentation du processus fibrotique atrial. À noter que la FA chronique, en présence d’un substrat anatomique de FLA, présente des caractéristiques électrophysiologiques originales, en terme de durée de cycle et de d’arythmie et de sa stabilité. De plus, l’ablation du FLA permet de diminuer significativement la durée mais pas la vulnérabilité à présenter des arythmies supra-ventriculaires. Le second axe de recherche a permis de caractériser le rôle différentiel de l’arythmie atriale de la réponse ventriculaire rapide en cas de FA dans le développement du remodelage atrial. Nos travaux ont caractérisé le remodelage atrial induit par l’arythmie atriale isolée en cas de FA : d’une part électrique via la diminution des PRE et l’augmentation de la vulnérabilité ; d’autre part structurel via la diminution des vitesses de conduction et les anomalies des canaux sodiques, des jonctions communicantes et du processus fibrotique. La réponse ventriculaire rapide isolée induit également un remodelage atrial à type d’augmentation de la vulnérabilité, de diminution des vitesses de conduction, d’anomalies modérées du processus fibrotique et des canaux sodiques. À noter une dégradation modérée de la fonction systolique ventriculaire gauche. Cependant, ce remodelage atrial est significativement différent du remodelage induit par l’insuffisance cardiaque. De plus, il existe un effet synergique au niveau du remodelage atrial de l’arythmie atriale et de la fréquence ventriculaire élevée en cas de FA, au niveau du processus fibrotique notamment. Le troisième axe de recherche a permis d’objectiver le rôle de la cilnidipine, un inhibiteur calcique de type N et L, dans la limitation du remodelage atrial en cas de FA chronique, à l’aide d’un modèle aigü et chronique canin. Nos travaux ont caractérisé l’action anti-remodelante de la cilnidipine au niveau électrique, via la limitation de la diminution des PRE, de l’augmentation de la vulnérabilité atriale et de la durée de FA. D’autre part, la cilnidipine semble limiter le remodelage atrial, ce qui est objectivé par la normalisation des vitesses de conduction, de l’expression des canaux sodiques, des jonctions communicantes et de la fibrose tissulaire. La cilnidipine, contrairement aux inhibiteurs calciques de type L tels que la nifédipine, possède une activité anti-remodelante via la modulation de l’activité du système nerveux autonome. Conclusion – Différents facteurs, tels que le flutter atrial, les fréquences atriales et ventriculaires en cas de FA, ont été caractérisés comme déterminants du développement du remodelage atrial. A contrario, la modulation d’un des déterminants du remodelage atrial, le système nerveux autonome via la cilnidipine, permet de de limiter le remodelage atrial secondaire à la FA. Ce travail fournit de nouvelles données sur les mécanismes impliqués dans le remodelage atrial lié à la FA et introduit de nouvelles approches préventives au développement de la FA. / Rational and objective - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Atrial remodeling, whether electrical or structural, leads to the development of atrial cardiomyopathy. The atrial cardiomyopathy results in various complications: on one hand, mechanical with an increased thromboembolic risk and heart failure, and on the other hand electrical prdeisposing to atrial arrhythmias including AF. The aim of the thesis was to characterize the determinants of atrial remodeling, and their proarrhythmic effect in AF. Main results - The first part of the thesis focused on the characterization of the atrial remodeling induced by sustained atrial flutter (AFL) in a chronic canine model in order to characterize the interrelationship between AF and AFL. AFL caused electrical remodeling, including increased AF vulnerability and decreased effective refractory periods (ERPs). However, failed to influence AF duration, atrial conduction velocities and fibrosis. Chronic AF in the presence of an anatomical substrate for AFL led to specific AF characteristics, in terms of cycle length and its variability. In addition, AFL ablation significantly reduced arrhythmia duration but not AF vulnerability. The second part of the thesis characterized the differential role of atrial arrhythmia and ventricular response in AF-induced atrial remodeling. We characterized the atrial remodeling induced by lone atrial arrhythmia in AF, with AV-block to prevent high ventricular rate: on the one hand electrical via decreased ERP, reduced expression of sodium channels and gap junctions, which increased AF vulnerability; on the other hand, structural fibrosis which contributed to conduction slowing. Lone high-rate ventricular response also induced atrial remodeling involving increased AF vulnerability, decreased atrial conduction velocities, moderate abnormalities of fibrosis and sodium channel downregulation. In addition, there was a synergistic effect on atrial remodeling of combined atrial arrhythmia and high ventricular rate, especially regarding fibrosis. Thus, atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodeling; both can contribute to the arrhythmogenic substrate. These results provide new insights into the determinants of AF-related remodeling and provide novel considerations for ventricular rate-control. The third part of the thesis studies the ability of cilnidipine, an N- and L-type calcium channel blocker, to alter autonomic, electrical and structural remodeling associated with chronic AF, in a subacute and chronic dog model. We found that the cilnidipine inhibits the electrophysiological, autonomic and structural consequences of AF-related remodeling and the AF-associated increase in AF-vulnerability and AF-duration; in contrast, the highly selective L-type calcium channel blocker nifedipine had no protective effects. The protective effects of cilnidipine on the remodeling consequences of short-term AF were principally manifested by reductions in AF-induced ERP-abbreviation. With longer-term AF, cilnidipine also attenuated conduction-velocity reductions, protecting against AF-induced fibrosis and downregulation of sodium-channel and connexin subunits. Cilnidipine’s anti-remodeling properties were associated with suppression of the changes in autonomic tone caused by AF. Conclusion - Thus, we have shown 1) the distinct remodeling phenotypes produced by the closely related atrial re-entrant arrhythmias AFL and AF, as well as the interaction when they co-exist; 2) the specific contributions of the atrial rhythm and ventricular rate consequences of AF and how they interact; and 3) the ability of autonomic outflow inhibition by blocking N-type Ca2+-channels to prevent both electrical and structural components of AF-induced profibrillatory remodeling. This work provides new insights into the mechanisms involved in AF-related atrial remodeling and introduces novel preventive approaches.

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/10251/191410 / Compendio