Atrial Fibrillation (AF) is a debilitating heart rhythm disorder affecting over 2.7 million people in the US and over 30 million people worldwide annually. It has a high correlation with causing a stroke and several other risk factors, resulting in increased mortality and morbidity rate. Currently, the non-pharmocological therapy followed to control AF is catheter ablation, in which the tissue surrounding the pulmonary veins (PVs) is cauterized (called the PV isolation - PVI procedure) aims to block the ectopic triggers originating from the PVs from entering the atrium. However, the success rate of PVI with or without other anatomy-based lesions is only 50%-60%. A major reason for the suboptimal success rate is the failure to eliminate patientspecific non-PV sources present in the left atrium (LA), namely reentry source (a.k.a. rotor source) and focal source (a.k.a. point source). It has been shown from several animal and human studies that locating and ablating these sources significantly improves the long-term success rate of the ablation procedure. However, current technologies to locate these sources posses limitations with resolution, additional/special hardware requirements, etc. In this dissertation, the goal is to develop an efficient algorithm to locate AF reentry and focal sources using electrograms recorded from a conventionally used high-resolution multi-pole diagnostic catheter. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / BACKGROUND: Atrial fibrillation (AF) that occurs during acute critical illnesses such as sepsis may have different risk factors than AF that occurs in the community setting. METHODS: We investigated associations between baseline electrocardiographic (ECG) parameters related to conduction, ischemia, and chamber size and new-onset AF that occurs in the setting of severe sepsis in a matched case-referent study. We matched 100 patients with new-onset AF during sepsis to 300 patients with similar age (plus or minus 5 years) who were hospitalized within Boston Medical Center intensive care units (ICU) between 2003-2009 with sepsis. Variables that were found to be significant (p<0.05) during conditional univariable logistic regression were entered into age, sex and race-adjusted conditional logistic regression in order to identify risk factors for new-onset AF during sepsis. RESULTS: Among 100 case and 300 referent patients with sepsis, the distribution of mean age was 69 +/-11 years vs. 71 +/- 11 years, sex was 42% female vs. 49% female, and race was 56% white and 33% black vs. 65% white and 21% black between cases and referents, respectively. Univariable analysis revealed that older age per year [OR 1.25 95% CI (1.07-1.46), p<0.01], longer PR interval per millisecond [168 +/- 43 ms vs. 157 +/- 30 ms; OR 1.01 95% CI (1.00-1.02), p=0.02], and presence of left bundle branch block (LBBB) [9 (9%) vs. 7 (2.3%); OR 4.42 95% CI (1.45-13.5), p<0.01] were significant risk factors among the new-AF cases. Our multivariable model found significant associations between new-onset AF during hospitalization and presence of prolonged PR interval per millisecond [OR 1.01 95% CI (1.00-1.02), p=0.04] and LBBB [OR 6.83 95% CI (1.68-27.8), p=0.01] on ICU admission ECG. CONCLUSION: Increased PR interval length and LBBB found on a 12-lead ECG upon ICU admission was associated with new-onset AF during hospitalization in the setting of sepsis. / 2031-01-01

Abstract Brugada syndrome is an inherited arrhythmia disorder that predisposes to sudden cardiac death. It is characterized by its distinct ECG pattern. The purpose of this thesis was to study the phenotype and genotype characteristics of subjects with Brugada syndrome type ECG. The first study population consisted of 2479 young male Air Force applicants and 542 healthy middle-aged subjects. The 12-lead ECG was analyzed to assess the prevalence and prognosis of Brugada pattern in Finnish population. The second population consisted of 168 patients with AF. The ECGs of the patients with family history of lone AF were analysed in order to characterize the ECG features of familial AF. The third population consisted of 200 patients with Brugada syndrome and their ECGs were analyzed for detection of distinct ECG characteristics. In a substudy, the H558R variant was genotyped and the clinical presentation of this variant was evaluated. The clinical characteristics were collected of 47 patients with induced Brugada ECG during fever or medication. The prevalence of type 2 or 3 Brugada ECG was 0.61% in the young population and 0.55% in the middle-aged Finnish population. In a retrospective analysis, none of the Brugada ECG carriers had died. In the AF study, the prevalence of type 2 or 3 Brugada ECG was significantly higher among the subjects with lone AF compared to the healthy controls (p &lt; 0.001). Many of the Brugada ECG carriers had a family history (> 30% of first-degree relatives) of AF. In patients with Brugada syndrome, the prolonged QRS duration was associated with previous symptoms. The R allele carriers in H558R variant had a trend towards less symptoms (p = 0.067) and had less conduction disturbances in 12-lead ECG than the HH genotype carriers (p &lt; 0.05 in all ECG analysis). Among the subjects with induced Brugada ECG, 51% exhibited arrhythmic symptoms during the medical condition that had provoked the ECG pattern. In conclusion, type 2 and 3 Brugada ECGs were found to be benign in the Finnish population since no mortality occurred during an extensive follow-up period. On the other hand, these ECG abnormalities seem to be a marker of familial AF. Among patients with the Brugada syndrome, a prolongation of QRS is associated with prior symptoms. The variant H558R R allele seems to be a protecting genetic modulator. Induced Brugada ECG is a medical emergency since the patients are at high risk of sudden cardiac death.

Class of 2015 Abstract / Objectives: Warfarin has historically been the anticoagulant used for the primary prevention of stroke in atrial fibrillation (AF), however three target specific oral anticoagulants, dabigatran, rivaroxaban, and apixaban, have recently been approved for use in this setting. Current literature lacks a comparison of these four drugs in relation to post-stroke outcomes, and this study aims to compare their performance in a natural setting. Methods: This retrospective cohort study identified stroke patients admitted to an academic medical center between January 2013 and December 2014 using the Quintiles, Inc.-American Heart Association Get With The Guidelines-Stroke database; pertinent data was collected from the database and patient electronic medical records. Primary endpoints measured were length of stay, 30-day readmission, and discharge disposition; secondary endpoints included rates of admission to the intensive care unit (ICU) and complications. Results: Of 940 stroke admissions, 53 ischemic stroke patients were identified as receiving an oral anticoagulant for stroke prevention in AF. The warfarin (n=40) and non-warfarin (dabigatran, rivaroxaban, and apixaban; n=13) groups were well matched regarding admission demographics, however patients taking warfarin were more likely to have an elevated INR at hospital admission (P=0.0053) and receive tPA (P=0.047). Patients in the warfarin group were also statistically significantly more likely to receive warfarin on discharge (P=0.004). No endpoints achieved statistical significance. Conclusions: No differences in post-stroke outcomes between warfarin and non-warfarin oral anticoagulants used for stroke prevention in AF were found.

Cardiovascular disease remains the leading cause of death in the developed world. In this thesis computational modelling techniques were used to study the mechanisms and genesis of atrial arrhythmias. It is separated into 2 parts: (1) The mechanistic links between mutations of the fast Na+ channel (INa) and the ability of the sinoatrial node to pace the surrounding atrial muscle were investigated. The mutations were separated into two groups, one for the mutations affecting the steady-state activation, and the other for those affecting steady-state inactivation. On the single cell level it was found that all mutations slowed the pacing rate of the sinoatrial node in a similar way, but at the 2D level the two mutation groups modulated the excitation of the tissue differently. One caused a conduction block between the sinoatrial node and atrium, where the other abolished pacemaking all together. (2) A new set of mathematical models were then developed for the sheep atria. This was incorporated into an anatomically detailed 3D geometry of the whole sheep atria to form a platform suitable for the study of clinical atrial fibrillation, and other atrial arrhythmias. Due to the lack of single cell electrophysiology data available, a method of cross-species modelling was utilised. A biophysically detailed model of the 3D sheep atria was created, and used in a preliminary study into the susceptibility of tissue to atrial fibrillation from the rapid pacing of the pulmonary vein area. It was found that both electrical heterogeneity and the complex fibre structure of the atria need to be considered for sustained atrial fibrillation to be seen.

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La fibrillation atriale (FA) est le trouble du rythme cardiaque le plus fréquent et dont la prévalence est en constante augmentation. Les extrasystoles déclenchant cette arythmie naissent le plus souvent des veines pulmonaires. Ainsi l’ablation des veines pulmonaires est devenue un traitement important de cette arythmie, surtout quand elle est paroxystique. Cependant le maintien de la FA est assuré par du substrat atrial pathologique.Le traitement endocavitaire de ce substrat comprend essentiellement l’ablation de potentielsfragmentés enregistrés en FA.Nous avons démontré que ces potentiels fragmentés existent aussi en rythme sinusal etqu’une partie de ces potentiels pouvait être générée par une activation vagale myocardiquelocale.Par ailleurs cette ablation de FA présente de nombresuses complications dont certaines sont potentiellement graves comme par exemple la tamponnade.Nous avons montré que la ponction transseptale nécessaire pour réaliser cette intervention pouvait être effectuée de manière sure en utilisant un monitorage du septum interatrial parechocardiographie endovasculaire utilisée par voie oesophagienne, diminuant ainsi le risque de tamponnade.Nous avons aussi montré que la présence d’une récidive d’arythmie précoce (<1 mois) postablationétait hautement prédictive d’une récidive tardive et qu’une réablation précoce dansle mois suivant la première intervention était efficace mais nécessitait un nombre plusimportant de procédures pour obtenir une efficacité stable dans le tempsPar ailleurs, nous avons montré que l’ablation de FA générait une importante inflammation systémique et que cette inflammation était associée à un taux plus faible de récidives précoces mais non tardives.Enfin nous avons montré qu’un cycle fibrillatoire rapide< 142 ms, une ancienneté de la FA >21 mois et une amplitude de l’onde fibrillatoire < 0.07 mV étaient des facteurs importants d’échec d’ablation de FA persistante. / Pas de résumé anglais

INTRODUÇÃO: O aumento da proporção de idosos implica estudar os determinantes dos principais agravos associados ao envelhecimento como a demência, principalmente a associada à doença cerebrovascular. Um fator de risco relevante para doença cerebrovascular é a freqüência de fibrilação atrial crônica. O São Paulo Health and Ageing Study com base populacional para estudo de distúrbio cognitivo e demência é uma oportunidade única para verificar a prevalência de fibrilação atrial e de sua associação com demência. MÉTODOS: Estudo transversal, por arrolamento de 1524 idosos com 65 anos ou mais estudo acima, no distrito do Butantã, cidade de São Paulo. O diagnóstico de fibrilação atrial foi feito com o eletrocardiograma de repouso de doze derivações e o de demência foi feito utilizando-se o protocolo do Research Group of Dementia 10/66. Estudaram-se variáveis sócio-econômicas e fatores de risco cardiovascular como hipertensão, diabetes, dislipidemia e obesidade. RESULTADOS: A amostra estudada tinha idade média de 72,2 anos, era predominantemente feminina, branca, casada, de baixa escolaridade e renda. A prevalência de fibrilação atrial associou-se ao aumento da idade e foi de 1,9% para o sexo feminino e 3,1% para o sexo masculino, com prevalência para ambos os sexos ajustada para idade de 2,7%. A prevalência de demência também se associou ao aumento da idade e sua prevalência idade ajustada foi de 4,9%, maior em mulheres (4,8%) do que em homens (3,6%). A razão de chances ajustada para idade para a associação de fibrilação atrial e demência foi de 2,88 (Intervalo de Confiança, IC 95% - 0,98 8,40) para ambos os sexos sendo e, de 1,50 (IC95% - 0,19 11,83) para homens e 4,48 (IC95% - 1,23 16,29) para mulheres. Encontrou-se maior risco de demência entre mulheres com fibrilação atrial (17,7%) do que entre os participantes do mesmo sexo sem demência (4,6%) Outras alterações no eletrocardiograma de repouso com interesse foram determinadas como com área inativa (código de Minnesotta q1- q2) de: 9,1% nas mulheres e 16,6% nos homens; e também bloqueio de ramo esquerdo de 3,3%, nas mulheres 3,0% e nos homens 3,6%. CONCLUSÃO: Mulheres idosas com fibrilação atrial têm diagnóstico de demência quase quatro vezes mais do que aquelas em ritmo sinusal / INTRODUCTION: The growing aging population proportion makes us study the most important illness related with aging of the population as dementia, specially the dementia associated to stroke. Atrial fibrillation is a main risk factor with cerebrovascular disease. The São Paulo Heath and Ageing Study a population based study for cognitive disturb and dementia is an unique opportunity to verify the atrial fibrillation prevalence and its association with dementia. Methods: This is a cross-sectional study. The population of this study was composed by 1,524 elderly people, over 65 years of age, covered by the Health Program Family in the Butantã district, São Paulo, who were recruited door by door. The diagnosis of atrial fibrillation was made using a twelve lead resting electrocardiogram and the diagnosis of dementia was made by the protocol of Research Group of Dementia 10/66. We studied socio economic variables and cardiovascular risk factors as hypertension, diabetes, dislipidemia and obesity. RESULTS: The studied population had a mean age of 72.2 years old and was predominantly female, white, married and of low educational and financial status. We found that atrial fibrillation prevalence increased throughout age-strata and was of 1.9% among the females and 3.1% among the males, and age-adjusted prevalence of 2.7%. The prevalence of dementia also increases with age and its ageadjusted prevalence was of 4.9%, greater among the females (4.8%) than among the males (3.6%). The odds ratio age-adjusted for the association of atrial fibrillations and dementia was of 2.88 (Confidence interval, 95% CI 0.98 8.40) for both sex: 1.50 among men (95% CI 0.19 11.83), and 4.48 among women (95% CI 1.23 16.29). We found a higher risk of dementia among the female with atrial fibrillation (17.7%) than among female participants without atrial fibrillation (4.6%). Other resting electrocardiogram alterations were determined as previous inactive areas (Minnesotta Code q1-q2) of 12.4%: among the females of 9.1% and among the males of 16.6%. The frequency of left bundle-branch block was of 3.3%: among the females of 3.0% and among the males of 3.6% .CONCLUSION: Elderly women with atrial fibrillation had the diagnosis of dementia almost four times greater than that of women with sinus rhythm