Made available in DSpace on 2015-07-22T20:50:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-26. Added 1 bitstream(s) on 2015-08-11T03:25:26Z : No. of bitstreams: 1 Publico-0021a.pdf: 1600053 bytes, checksum: 7857382dabdbe2c1244a470f04a307d0 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:26Z : No. of bitstreams: 2 Publico-0021a.pdf: 1600053 bytes, checksum: 7857382dabdbe2c1244a470f04a307d0 (MD5) Publico-0021b.pdf: 1840605 bytes, checksum: 6332e90958fa262a4e0df6f8545a5303 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:26Z : No. of bitstreams: 3 Publico-0021a.pdf: 1600053 bytes, checksum: 7857382dabdbe2c1244a470f04a307d0 (MD5) Publico-0021b.pdf: 1840605 bytes, checksum: 6332e90958fa262a4e0df6f8545a5303 (MD5) Publico-0021c.pdf: 2001738 bytes, checksum: a1284696a0e1de7fec9bd415286e36b2 (MD5) / INTRODUÇÃO: Taquicardias Ventriculares Sustentadas (TVs) epicárdicas são comuns na Cardiopatia Chagásica Crônica (CCC). A ablação por cateter com radiofrequência, pode ser realizada com o auxílio de mapeamento eletroanatômico. O mapeamento eletroanatômico, por sua vez, necessita de definição especial, que pode ser incrementada com a integração de imagens oriundas de Tomografia Computadorizada do coração (TC do coração). A TC do coração pode fornecer a localização das áreas de fibrose, a extensão do comprometimento miocárdico, as características da anatomia coronariana e a função ventricular (esquerda e direita). Enquanto o acoplamento de imagens foi exaustivamente estudado no endocárdio, o acoplamento epicárdico e as informações advindas da aquisição de tomografia pré-procedimento não foram adequadamente avaliados até o momento. OBJETIVOS: Determinar a viabilidade técnica e a acurácia do mapeamento eletroanatômico com a integração de imagens associadas à TC em pacientes com TVS e CCC. Avaliar a precisão da TC em delimitar áreas de miocárdio anormal em comparação com o mapeamento eletroanatômico em portadores de CCC e TVS. MÉTODOS E RESULTADOS: Foi realizado o mapeamento e a ablação endocárdica e epicárdica em 8 pacientes portadores de CCC e TVS utilizando Carto® XP e sistema de integração de imagens Carto® Merge. A integração de imagens foi realizada utilizando TC em 3 fases para a obtenção do escore de cálcio, angiotomografia de coronárias e realce tardio. Para a comparação das imagens tridimensionais do sistema de mapeamento eletroanatômico e bidimensional da fluoroscopia, foi utilizado um editor gráfico vetorial. Este permitiu a comparação da distância entre a posição do cateter observado pela fluoroscopia e a obtida pelo mapa eletroanatômico. A diferença média entre os métodos analisados foi de 6,03mm (DP ±2,09mm). Cicatrizes estavam presentes no endocárdio e epicárdio de ambos ventrículos, sendo encontradas mais frequentemente na região póstero-basal de VE. A análise da contratilidade segmentar demonstrou-se superiora à técnica de realce tardio para a localização de miocárdio anormal conforme delimitado pelo mapeamento eletroanatomico em sensibilidade, valor preditivo positivo, acurácia e concordância. CONCLUSÃO: A combinação de mapeamento eletroanatômico e TC é tecnicamente possível e pode fornecer informações importantes para a ablação de pacientes com TV e CCC. / BACKGROUND: Chronic Chagasic Cardiomiopathy (CCC) is a parasitic disease where epicardial VTs are common. Eletroanatomic mapping merged with CT scan data is a useful tool for mapping the endocardium, and its accuracy in guiding ablation on the epicardium was not adequately evaluated . OBJECTIVE: Compare electronatomic map merged with Heart CT to fluoroscopy for epicardial ablation of CCC. Describe the distribution of the scars on CCC. METHODS AND RESULTS: We performed epicardial and endocardial mapping and ablation using electroanatomic mapping on eight patients and merged the map with coronary arteries CT Scan using at least three landmarks. To compare the 3D image obtained with 3dEA mapping with image integration capabilities and the 2D fluoroscopic image obtained during the ablation procedure we used vectorial computer graphic software in order to prove the images were equivalent and to compare the distance between the catheter tip on fluoroscopy to catheter tip on 3D EA map. EPRFCA was successfully performed in all patients and they did not present recurrence for at least 3 months follow up. The mean difference between the tip of the catheter on fluoroscopy and on the 3D model was 6.03 ± 2.09mm. Scars were present in the epicardium and endocardium and most of patients presented with posterior wall scars and RV scar. CONCLUSION: The combination of electroanatomic map and heart CT scan data is feasible and can be an important tool for EPRFCA in patients with CCC and VT. / TEDE / BV UNIFESP: Teses e dissertações

Introdução: A morte súbita é a principal causa de morte na doença de Chagas, correspondendo de 55 a 65% dos casos. Observa-se que parte destas, ocorre em pacientes com função ventricular esquerda (FEVE) preservada, levando a acreditar que fatores desestabilizadores do substrato arritmogênico exercem um importante papel nestes eventos. Evidências já demonstraram a depressão parassimpática como fator contribuinte na gênese de arritmias diversas em presença de cardiopatia isquêmica. Assim, insiste-se na necessidade de se identificar precocemente quais os pacientes, no contexto da cardiopatia chagásica crônica, apresentam risco aumentado para o desenvolvimento de eventos arrítmicos complexos. Acredita-se que a avaliação autonômica identifique subgrupos distintos de risco. O presente estudo teve como objetivo determinar a sensibilidade do barorreflexo (SBR) em pacientes com doença de Chagas, nas formas indeterminada (GI) e arritmogênica com taquicardia ventricular não sustentada (GII) e com taquicardia ventricular sustentada (GIII) e, secundariamente, avaliar a associação entre a severidade da arritmia ventricular com o grau de comprometimento da SBR. Métodos: 42 pacientes foram submetidos à monitorização cardiovascular não invasiva pelo sistema Task Force ® onde foi determinada a SBR, utilizando o método da fenilefrina e analisada a variabilidade da frequência cardíaca (VFC) no domínio do tempo por meio da eletrocardiografia dinâmica de 24horas e a FEVE, por meio da ecocardiografia. Resultados: Observou-se diferença estatística significativa entre os grupos em relação à SBR em resposta à fenilefrina. O GIII apresentou o menor valor de SBR (6,09 ms/mmHg) quando comparado aos GII (11,84ms/mmHg) e GI (15,23ms/mmHg). Após comparação múltipla entre os grupos, verificou-se diferença significativa entre GI e GIII (p= 0,01). Quando se correlacionou SBR e densidade de extra-sístoles ventriculares (EV), observou-se que todos os pacientes portadores de baixa densidade de EV (< 10/hora) apresentavam SBR preservada (6,1ms/mmHg).Em contrapartida, entre aqueles com alta densidade de EV (>10/hora) somente 59% tinham SBR preservada (p=0,003). Nos pacientes com SBR deprimida (3,0-6,0 ms/mmHg) houve maior densidade de EV (p=0,01). Pacientes com SBR preservada apresentaram tanto função ventricular normal como moderadamente comprometida (66,7% com FEVE<40% e 79,5% com FEVE40%; p=0,62). O mesmo observou-se em pacientes com SBR moderadamente deprimida, (15,4% com FEVE<40% e 33,3% com FEVE40%; p=0,46). Não foi verificada correlação entre SBR e VFC. Ao se aplicar o modelo de regressão logística, observou-se que somente a SBR influenciou o aparecimento da taquicardia ventricular sustentada (p=0.028). Conclusão: A SBR está preservada na forma indeterminada da doença de Chagas e diminuída na forma arritmogênica. O comprometimento da SBR é progressivo e acompanha a evolução da doença, sendo mais intenso nos pacientes com arritmias ventriculares mais complexas. O grau de disfunção autonômica não se correlacionou com a função ventricular, mas, sim, com a densidade e a complexidade das arritmias / Introduction: Sudden death is the main cause of death in Chagas disease, corresponding to 55 to 65% of the cases. Some of these occur in patients with normal or almost normal left ventricular function (LVF), leading us to believe that factors that destabilize the arrhythmogenic substrate play an important role in these events. Evidences show parasympathetic depression to be a contributing factor in the genesis of diverse arrhythmias in the presence of ischemic heart disease. Thus, we insist on the need of an early identification of the patients, in the context of chronic Chagas heart disease, that are at increased risk of developing complex arrhythmic events. It is possible that autonomic assessment allows the identification of distinct risk subgroups. The objective of this study was to determine the baroreflex sensitivity (BRS) in patients with the indeterminate form of Chagas disease, (GI), and with the arrhythmogenic form of Chagas disease with nonsustained ventricular tachycardia (GII) and sustained ventricular tachycardia (GIII) and to assess the correlation between the severity of ventricular arrhythmia and the degree of BRS impairment. Methods: Forty-two patients were subjected to noninvasive cardiovascular monitoring using the Task Force® system. The phenylephrine method was used to determine BRS, 24- hour dynamic electrocardiography was used to analyze heart rate variability (HRV) over time and echocardiography was used to determine LVF. Results: A statistical difference was observed between the groups regarding their BRS to phenylephrine. GIII presented the lowest BRS value (6.09 ms/mmHg) when compared with GII (11.84ms/mmHg) and GI (15.23ms/mmHg). After multiple comparisons among the groups, a significant difference was found between GI and GIII (p=0.01). When BRS was correlated with ventricular extrasystole (VE) density, all patients who had low VE density (<10/hour) had preserved BRS (6.1ms/mmHg). On the other hand, only 59% of those with high EV density (>10/hour) had preserved BRS (p=0.003). In patients with moderately depressed BRS (3.0-6.0 ms/mmHg) there was a greater density of EV (p=0.01). Patients with preserved BRS had preserved or moderately compromised LVF (66.7% with LVF<40% and 79.5% with LVF40%; p=0.62) as had patients with moderately depressed BRS (15.4% with LVF<40% and 33.3% with LVF40%; p=0.46). There was no correlation between BRS and LVF. When the logistic regression model was applied, only BRS influenced the presence of sustained ventricular tachycardia (p=0.028). Conclusion: BRS is preserved in indeterminate Chagas disease and diminished in the arrhythmogenic form. The BRS impairment is progressive as the disease progresses, being more evident in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with ventricular function but with the density and complexity of the arrhythmias

The aim of this thesis is a diagnosis of ventricular tachycardias, fibrillations and flutters from electrocardiogram. These disturbances of heart rate are ranked among the life threatening arrhytmias. This work presents own method of the automatic detection, which is created for the ECG holter monitoring system. The proposed algorithm is based on the detection in the spectral domain, which is supported by the detection in the time domain. The results show the discrimination of arrhytmias from the normal sinus rhythm and the discrimination from the noise. The method is tested with ECG records from the The AHA Database (American Heart Association) and from The MIT-BIH Malignant Ventricular Arrhythmia Database.

Idiopathic ventricular tachycardias, which occur in patients without structural heart disease, are a common entity, representing up to 10% of all ventricular tachycardias evaluated by cardiac electrophysiology services. Pregnancy can increase the incidence of various cardiac arrhythmias. Factors that can potentially promote arrhythmias in pregnancy include the effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia, and underlying heart disease. Ventricular arrhythmias in pregnancy are repetitive monomorphic ventricular premature complexes and couplets that frequently originate at the right ventricular outflow tract. New onset symptomatic repetitive right ventricular outflow tract ventricular tachycardia during pregnancy has been inadequately reported in the literature. We present a case of symptomatic repetitive right ventricular outflow tract tachycardia that started during pregnancy and continued in the postpartum period, requiring curative treatment with electrophysiology study and radiofrequency ablation.

Polymorphic ventricular tachycardia (PVT) is a life-threatening arrhythmia that is typically related to long QT syndrome, organic heart disease, electrolyte abnormalities, cardiotoxic drugs, or adrenergic stimulation. A review of the literature reveals that PVT with normal QT interval and without underlying cause is quite rare. We report a case of idiopathic spontaneous PVT with structurally normal heart and without electrolyte abnormalities, drug reactions, or evidence of catecholamine induced arrhythmia. We also review the literature on the electrocardiographic characteristics and management of idiopathic PVT.

Thesis advisor: Vassilios Bezzerides / The aim of this study was to utilize a massively parallel reporter assay (MPRA) to identify organ-specific microRNA (miRNA) target sequences to refine the timing and expression of transgene expression for gene therapy. We previously had developed a cardiac gene therapy for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) using a systemically delivered adeno-associated virus (AAV9) vector. We hypothesized that incorporation of organ specific miRNA target sites into our vector construct could improve our therapy’s tissue specificity due to the ability of miRNAs to silence transgene expression. Initially, we attempted to incorporate mir-124 target sequences into our vector to detarget the brain. Although these initial attempts were unsuccessful, the study allowed us to develop a protocol to test the effectiveness of miRNA target sequences. Thereafter, we developed a method to screen thousands of putative miRNA target sequences simultaneously. In this study, target sequences of miRNAs specific to the heart, brain and liver were incorporated into a plasmid library. This plasmid library was subsequently made into AAV and injected into mice from a CPVT transgenic line. Total DNA and RNA was later extracted from the target organs, converted into genomic DNA (gDNA) and complementary DNA (cDNA) libraries respectively, and sent for amplicon sequencing. We analyzed the results using Comparative Microbiome Analysis 2.0 software (CoMA) and a custom python script to count the occurrence of each specified barcode per sample. In doing so, we showed that the miRNA suppression mechanism is not only effective but also organ specific. Furthermore, we developed a second script to create a combinatorial library from a set list of miRNA target sequences enabling us to efficiently test thousands of target sequence combinations at once. In doing so, we will be able to identify effective miRNA target sequence combinations to further improve gene therapy specificity. / Thesis (BS) — Boston College, 2021. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Biology.

Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic's Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients' charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p<0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p<0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility. On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility. Conclusions This study suggests that GI symptoms are relatively common among patients with hEDS. Of the patients tested for dysmotility, 76.2% were found to have some form of dysmotility. POTS was found to be an independent predictive factor for GI dysmotility.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24878号 / 医博第5012号 / 新制||医||1068(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 萩原 正敏, 教授 湊谷 謙司, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1998. / Typescript. Bibliography: leaves 118-128.