No description available.

Introdução: O miocárdio não compactado (MNC) é uma cardiomiopatia rara, cujas principais manifestações clínicas são insuficiência cardíaca, embolias e arritmias. A evolução desses pacientes é pouco conhecida. Dessa forma, o objetivo desse estudo é analisar o seguimento tardio de pacientes com MNC isolado ou associado a outras doenças, adultos e crianças com a doença, e de seus familiares, que foram acompanhados em hospital universitário de cardiologia, bem como avaliar os desfechos clínicos e de exames de imagem em cardiologia nesses pacientes. Métodos: Pacientes com diagnóstico de MNC confirmado por critérios ecocardiográficos e/ou ressonância magnética cardíaca (RMC) foram selecionados. Durante seu acompanhamento, foram convocados familiares de primeiro, segundo e terceiro graus para rastreamento da doença. Foram avaliados os seguintes desfechos: óbito, transplante cardíaco, eventos embólicos como acidente vascular cerebral (AVC) isquêmico, tromboembolismo pulmonar, embolia arterial periférica, internações hospitalares por insuficiência cardíaca (IC), ocorrência arritmias ventriculares complexas, e índices de exame de imagem como eletrocardiograma, Holter 24 horas, ecocardiograma transtorácico e RMC, que poderiam apresentar valor prognóstico nesses pacientes. Crianças (idade inferior a 12 anos) foram analisadas separadamente. Resultados: Foram acompanhados 215 pacientes com MNC, idade de 36,96 + 17,6 anos, 108 (50,2%) homens, que foram seguidos por 5,9 + 4,47 anos. Os pacientes foram divididos em 2 grupos: 193 com MNC isolado (Grupo 1) e 22 com MNC misto (associado a doenças genéticas, congênitas, doença de Chagas, coronariopatia, cardiomiopatia hipertrófica e miocardite de células gigantes; Grupo 2). A palpitação foi o sintoma clínico mais frequente, estando presente em 42,8% deles. A sobrevida foi menor nos pacientes do Grupo 2, nos que apresentaram FE do ventrículo esquerdo (VE) menor que 50% (p= 0,004), naqueles com aumento dos diâmetro e volume diastólicos finais do VE (p=0,018 e 0,017, respectivamente), com aumento do diâmetro do átrio esquerdo (p < 0,001), com disfunção diastólica do VE (p= 0,049), com disfunção sistólica do ventrículo direito (p= 0,003), nos que apresentaram internações hospitalares (p < 0,001), nos com eventos embólicos (p= 0,022), com arritmias ventriculares complexas (p= 0,010), com hipertensão arterial pulmonar pelo ecocardiograma (p < 0,001) . A ocorrência de FA foi estatisticamente significativa entre os pacientes com disfunção sistólica do VE (p= 0,0485) e todos os que apresentaram FA, tinham FEVE inferior a 40% (p= 0,048). Vinte e três pacientes eram crianças, seguidos por 4,41 ± 4,91 anos, idade média de 5,52 ± 3,62 anos, 12 (52,2%) do sexo masculino. A proporção de óbitos ou transplante cardíaco foi 3 vezes maior do que na população adulta (34,8%) e a IC foi o resultado mais comum. As arritmias cardíacas foram raras e os eventos embólicos não foram encontrados neste grupo. O rastreio familiar diagnosticou MNC em 36,7% dos pacientes. Na análise multivariada, a precocidade dos sintomas e a ocorrência de acidente vascular cerebral ou acidente isquêmico transitório foram os fatores mais importantes no prognóstico dos pacientes e capazes de predizer sobrevida (p < 0,001 e p= 0,008, respectivamente). Conclusão: O seguimento clínico e por métodos de imagens cardíacas por longo período de pacientes com MNC permite traçar um perfil dessa população e estimar o risco de complicações, reforçando a necessidade de diagnóstico e tratamento precoces. Em crianças, o MNC geralmente evolui de forma mais agressiva, com maior morbi-mortalidade. O rastreamento familiar consiste em uma ferramenta muito importante nesse contexto, permitindo a identificação de pacientes na fase subclínica da doença / Background: Non-compaction cardiomyopathy (NCC) is a rare disease, which main clinical manifestations are heart failure, arrhythmias and embolic events. The evolution of these patients is poorly known. Thus, the aims of this study was to analyze the late follow-up of patients with isolated NCC or associated with other diseases, adult and children with the disease and their relatives, which were followed at a university cardiology hospital, and to evaluate the clinical and the cardiology imaging outcomes in these patients. Methods: Patients with NCC confirmed by echocardiographic (echo) and / or cardiac magnetic resonance imaging (CMRI) criteria were selected. During their follow-up, their first, second and third degree relatives were recruited to perform screening of the disease using echo. The following variables were included: death, cardiac transplantation, embolic events such as stroke, pulmonary embolism, peripheral arterial embolism, hospital admissions for heart failure, complex ventricular arrhythmias, and imaging indexes of imaging exams such as electrocardiogram, Holter 24 hours, echocardiogram and CMRI, which could have prognostic value in these patients. Children (under 12 years old) were analyzed separately. Results: Two hundred and fifteen patients with NCC were followed for 5.9 ± 4.47 years, mean age of 36,96 ±17,6 years, 108 (50.2%) males. Patients were divided into 2 groups: 193 with isolated NCC (Group 1) and 22 with mixed NCC (associated with genetic and congenital diseases, Chagas disease, coronary disease, hypertrophic cardiomyopathy and giant cell myocarditis; Group 2). Palpitation was the most frequent clinical symptom, present in 42,8% of them. The survival rate was lower in Group 2 patients (p < 0.05), left ventricular (LV) ejection fraction (EF) less than 50% (p= 0.004), increased LV end-diastolic diameter and volume by echo (p= 0.018 and 0.017, respectively), with LV diastolic dysfunction (p= 0.049), with increased left atrium dimensions (p < 0,001), with right ventricular systolic dysfunction (p= 0.003), hospital admissions (p < 0.001), embolic events (p= 0.022), complex ventricular arrhythmias (p = 0.010) and pulmonary hypertension by echo (p < 0.001). All patients with isolated NCC and AF presented LVEF less than 0.40, and between patients without AF, only 41.7% presented LVEF less than 0.40 (p = 0.048). Twenty-three patients was children, followed for 4.41 ± 4.91 years, mean age of 5.52 ± 3.62 years, 12 (52.2%) males. The proportion of deaths or cardiac transplantation was 3 times higher than in the adult population (34,8%) and heart failure was the most common outcome. Cardiac arrhythmias were rare, and the embolic events were not found in this group. The familiar screening diagnosed NCC in 36.7% of the patients. In the multivariate analysis, the precocity of the symptoms and the occurrence of stroke or transient ischemic attack were the most important factors in the prognosis of this patients and it is able to predict survival (p < 0.001 and p= 0.008, respectively). Conclusion: The clinical and cardiac imaging methods allows us to draw a profile of this population and to estimate the risk of complications, emphasizing the need for early diagnosis and treatment. In children, NCC used to develop more severe disease. Family screening is a very important tool, allowing the identification of patients with subclinical stage of the disease

This diploma thesis deals with the use of some methods of cluster analysis on the ECG signal in order to sort QRS complexes according to their morphology to normal and abnormal. It is used agglomerative hierarchical clustering and non-hierarchical method K – Means for which an application in Mathworks MATLAB programming equipment was developed. The first part deals with the theory of the ECG signal and cluster analysis, and then the second is the design, implementation and evaluation of the results of the usage of developed software on the ECG signal for the automatic division of QRS complexes into clusters.

No description available.

Les cardiomyopathies sont une atteinte du myocarde qui se présente sous différentes formes telles que l’hypertrophie ou la dilatation des chambres cardiaques. Ces maladies du muscle cardiaque peuvent affecter la contraction cardiaque et dégénèrer en insuffisance cardiaque. Aussi, l’hypertrophie et l’insuffisance cardiaques sont associées à une augmentation de la morbidité et de la mortalité cardiovasculaires principalement due au remodelage électrique et à la survenue d’arythmies. De plus, le retard de repolarisation, associé à une diminution des courants K+, est un des troubles cardiaques les plus couramment observés lors de ces pathologies cardiaques. L’angiotensine II (Ang II) et la norépinéphrine, principaux effecteurs du système rénine-angiotensine et du système nerveux sympathique, peuvent tous deux agir directement sur le cœur en liant les récepteurs de type 1 de l’Ang II (AT1) et les récepteurs adrénergiques. L’Ang II et la norépinéphrine sont associées au développement des cardiomyopathies, au remodelage cardiaque et à une prolongation de la durée du potentiel d'action cardiaque. Deux modèles de souris trangéniques surexprimant spécifiquement au niveau cardiaque les récepteurs AT1 (la souris AT1R) ou les récepteurs α1B-adrénergiques (la souris α1B-AR) ont été créés afin d’étudier les effets de ces stimuli sur le cœur. Ces deux modèles de souris développent du remodelage cardiaque, soit de l’hypertrophie chez les souris AT1R (cardiomyopathie hypertrophique) ou une dilatation des chambres cardiaques chez les souris α1B-AR (cardiomyopathie dilatée). Au stade avancé de la maladie, les deux modèles de souris transgéniques sont insuffisants cardiaques. Des données préliminaires ont aussi montré que les souris AT1R et les souris α1B-AR ont une incidence accrue d’arythmies ainsi qu’une prolongation de la durée du potentiel d’action. De plus, ces deux modèles de souris meurent subitement et prématurément, ce qui laissait croire qu’en conditions pathologiques, l’activation des récepteurs AT1 ou des récepteurs α1B-adrénergiques pouvait affecter la repolarisation et causer l’apparition d’arythmies graves. Ainsi, l’objectif de ce projet était de caractériser la repolarisation ventriculaire des souris AT1R et α1B-AR afin de déterminer si la suractivation chronique des récepteurs de l’Ang II ou des récepteurs 1B-adrénergiques pouvait affecter directement les paramètres électrophysiologiques et induire des arythmies. Les résultats obtenus ont révélé que les souris AT1R et les souris α1B-AR présentent un retard de repolarisation (prolongation de l’intervalle QTc (dans l’électrocardiogramme) et de la durée du potentiel d’action) causé par une diminution des courants K+ (responsables de la repolarisation). Aussi, l’incidence d’arythmies est plus importante dans les deux groupes de souris transgéniques comparativement à leur contrôle respectif. Finalement, nous avons vu que les troubles de repolarisation se produisent également dans les groupes de souris transgéniques plus jeunes, avant l’apparition de l’hypertrophie ou du remodelage cardiaque. Ces résultats suggèrent qu’en conditions pathologiques, l’activation chronique des récepteurs de l’Ang II ou des récepteurs α1B-adrénergiques peut favoriser le développement d’arythmies en retardant la repolarisation et cela, indépendamment de changements hémodynamiques ou du remodelage cardiaque. Les résultats de ces études pourront servir à comprendre les mécanismes responsables du développement d’arythmies cardiaques lors du remodelage et de l’insuffisance cardiaques et pourraient aider à optimiser le choix des traitements chez ces patients atteints ou à risque de développer de l’hypertrophie ou du remodelage cardiaque. / Cardiomyopathies are diseases of the myocardium that may have several causes and comes in different forms such as cardiac hypertrophy or dilatation. Cardiomyopathies are often progressive diseases that cause a loss of heart function and lead to heart failure. In addition, hypertrophy and heart failure are associated with increased morbidity and mortality mainly due to electrical remodeling and arrhythmias. Delayed repolarization associated with a decrease of K+ currents, is one of the most common cardiac disorders associated with cardiac remodeling. Angiotensin II (Ang II) and norepinephrine, the main effectors of the renin-angiotensin system and of the sympathetic nervous system, can both act directly on the heart by binding the Ang II type 1 receptor (AT1) and the adrenergic receptors. Ang II and norepinephrine are both associated with the development of cardiomyopathy, cardiac remodeling and prolongation of action potential duration. Two transgenic mouse models overexpressing the AT1 receptors (AT1R mouse) or the α1B-adrenergic receptors (α1B-AR mouse) specifically in the myocardium have been developed to study the effects of these stimuli on the heart. These two mouse models developed cardiac remodeling such as hypertrophy for the AT1R mice (hypertrophic cardiomyopathy) and dilatation of cardiac chambers for α1B-AR mice (dilated cardiomyopathy). In advanced stage of the disease, the two transgenic mouse models exhibit heart failure. Preliminary data showed that both transgenic mouse models experience cardiac arrhythmias and have a prolongation of the action potential duration. Moreover, AT1R and α1B-AR mice die suddenly and prematurely, which suggested that in pathological conditions, activation of the Ang II type 1 receptor or of the α1B-adrenergic receptor may affect repolarization and can be responsible for the incidence of serious arrhythmias causing the death of these mice. Base on these informations, the objective of this project was to characterize the ventricular repolarization in AT1R and α1B-AR mice to see if an increase of the activation of the Ang II type 1 receptor or of the 1B-adrenergic receptor could directly affect electrophysiological parameters and lead to severe arrhythmias. Results showed that both AT1R mice and α1B-AR mice have a delayed ventricular repolarization (prolongation of the QTc interval and action potential duration) caused by a decrease in outward K+ currents (responsible for the repolarization). In addition, the incidence of arrhythmias is higher in both groups of transgenic mice compared with their respective control. Finally, we have seen that repolarization disorders also occur in younger mice of both models of cardiomyopathy that do not present sign of hypertrophy and cardiac remodeling. These results suggest that under pathological conditions, the overactivation of the Ang II type 1 receptor or of the α1B-adrenergic receptor can directly promote the development of arrhythmias by delaying the repolarization independently of hemodynamic variations and pathological phenotype. The results of these studies can be useful to understand the mechanisms underlying the development of cardiac arrhythmias in patients suffering from cardiac hypertrophy or failure and may help to choose the best treatment for these patients.

L'arrêt cardiaque est principalement d'étiologie cardio-vasculaire. Dans le contexte actuel des arrêts cardiaques extrahospitaliers, 20 à 25% des victimes présentent une fibrillation ventriculaire. Environ 3 à 5% des personnes sont sauvées sans séquelle neurologique. La survie à un arrêt cardiaque extrahospitalier dépend d'une prise en charge précoce et rapide de la victime. Les premiers témoins actifs réalisant la réanimation cardio-pulmonaire combinée à l'utilisation d'un défibrillateur sont ainsi un maillon important pour sauver la victime.Notre objectif principal est d'améliorer le taux de survie à un arrêt cardiaque extrahospitalier. Une première voie d'investigation est de proposer un fonctionnement de défibrillateur optimal combinant judicieusement les différents modules de détection embarqués (détection de fibrillation ventriculaire, détection de massage cardiaque, détection d'interférences électromagnétiques) afin de réduire les temps de pause péri-choc durant la procédure de réanimation. En effet, pendant ces temps, dits « hands-off » en anglais, aucun geste de secours n'est administré au patient qui, lui, voit d'une part sa pression de perfusion coronarienne chuter, d'autre part la probabilité de succès des tentatives de défibrillation décroître. C'est pourquoi une deuxième voie d'investigation porte sur la prédiction de l'efficacité de choc. Dans ce contexte, nous proposons de combiner des paramètres de l'électrocardiogramme dans les domaines temporel, fréquentiel et de la dynamique non-linéaire. Un classifieur bayésien utilisant le modèle de mélange de gaussiennes a été appliqué aux vecteurs de paramètres les plus prédicteurs de l'issue de la défibrillation et l'algorithme Espérance-Maximisation a permis de mener à bien la procédure d'apprentissage des paramètres du modèle probabiliste représentant les distributions conditionnelles de classe.L'ensemble des méthodes proposées a permis d'atteindre des résultats prometteurs pour à la fois réduire les temps de pause péri-choc et prédire l'efficacité de défibrillation et ainsi espérer améliorer le taux de survie à un arrêt cardiaque / The cardiac arrest is mainly of cardiovascular etiology. In the actual context of out-of-hospital cardiac arrests, 20 to 25% of the victims present a ventricular fibrillation. About 3 to 5% of the victims are saved without neurological damage. The chance of surviving a cardiac arrest outside an hospital depends on the early and fast support of the victim. The first active witnesses performing cardiopulmonary resuscitation combined with the use of a defibrillator are an important link to save the victim.Our main objective is to improve survival rate in out-of-hospital cardiac arrest cases. A first way of investigation is to propose an optimal functioning of defibrillator combining wisely the different processes of detection embedded (ventricular fibrillation detection, chest compressions detection, electromagnetic interferences detection), in order to reduce the peri-shock pauses during the resuscitation procedure. In fact, during these pauses, known as "hands-off" pauses, no emergency action is provided to the patient, what is correlated to a drop of the coronary pression, but also to a decrease of the chance of successful defibrillation. That is the reason why, a second way of investigation is based on the prediction of the efficiency of defibrillation. In this context, we propose to use a combination of parameters extracted from electrocardiogram in time, frequency and non-linear dynamics domains. A bayesian classifier using a gaussian mixture model was applied to the vectors of parameters, which are the most predictor of the defibrillation outcome and the algorithm Expectation-Maximization allowed to learn the parameters of the probabilistic model representing the class conditional distributions.All of the proposed methods allowed to reach promising results for both reducing the peri-shock pauses and predicting the efficiency of defibrillation in hope to improve the survival rate in cardiac arrest cases

Introdução: A cardiomiopatia hipertrófica (CMH) é definida, como a hipertrofia miocárdica ocorrida na ausência de doença cardíaca ou sistêmica, sendo a mais prevalente das cardiopatias de transmissão genética e a principal causa de morte súbita em jovens e atletas. A única opção de tratamento para prevenção dessa complicação é a indicação do cardiodesfibrilador implantável (CDI). Alguns marcadores de risco foram identificados, como: pacientes que sobreviveram à parada cardíaca por fibrilação ventricular, episódio de taquicardia ventricular sustentada; história familiar precoce de MSC; síncope inexplicada; espessura septal >= 30 mm; taquicardia ventricular não sustentada (TVNS) no Holter; queda da pressão sistólica (PAS) > 20 mmHg ou aumento < 20 mmHg no esforço. Entretanto, a sensibilidade e especificidade desses critérios são limitadas, tornando necessário o conhecimento de novos métodos diagnósticos com capacidade de predizer MSC. A micro-alternância da onda T (MAOT) é utilizada como ferramenta diagnóstica na estratificação de pacientes com riscos de desenvolver arritmias ventriculares malignas e MSC auxiliando na indicação do CDI. Na CMH há poucos estudos realizados com objetivos e resultados diferentes e, atualmente, uma nova metodologia na realização desses exames foi desenvolvida, não sendo testada nesta população. Os objetivos do presente estudo foram: caracterizar os valores da MAOT pela metodologia Média Móvel Modificada (MMM) e avaliar a associação de seus resultados com os fatores de risco clínicos para MSC. Metodologia: Foram selecionados 132 pacientes com CMH que foram divididos em dois grupos: 1) Alto Risco, 67 pacientes, que apresentavam, pelo menos, um fator de risco para morte súbita cardíaca (história familiar de morte súbita; síncope inexplicada; espessura septal do miocárdio >=30 mm; taquicardia ventricular não sustentada; queda da pressão sistólica no teste de esforço) e 2) Baixo Risco, 65 pacientes, sem fatores de risco. A idade média foi de 37 ± 11,3 anos, sendo 63% do sexo masculino. A média da espessura de septo interventricular foi 23,9 ± 6,2 mm, da fração de ejeção 72 ± 8,1% e 26% apresentavam forma obstrutiva da doença. A MAOT foi avaliada pelo teste ergométrico com protocolo Naughton modificado, com dois fatores de atualização (FaT) 1/8 e 1/32, de forma quantitativa e qualitativa (positivo e negativo) e com três formas de análises: considerando todas as derivações do eletrocardiograma (plano periférico, frontal e ortogonal); desconsiderando os resultados do plano periférico e desconsiderando as derivações ortogonais. Resultados: A aferição da MAOT com FaT 1/8 apresentou maior sensibilidade em comparação com FaT 1/32 (FaT 1/8 MAOTméd. = 69,2 uV a 78,2 uV vs FaT 1/32 MAOTméd. = 33,2 uV a 38,7 uV, p < 0,01), resultando nas análises quantitativas de valores maiores da micro-alternância (MAOTmáx. - FaT 1/8 = 528 uV vs 124 uV = FaT 1/32, p < 0,01) e na análise qualitativa maior número de exames positivos (MAOT positiva - FaT 1/8 = 57,5% vs 19,0% = FaT 1/32). Os pacientes do grupo Alto risco apresentavam maiores valores de MAOT (Alto Risco MAOT média = 101,4 uV vs 54,3 uV Baixo Risco, p < 0,001) e 84% apresentavam exame positivo (56/67). A MAOT mostrou associação significativa com os fatores de risco para MSC: espessura septal >= 30 mm (p < 0,001), TVNS no Holter 24 h (p = 0,001), história familiar de MSC (p = 0,006) e queda da pressão arterial no esforço (p = 0,02). No rastreamento de pacientes de Alto risco, com ponto de corte de 53 uV o teste apresentou sensibilidade e especificidade de 84% e 71%, com acurácia de 0,77 (IC de 95%: 0,69 a 0,86). Conclusões: Os melhores resultados da MAOT pela metodologia Média Móvel Modificada foram encontrados analisando todas as derivações eletrocardiográficas (plano periférico, horizontal e derivações ortogonais), realizados de forma quantitativa, com Fator de Atualização 1/8 e ponto de corte para positividade 53 uV. A MAOT demonstrou associação significativa com a maioria dos fatores de risco clínicos apresentando boa acurácia no rastreamento dos pacientes de Alto Risco para MSC / Introduction: Hypertrophic cardiomyopathy (HCM) is defined as the myocardial hypertrophy in the absence of cardiac or systemic disease, being the most common genetic transmission cardiopathy and responsible for sudden cardiac death (SCD) in young adults and athletes. The first-line treatment option for prevention of SCD is the implantable cardioverter-defibrillator (ICD). Some clinical factors have been identified as high risk for the occurrence of SCD: history of cardiac resuscitation for ventricular fibrillation, episode of sustained ventricular tachycardia, family history of premature SCD, unexplained syncope, ventricular septal thickness >= 30 mm; nonsustained ventricular tachycardia (NSVT) in Holter and inadequate response of blood pressure to exercise: decrease in systolic blood pressure (SBP) > 20 mmHg or increase < 20 mmHg during effort. These criteria, however, are limited in sensitivity and specificity and new diagnostic methods have been required. The microvolt T-wave alternans (MTWA) is used as a diagnostic tool to identify high-risk patients predisposed to malignant ventricular arrhythmias and SCD. Therefore, MTWA may be helpful to indicate ICD. There are no reports in the literature concerning the use of MTWA in HCM. This research aims to evaluate the values of MTWA by modified moving average (MMA) method and the association with clinical factors for SCD. Methods: We enrolled 132 patients with HCM that were divided into two groups: 1) High Risk (HR) group, 67 patients, that had at least one risk factor for sudden cardiac death (family history of SCD; unexplained syncope; ventricular septal thickness >= 30 mm; nonsustained ventricular tachycardia; inadequate response of blood pressure to exercise) and 2) Low Risk (LR) group, 65 patients, without risk factors. The most participants were male (63%) and their mean age was 37 (± 11.3) years. All individuals were evaluated by echocardiography: 23,9 ± 6,2 mm interventricular septal thickness; 72 ± 8.1% ejection fraction and 26% left ventricular outflow gradient of more than 30 mmHg. Patients performed exercise stress testing with modified Naughton Protocol. In the present study, MTWA was assessed with the MMA method, updating factor (UF) 1/8 and 1/32, quantitative and qualitative way (positive and negative). In addition, the values of the MTWA were evaluated in three ways: all the leads of electrocardiogram; disregarding the leads of peripheral plane; disregarding the orthogonal leads. Results: The analysis of MTWA with UF 1/8 showed greater sensitivity compared with UF 1/32 (Mean MTWA, UF 1/8 = 69.2 uV to 78.2 uV vs UF 1/32 = 33.2 uV to 38.7 uV, p < 0.01). Like this, in quantitative and qualitative (positive and negative) analysis of MTWA, the values were larger in the group of UF 1/8 (UF1/8 = 528 uV vs UF 1/32 = 124 uV, p < 0.01/ Positive MTWA, UF 1/8 = 57.5% vs UF 1/32 = 19.0%, p < 0.01). The patients of High Risk group presents higher values of MTWA (HR = 101.4 uV vs LR = 54.3 uV, p < 0.001) and 84% had the positive test. The MTWA was significantly associated with risk factors for SCD: ventricular septal thickness >= 30 mm (p < 0.001), NSVT (p = 0.001), family history of SCD (p = 0.006), inadequate response of blood pressure to exercise (p = 0.02). In the analysis of high risk group, using a cutoff value of 53 uV, we observed a sensitivity of 84%, specificity of 71% and accuracy of 0.77 (95% confidence interval: 0.69 to 0.86). Conclusions: The best results of MTWA by MMA method were found by analyzing all lead ECG (frontal and peripheral plane and orthogonal leads), using UF 1/8, quantitative analysis and cut-off value 53 uV. The MTWA was significantly associated with clinical risk factors, showing a good accuracy, and can be used to effectively select high-risk patients for SCD

Luis Calandre Ibáñez (Cartagena 23/3/1890-Madrid 29/9/1961), estudió Medicina en Madrid, siendo discípulo de Cajal, Achúcarro y Madinaveitia en Madrid y de Nicolai y Benda en Alemania. Realizó estudios de Histología sobre la esructura de la fibra cardiaca, para comprender mejor la fisiopatología del corazón, campo de su especial dedicación, siendo uno de los introductores de la electrocardiografía en España, estudiando especialmente los trastornos del ritmo basándose en ella.Fundó y dirigió el Laboratorio de Anatomía Microscópica de la Residencia de Estudiantes (1914-1931). Fue Jefe del Servicio de Cardiología del Hospital Central de la Cruz Roja y Director del Hospital de Carabineros durante la guerra civil (1937.1939). Publicó más de setenta artículos en revistas especializadas y ocho libros de contenido científico. Fundó y dirigió la revista "Archivos de Cardiología y Hematología" (1920-1936). Desarrolló una intensa labor social, política y cultural y al finalizar la guerra civil fue procesado y condenado padeciendo el exilio interior y el olvido científico. / Luis Calandre Ibáñez (Cartagena 1890-Madrid 1961), studied medicine in Madrid, where he was a disciple of Cajal, Achúcarro and Madinaveitia and then of Nicolai and Benda in Germany. He specialised in cardiac physiopathology, and studied histology on the struc Civil war. He published more than seventy articles in specialist journals and eightscientificbooks. He founded and directed the journal "Archivos de Cardiología y Hematología" (1920-1936). Intensely involved in social, political and cultural activities, he was tried and sentenced at the

Les cardiomyopathies sont une atteinte du myocarde qui se présente sous différentes formes telles que l’hypertrophie ou la dilatation des chambres cardiaques. Ces maladies du muscle cardiaque peuvent affecter la contraction cardiaque et dégénèrer en insuffisance cardiaque. Aussi, l’hypertrophie et l’insuffisance cardiaques sont associées à une augmentation de la morbidité et de la mortalité cardiovasculaires principalement due au remodelage électrique et à la survenue d’arythmies. De plus, le retard de repolarisation, associé à une diminution des courants K+, est un des troubles cardiaques les plus couramment observés lors de ces pathologies cardiaques. L’angiotensine II (Ang II) et la norépinéphrine, principaux effecteurs du système rénine-angiotensine et du système nerveux sympathique, peuvent tous deux agir directement sur le cœur en liant les récepteurs de type 1 de l’Ang II (AT1) et les récepteurs adrénergiques. L’Ang II et la norépinéphrine sont associées au développement des cardiomyopathies, au remodelage cardiaque et à une prolongation de la durée du potentiel d'action cardiaque. Deux modèles de souris trangéniques surexprimant spécifiquement au niveau cardiaque les récepteurs AT1 (la souris AT1R) ou les récepteurs α1B-adrénergiques (la souris α1B-AR) ont été créés afin d’étudier les effets de ces stimuli sur le cœur. Ces deux modèles de souris développent du remodelage cardiaque, soit de l’hypertrophie chez les souris AT1R (cardiomyopathie hypertrophique) ou une dilatation des chambres cardiaques chez les souris α1B-AR (cardiomyopathie dilatée). Au stade avancé de la maladie, les deux modèles de souris transgéniques sont insuffisants cardiaques. Des données préliminaires ont aussi montré que les souris AT1R et les souris α1B-AR ont une incidence accrue d’arythmies ainsi qu’une prolongation de la durée du potentiel d’action. De plus, ces deux modèles de souris meurent subitement et prématurément, ce qui laissait croire qu’en conditions pathologiques, l’activation des récepteurs AT1 ou des récepteurs α1B-adrénergiques pouvait affecter la repolarisation et causer l’apparition d’arythmies graves. Ainsi, l’objectif de ce projet était de caractériser la repolarisation ventriculaire des souris AT1R et α1B-AR afin de déterminer si la suractivation chronique des récepteurs de l’Ang II ou des récepteurs 1B-adrénergiques pouvait affecter directement les paramètres électrophysiologiques et induire des arythmies. Les résultats obtenus ont révélé que les souris AT1R et les souris α1B-AR présentent un retard de repolarisation (prolongation de l’intervalle QTc (dans l’électrocardiogramme) et de la durée du potentiel d’action) causé par une diminution des courants K+ (responsables de la repolarisation). Aussi, l’incidence d’arythmies est plus importante dans les deux groupes de souris transgéniques comparativement à leur contrôle respectif. Finalement, nous avons vu que les troubles de repolarisation se produisent également dans les groupes de souris transgéniques plus jeunes, avant l’apparition de l’hypertrophie ou du remodelage cardiaque. Ces résultats suggèrent qu’en conditions pathologiques, l’activation chronique des récepteurs de l’Ang II ou des récepteurs α1B-adrénergiques peut favoriser le développement d’arythmies en retardant la repolarisation et cela, indépendamment de changements hémodynamiques ou du remodelage cardiaque. Les résultats de ces études pourront servir à comprendre les mécanismes responsables du développement d’arythmies cardiaques lors du remodelage et de l’insuffisance cardiaques et pourraient aider à optimiser le choix des traitements chez ces patients atteints ou à risque de développer de l’hypertrophie ou du remodelage cardiaque. / Cardiomyopathies are diseases of the myocardium that may have several causes and comes in different forms such as cardiac hypertrophy or dilatation. Cardiomyopathies are often progressive diseases that cause a loss of heart function and lead to heart failure. In addition, hypertrophy and heart failure are associated with increased morbidity and mortality mainly due to electrical remodeling and arrhythmias. Delayed repolarization associated with a decrease of K+ currents, is one of the most common cardiac disorders associated with cardiac remodeling. Angiotensin II (Ang II) and norepinephrine, the main effectors of the renin-angiotensin system and of the sympathetic nervous system, can both act directly on the heart by binding the Ang II type 1 receptor (AT1) and the adrenergic receptors. Ang II and norepinephrine are both associated with the development of cardiomyopathy, cardiac remodeling and prolongation of action potential duration. Two transgenic mouse models overexpressing the AT1 receptors (AT1R mouse) or the α1B-adrenergic receptors (α1B-AR mouse) specifically in the myocardium have been developed to study the effects of these stimuli on the heart. These two mouse models developed cardiac remodeling such as hypertrophy for the AT1R mice (hypertrophic cardiomyopathy) and dilatation of cardiac chambers for α1B-AR mice (dilated cardiomyopathy). In advanced stage of the disease, the two transgenic mouse models exhibit heart failure. Preliminary data showed that both transgenic mouse models experience cardiac arrhythmias and have a prolongation of the action potential duration. Moreover, AT1R and α1B-AR mice die suddenly and prematurely, which suggested that in pathological conditions, activation of the Ang II type 1 receptor or of the α1B-adrenergic receptor may affect repolarization and can be responsible for the incidence of serious arrhythmias causing the death of these mice. Base on these informations, the objective of this project was to characterize the ventricular repolarization in AT1R and α1B-AR mice to see if an increase of the activation of the Ang II type 1 receptor or of the 1B-adrenergic receptor could directly affect electrophysiological parameters and lead to severe arrhythmias. Results showed that both AT1R mice and α1B-AR mice have a delayed ventricular repolarization (prolongation of the QTc interval and action potential duration) caused by a decrease in outward K+ currents (responsible for the repolarization). In addition, the incidence of arrhythmias is higher in both groups of transgenic mice compared with their respective control. Finally, we have seen that repolarization disorders also occur in younger mice of both models of cardiomyopathy that do not present sign of hypertrophy and cardiac remodeling. These results suggest that under pathological conditions, the overactivation of the Ang II type 1 receptor or of the α1B-adrenergic receptor can directly promote the development of arrhythmias by delaying the repolarization independently of hemodynamic variations and pathological phenotype. The results of these studies can be useful to understand the mechanisms underlying the development of cardiac arrhythmias in patients suffering from cardiac hypertrophy or failure and may help to choose the best treatment for these patients.

Introdução: A cardiomiopatia hipertrófica (CMH) é definida, como a hipertrofia miocárdica ocorrida na ausência de doença cardíaca ou sistêmica, sendo a mais prevalente das cardiopatias de transmissão genética e a principal causa de morte súbita em jovens e atletas. A única opção de tratamento para prevenção dessa complicação é a indicação do cardiodesfibrilador implantável (CDI). Alguns marcadores de risco foram identificados, como: pacientes que sobreviveram à parada cardíaca por fibrilação ventricular, episódio de taquicardia ventricular sustentada; história familiar precoce de MSC; síncope inexplicada; espessura septal >= 30 mm; taquicardia ventricular não sustentada (TVNS) no Holter; queda da pressão sistólica (PAS) > 20 mmHg ou aumento < 20 mmHg no esforço. Entretanto, a sensibilidade e especificidade desses critérios são limitadas, tornando necessário o conhecimento de novos métodos diagnósticos com capacidade de predizer MSC. A micro-alternância da onda T (MAOT) é utilizada como ferramenta diagnóstica na estratificação de pacientes com riscos de desenvolver arritmias ventriculares malignas e MSC auxiliando na indicação do CDI. Na CMH há poucos estudos realizados com objetivos e resultados diferentes e, atualmente, uma nova metodologia na realização desses exames foi desenvolvida, não sendo testada nesta população. Os objetivos do presente estudo foram: caracterizar os valores da MAOT pela metodologia Média Móvel Modificada (MMM) e avaliar a associação de seus resultados com os fatores de risco clínicos para MSC. Metodologia: Foram selecionados 132 pacientes com CMH que foram divididos em dois grupos: 1) Alto Risco, 67 pacientes, que apresentavam, pelo menos, um fator de risco para morte súbita cardíaca (história familiar de morte súbita; síncope inexplicada; espessura septal do miocárdio >=30 mm; taquicardia ventricular não sustentada; queda da pressão sistólica no teste de esforço) e 2) Baixo Risco, 65 pacientes, sem fatores de risco. A idade média foi de 37 ± 11,3 anos, sendo 63% do sexo masculino. A média da espessura de septo interventricular foi 23,9 ± 6,2 mm, da fração de ejeção 72 ± 8,1% e 26% apresentavam forma obstrutiva da doença. A MAOT foi avaliada pelo teste ergométrico com protocolo Naughton modificado, com dois fatores de atualização (FaT) 1/8 e 1/32, de forma quantitativa e qualitativa (positivo e negativo) e com três formas de análises: considerando todas as derivações do eletrocardiograma (plano periférico, frontal e ortogonal); desconsiderando os resultados do plano periférico e desconsiderando as derivações ortogonais. Resultados: A aferição da MAOT com FaT 1/8 apresentou maior sensibilidade em comparação com FaT 1/32 (FaT 1/8 MAOTméd. = 69,2 uV a 78,2 uV vs FaT 1/32 MAOTméd. = 33,2 uV a 38,7 uV, p < 0,01), resultando nas análises quantitativas de valores maiores da micro-alternância (MAOTmáx. - FaT 1/8 = 528 uV vs 124 uV = FaT 1/32, p < 0,01) e na análise qualitativa maior número de exames positivos (MAOT positiva - FaT 1/8 = 57,5% vs 19,0% = FaT 1/32). Os pacientes do grupo Alto risco apresentavam maiores valores de MAOT (Alto Risco MAOT média = 101,4 uV vs 54,3 uV Baixo Risco, p < 0,001) e 84% apresentavam exame positivo (56/67). A MAOT mostrou associação significativa com os fatores de risco para MSC: espessura septal >= 30 mm (p < 0,001), TVNS no Holter 24 h (p = 0,001), história familiar de MSC (p = 0,006) e queda da pressão arterial no esforço (p = 0,02). No rastreamento de pacientes de Alto risco, com ponto de corte de 53 uV o teste apresentou sensibilidade e especificidade de 84% e 71%, com acurácia de 0,77 (IC de 95%: 0,69 a 0,86). Conclusões: Os melhores resultados da MAOT pela metodologia Média Móvel Modificada foram encontrados analisando todas as derivações eletrocardiográficas (plano periférico, horizontal e derivações ortogonais), realizados de forma quantitativa, com Fator de Atualização 1/8 e ponto de corte para positividade 53 uV. A MAOT demonstrou associação significativa com a maioria dos fatores de risco clínicos apresentando boa acurácia no rastreamento dos pacientes de Alto Risco para MSC / Introduction: Hypertrophic cardiomyopathy (HCM) is defined as the myocardial hypertrophy in the absence of cardiac or systemic disease, being the most common genetic transmission cardiopathy and responsible for sudden cardiac death (SCD) in young adults and athletes. The first-line treatment option for prevention of SCD is the implantable cardioverter-defibrillator (ICD). Some clinical factors have been identified as high risk for the occurrence of SCD: history of cardiac resuscitation for ventricular fibrillation, episode of sustained ventricular tachycardia, family history of premature SCD, unexplained syncope, ventricular septal thickness >= 30 mm; nonsustained ventricular tachycardia (NSVT) in Holter and inadequate response of blood pressure to exercise: decrease in systolic blood pressure (SBP) > 20 mmHg or increase < 20 mmHg during effort. These criteria, however, are limited in sensitivity and specificity and new diagnostic methods have been required. The microvolt T-wave alternans (MTWA) is used as a diagnostic tool to identify high-risk patients predisposed to malignant ventricular arrhythmias and SCD. Therefore, MTWA may be helpful to indicate ICD. There are no reports in the literature concerning the use of MTWA in HCM. This research aims to evaluate the values of MTWA by modified moving average (MMA) method and the association with clinical factors for SCD. Methods: We enrolled 132 patients with HCM that were divided into two groups: 1) High Risk (HR) group, 67 patients, that had at least one risk factor for sudden cardiac death (family history of SCD; unexplained syncope; ventricular septal thickness >= 30 mm; nonsustained ventricular tachycardia; inadequate response of blood pressure to exercise) and 2) Low Risk (LR) group, 65 patients, without risk factors. The most participants were male (63%) and their mean age was 37 (± 11.3) years. All individuals were evaluated by echocardiography: 23,9 ± 6,2 mm interventricular septal thickness; 72 ± 8.1% ejection fraction and 26% left ventricular outflow gradient of more than 30 mmHg. Patients performed exercise stress testing with modified Naughton Protocol. In the present study, MTWA was assessed with the MMA method, updating factor (UF) 1/8 and 1/32, quantitative and qualitative way (positive and negative). In addition, the values of the MTWA were evaluated in three ways: all the leads of electrocardiogram; disregarding the leads of peripheral plane; disregarding the orthogonal leads. Results: The analysis of MTWA with UF 1/8 showed greater sensitivity compared with UF 1/32 (Mean MTWA, UF 1/8 = 69.2 uV to 78.2 uV vs UF 1/32 = 33.2 uV to 38.7 uV, p < 0.01). Like this, in quantitative and qualitative (positive and negative) analysis of MTWA, the values were larger in the group of UF 1/8 (UF1/8 = 528 uV vs UF 1/32 = 124 uV, p < 0.01/ Positive MTWA, UF 1/8 = 57.5% vs UF 1/32 = 19.0%, p < 0.01). The patients of High Risk group presents higher values of MTWA (HR = 101.4 uV vs LR = 54.3 uV, p < 0.001) and 84% had the positive test. The MTWA was significantly associated with risk factors for SCD: ventricular septal thickness >= 30 mm (p < 0.001), NSVT (p = 0.001), family history of SCD (p = 0.006), inadequate response of blood pressure to exercise (p = 0.02). In the analysis of high risk group, using a cutoff value of 53 uV, we observed a sensitivity of 84%, specificity of 71% and accuracy of 0.77 (95% confidence interval: 0.69 to 0.86). Conclusions: The best results of MTWA by MMA method were found by analyzing all lead ECG (frontal and peripheral plane and orthogonal leads), using UF 1/8, quantitative analysis and cut-off value 53 uV. The MTWA was significantly associated with clinical risk factors, showing a good accuracy, and can be used to effectively select high-risk patients for SCD