INTRODUÇÃO: A prevalência da fibrilação atrial, os gastos com o sistema de saúde e a elevada morbidade e mortalidade associados a ela, têm justificado a procura por um melhor entendimento de suas bases fisiopatológicas e por novas abordagens terapêuticas. O objetivo deste manuscrito é avaliar a exeqüibilidade, a segurança e os resultados em três meses da cirurgia vídeo-assistida para a ablação da fibrilação atrial com radiofreqüência bipolar. MÉTODOS: Dez pacientes (90% homens) com fibrilação atrial sintomática e refratária à terapia medicamentosa foram submetidos ao procedimento cirúrgico proposto no Instituto Nacional de Cardiologia, Rio de Janeiro, no período de Maio 2007 a Maio de 2008. Foram analisadas variáveis de peri e pós-operatório. Além da avaliação clínica dos sintomas, todos os pacientes foram submetidos a um ecocardiograma e Holter de 24horas antes e três meses após a cirurgia. Realizou-se também uma angiotomografia de veias pulmonares no terceiro mês de seguimento pós-operatório. RESULTADOS: O procedimento foi realizado conforme planejado em todos os pacientes. Cem por cento das veias pulmonares direitas e 90% das esquerdas tiveram o isolamento elétrico confirmado. Não houve lesão iatrogênica de estruturas intra-torácicas ou óbitos. Dois pacientes apresentaram pneumonia pós-operatória e longo tempo de permanência hospitalar no início da experiência clínica. Nove dos dez pacientes saíram do centro cirúrgico em ritmo sinusal. Houve uma recorrência da fibrilação atrial em três meses (11,1%). No total, 80% dos pacientes estão livres de fibrilação atrial em três meses. Houve melhora significativa da função diastólica avaliada ecocardiograficamente pela relação E/E após a cirurgia (9,0 ± 2,23 para 7,7 ± 1,07; p=0,042) que se associa a uma melhora dos sintomas de insuficiência cardíaca classe funcional da New York Heart Association (2,4 ± 0,5 para 1,6 ± 0,7; p=0,011). Não houve evidência de estenose de veias pulmonares à angiotomografia nesta série. CONCLUSÃO: A cirurgia torácica vídeo-assistida para o tratamento da fibrilação atrial é exeqüível e segura mas a incorporação desta nova técnica à prática clínica requer uma curva de aprendizado da equipe envolvida. A melhora dos sintomas de insuficiência cardíaca está relacionada à melhora da função diastólica do ventrículo esquerdo / BACKGROUND: Atrial fibrillation prevalence, its health system cost and the high morbidity and mortality associated with it have justified the search for a better understanding of its pathophysiology and new therapeutic management. The objective of this study was to assess the feasibility, the safety and the three months results of the video-assisted thoracoscopic surgery for the ablation of atrial fibrillation using bipolar radiofrequency. METHODS: Ten patients (90% male) with symptomatic and refractory atrial fibrillation underwent the proposed surgical procedure at the National Institute of Cardiology, Rio de Janeiro, Brazil, from May 2007 to May 2008. Peri and post-operative data were collected for analysis. Besides clinical evaluation, all patients have been submitted to an echocardiogram and a 24h Holter monitoring before and three months after the procedure. A pulmonary veins angiotomography was also performed three months after surgery. RESULTS: The surgical procedure was done as planned in all patients and 100% of the right pulmonary veins were isolated. Ninety per cent of the left pulmonary veins were confirmed to be electrically isolated. There was no surgical injury to any intra thoracic organ or death in this series. Two patients had post-operative pneumonia that required prolonged in hospital stay early in the experience. Nine of ten patients were in sinus rhythm just after surgery. There was one recurrence of atrial fibrillation within the three months follow up (11,1%). In general, eighty per cent (80%) of the patients are free of atrial fibrillation three months after surgery. There was a significant improvement in diastolic function measured by the relation E/E on the echocardiogram before and after the procedure (9,0 ± 2,23 to 7,7 ± 1,07; p=0,042). This was associated to an improvement of heart failure symptoms of New York Heart Association (2,4 ± 0,5 to 1,6 ± 0,7; p=0,011). There was no pulmonary vein stenosis in this cohort. CONCLUSIONS: Video-assisted thoracoscopic surgery for the treatment of atrial fibrillation is feasible and safe although it requires a learning curve to incorporate this new technique to clinical practice. The improvement on heart failure symptoms is associated to an improvement on diastolic left ventricular function

Submitted by Fabiana Gonçalves Pinto (benf@ndc.uff.br) on 2015-12-14T13:43:05Z No. of bitstreams: 1 Maria Cecilia Pereira Bosa.pdf: 2708979 bytes, checksum: 3b6806151684db7e144dbe27a092377c (MD5) / Made available in DSpace on 2015-12-14T13:43:05Z (GMT). No. of bitstreams: 1 Maria Cecilia Pereira Bosa.pdf: 2708979 bytes, checksum: 3b6806151684db7e144dbe27a092377c (MD5) Previous issue date: 2012 / Mestrado Profissional em Enfermagem Assistencial / Trata-se de uma pesquisa desenvolvida no Programa de Mestrado Profissional de Enfermagem Assistencial da Escola de Enfermagem Aurora Afonso Costa – EEAAC, da Universidade Federal Fluminense – UFF. Estudo não experimental, observacional, tipo caso controle com abordagem quantitativa para análise da ocorrência dos desfechos tromboembólicos e hemorrágicos de pacientes cardiopatas portadores fibrilação atrial crônica em uso de varfarina sódica, acompanhados no ambulatório de anticoagulação oral do Instituto Nacional de Cardiologia no município do Rio de Janeiro. Objetivo geral: avaliar o efeito das intervenções de enfermagem na adequação do Coeficiente Internacional Normatizado (INR) alvo, segundo variáveis demográficas e clínicas relacionadas ao uso da terapia de anticoagulação oral (TAO). Objetivos específicos: identificar eventos trombóticos ou hemorrágicos; correlacionar possíveis intercorrências clínicas a fatores como adesão e compreensão ao tratamento; analisar a o processo do conhecimento e aprendizado do paciente através das orientações contidas na cartilha de anticoagulação oral. Método: caso controle amostra não probabilística de conveniência limitada ao recorte temporal de seis meses a partir da segunda consulta no período de agosto de 2011 a fevereiro de 2012, após Consentimento Informado (CI), através entrevistas individuais e consulta ao banco de dados do referido ambulatório. O projeto foi submetido ao Comitê de Ética em Pesquisa do Instituto Nacional de Cardiologia do Ministério da Saúde e aprovado em 09/08/2011 sob n° 0341/21-06-2011. O tratamento dos dados estará baseado em estatística descritiva e cálculo de risco relativo. O ambulatório de Anticoagulação Oral (ACO) desta Instituição tem como proposta minimizar estas intercorrências clínicas através de acompanhamento específico deste paciente. Utilizando um Protocolo criado e Normatizado por equipe interdisciplinar da Instituição (Anexo II), que permeia o fluxo do atendimento e as intervenções. Principais resultados, e conclusão A pesquisa deverá contribuir com a prática da enfermagem dirigida a estes clientes, fornecendo subsídios teóricos científicos para a assistência de enfermagem, de modo a delinear as ações de avaliação e do cuidado de enfermagem, numa prática de cuidado singular, diferenciado e humanizado. Vislumbrando a minimização dos agravos decorrentes da TAO / Non-observational study, experimental, prospective cohort type with quantitative approach to analysis of occurrence of hemorrhagic and thromboembolic events outcomes of cardiopatas patients with chronic atrial fibrillation in use of warfarin, accompanied in oral anticoagulation clinic of the National Institute of Cardiology in the municipality of Rio de Janeiro. General Purpose: evaluate the impact of nursing Consultation guidelines regarding the occurrence of hemorrhagic or thrombotic effects, according to demographic and clinical variables related to the use of oral anticoagulation therapy (TAO), through the International Standardised coefficient evaluation (INR). Specific objectives: identify the association between the presence of complications by use of TAO to possible factors such as membership and understanding to treatment; evaluate effectiveness of nursing interventions through an educational process in the construction of knowledge and leaINRng from patient and in TAO. Method: prospective cohort of non-probability convenience sample limited to temporal clipping of six months from the second query in the period August 2011 to January 2012, after informed consent (CI), through individual interviews and database query of that clinic. The project was submitted to the Committee of ethics in research of the National Institute of Cardiology of the Ministry of health passed in 8/9/2011 under n° 0341/6/21/2011. The data controller is based on descriptive statistics and calculation of relative risk. The ambulatory Oral Anticoagulation (ACO) this institution has as a proposal to minimize these uneventful clinics through specific monitoring of the patient. Using a protocol created and Regulated by an interdisciplinary team of the institution (Annex II), which permeates the flow of care and interventions. The research should help with the practice of nursing addressed to these clients, providing theoretical grants for scientific nursing assistance, so as to delineate the actions of assessment and nursing care, in a singular, differentiated care practice and humanized. Envisioning the minimisation of grievances arising from the TAO

Abstract The incidence of sudden cardiac death (SCDs) in the western countries is 50 – 100 in a population of 100,000. The most common disease causing SCDs is coronary heart disease. A large proportion of the victims are unaware of the underlying cardiac disease or only mildly symptomatic. Many SCDs could be prevented with therapies targeted to the underlying cardiac disease and with implantable cardioverter defibrillators. However, current protocols identify only patients at highest risk and only a minority of SCDs occur in this group. Thus, markers for identifying subjects at risk for SCD are needed. The aim of this thesis was to study the roles of abnormalities in the electrocardiogram (ECG), obesity, and diabetes in SCD risk stratification. The prevalence and prognostic significance of the location of QRS transition zone (the chest lead in the ECG in which R wave amplitude ≥ S wave amplitude) and abnormal P terminal force in lead V1 of the ECG were assessed. In addition, the value of ECG abnormalities in SCD risk stratification in subjects with different relative weights were studied. These topics were assessed in a cohort of 10,000 middle-aged Finnish subjects followed over 30 years from national registers. Delayed QRS transition (occurring at V4 or leftwards) occurred in 16.4% of subjects and a markedly delayed QRS transition (at V5 or leftwards) occurred in 1.3% of subjects. Delayed QRS transition was associated with an increased risk of death and SCD and the risk of SCD was over 1.5-fold among those with markedly delayed QRS transition. An abnormal PTF (≥ 0.04mm∙s) was present in 4.8% of subjects and a markedly abnormal PTF (≥ 0.06mm∙s) in 1.2% of subjects. A markedly abnormal PTF was associated with an almost 2-fold risk of death and atrial fibrillation, but it did not predict SCDs. Both obesity and diabetes were associated with an increased risk of SCD, but the proportion of SCDs of all cardiac deaths did not increase in subjects with either of these conditions. ECG abnormalities provided most value in SCD risk stratification among normal weight subjects with a low level of risk factors. Overall, these studies provide information on the predictive value of some ECG risk markers and cardiovascular risk factors. However, the definite role of these risk markers in predicting the risk of SCD in general population at an individual level remains indecisive. / Tiivistelmä Sydänperäisten äkkikuolemien ilmaantuvuus länsimaissa on 50 – 100 tapausta 100000 ihmisen väestössä vuodessa. Suurin osa näistä kuolemista kohdistuu henkilöihin, joilla ei ole todettu sydänsairautta tai jotka ovat vähäoireisia. Yleisin sydänperäisen äkkikuoleman taustasairaus on sepelvaltimotauti. Näitä kuolemia voidaan ehkäistä sydänsairauksien hoidolla ja rytmihäiriötahdistimilla, mutta vain suurimman riskin potilaat tunnistetaan nykymenetelmin. Toimivia riskimarkkereita tarvitaan, jotta lisää potilaita saataisiin prevention piiriin. Tämän tutkimuksen tavoite oli tutkia 12-kytkentäisestä EKG:sta määritettävien QRS-transitioalueen (rintakytkentä, jossa R-aallon amplitudi ≥ S-aallon amplitudi) ja poikkeavan P terminal forcen (PTF) yleisyyttä ja yhteyttä sydänperäisiin äkkikuolemiin. Lisäksi tavoitteena oli tutkia lihavuuden ja diabeteksen vaikutusta sydänperäisen äkkikuoleman riskiin ja EKG-muutosten ennustearvoa eri painoisilla henkilöillä sydänperäisen äkkikuoleman riskiarviossa. Tutkimusaineistona käytettiin yli 10000:n keski-ikäisen suomalaisen väestökohorttia, jota seurattiin kansallisista rekistereistä. QRS-transitio tapahtui myöhään (V4:ssä tai siitä vasemmalle) 16.4 %:lla tutkituista ja huomattavan myöhään (V5:ssä tai siitä vasemmalle) 1.3 %:lla tutkituista. Myöhäinen QRS-transitio liittyi kuoleman ja sydänperäisen äkkikuoleman riskiin. Sydänperäisen äkkikuoleman riski oli yli 1.5-kertainen henkilöillä, joilla oli huomattavan myöhäinen QRS-transitio. Poikkeava PTF (≥ 0.04 mm∙s) todettiin 4.8 %:lla väestöstä ja huomattavan poikkeava PTF (≥ 0.06 mm∙s) 1.2 %:lla väestöstä. Huomattavan poikkeavaan PTF:en liittyi lähes kaksinkertainen kuoleman ja eteisvärinän riski, mutta ei äkkikuolemariskiä. Lihavuuteen ja diabetekseen liittyi kohonnut sydänperäisen äkkikuoleman riski. Toisaalta lihavilla ja diabeetikoilla myös ei-äkillisten sydänkuolemien riski oli suurentunut, eikä äkillisten kuolemien osuus sydänkuolemista korostunut. Sydänperäisen äkkikuoleman riskiin liitetyt EKG-muutokset paransivat riskiarviota eniten normaalipainoisilla henkilöillä, joilla oli vähemmän sydän- ja verisuonitautien riskitekijöitä. Kokonaisuutena nämä tutkimukset luovat uutta tietoa EKG-riskimarkkereista, lihavuudesta ja diabeteksesta sydänperäisen äkkikuoleman riskiarviossa. Näiden biomarkkereiden lopullinen rooli yksilötasolla perusväestössä vaatii kuitenkin vielä lisätutkimuksia.

Ce manuscrit présente des travaux de recherche sur l’analyse et la détection des Electrogrammes Auriculaires Complexes Fractionnés (EACF). Dans une première partie faisant suite à une présentation des mécanismes et des signaux bioélelectriques de la Fibrillation Auriculaire (FA), les outils les plus couramment utilisés pour l’analyse des signaux EACF sont présentés. Des outils linéaires sont dans un premier temps appliqués aux signaux intracardiaques issus des procédures d’ablation de la FA par radiofréquence puis des outilsnon linéaires sont présentés et intégrés à un algorithme de détection des EACF. Ce dernier s’appuie sur la quantification des propriétés de récurrence des électrogrammes. Dans la seconde partie, la cellule et le tissu musculaire cardiaque sont détaillés puis simulés à l’aide de plusieurs modèles mathématiques. Ceux de FitzHugh Nagumo, Aliev Panfilov et Courtemanche Ramirez Nattel sont mis en oeuvre afin de reproduire les mécanismes de la FA évoqués dans la présentation de cette pathologie. L’acquisition des champs de potentiels est également reproduite à l’aide d’un modèle numérique de cathéter tel que celui utilisé lors des procédures. Les signaux temporels ainsi générés permettent de lier les activations spatiotemporelles au niveau du substrat aux motifs observables dans les EACF. Un modèle expérimental vient compléter la partie modélisation. Les cultures de cellules de rats nouveaux nés sur puces MEA (Micro Electrode Array) permettent de recréer des conditions de fibrillation et d’acquérir des potentiels extracellulaires. Là encore, les électrogrammes sont comparés aux signaux issus des simulations numériques ainsi qu’aux signaux cliniques. L’analyse des séquences de motifs via les trois types de modèles utilisés permet de rattacher les motifs observés dans les électrogrammes aux mécanismes se produisant au niveau du tissu cardiaque lors de la FA. Une analyse en temps réel permettrait de fournir au praticien des informations déterminantes lors de l’ablation concernant la nature et la localisation des sources d’arythmie / This manuscript presents research on the analysis and the detection of Complex Fractionated Atrial Electrograms (CFAE). In the first part, following a presentation over Atrial Fibrillation (AF) mechanisms and bioelectrical signals, the most commonly used tools for analyzing CFAE are presented. Linear tools are initially applied to signals from AF ablation procedures, then nonlinear tools are shown and integrated intoa CFAE detection algorithm. This one is based on the quantification of electrogram recurrence properties. In the second part, the cell and cardiac muscle tissue are described and simulated using mathematical models. Models such as FitzHugh Nagumo, Aliev Panfilov and Courtemanche Ramirez Nattel are implemented to reproduce the mechanisms of AF mentioned in the presentation of this disease. The acquisition of fields of potential is also reproduced using a numerical model of catheter as the one used during ablation process. Time signals thus generated are used to match the spatiotemporal activations at the substrate level with the patterns to be observed in CFAE. An experimental model completes the analysis. Cell cultures of newborn rats on MEA (Micro ElectrodeArray) can recreate fibrillation conditions and acquire extracellular potentials. Again, electrogramsare compared with signals from computer simulations and the clinical database signals. The analysisof pattern sequence via the three types of models can attach the observed patterns in electrograms with the mechanisms occurring at the cardiac tissue level during AF. Real-time analysis would allow the practitioner to receive critical information during ablation about the nature and the location of arrhythmia sources

En utilisant la méthode de génétique inverse, la mutation causale d'un bloc de conduction cardiaque familial a été localisée sur le bras long du chromosome 19 en 13.3 dans une grande famille libanaise. Après avoir testé 12 gènes candidats, nous avons trouvé 3 mutations différentes dans trois familles indépendantes de bloc de conduction cardiaque isolé. Les conséquences des 3 mutations ont été explorées par des études électrophysiologiques. Il s'agit dans les 3 cas d'un gain de fonction. Puis, une cohorte de 248 patients atteints de syndrome de Brugada a été étudiée. Onze mutations du gène TRPM4 ont été trouvées chez 20 patients. Les conséquences électrophysiologiques des mutations étaient diverses. Ensuite, des cohortes de patients atteints de syndrome du QT long, de fibrillation auriculaire ou de cardiomyopathie dilaté ont été étudiées. Nous avons également trouvé des mutations ou des variants prédisposants du gène TRPM4 chez ces patients. Une étude électrophysiologique doit être réalisée pour comprendre le rôle de TRPM4 dans ces autres pathologies. Enfin, notre étude immunohistochimique a démontré que TRPM4 est fortement exprimé dans le système de conduction cardiaque mais aussi plus faiblement dans les cardiomyocytes auriculaires et ventriculaires communs. Ce travail a permis d'impliquer pour la première fois le gène TRPM4 dans des maladies humaines. Ce travail donne les bases pour comprendre le rôle du canal TRPM4 dans le fonctionnement cardiaque. C'est le préalable nécessaire avant de pouvoir développer de nouvelles thérapeutiques dans le futur / By using reverse genetics, the causal mutation of a familial cardiac conduction block was localized to the long arm of chromosome 19 in 13.3. After screening 12 candidate genes, we found 3 different mutations in three independent families with isolated cardiac conduction block. The consequences of these 3 mutations were explored by electrophysiological studies. In all 3 mutations it was a gain of function. Then, a cohort of 248 patients with a Brugada syndrome was studied. Eleven mutations were found in the TRPM4 gene in 20 patients. The electrophysiological consequences of these mutations were diverse. Then, cohorts of patients with long QT syndrome, atrial fibrillation, and dilated cardiomyopathy were studied. We found also mutations or predisposing variants in these patients. An electrophysiology study should be conducted to understand the role of TRPM4 in these other pathologies. Finally, our immunohistochemical study showed that TRPM4 is highly expressed in the cardiac conduction system but also although with less intensity in common auricular and ventricular cardiomyocytes. This work implied for the first time the TRPM4 gene in human diseases. This work provides the basis to understand the role of the TRPM4 channel in cardiac function. This is a prerequisite to be able to develop novel therapies in the future

L’adénosine (ADO) est un nucléoside ubiquitaire issu de l’ATP et du cycle de la méthionine. Via les récepteurs A1 (A1R), elle favorise la fibrillation atriale (FA). Via les récepteurs A2A (A2AR), elle induit une dilatation coronaire. L’ADO est donc un intermédiaire métabolique et un neurotransmetteur du système cardiovasculaire.La 1ère étude montre que, chez les patients coronariens, l’ADO est corrélée à l’homocystéine (Hcy) et l’uricémie. De plus, l’ADO et l’Hcy sont corrélées au score évaluant l’étendue de l’athérosclérose (score SYNTAX). Enfin, sur un modèle d’hépatocyte, l’ADO induit la production d’Hcy selon un effet dose et un effet temps. L’hyperadénosinémie semble ainsi participer à l’augmentation de l’homocystéinémie et de l’uricémie. Ces données apportent un nouvel éclairage sur la physiopathologie de la maladie coronarienne.Dans le 2nd travail, l’ADO augmente significativement uniquement chez les patients coronariens à test d’effort positif. De plus, leur expression des A2AR est plus faible que les patients à test négatif. Ainsi, la faible expression A2AR chez les coronariens à test d’effort positif participe au défaut d’adaptation coronaire durant le test. Un faible niveau d’A2AR pourrait être alors un biomarqueur de coronaropathie.Dans la 3ème étude, les patients avec FA sans cardiopathie sous-jacente ont une adénosinémie normale et une surexpression des A2AR. Sachant que l’ADO peut favoriser la FA, la surexpression des A2AR pourrait donc participer au déclenchement de FA en augmentant la sensibilité à l’adénosine.En conclusion, les médicaments modulant le système adénosinergique pourraient être utiles au traitement de la coronaropathie ou de la FA. / Adenosine (ADO) is an ubiquitous nucleoside that comes from ATP and from the methionine cycle. Via A1 receptors (A1R), it promotes atrial fibrillation (AF). Via A2A receptors (A2AR), it leads to coronary vasodilatation. Thus, adenosine is a metabolic intermediate and a neurotransmitter of the cardiovascular system.The first study showed that adenosine plasma level (APL) is correlated with homocystein (Hcy) and uric acid in coronary artery disease (CAD) patients. Furthermore, APL and Hcy are correlated with the SYNTAX score which evaluate CAD severity. Finally, in cellulo, ADO induced a dose and time dependant increase of HCY production by human hepatocytes. We concluded that high APL may participate into the high HCY and uric acid levels. These data bring new highlight on the physiopathology of CAD.In the second work, APL increased significantly only in patients with positive exercise stress testing (EST). Furthermore, A2AR expression was lower in positive EST patients compared with those with negative EST. Then, we concluded that the low expression of A2AR in CAD patients with positive EST, participates in the lack of adaptive response (coronary vasodilatation) to the EST. This result suggests that low A2AR expression may be a biological marker of CAD.In the third study, patients with AF and no structural heart disease have a normal APL but an increase in A2AR expression. Because adenosine promotes AF, we concluded that high A2AR expression may participate into the triggering of AF by increasing the sensitivity to adenosine.In conclusion, drugs that modulate the purinergic system should be useful tools for the treatment of CAD or AF.

La fibrillation atriale (FA) est l'arythmie cardiaque soutenue la plus fréquente chez les adultes. Elle est associée à une augmentation du risque d'accident vasculaire cérébral, d'insuffisance cardiaque et de la mortalité. Un mécanisme de torsades auriculaires a été décrit chez des patients atteints du syndrome du QT long congénital (SQTL). Malgré une littérature très riche sur le sujet, les mécanismes impliqués dans la genèse et le maintien de ces arythmies restent mal connus et constituent un obstacle dans le diagnostic et la prise en charge de ces maladies. Dans la première partie de ce travail, nous avons abordé l'histologie et la distribution des connexines (Cxs) chez deux groupes de patients avec et sans FA par une approche de microscopie confocale. Nous avons ainsi décrit d'une part un réseau entre fibroblastes et myocytes communiquant via les Cx 40 et 43 et d'autre part la présence de myofibroblastes, d'une forte fibrose et d'un remodelage des Cx 40 et 43 dans le tissu de patients FA. Par ailleurs, pour identifier de nouvelles mutations impliquées dans ces arythmies, nous avons étudié une cohorte de 60 patients atteints de FA. Les recherches génétiques et l'étude fonctionnelle nous ont permis d'associer 5 nouvelles mutations: P41S et M207V (PITX2), G277E (Cx 40) A253V (Cx 43) et P1034H (KCNH2) à la FA. Celles-ci semblent jouer un rôle clé dans la constitution du substrat arythmogène. Enfin, dans la dernière partie, nous avons exploré l'impact électrophysiologique d'un variant de KCNH2, R148W, trouvé tout d'abord chez un enfant décédé de mort subite pendant le sommeil, puis chez plusieurs membres de la famille, dont certains présentent un intervalle QT allongé. Ce variant, exprimé dans les ovocytes de Xénope et étudié en voltage-clamp, réduit le courant de 29% et pourrait alors prédisposer à la survenue de torsades de pointes et expliquer en partie l'allongement du QTc. Outre les nouveaux variants géniques découverts, ce travail est le premier à associer un gain de fonction du facteur de croissance PITX2c en relation avec la FA. Le remodelage histologique des Cx et les variants nucléotidiques touchant les gènes GJA1, GJA5, PITX2 et KCNH2 pourraient ainsi participer à l'étiologie de la FA et du QT long / Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. It is associated with an increased risk of stroke, heart failure and mortality. A mechanism of atrial torsades has been described in patients with congenital long QT syndrome (LQTS). Despite the already existing body of literature, the mechanisms involved in the genesis and maintenance of these arrhythmias remain poorly understood and constitute an obstacle in diagnosis and management of these diseases. In the first part of this work, we discussed the histology of connexins (Cxs) and their distribution in two groups of patients (with and without FA), by confocal microscopy approach. We have described a network of fibroblasts and myocytes communicating across Cx 40 and 43 and the presence of myofibroblasts, of a strong fibrosis and of a remodeling of Cx 40 and 43 distribution in the tissue of AF patients. In addition, to identify new mutations involved in these arrhythmias, we studied a cohort of 60 patients with AF. Genetic investigations and functional study enabled us to associate five novel mutations with AF: M207V and P41S (PITX2), G277E (Cx 40) A253V (Cx 43) and P1034H (KCNH2). These mutations likely play a key role in the formation of the arrhythmogenic substrate. Finally, we explored the electrophysiological impact of a KCNH2 variant, R148W, initially found in a child who died suddenly during sleep and subsequently disclosed in several family members, some with a long QT interval. When expressed in Xenopus oocytes and studied in voltage-clamp, this variant reduces the current by 29%, which might predispose to torsades de pointes and partly explain the QTc prolongation. In addition to these newly discovered gene variants, this work is the first to report a gain-of-function mutation of the transcription factor PITX2c in AF. Histological remodeling of Cxs and the nucleotide variants affecting GJA1, GJA5, PITX2 and KCNH2 might thus participate in the etiology of AF and LQTS

La fibrillation atriale (FA) est une complication fréquente de la phase aiguë de l’infarctus (IDM) avec un moins bon pronostic des patients. Sa forme silencieuse pourrait être fréquente après un IDM. Cependant, toutes les études ayant porté sur la FA se sont focalisées sur les formes symptomatique, paroxystique ou persistante. De plus, la réduction de la biodisponibilité du •NO et la dysfonction endothéliale peuvent altérer le pronostic des patients en FA. Or, l’asymétrique diméthylarginine (ADMA) en inhibant de façon endogène l’action des NO synthases peut conduire à une dysfonction endothéliale, une inflammation ou encore à un stress oxydatif, qui sont impliqués dans de nombreuses pathologies cardiovasculaires. Cependant, au-cune étude n’a évalué la relation potentielle entre le taux plasmatique d’ADMA et la survenue d’une FA après un IDM.Notre objectif a été d’évaluer dans le cadre d’une étude prospective le pronos-tic hospitalier et à un an des patients présentant de la FA silencieuse en phase ai-guë d’IDM, et évaluer le lien potentiel entre les dimethylarginines et l’apparition d’une FA. Notre première étude prospective montre pour la première fois que la FA si-lencieuse est plus fréquente que la FA symptomatique et est associée à un moins bon pronostic après un IDM.Notre second travail, démontre que l’impact négatif de la FA silencieuse sur le pronostic des patients se maintient à un an après l’IDM.Notre troisième travail montre également, que l’ADMA est associée de ma-nière indépendante à la survenue d’une FA symptomatique après un IDM. Ces données suggèrent qu’un dépistage et qu’une prise en charge spécifiques de la FA après un IDM pourraient améliorer le pronostic des patients. L’ADMA pourrait ainsi être utilisée comme un marqueur de risque de passage en FA après un IDM. / Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI) with a poorer prognosis. Silent atrial fibrillation has been suggested to be frequent after AMI. However, most part of the studies has targeted only paroxysmal or persistent AF. Thus, Reduced Nitric Oxide availability and endothelial dysfunction has been recently recognized as a possible contributor to altered prognosis in AF. Asymmetric dimethylarginine (ADMA) can inhibit nitric oxide synthase and leads to endothelial dysfunction, inflammation and oxidative stress in multiple cardiovascular diseases. However, any study has addressed the relationship between ADMA levels and the occurrence of AF in AMI.We aimed to assess in-hospital and 1-year prognosis in patients experiencing silent AF in AMI and evaluate the potential relationship between dimethylarginines plasma levels and the occurrence AF after acute myocardial infarction.Our first prospective study shows for the first time that silent AF is more frequent than symptomatic AF after AMI and is associated with a worse prognosis.Our second work confirms the impact of silent AF on prognosis, with a prognosis that remains worse one year after the acute phase of MI. Our third work proved that ADMA is independently associated with symptomatic AF after AMI and strengthen the capacity to estimate symptomatic AF occurrence. In conclusion our studies highlight that AF is not a negligible event after AMI, in particular silent AF. That suggests that systematic screening and specific management should be investigated in order to improve outcomes of patients. ADMA appears to be a potential predictor of AF after AMI, because of its significant association.

Background: Management of atrial fibrillation (AF) is complex and requires active patient engagement in shared decision making to achieve better clinical outcomes, greater medication adherence, and increased treatment satisfaction. Efficacy in patient-physician interactions is a critical component of patient engagement, but factors associated with efficacy in older AF patients have not been well-characterized. Methods: We performed a cross-sectional analysis of baseline data from the ongoing Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF) study, a cohort study of older adults (age ≥ 65) with non-valvular AF and CHA2DS2-VASc score ≥ 2. Participants were classified according to their Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) score (lower: 0-44; higher: 45-50). Logistic regression analysis was used to identify sociodemographic, clinical (AF type, AF treatment, medical comorbidities), and geriatric (cognitive impairment, sensory impairment, frailty, independent functioning) factors associated with lower reported efficacy. Results: Participants (n = 1209; 49% female) had a mean age of 75. A majority (66%) reported higher efficacy in their interactions with physicians. Lower efficacy was associated with persistent AF (adjusted odds ratio [aOR] = 1.52; 95% confidence interval [CI] = 1.13-2.04) and with symptoms of depression (aOR = 1.67; CI = 1.20-2.33) or anxiety (aOR = 1.40; CI = 1.01-1.94). Decreased odds of lower efficacy were observed in participants with chronic kidney disease (aOR = 0.68; CI = 0.50-0.92) and those classified as pre-frail compared to those classified as not frail (aOR = 0.71; CI = 0.53-0.95). Conclusion: Older patients with persistent AF or symptoms of depression or anxiety have decreased efficacy in patient-physician interactions. These individuals merit greater attention from physicians when engaged in shared decision making.

Atrial fibrillation is an arrhythmia commonly detected from ECG using its specific characteristics. An early detection of this arrhythmia is a key to prevention of more serious conditions. Nowadays, atrial fibrillation detection is being implemented more often using deep learning. This work presents detection of atrial fibrillation from 12lead ECG using deep convolutional network. In the first section, there is a theoretical context of this work, then there is a description of proposed algorithm. Detection is implemented by a program in Python in two variations and their accuracy is rated by Accuracy and F1 measure. Results of the work are being discussed, mutually compared and compared to other similar publications.