Orientador: Maria Julia Marques / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T07:19:08Z (GMT). No. of bitstreams: 1 Moreira_DrielendeOliveira_M.pdf: 2075338 bytes, checksum: 00bb5917e4f176b73c58453340cb3a5e (MD5) Previous issue date: 2012 / Resumo: A Distrofia muscular de Duchenne (DMD) é uma doença caracterizada pela fraqueza muscular progressiva que leva à insuficiência respiratória e cardíaca, resultando em morte por volta dos 30 anos de idade. No camundongo mdx, modelo experimental da DMD, os músculos diafragma e cardíaco são severamente afetados apresentando fibrose semelhante à observada na patologia humana. O objetivo deste trabalho foi investigar os efeitos do tratamento a longo prazo com suramina, uma droga anti-fibrótica, nos músculos diafragma e cardíaco de camundongos mdx idosos. Camundongos mdx (n=20; 8 meses de idade) receberam injeções intraperitoneais de suramina (60 mg/kg), durante 3 meses. Controles mdx (n=20; 8 meses) e C57BL/10 (n=18; 8 meses) foram injetados com solução salina. Os camundongos da linhagem C57BL/10 expressam distrofina e são utilizados como controle da linhagem mdx. A suramina diminuiu os níveis de CK e atenuou a perda da força muscular. No músculo diafragma, a suramina reduziu a área de fibrose e a mionecrose. No músculo cardíaco, houve redução da fibrose, da inflamação e melhora significativa de parâmetros funcionais cardíacos (amplitude das ondas P, Q, R e S do eletrocardiograma). Sugere-se que a suramina possa ser potencialmente útil nas distrofinopatias, atenuando a miopatia nos músculos mais afetados, o coração e o diafragma, nos estágios tardios da doença / Abstract: Duchenne muscular dystrophy (DMD) is a disease characterized by progressive muscle weakness leading to respiratory and cardiac failure, resulting in death around 30 years of age. In the mdx mice model of DMD, diaphragm and cardiac muscles are severely affected in the later stages of the disease, showing intense fibrosis similar to that observed in human pathology. The aim of the present study was to investigate the effects of long-term treatment with suramin, an anti-fibrotic agent, in the diaphragm and cardiac muscles of the mdx mice. Mdx mice (n=20; 8 months of age) received intraperitoneal injections of suramin (60 mg/kg) for 3 months. Mdx controls (n=20; 8 months) and C57BL/10 (n=18; 8 months old) were injected with saline. C57BL/10 mice express dystrophin and are the control strain for the mdx mice. Suramin decreased CK levels and reduced the loss of muscle strength. Suramin reduced fibrosis and myonecrosis in diaphragm. In the cardiac muscle, suramin decreased fibrosis, inflammation and improved cardiac functional parameters (P, Q, R and S waves of the electrocardiogram). It is suggested that suramin may be a potential therapy for distrophinopaties, attenuating the dystrophic phenotype of the most affected cardiac and diaphragm muscles of the mdx mice, during later stages of the disease / Mestrado / Anatomia / Mestre em Biologia Celular e Estrutural

Submitted by Fabiana Gonçalves Pinto (benf@ndc.uff.br) on 2015-10-14T17:08:25Z No. of bitstreams: 1 Roberta Neves.pdf: 2013363 bytes, checksum: 02dd0656ebbb2438dc6715d64f374fdb (MD5) / Made available in DSpace on 2015-10-14T17:08:25Z (GMT). No. of bitstreams: 1 Roberta Neves.pdf: 2013363 bytes, checksum: 02dd0656ebbb2438dc6715d64f374fdb (MD5) Previous issue date: 2014 / Mestrado Profissional em Enfermagem Assistencial / O estudo aborda os processos de limpeza e desinfecção dos principais dispositivos de monitoramento não críticos (termômetros, esfigmomanômetro, cabos de eletrocardiograma e oxímetro) considerando a sua participação na transmissão das infecções relacionadas à assistência à saúde. Estes equipamentos têm sido apontados como uma das principais fontes de infecção por bactérias multirresistentes causadoras de surtos infecciosos em ambiente hospitalar portanto, exigem padronização da limpeza e desinfecção, mediante um protocolo que norteie o processo de trabalho. Este estudo teve como objetivos: elaborar um protocolo de limpeza/desinfecção dos principais dispositivos de monitoramento não críticos, com base nas boas práticas e evidências na literatura, e validar este protocolo com avaliação de experts em infecção hospitalar. Trata-se de estudo descritivo e exploratório, que no seu desenvolvimento seguiu as seguintes etapas: revisão integrativa da literatura, elaboração do protocolo de limpeza e desinfecção dos principais dispositivos de monitoramento não críticos e validação do protocolo por experts em infecção hospitalar. A elaboração do protocolo ocorreu a partir das boas práticas identificadas nos estudos selecionados na revisão integrativa, livros, teses, dissertações e documentos de órgãos nacionais e internacionais sobre a temática. Para validação do protocolo foram selecionados cinco experts em infecção hospitalar, de acordo com os critérios de seleção sugeridos no estudo. Após avaliação de cada recomendação do protocolo proposto, em um questionário, foi calculado o grau de concordância entre eles por média ponderada. A partir da análise dos registros dos experts e, considerando o grau de concordância das respostas, foi elaborado o protocolo final. Assim, respondendo aos objetivos do estudo, inicialmente tem-se o protocolo construído a luz do conhecimento científico que foi chancelado por um grupo de experts gerando o protocolo final. Este protocolo é portanto, o produto desta pesquisa e com ele pretende-se padronizar os processos de limpeza e desinfecção destes dispositivos, visando preencher as lacunas do conhecimento teórico/prático identificadas sobre a temática e reduzir os riscos de transmissão de infecção por estes artigos. Este protocolo será proposto à Comissão de Controle de Infecção Hospitalar da Secretaria Estadual de Saúde do Rio de Janeiro, a fim de implementá-lo nas unidades de pronto atendimento 24 horas (UPAs 24hs) testando sua aplicabilidade e futuramente sua eficácia. / The study discusses the procedures of cleaning and disinfection of the main non-critical monitoring devices (thermometers, sphygmomanometer, electrocardiography wires and oximeters wires) considering their participation in the transmission of infections related with health care. These equipments have been identified as the major source of infection by multiresistant bacteria that causes hospital infections, therefore, require standardization of cleaning and disinfection, by using a protocol that guides the work process. This study aims to: develops a protocol for cleaning / disinfection of the main non-critical monitoring devices, based on best practices and evidence in the literature, and validate this protocol with assessment of experts in hospital infections. It is descriptive and exploratory study, which involved the following steps: integrative literature review, development of the protocol for cleaning and disinfection of the main devices of non-critical monitoring and a validation of this protocol by the experts of hospital infection. The protocol development is based on best practices identified in the studies selected in integrative review, books, thesis, dissertations and national and international documents on the subject. To validate the protocol, five experts in hospital infection were selected according to the selection criteria suggested in the study. After evaluating each recommendation of the proposed protocol, in a questionnaire, the degree of agreement was calculated by weighted average. From the analysis of the observations of experts and considering the degree of agreement of answers, a final protocol was developed. So, to answer the aim of this work, first of all, a protocol was developed with scientific knowledge and afterward judged by some experts, which leads to a final protocol. Therefore this final protocol is the result of this study and it is intended to standardize the process of cleaning and disinfection of these devices, fill gaps in theoretical/practical knowledge on the subject and reduce the risk of infection transmission by these objects. These protocol will be proposed to the of Hospital Infection Control Committee at the State Department Health of Rio de Janeiro, to implement it in emergency care unit (called “UPAs 24 hs”) testing its applicability and future effectiveness.

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.

Chronic stress is a prevalent and universally present hazard in modern society. It lowers the quality of life for individuals and significantly con- tributes to unsustainable health care costs. Therefore it is important to have natural and noninvasive ways of controlling stress. One such way is meditation, a technique which has been practiced for over five thousand years to improve stress regulation. Also, proceedings in sensing technologies lead to the discovery of biofeedback as another cost-effective technique for stress assessment and reduction. In continuation of research on real-time reflective human-computer-interfaces, this thesis combines these techniques by exploring the application of electrocardiography sensing technology in a heart rate variability (HRV) biofeedback system for the scenario of medita- tion practice. A proof-of-concept prototype was designed and implemented which quantifies stress and gives feedback on meditation effectiveness. For evaluation, a user study has been performed. Results were analysed in a systematic way to evaluate the feasibility and acceptance of the solution as well as the fidelity of HRV data that was measured during user tests. The prototype was found to be feasible in the context of technology acceptance while the fidelity of data, acquired by an algorithm for time and frequency domain analysis of HRV, was confirmed. A final conclusion is that the reflective aspect of the implemented real-time biofeedback system helps to improve regulatory capacity and thus lowers stress in individuals.

Abstract Based on experimental studies, heterogeneous ventricular repolarization has been suggested to predispose to the onset of life-threatening ventricular arrhythmias and subsequent studies in various patient populations have associated it with poor clinical outcome. The aim of this study was to assess the dynamics of ventricular repolarization from electrocardiogram (ECG) during a standard exercise stress test with techniques based on principal component analysis, and to investigate whether they would yield valuable prognostic information on cardiac mortality and sudden cardiac death. Exercise ECG recordings from 40 healthy men and women were analyzed in order to establish normal dynamics and rate-dependence for the spatial QRS/T angle and total cosine R to T (TCRT), which reflects the spatial deviation between the depolarization and repolarization wave-fronts. Subsequently, exercise ECG recordings from 20 patients with previous myocardial infarction (MI) were compared with 20 controls in order to assess the modulation of previous MI on the dynamics of TCRT. The prognostic value of abnormal dynamics and rate-dependence of TCRT and spatial QRS/T angle were assessed in 1,297 patients referred to a clinically indicated exercise stress test. The spatial QRS/T angle and TCRT were found to be significantly rate-dependent during both exercise and recovery periods as TCRT and the cosine of the spatial QRS/T angle decreased at higher heart rates (HR), indicating increase in the global heterogeneity of the ventricular repolarization. In the post-MI group, the dynamics of TCRT were impaired with a significantly lower rate-dependence in contrast to the healthy and control groups. In the study cohort, impaired rate-dependence of TCRT during both exercise and recovery periods was an independent predictor of cardiac and sudden cardiac death during the follow up of the study. Similarly, reduction of the area between the exercise and three-minute recovery TCRT/HR curves was associated with an increased risk of cardiac and sudden cardiac death. In conclusion, dynamics and rate-dependence of TCRT and spatial QRS/T angle are able to discriminate subjects with an increased risk of cardiac and sudden cardiac death. Reduced rate-dependence of TCRT during exercise and recovery periods, as well as decreased exercise-recovery hysteresis of TCRT, are significant predictors of cardiac and sudden cardiac death. / Tiivistelmä Sydämen kammioiden poikkeavan palautumisen on kokeellisissa tutkimuksissa havaittu altistavan kammioperäisille rytmihäiriöille. Lisäksi, useat tutkimukset erilaisissa potilasaineistoissa ovat osoittaneet sen olevan yhteydessä heikkoon kliiniseen ennusteeseen. Tämän työn tarkoituksena oli analysoida sydämen kammioiden repolarisaation dynamiikkaa sydänsähkökäyrästä (EKG) rasituskokeen aikana pääkomponenttianalyysiin perustuvilla menetelmillä sekä tutkia, ennustavatko uudet muuttujat sydänperäistä kuolemaa tai sydänperäistä äkkikuolemaa. Neljänkymmenen terveen miehen ja naisen rasitus-EKG:t analysoitiin depolarisaatio- ja repolarisaatioaaltojen välistä avaruudellista kulmaa kuvaavan ’total cosine R to T’:n (TCRT) sekä kolmiulotteisen QRS/T-kulman dynamiikan sekä sykeriippuvuuden normaaliarvojen määrittämiseksi. Lisäksi, vertailtiin 20 sydäninfarktin sairastaneen sekä 20 kontrollipotilaan rasitusmittauksia aiemman infarktin TCRT:n dynamiikkaan sekä sykeriippuvuuteen aiheuttaman modulaation määrittämiseksi. Muuttujien poikkeavan dynamiikan ennustearvoa testattiin 1297 rasitus-EKG-mittaukseen lähetteen saaneella potilaalla. Sekä TCRT että avaruudellisen QRS/T-kulman kosini olivat molemmat erittäin sykeriippuvaisia sekä rasituksessa että palautumisessa. Molemmat muuttujat pienenivät sykkeen (HR) kasvaessa, osoittaen kammioiden repolarisaation heterogeenisyyden kasvua korkeammilla syketaajuuksilla. Sydäninfarktin sairastaneilla potilailla muuttujien dynamiikka ja sykeriippuvuus olivat heikentyneitä. Kohorttiaineistossa heikentynyt sykeriippuvuus sekä rasituksen että palautumisen aikana ennustivat myöhempää sydänperäistä kuolemaa sekä sydänperäistä äkkikuolemaa itsenäisesti. Vastaavasti, rasituksen ja kolmen minuutin palautumisen aikaisten TCRT/HR kuvaajien väliin jäävän pinta-alan pienentyminen oli yhteydessä korkeampaan sydänperäisen kuoleman sekä sydänperäisen äkkikuoleman riskiin. Kammioiden repolarisaation dynamiikkaa kuvaavat muuttujat pystyvät erottelemaan potilaat, joilla on korkeampi riski kokea sydänperäinen kuolema tai sydänperäinen äkkikuolema. Poikkeavan alhainen sykeriippuvuus rasituksen ja palautumisen aikana sekä alentunut rasituksen ja palautumisen välinen hystereesi olivat merkittäviä sydänperäisen kuoleman sekä sydänperäisen äkkikuoleman ennustajia.

Abstract Cardiovascular abnormalities are frequent after non-traumatic intracranial hemorrhage (NT-IH). They have mainly been studied in patients with subarachnoid hemorrhage (SAH), in which they have been reported to be associated with a poorer outcome. The aim of this observational clinical study was to evaluate cardiovascular abnormalities in patients with NT-IH requiring intensive care: clinical picture, predisposing factors and impact on outcome were examined. Additionally, the validity of cardiac output (CO) monitoring via uncalibrated arterial pressure waveform analysis (APCO, FloTrac/Vigileo™) was evaluated. The thesis was comprised of retrospective (n=229) and prospective (n=108) studies. The cardiovascular abnormalities evaluated were repolarization abnormalities (RAs) in electrocardiography (ECG), myocardial injury and dysfunction, and neurogenic pulmonary edema (NPE). Cardiovascular dysfunction severity was assessed using the Sequential Organ Failure Assessment cardiovascular (SOFAcv) score. Predisposing factors for RAs and NPE were examined. The one-year mortality and functional outcome were assessed. APCO was compared with the intermittent bolus thermodilution technique (TDCO). Cardiovascular abnormalities were almost universal after NT-IH and comparable after intracerebral hemorrhage (ICH) and SAH. Each RAs (QT interval prolongation, ischemic-like ECG changes and morphological end-repolarization abnormalities) had characteristic predisposing factors. The Acute Physiology And Chronic Health Evaluation (APACHE) II score ≥20 and systemic interleukin 6 concentration >40 pg/mL were independent predictors for NPE. In the retrospective study the mortality rate was 32% after SAH and 44% after ICH. In the prospective study the rates for mortality were 18% vs. 29% and for a poor functional outcome 41% vs. 69%, respectively. Ischemic-like ECG changes were associated with a poorer functional outcome. APCO underestimated CO compared to TDCO and was biased by low systemic vascular resistance (SVR). In conclusion, cardiovascular abnormalities after NT-IH are comparable after SAH and ICH. Predisposing factors for each RAs vary. Inflammatory mechanisms play an important role in NPE development. Ischemic-like ECG changes are associated with a poorer one-year functional outcome. The validity of APCO is insufficient and biased by low SVR in patients with NT-IH. / Tiivistelmä Sydämen ja verenkierron toimintahäiriöt ovat yleisiä ei-traumaattisen aivoverenvuodon (NT-IH) jälkeen. Niitä on tutkittu lähinnä lukinkalvonalaisvuotopotilailla (SAV), joilla niiden on todettu olevan yhteydessä huonompaan ennusteeseen. Tässä havainnoivassa kliinisessä tutkimuksessa selvitettiin tehohoidettujen NT-IH -potilaiden sydämen ja verenkierron toimintahäiriöiden kliinistä oirekuvaa, altistavia tekijöitä ja vaikutusta ennusteeseen. Tutkimuksessa arvioitiin myös valtimopainekäyräanalyysiin perustuvan monitorointimenetelmän (APCO, FloTrac/Vigileo™) luotettavuutta mitattaessa sydämen minuuttitilavuutta. Väitöskirjatyö koostui retrospektiivisesta (n=229) ja prospektiivisesta (n=108) tutkimuksesta. Tutkittavia toimintahäiriöitä olivat elektrokardiografiassa (EKG) nähtävät repolarisaatiohäiriöt (RAs), sydänlihaksen vaurio ja supistumishäiriö sekä keuhkopöhö. Sydämen ja verenkierron toimintahäiriön yleistä vaikeusastetta arvioitiin SOFAcv -pisteytyksellä. RAs:lle ja keuhkopöhölle altistavia tekijöitä määritettiin. Potilaiden kuolleisuus ja toiminnallinen ennuste selvitettiin vuoden seuranta-aikana. APCO:a verrattiin lämpölaimennusmenetelmään (TDCO). Sydämen ja verenkierron toimintahäiriöitä esiintyi lähes kaikilla, eivätkä ne oirekuvaltaan eronneet aivokudoksen sisäistä vuotoa (ICH) ja SAV:a sairastavilla potilailla. Eri RAs:llä (QT-ajan pidentyminen, iskeemistyyppiset EKG-muutokset ja loppurepolarisaation morfologiset poikkeavuudet) oli kullekin ominaiset altistavat tekijät. APACHE II –pisteet ≥20 ja veren interleukiini 6 –pitoisuus >40 pg/ml ennustivat keuhkopöhön kehittymistä. Retrospektiivisessä aineistossa kuolleisuus oli 32 % SAV-potilailla ja 44 % ICH-potilailla. Prospektiivisessa aineistossa kuolleisuus ja huono toiminnallinen ennuste olivat vastaavasti 18 % vs. 29 % ja 41 % vs. 69 %. Iskeemistyypiset EKG-muutokset olivat yhteydessä huonompaan toiminnalliseen ennusteeseen. APCO aliarvioi TDCO:a matalan systeemiverenkierron vastuksen (SVR) kasvattaessa harhaa. Yhteenvetona todettakoon, että sydämen ja verenkierron toimintahäiriöt eivät eroa SAV- ja ICH-potilailla. Eri RAs:lle altistavat kullekin ominaiset tekijät. Tulehdukselliset mekanismit ovat keskeisiä keuhkopöhön kehittymisessä. Iskeemistyyppiset EKG-muutokset ovat yhteydessä huonompaan toiminnalliseen ennusteeseen. APCO:n luotettavuus NT-IH -potilailla on riittämätön, ja harhaa lisää matala SVR.

L'apnée est une complication fréquente chez les nouveaux-nés prématurés. L'un des problèmes les plus fréquents est l'épisode d'apnée bradycardie dont la répétition influence de manière négative le développement de l'enfant. C'est pourquoi les enfants prématurés sont surveillés en continu par un système de monitoring. Depuis la mise en place de ce système, l'espérance de vie et le pronostic de vie des prématurés ont été considérablement améliorés et ainsi la mortalité réduite. En effet, les avancées technologiques en électronique, informatique et télécommunications ont conduit à l'élaboration de systèmes multivoies de monitoring néonatal de plus en plus performants. L'un des principaux signaux exploités dans ces systèmes est l'électrocardiogramme (ECG). Toutefois, même si l'analyse de l'ECG a évolué au fil des années, l'ensemble des informations qu'il fournit n'est pas encore totalement exploité dans les processus de décision, notamment en monitoring en Unité de Soins Intensifs en Néonatalogie (USIN). L'objectif principal de cette thèse est d'améliorer la prise en compte des dynamiques multi-dimensionnelles en proposant de nouvelles approches basées sur un formalisme bayésien, pour la détection précoce des apnées bradycardies chez le nouveau-né prématuré. Aussi, dans cette thèse, nous proposons deux approches bayésiennes, basées sur les caractéristiques de signaux biologiques en vue de la détection précoce de l'apnée bradycardie des nouveaux-nés prématurés. Tout d'abord avec l'approche de Markov caché, nous proposons deux extensions du Modèle de Markov Caché (MMC) classique. La première, qui s'appelle Modèle de Markov Caché Couplé (MMCC), créé une chaîne de Markov à chaque dimension de l'observation et établit un couplage entre les chaînes. La seconde, qui s'appelle Modèle Semi-Markov Caché Couplé (MSMCC), combine les caractéristiques du modèle de MSMC avec le mécanisme de couplage entre canaux. Pour les deux nouveaux modèles (MMCC et MSMCC), les algorithmes récursifs basées sur la version classique de Forward-Backward sont introduits pour résoudre les problèmes d'apprentissage et d'inférence dans le cas couplé. En plus des modèles de Markov, nous proposons deux approches passées sur les filtres de Kalman pour la détection d'apnée. La première utilise les modifications de la morphologie du complexe QRS et est inspirée du modèle générateur de McSharry, déjà utilisé en couplant avec un filtre de Kalman étendu dans le but de détecter des changements subtils de l'ECG, échantillon par échantillon. La deuxième utilise deux modèles AR (l'un pour le processus normal et l'autre pour le processus de bradycardie). Les modèles AR sont appliqués sur la série RR, alors que le filtre de Kalman suit l'évolution des paramètres du modèle AR et fournit une mesure de probabilité des deux processus concurrents. / Apnea-bradycardia episodes (breathing pauses associated with a significant fall in heart rate) are the most common disease in preterm infants. Consequences associated with apnea-bradycardia episodes involve a compromise in oxygenation and tissue perfusion, a poor neuromotor prognosis at childhood and a predisposing factor to sudden-death syndrome in preterm newborns. It is therefore important that these episodes are recognized (early detected or predicted if possible), to start an appropriate treatment and to prevent the associated risks. In this thesis, we propose two Bayesian Network (BN) approaches (Markovian and Switching Kalman Filter) for the early detection of apnea bradycardia events on preterm infants, using different features extracted from electrocardiographic (ECG) recordings. Concerning the Markovian approach, we propose new frameworks for two generalizations of the classical Hidden Markov Model (HMM). The first framework, Coupled Hidden Markov Model (CHMM), is accomplished by assigning a Markov chain (channel) to each dimension of observation and establishing a coupling among channels. The second framework, Coupled Hidden semi Markov Model (CHMM), combines the characteristics of Hidden semi Markov Model (HSMM) with the above-mentioned coupling concept. For each framework, we present appropriate recursions in order to use modified Forward-Backward (FB) algorithms to solve the learning and inference problems. The proposed learning algorithm is based on Maximum Likelihood (ML) criteria. Moreover, we propose two new switching Kalman Filter (SKF) based algorithms, called wave-based and R-based, to present an index for bradycardia detection from ECG. The wave-based algorithm is established based on McSarry's dynamical model for ECG beat generation which is used in an Extended Kalman filter algorithm in order to detect subtle changes in ECG sample by sample. We also propose a new SKF algorithm to model normal beats and those with bradycardia by two different AR processes.

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En dépit du développement rapide de la médecine, les maladies cardiovasculaires restent la première cause de mortalité dans le monde. En France, chaque année, plus de 50 000 personnes meurent subitement en raison d'arythmies cardiaques. L'identification des patients à risque élevé de décès soudain est toujours un défi. Pour détecter les arythmies cardiaques, actuellement Holter est généralement utilisé pour enregistrer les signaux électrocardiogramme (ECG) à 1~3 dérivations pendant 24h à 72h. Cependant l'utilisation de Holter est limitée parmi la population en raison de son encombrement (pas convivial) et de son coût. Un Holter mono puce portable nommé SoC-Holter qui permet d'enregistrer 1 à 4 dérivations est introduit. Le déploiement d'un réseau de capteurs sans fil exige que chaque SoC-Holter soit peu encombrant et peu cher, et consomme peu d’énergie. Afin de minimiser la consommation d'énergie et le coût du système, la technologie Complementary Metal Oxide Semiconductor (CMOS) (0.35μm) est utilisée pour la première implémentation de SoC-Holter. Puis une nouvelle méthode de détection basée sur Acquisition Comprimée (CS) est introduite pour résoudre les problèmes de consommation d'énergie et de capacité de stockage de SoC-Holter. Le principe premier de cette plate-forme est d'échantillonner les signaux ECG sous la fréquence de Nyquist ‘sub-Nyquist’ et par la suite de classer directement les mesures compressées en états normal et anormal. Minimiser le nombre de fils qui relient les électrodes à la plate-forme peut rendre l’utilisateur de SoC-Holter plus confortable, car deux électrodes sont très proches sur la surface du corps. La différence ECG enregistrée est analysée à l'aide de Vectocardiogramme (VCG). Les résultats expérimentaux montrent qu'une approche intégrée, à faible coût et de faible encombrement (SoC-Holter) est faisable. Le SoC-Holter consomme moins de 10mW en fonctionnement. L'estimation des paramètres du signal acquis est effectuée directement à partir de mesures compressées, éliminant ainsi l'étape de la reconstruction et réduisant la complexité et le volume des calculs. En outre, le système fournit les signaux ECG compressés sans perte d'information, de ce fait il réduit significativement la consommation d'énergie pour l'envoi de message et l’espace de stockage mémoire. L'effet de placement des électrodes est évalué sur la QRS complexe lorsqu'il a enregistré avec deux électrodes adjacentes. La méthode est basée sur l'algorithme de ‘QRS-VCG loop alignment’. La méthode moindre carré est utilisée pour estimer la corrélation entre une boucle VCG observée et une boucle de référence en respectant les transformations de rotation et la synchronisation du temps. Les emplacements d'électrodes les moins sensibles aux interférences sont étudiés. / According to the figures released by World Health Organization (WHO), cardiovascular disease is the number one cause of death in the world. In France every year more than 50,000 people die suddenly due cardiac arrhythmias. Identification of high risk sudden death patients is still a challenge. To detect cardiac arrhythmias, currently Holter is generally used to record 1~4 leads electrocardiogram (ECG) signals during 24h to 72h. However the use of Holter is limited among the population due to its form factor (not user-friendly) and cost. An integrated single chip wearable Holter named SoC-Holter that enables to record 1 to 4 leads ECG is introduced. Deployment of wireless sensor network requires each SoC-Holter with less power consumption, low-cost charging system and less die area.To minimize energy consumption and system cost, Complementary Metal Oxide Semiconductor (CMOS) technology (0.35μm) is used to prototype the first implementation of SoC-Holter. Then a novel method based on Compressed Sensing (CS) technique is introduced for solving the problems of power consumption and storage capacity of SoC-Holter. The main principle underlying this framework is to sample analog signals at sub-Nyquist rate and to classify directly compressed measurement into normal and abnormal state. Minimizing the wire connected electrodes to the platform can make the carrier more comfortable because two electrodes are attached closely on the surface of the body. Recording difference ECG is analyzed using Vectorcardiogram (VCG) theory. Experimental results show that an integrated, low cost, and user-friendly SoC-Holter is feasible. SoC-Holter consumes less than 10mW while the device is operating. It takes advantage of estimating parameters directly from compressed measurements, thereby eliminating the reconstruction stage and reducing the computational complexity on the platform. In addition, the framework provides compressed ECG signals without loss of information, reducing significantly the power consumption for message sending and memory storage space. The effect of electrode placement is evaluated by estimating QRS complex in recorded ECG signals by two adjacent electrodes. The method is based on the QRS-VCG loop alignment algorithm that estimates Least Square (LS) between an observed VCG loop and a reference loop with respect to the transformations of rotation and time synchronization. The electrode location with less sensitive to interference is investigated.

Heart arrhythmias are a very common heart disease whose incidence is rising. This thesis is focused on the detection of premature ventricular contractions from 12-lead ECG records by means of deep learning. The location of these arrhythmias (key instances) in the record was found using a technique based on Multiple-Instance Learning. In the theoretical part of the thesis, basic electrophysiology of the heart and deep learning with a focus on the convolutional neural networks are described. Afterward, a program was created using the Python programming language, which contains a model based on the InceptionTime architecture, using which classification of the signals into the selected classes was performed. Grad-CAM was implemented to find locations of the key instances in the ECGs. The evaluation of the arrhythmia detection quality was done using the F1 score and the results were discussed at the end of the thesis.