Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The geraniol (C10H18O) is an acyclic monoterpene alcohol, present in the essential oil of some medicinal plants, herbs and citrus fruits, especially species of the genus Cymbopogon. Were described biochemical and pharmacological properties such as anticonvulsant action, analgesic, antinflammatory, antioxidant, anticancer and antimicrobial activities. In this study we sought to characterize the effects produced by geraniol on contractility, electrical activity and its possible antiarrhythmic potential in mammalian heart. For this, we used guinea-pig (Cavia porcellus) and mice (Mus musculus) of C57Bl/6J strain. The contractile studies were performed in the left atria drawn 1GF and stimulated with pulses of suprathreshold current, maintained in Cuba for isolated organ submerged in modified Tyrode solution (8 mL) and aerated with carbogenic mixture (95% O2 and 5% CO2). The force of atrial contraction was recorded by an isometric transducer. Electrocardiographic recordings were performed on isolated heart under constant aortic perfusion flow (8 mL/min) in a Langendorff system. To study the effects of geraniol on current membrane, experiments were performed using the technique of patch-clamp in rat ventricular cardiomyocytes setup whole-cell. In the atrium, geraniol reduced the force of contraction (~ 98%, EC50 = 1510 ± 160 M) whereas nifedipine, used as positive control, showed a EC50 of 0.90 ± 0.66 M. Geraniol, at 3 mM, decreased the positive inotropism of both CaCl2 and BAY K8644. In ventricular cardiomyocytes, the ICa,L was reduced by 50.7% (n = 5, p < 0.0001) after perfusion with 300 M of geraniol. Furthermore, geraniol prolonged the action potential duration (APD) measured at 50% of repolarization (49.7%, n = 5, p < 0.05), without changing the resting potential. The increase in APD can be attributed to blockade of K+ channel transient outward (Ito) (59.7%, n = 4, p < 0.001), the K+ current non-inactivated (Iss) (39.2 %, n = 4, p < 0.05) and K+ current to inward rectifier (Ik1) (33.7%, n = 4, p < 0.0001). In isolated heart, geraniol increased PRi and QTi without affecting the QRS (n = 6) complex, and reduced both left ventricular pressure (83%) and heart rate (16.5%). Furthermore, geraniol delayed time for the start of ouabain-induced arrhythmias in 128%, preventing in 30% the increase of diastolic tension, however, without affect the positive inotropic effect induced by ouabain (n = 6). Geraniol exerts negative inotropic and chronotropic responses in the mammalian heart by decreasing the L-type Ca2+ current and prolongs the duration of ventricular action potential by reducing potassium currents voltage-dependent. Such effects may be responsible for the antiarrhythmic effect of geraniol front the arrhythmias induced by ouabain in vitro. / O geraniol (C10H18O) é um monoterpeno alcoólico acíclico, presente no óleo essencial de algumas plantas medicinais, frutas cítricas e ervas aromáticas, principalmente espécies do gênero Cymbopogon. São descritas propriedades bioquímicas e farmacológicas, tais como ação anticonvulsivante, analgésica, anti-inflamatória, antioxidante, anticancerígena e antimicrobiana. Neste trabalho buscou-se caracterizar os efeitos produzidos pelo geraniol sobre a contratilidade, atividade elétrica e seu possível potencial antiarrítmico em coração de mamífero. Para tanto, foram utilizados cobaia (Cavia porcellus) e camundongos (Mus musculus) da linhagem C57Bl/6J. Os estudos contráteis foram realizados em átrio esquerdo estirado a 1gf e estimulados com pulsos de corrente supralimiares, mantido em cuba para órgão isolado, submerso em solução de Tyrode modificada (8 mL) e aerado com mistura carbogênica (95 % O2 e 5 % CO2). A força de contração atrial foi captada por um transdutor isométrico. Os registros eletrocardiográficos foram realizados em coração isolado, sob perfusão aórtica de fluxo constante (8 mL/min), em sistema de Langendorff. Para estudar os efeitos do geraniol sobre as correntes de membrana, foram executados experimentos através da técnica de patch-clamp , na configuração whole-cell , em cardiomiócitos ventriculares de camundongo. No átrio, o geraniol reduziu a força de contração (~ 98%, EC50 = 1510 ± 160 M) enquanto que a nifedipina, usada como controle positivo, apresentou uma EC50 de 0,90 ± 0,66 M. O geraniol, na concentração de 3 mM, diminuiu o inotropismo positivo de ambos CaCl2 e BAY K8644. Em cardiomiócito ventricular, a ICa,L foi reduzida em 50,7% (n = 5, p < 0,0001), após a perfusão com 300 μM de geraniol. Além disso, o geraniol prolongou a duração do potencial de ação (DPA), medida a 50 % da repolarização (49,7%, n = 5, p < 0,05), sem alterar o potencial de repouso. O aumento da DPA pode ser atribuído ao bloqueio dos canais para K+ transient-outward (Ito) (59,7 %, n = 4, p < 0,001), canal de K+ não-inativado (Iss) (39,2 %, n = 4, p < 0,05) e do canal para K+ inward rectifier (IK1) (33,7% , n = 4, p < 0,0001). Em coração isolado (n = 6), o geraniol aumentou o PRi e QTi sem afetar a duração do complexo QRS, reduzindo a pressão ventricular esquerda (83%) e a frequência cardíaca (16,5%). Além disso, o geraniol retardou o tempo para o início das arritmias induzidas por ouabaína em 128%, evitando em 30% o aumento da tensão diastólica sem, contudo, afetar o efeito inotrópico positivo da ouabaína (n = 6). O geraniol exerce respostas inotrópicas e cronotrópicas negativas no coração de mamífero, por meio da diminuição das correntes para Ca2+ tipo-L e, prolonga a duração do potencial de ação ventricular por reduzir as correntes para K+ dependentes de voltagem. Tais efeitos podem ser responsáveis pelo efeito antiarrítmico do geraniol frente às arritmias induzidas por ouabaína in vitro .

INTRODUÇÃO: pacientes com doença renal crônica em diálise apresentam elevada mortalidade anual, principalmente decorrente de eventos cardiovasculares, com destaque para morte súbita cardíaca (MSC). Os eventos arrítmicos (EA) são considerados os principais responsáveis pela MSC, tornando relevante a sua avaliação. Dispositivos cardíacos modernos como o looper implantável, que tem capacidade de monitorar o ritmo cardíaco por longo período de tempo e diagnosticar EA, podem contribuir na estratificação de risco desta população. OBJETIVOS: avaliar a taxa de ocorrência dos EA em candidatos a transplante renal com looper implantável e identificar fatores associados; determinar a significância prognóstica dos EA na MSC e mortalidade total; avaliar eficiência diagnóstica do looper e o papel da diálise. MÉTODOS: estudo clínico observacional, prospectivo e aberto que incluiu cem candidatos a transplante renal, em hemodiálise e com alto risco para transplante (idade >=50 anos, DM ou doença cardiovascular). Entre junho/2009 e janeiro/2010, os pacientes foram submetidos ao implante do looper para detecção dos EA e seguimento clínico de um ano. A idade média do grupo foi 59 anos; 65% homens; 97% hipertensos, 70% diabéticos, 34% com infarto prévio e tempo médio de 53,8 meses em hemodiálise. O diagnóstico dos EA seguiu protocolo específico e foram descritos todos os eventos clínicos fatais e não fatais. A estatística incluiu: análise descritiva dos EA, associação destes com variáveis exploratórias pelos testes de qui-quadrado, exato de Fischer, t-Student, Mann-Whitney e regressão logística stepwise selection para análise multivariada (p<0,05). RESULTADOS: foram diagnosticados 5075 EA em 98 pacientes em seguimento médio de 425 dias. A taxa de ocorrência dos EA na casuística foi: bradiarritmias (25%), arritmias supraventriculares (94%) e arritmias ventriculares (79%). Os EA mais comuns foram: taquicardia sinusal (39%) e atrial não sustentada (27%), extrassístoles ventriculares e atriais isoladas (16% e 5,4%) e taquicardia ventricular não sustentada (TVNS - 5,3%). Foram preditores para ocorrência dos EA: duração intervalo PR (p=0,0008; OR=1,05; IC-95%=1,02-1,08) e QT longo (p=0,002; OR=7,28; IC- 95%=2,01-26,35) para bradiarritmias; duração intervalo QTc (p=0,022; OR=1,02; IC-95%=1,01-1,04) e presença de insuficiência cardíaca (p=0,034; OR=9,87; IC- 95%=1,17-82,79) para arritmias ventriculares e dilatação ventricular esquerda (p=0,041; OR=2,83; IC-95%=1,01-7,96) para TVNS. Ocorreram 35 eventos clínicos não fatais, 14 transplantes renais e 18 óbitos. Dentre os óbitos, 38,9% foram cardiovasculares súbitos: quatro arritmogênicos, um IAM e dois indeterminados. Não houve associação entre EA e eventos fatais; fibrilação atrial e bradiarritmias tiveram associação significativa com eventos não fatais. O mecanismo de morte (arritmogênico) foi elucidado pelo looper em quatro pacientes com MSC; um paciente apresentou bloqueio atrioventricular e necessitou de marca-passo. A taxa de EA foi superior no período intradiálise em comparação ao interdiálise (p<0,001). CONCLUSÕES: neste estudo, que avaliou a monitorização cardíaca prolongada com looper implantável em candidatos a transplante renal, a taxa de ocorrência de EA foi elevada; foram preditores dos EA: a duração intervalo PR e presença de QT longo para bradiarritmias, duração intervalo QTc e insuficiência cardíaca para arritmias ventriculares e dilatação ventricular para TVNS; a taxa de mortalidade foi elevada, com importante contribuição da MSC; não houve associação entre EA e mortalidade total ou súbita; houve associação entre as bradiarritmias e a fibrilação atrial com a ocorrência de eventos não fatais; os EA foram mais frequentes no período intradiálise; o looper implantável foi eficiente na elucidação diagnóstica, com poucas complicações. / INTRODUCTION: chronic kidney disease patients undergoing dialysis have a high annual mortality rate, mainly due to cardiovascular disease. Sudden cardiac death (SCD), attributed to arrhythmic mechanisms, is considered the major cause of these high death rates. The implantable loop recorder (ILR), a modern cardiac device has the ability for long-term cardiac rhythm monitoring and diagnosing arrhythmic events (AE), which in fact may contribute to the risk stratification of this population. OBJECTIVES: this study was designed to evaluate the incidence and predictors of AE in renal transplant candidates with ILR; to determine the prognostic significance of AE in SCD and all-cause mortality, evaluate the diagnostic effectiveness of ILR and the role of dialysis. METHODS: a prospective, open, observational clinical study was conducted, including one hundred renal transplant candidates undergoing hemodialysis, at high risk for transplantation (age >=50 years, diabetes or cardiovascular disease). Between June/2009 and January/2010, patients received an ILR for detection of AE with a one-year follow-up. Mean age of the group was 59 years; 65% were men; 97% hypertensive, 70% diabetic, 34% had previous myocardial infarction and mean hemodialysis time was 53.8 months. The diagnosis of AE followed specific protocol and all fatal and non-fatal clinical events were described. The statistical analysis included: descriptive analysis of AE, an association between these events and exploratory variables by chi-square tests, Fisher exact test, Student\'s t test, Mann-Whitney test and logistic regression using stepwise selection for multivariate analysis (p<0.05). RESULTS: during mean follow-up of 425 days, 5075 AE were diagnosed by ILR in 98 patients. The rate of occurrence of EA in this patients was: bradyarrhythmias (25%), supraventricular arrhythmias (94%) and ventricular arrhythmias (79%). The most common AE were: sinus tachycardia (39%), nonsustained atrial tachycardia (27%), isolated premature ventricular beats (16%), isolated premature atrial beats (5.4%) and nonsustained ventricular tachycardia (NSVT - 5.3%). Predictors for the occurrence of AE were: duration of PR interval (p=0.0008; OR=1.05; 95%CI=1.02-1.08) and long QT (p=0.002; OR=7.28; 95%CI=2.01-26.35) for bradyarrhythmia; duration of QTc interval (p=0.022; OR=1.02; 95%CI=1.01-1.04) and presence of heart failure (p=0.034; OR=9.87; 95%CI=1.17-82.79) for ventricular arrhythmia and left ventricular dilatation (p=0.041; OR=2.83; 95%CI=1.01-7.96) for NSVT. There were 35 non-fatal clinical events, 14 renal transplantations and 18 deaths during follow-up. Regarding causes of death, 38.9% were due to sudden cardiovascular event: four were arrhythmogenic, one resulted from acute myocardial infarction and two were indeterminate. There was no association between AE and all cause or sudden mortality; bradyarrhythmias and atrial fibrillation were associated with the occurrence of non-fatal clinical events. The mechanism of death (arrhythmogenic) was elucidated by ILR in four patients with SCD; one patient had atrioventricular block and required pacemaker insertion. The rate of AE was higher in the intradyalitic period compared to interdialytic (p <0.001). CONCLUSIONS: in this study, which evaluate long-term cardiac rhythm monitoring with ILR in renal transplant candidates, the incidence of AE was high; predictors for the occurrence of AE were: duration of PR interval and presence of long QT for bradyarrhythmia, duration of QTc interval and heart failure for ventricular arrhythmia and left ventricular dilatation for NSVT; mortality rate was high and SCD made an important contribution. There was no association between AE and all-cause mortality and SCD; bradyarrhythmias and atrial fibrillation were associated with non-fatal events; the EA rate was higher at intradialytic period; the ILR was efficient in elucidating diagnoses and had few complications.

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.

Sudden cardiac death is one of the leading causes of mortality in the western world. One of the main factors is myocardial ischaemia, when there is a mismatch between blood demand and supply to the heart, which may lead to disturbed cardiac excitation patterns, known as arrhythmias. Ischaemia is a dynamic and complex process, which is characterised by many electrophysiological changes that vary through space and time. Ischaemia-induced arrhythmic mechanisms, and the safety and efficacy of certain therapies are still not fully understood. Most experimental studies are carried out in animal, due to the ethical and practical limitations of human experiments. Therefore, extrapolation of mechanisms from animal to human is challenging, but can be facilitated by in silico models. Since the first cardiac cell model was built over 50 years ago, computer simulations have provided a wealth of information and insight that is not possible to obtain through experiments alone. Therefore, mathematical models and computational simulations provide a powerful and complementary tool for the study of multi-scale problems. The aim of this thesis is to investigate pro-arrhythmic electrophysiological consequences of acute myocardial ischaemia, using a multi-scale computational modelling and simulation framework. Firstly, we present a novel method, combining computational simulations and optical mapping experiments, to characterise ischaemia-induced spatial differences modulating arrhythmic risk in rabbit hearts. Secondly, we use computer models to extend our investigation of acute ischaemia to human, by carrying out a thorough analysis of recent human action potential models under varied ischaemic conditions, to test their applicability to simulate ischaemia. Finally, we combine state-of-the-art knowledge and techniques to build a human whole ventricles model, in which we investigate how anti-arrhythmic drugs modulate arrhythmic mechanisms in the presence of ischaemia.

There is a growing consensus that life-threatening cardiac arrhythmias like ventricular tachycardia (VT) or ventricular fibrillation (VF) arise because of the formation of spiral waves of electrical activation in cardiac tissue; unbroken spiral waves are associated with VT and broken ones with VF. Several experimental studies have shown that inhomogeneities in cardiac tissue can have dramatic effects on such spiral waves. In this thesis we try to understand these experimental results by carrying out detailed and systematic studies of the interaction of spiral waves with different types of inhomogeneities in mathematical models for cardiac tissue. In Chapter 1 we begin with a general introduction to cardiac arrhythmias, the cardiac conduction system, and the connection between electrical activation waves in cardiac tissue and cardiac arrhythmias. As we have noted above, VT and VF are believed to be associated with spiral waves of electrical activation on cardiac tissue; such spiral waves form because cardiac tissue is an excitable medium. Thus we give an overview of excitable media, in which sub-threshold perturbations decay but super-threshold perturbations lead to an action potential that consists of a rapid stage of depolarization of cardiac cells followed by a slow phase of repolarization. During this repolarization phase the cells are refractory. We then give an overview of earlier studies of the effects of inhomogeneities in cardiac tissue; and we end with a brief description of the principal problems we study here. Chapter 2 describes the models we use in our work. We start with a general introduction to the cable equation and then discuss the Hodgkin-Huxley-formalism for the transport of ions across a cell membrane through voltage-gated ion channels. We then describe in detail the three models that we use for cardiac tissue, which are, in order of increasing complexity, the Panfilov model, the Luo Rudy Phase I (LRI) model, and the reduced Priebe Beuckelmann (RPB)model. We then give the numerical schemes we use for solving these model equations and the initial conditions that lead to the formation of spiral waves. For all these models we give representative results from our simulations and compare the states with spiral turbulence. In Chapter 3 we investigate the effects of conduction inhomogeneities (obstacles) in the three models introduced in Chapter 2. We outline first the experimental results that have provided the motivation for our study. We then discuss how we introduce obstacles in our simulations of the Panffilov, LRI, and RPB models for cardiac tissue. Next we present the results of our numerical studies of the effects, on spiral-wave dynamics, of the sizes, shapes, and positions of the obstacles. Our Principal result is that spiral-wave dynamics in these models depends sensitively on the position of the obstacle. We find, in particular, that, merely by changing the position of a conduction inhomogeneity, we may convert spiral turbulence (the analogue in our models of VF) to a single rotating spiral (the analogue of VT) anchored to the obstacle or vice versa; even more exciting is the possibility that, at the boundary between these two types of behaviour, we find a quiescent state Q with no spiral waves. Thus our study obtains all the possible qualitative behaviours found in experiments, namely, (1) VF might persist even in the presence of an obstacle, (2) it might be suppressed partially and become VT, or (3) it might be eliminated completely. In Chapter 4 we extend our work on conduction inhomogeneities (Chapter 3) to ionic inhomogeneities. Unlike conduction inhomogeneities, ionic inhomogeneities allow the conduction of activation waves. We find, nevertheless, that they too can lead to the anchoring of spiral waves or even the complete elimination of spiral-wave turbulence. Since spiral waves can enter the region in which there is an ionic inhomogeneity, their behaviours in the presence of such an inhomogeneity are richer than those with conduction inhomogeneities. We find, in particular, that a single spiral wave anchored at an ionic inhomogeneity can show temporal evolution that may be periodic, quasiperiodic, or even chaotic. In the last case the spiral wave shows a chaotic pattern inside the ionic inhomogeneity and a regular one outside it. Defibrillation is the control of arrhythmias such as VF. Most often defibrillation is effected electrically by administering a shock, either externally or via an internally implanted defibrillator. The development of low-amplitude defibrillation schemes, which minimise the deleterious effects of the applied shock, is a major challenge in the treatment of cardiac arrhythmias. Numerical studies of models for cardiac tissue provide us with convenient means of studying the elimination of spiral-wave turbulence by the application of external electrical stimuli; this is the numerical analogue of defibrillation. Over the years some low-amplitude defibrillation schemes have been suggested on the basis of such numerical studies. In Chapter 5 we discuss two such schemes that have been shown to suppress spiral-wave turbulence in two-dimensional models for cardiac tissue and also scroll-wave turbulence in three-dimensional models. One of these schemes uses local electrical pacing, typically in the centre of the simulation domain; the other applies the external electrical stimuli over a mesh. We study the efficacy of these schemes in the presence of conduction inhomogeneities. We find, in particular, that the local-pacing scheme, though effective in a homogeneous simulation domain, fails to control spiral turbulence in the presence of an obstacle and, indeed, might even facilitate spiral-wave break up. By contrast, the second scheme, which uses a mesh, succeeds in eliminating spiral-wave turbulence even in the presence of an obstacle. We end with some concluding remarks about the possible experimental implications of our study in Chapter 6.

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.

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.

Die vorliegende Arbeit gibt einen aktuellen Überblick über Einsatzmöglichkeiten des Telemonitorings in der Kardiologie. Zunächst werden telemedizinische Verfahren in der Diagnostik des akuten Koronarsyndroms dargestellt. In einem weiteren Kapitel wird auf den Einsatz der Telemedizin (Tele-EKG-Recorder, Herzfrequenzanalyse mittels Smartphones und Smartwatches, externe und implantierbare Loop-Recorder) eingegangen. Weiterhin werden Einsatzmöglichkeiten des Telemonitorings bei Patienten mit aktiven kardialen Implantaten (antibradykarde Herzschrittmacher, ICDs, CRT-Systeme) aufgezeigt. Ein weiteres Kapitel beschäftigt sich mit dem Einsatz des Telemonitorings bei Patienten mit chronischer Herzinsuffizienz. Außerdem werden telemedizinische Anwendungen bei Patienten mit arterieller Hypertonie besprochen. Schließlich werden juristische Aspekte des Telemonitorings in der Kardiologie diskutiert.:Danksagung Abkürzungsverzeichnis Studienakronyme 1 Motivation 2 Telemonitoring bei Patienten mit koronarer Herzkrankheit 2.1 Telemedizinische EKG-Übertragung bei Patienten mit akutem STEMI 2.2 Telemedizinische Überwachung von Patienten während der kardiologischen Rehabilitation 2.3 Neue Entwicklungen in der EKG-Aufzeichnung und -Analyse 2.4 Schlussfolgerungen zum Telemonitoring bei Patienten mit koronarer Herzkrankheit 3 Telemonitoring bei Patienten mit Herzrhythmusstörungen 3.1 Tele-EKG-Eventrecorder 3.2 EKG-Aufzeichnung und Herzrhythmusanalyse mit Smartphones und Wearables 3.2.1 Entwicklung und technische Grundlagen 3.2.2 Detektion von Vorhofflimmern mit Smartphones und Smartwatches 3.2.3 Probleme und Perspektiven in der Anwendung von Smartphones und Wearables in der klinischen Praxis 3.3 Externe EKG-Loop-Recorder mit telemedizinischer EKG-Übertragung 3.4 Implantierbare Loop-Recorder mit telemedizinischer EKG-Übertragung 3.5 Telemonitoring bei Patienten mit tragbaren Kardiovertern-Defibrillatoren 3.6 Schlussfolgerungen zum Telemonitoring bei Patienten mit Herzrhythmusstörungen 4 Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.1 Aktuelle Herausforderungen in der Therapie mit aktiven kardialen Implantaten 4.2 Ziele und Methodik des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.3 Technik des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.3.1 Entwicklung der Technologie 4.3.2 Technische Umsetzungen durch die einzelnen Hersteller 4.3.2.1 Home Monitoring®-System 4.3.2.2 CareLink®-System 4.3.2.3 Merlin.net®-System 4.3.2.4 Latitude®-System 4.3.2.5 Smartview®-System 4.3.3 Cyber-Security bei vernetzten, aktiven kardialen Implantaten 4.4 Klinische Studien zum Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.4.1 Sicherheit der Datenübertragung und Erkennung von Aggregat- und Elektrodenfehlfunktionen 4.4.2 Detektion klinisch relevanter Rhythmusereignisse 4.4.2.1 Atriale Tachyarrhythmien 4.4.2.2 Ventrikuläre Tachykardien und Schockabgaben bei Patienten mit ICDs 4.4.3 Detektion kardialer Dekompensationen bei Patienten mit aktiven kardialen Implantaten 4.4.3.1 Telemedizinische Überwachung der Thoraximpedanz bei Patienten mit aktiven kardialen Implantaten 4.4.3.2. Überwachung von Patienten mit aktiven kardialen Implantaten mittels Multiparameter-Algorithmen 4.4.3.3 Kontrollierte Studien und Registerdaten zur frühzeitigen Erfassung kardialer Dekompensationen mittels Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.4.4 Potenzielle Reduktion ambulanter Nachsorgen und Reduktion der Behandlungskosten 4.4.5 Management der übermittelten Daten und Akzeptanz des Telemonitorings durch Patienten und Ärzte 4.4.6 Bewertung der klinischen Studien und Registerdaten und aktuelle Empfehlungen zum Einsatz des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.5 Nutzenbewertung und Kostenerstattung des Telemonitorings bei Patienten mit aktiven kardialen Implantaten in der klinischen Praxis 4.6 Telemonitoring bei Patienten mit S-ICDs 4.7 Schlussfolgerungen zum Telemonitoring bei Patienten mit aktiven kardialen Implantaten 5 Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 5.1 Ziele des Telemonitorings bei Patienten mit chronischer Herzinsuffizienz 5.2 Betreuungskonzepte bei chronisch herzinsuffizienten Patienten 5.2.1 Betreuungskonzepte mit Heart-Failure-Nurses 5.2.2 Betreuungskonzepte mittels Telemonitoring 5.2.2.1 Device-basiertes Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 5.2.2.2 Hämodynamisches Telemonitoring mit implantierbaren Sensoren bei Patienten mit chronischer Herzinsuffizienz 5.2.2.3 Telemonitoring bei Patienten mit chronischer Herzinsuffizienz mit externen Sensoren 5.3. Nutzenbewertung und Umsetzung des Telemonitorings bei chronisch herzinsuffizienten Patienten in der klinischen Praxis 5.4 Schlussfolgerungen zum Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 6 Telemonitoring bei Patienten mit arterieller Hypertonie 6.1 Behandlungsziele bei Patienten mit arterieller Hypertonie 6.2 Methodik des Telemonitorings bei arterieller Hypertonie 6.2.1 Komponenten des Telemonitorings bei arterieller Hypertonie 6.2.2 Neue Verfahren zur Blutdruckmessung 6.2.3 Datenfluss und Datenmanagement 6.2.4 Apps für Patienten mit arterieller Hypertonie 6.3 Studien zum Telemonitoring bei arterieller Hypertonie 6.4 Einsatz des Telemonitorings bei Patienten mit arterieller Hypertonie in der klinischen Praxis 6.5 Schlussfolgerungen zum Telemonitoring bei Patienten mit arterieller Hypertonie 7 Juristische Aspekte des Telemonitorings in der Kardiologie 8 Ausblick Literaturverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Thesen zur Habilitation / The present work provides an up-to-date overview of the possible applications of telemonitoring in cardiology. First, the telemedicine procedures are presented that are employed in the diagnosis of acute coronary syndrome. Another chapter covers the use of telemedicine (e.g., tele-ECG recorders, heart rate analysis by means of smart phones and smart watches, and external and implantable loop recorders). Furthermore, the possible applications of telemonitoring to patients with active cardiac implants are presented (e.g., antibradycardia pacemakers, ICDs, and CRT systems). A subsequent chapter is concerned with the use of telemonitoring in patients with chronic heart failure. Moreover, the applications of telemedicine in patients with arterial hypertension are also considered. Finally, the legal aspects of telemonitoring in cardiology are discussed.:Danksagung Abkürzungsverzeichnis Studienakronyme 1 Motivation 2 Telemonitoring bei Patienten mit koronarer Herzkrankheit 2.1 Telemedizinische EKG-Übertragung bei Patienten mit akutem STEMI 2.2 Telemedizinische Überwachung von Patienten während der kardiologischen Rehabilitation 2.3 Neue Entwicklungen in der EKG-Aufzeichnung und -Analyse 2.4 Schlussfolgerungen zum Telemonitoring bei Patienten mit koronarer Herzkrankheit 3 Telemonitoring bei Patienten mit Herzrhythmusstörungen 3.1 Tele-EKG-Eventrecorder 3.2 EKG-Aufzeichnung und Herzrhythmusanalyse mit Smartphones und Wearables 3.2.1 Entwicklung und technische Grundlagen 3.2.2 Detektion von Vorhofflimmern mit Smartphones und Smartwatches 3.2.3 Probleme und Perspektiven in der Anwendung von Smartphones und Wearables in der klinischen Praxis 3.3 Externe EKG-Loop-Recorder mit telemedizinischer EKG-Übertragung 3.4 Implantierbare Loop-Recorder mit telemedizinischer EKG-Übertragung 3.5 Telemonitoring bei Patienten mit tragbaren Kardiovertern-Defibrillatoren 3.6 Schlussfolgerungen zum Telemonitoring bei Patienten mit Herzrhythmusstörungen 4 Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.1 Aktuelle Herausforderungen in der Therapie mit aktiven kardialen Implantaten 4.2 Ziele und Methodik des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.3 Technik des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.3.1 Entwicklung der Technologie 4.3.2 Technische Umsetzungen durch die einzelnen Hersteller 4.3.2.1 Home Monitoring®-System 4.3.2.2 CareLink®-System 4.3.2.3 Merlin.net®-System 4.3.2.4 Latitude®-System 4.3.2.5 Smartview®-System 4.3.3 Cyber-Security bei vernetzten, aktiven kardialen Implantaten 4.4 Klinische Studien zum Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.4.1 Sicherheit der Datenübertragung und Erkennung von Aggregat- und Elektrodenfehlfunktionen 4.4.2 Detektion klinisch relevanter Rhythmusereignisse 4.4.2.1 Atriale Tachyarrhythmien 4.4.2.2 Ventrikuläre Tachykardien und Schockabgaben bei Patienten mit ICDs 4.4.3 Detektion kardialer Dekompensationen bei Patienten mit aktiven kardialen Implantaten 4.4.3.1 Telemedizinische Überwachung der Thoraximpedanz bei Patienten mit aktiven kardialen Implantaten 4.4.3.2. Überwachung von Patienten mit aktiven kardialen Implantaten mittels Multiparameter-Algorithmen 4.4.3.3 Kontrollierte Studien und Registerdaten zur frühzeitigen Erfassung kardialer Dekompensationen mittels Telemonitoring bei Patienten mit aktiven kardialen Implantaten 4.4.4 Potenzielle Reduktion ambulanter Nachsorgen und Reduktion der Behandlungskosten 4.4.5 Management der übermittelten Daten und Akzeptanz des Telemonitorings durch Patienten und Ärzte 4.4.6 Bewertung der klinischen Studien und Registerdaten und aktuelle Empfehlungen zum Einsatz des Telemonitorings bei Patienten mit aktiven kardialen Implantaten 4.5 Nutzenbewertung und Kostenerstattung des Telemonitorings bei Patienten mit aktiven kardialen Implantaten in der klinischen Praxis 4.6 Telemonitoring bei Patienten mit S-ICDs 4.7 Schlussfolgerungen zum Telemonitoring bei Patienten mit aktiven kardialen Implantaten 5 Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 5.1 Ziele des Telemonitorings bei Patienten mit chronischer Herzinsuffizienz 5.2 Betreuungskonzepte bei chronisch herzinsuffizienten Patienten 5.2.1 Betreuungskonzepte mit Heart-Failure-Nurses 5.2.2 Betreuungskonzepte mittels Telemonitoring 5.2.2.1 Device-basiertes Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 5.2.2.2 Hämodynamisches Telemonitoring mit implantierbaren Sensoren bei Patienten mit chronischer Herzinsuffizienz 5.2.2.3 Telemonitoring bei Patienten mit chronischer Herzinsuffizienz mit externen Sensoren 5.3. Nutzenbewertung und Umsetzung des Telemonitorings bei chronisch herzinsuffizienten Patienten in der klinischen Praxis 5.4 Schlussfolgerungen zum Telemonitoring bei Patienten mit chronischer Herzinsuffizienz 6 Telemonitoring bei Patienten mit arterieller Hypertonie 6.1 Behandlungsziele bei Patienten mit arterieller Hypertonie 6.2 Methodik des Telemonitorings bei arterieller Hypertonie 6.2.1 Komponenten des Telemonitorings bei arterieller Hypertonie 6.2.2 Neue Verfahren zur Blutdruckmessung 6.2.3 Datenfluss und Datenmanagement 6.2.4 Apps für Patienten mit arterieller Hypertonie 6.3 Studien zum Telemonitoring bei arterieller Hypertonie 6.4 Einsatz des Telemonitorings bei Patienten mit arterieller Hypertonie in der klinischen Praxis 6.5 Schlussfolgerungen zum Telemonitoring bei Patienten mit arterieller Hypertonie 7 Juristische Aspekte des Telemonitorings in der Kardiologie 8 Ausblick Literaturverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Thesen zur Habilitation

Author's name: Bc. Irena Malá School: Charles university, Prague 1st Faculty of Medicine Institut of Theory and Practice of Nursing Vídeňská 800, 140 59 Prague 4 - Krč Program: Health Care Administration Title: Early postoperative care of the patient with the left ventricular assist device HeartMate II Diploma thesis supervisor: PhDr. Hocková Jana, PhD. Number of pages: 170 Number of attachments: 41 Year: 2013 Key words: early postoperative care, hypotermia, blood transfusion, fluid resuscitation, perioperative cardiovascular dysfunction, pharmacologic support, ventricular assist device HeartMateII, monitoration, device, cardiac arrhythmias, ventilation management, postoperative anticoagulation, glycemic kontrol, renal insufficiency, nutrition, nursing, complications, physiotherapy, psychological aspects The occurrence of the heart failure is similar to an epidemic with high mortality. This fact, together with stagnate or even decreasing number of suitable donors, led to a need of replacing the heart pump activity with an artificial one. Mechanical cardiac support systems are sophisticated devices that are able to support a certain period of time or completely replace the function of the heart as a pump. The indications implantation of mechanical cardiac support is significant symptomatic heart...