The thesis discusses the education of patients with left ventricular support HeartMate II. Theoretical part is focused on education and its ethical and legal aspects, on the description of the educational process. Furthermore it focuses on heart supports, especially on left ventricular assist device HeartMate II. To provide a comprehensive overview, I have included also information about the anatomy and physiology of the cardiovascular system and the section on heart failure. I described the specifics of nursing care for patients with implanted HeartMate II system and the educational topics that should be part of the education of these patients. The empirical part was prepared as a quantitative research, where research sample was 47 respondents. Respondents consisted of nurses who educate patients after implantation of the HeartMate II at the cardiovascular surgical intensive care unit. To create the feedback I complemented a quantitative research with structured interviews with patients after implantation of the HeartMate II. The aim of the research was to determine the status and range of education of patients with left ventricular assist device HeartMate II. This thesis further maps the topics on which is placed the emphasis in education and vice versa topics that would need to focus more on....

Each year all over the world, Millions of patients from infants to adults are diagnosed with heart failure. A limited number of donor hearts available for these patients results in a tremendous demand of mechanical circulatory support (MCS) system, either in the form of total artificial heart (TAH) or a ventricular assist device (VAD). Physiologically MCS are expected to provide heart; a time to rest and potential recovery by unloading the ventricle, while maintaining the adequate peripheral as well as coronary circulation. Existing ventricular assist devices (VAD) have employed either displacement type pulsatile flow pumping systems or continuous flow type centrifugal/rotodynamic pumps systems. Displacement type devices produce a pulsatile outflow, which has significant benefits on vital organ function and end organ recovery. Continuous flow devices are small and can be placed within body using minimal invasive procedures, in addition they reduces infection as well as mechanical failure related complications. Despite availability of success stories for both types of pumping systems, the selection of the either of them is an ongoing debate. This thesis aims to merge the advantages of displacement pumps (pulsatile flow) and axial-flow pumps (continuous flow) into a novel left vertical assist device (LVAD), by designing a novel minimal invasive, miniature axial-flow pump producing pulsating outflow for the patients having early heart failure and myocardial infarction as a Bridge-To-Recovery (BTR) or Bridge-To-Decision (BTD) device. The design of VAD, the experimental setup and dedicated control system were developed for the in vitro evaluation of pulsatile flow. Computational fluid dynamics (CFD) had been employed for the detail investigation of pulsatile flow. In addition, CFD was also applied to optimize the pulse generation for low haemolysis levels. Outcome of the study produces comprehensive understanding for the generation of pulsatile flow using an axial flow pump. Further, it provides the means of generating a controlled pulse that can regulate flow rate for varying heart rate within low haemolysis levels.

Numerical modelling and simulation are powerful tools for analysis and design, and with the improvement of computational power and numerical methods they are being applied on complex phenomena and systems. This work shows examples of the application of a very sophisticated numerical method, namely the Spectral/hp element method, in the study of the flow inside bioinspired complex geometries. The two topics investigated are fluid dynamic instabilities in a constricted channel and flow inside a paediatric ventricular assist device were studied by means of computational fluid mechanics. The constricted channel is an idealized model of a nasal cavity, which is characterized by complex airway channels, and also bears some resemblance to a human artery in the presence of an atherosclerotic plaques. The paediatric ventricular assist device is an actual device, designed by the Bioengineering research group of the Heart Institute of the Medicine School of the University of São Paulo, which works as a pump that assists the left ventricle of patients waiting for transplantation. Therefore, the aim of this thesis is to contribute in the understanding of biological and bio-inspired geometries flows, using computational tools. Linear and nonlinear stability were carried out for the constricted channel. Three different flow regimes were investigated: symmetric steady flow, which is stable for low Reynolds number, asymmetric steady flow, which rises as a result of the primary bifurcation of the symmetric flow and pulsatile flow. Direct stability analysis was carried out to determine the unstable regions and the critical values for each flow regime. The physical mechanisms behind the transition processes were studied by means of direct numerical simulations to characterize the bifurcations. Since the bifurcations had subcritical behaviour, the relevance of non-normal growth in these flows was assessed. Dependence on phase, Reynolds number and spanwise wavenumber of optimal modes were extensively investigated in stable regions of the three flow regimes. Convective instabilities were also studied in order to comprehend the physical mechanisms which led the optimal modes to their maxima growth, and different convective mechanisms were found. The flow inside the paediatric ventricular assist device was analyzed by means of threedimensional numerical simulations. A computational model based on special boundaries conditions was developed to model the pulsatile flow. In this model, the opening and closure of the mitral valve and diaphragm were represented with the use of specially devised boundary conditions. The driving force and the flow direction of the diaphragm were defined by velocity distribution on the diaphragm wall, and the opening and closure of the mitral valve were performed by a velocity waveform which goes to zero in the systolic period. Flow patterns, velocity fields and time-average wall shear rate were analyzed to evaluate the performance of the device. / Modelagem e simulação numéricas são ferramentas poderosas para análise e design, e com a melhoria do poder computacional e dos métodos numéricos, eles estão sendo aplicados em fenômenos e sistemas complexos. Este trabalho mostra exemplos de aplicações de um método numérico sofisticado, o método dos elementos espectrais/hp, no estudo do escoamento dentro de geometrias complexas bio-inspiradas. Os dois tópicos investigados são: instabilidades em dinâmica de fluido em um canal constrito e o escoamento dentro de um dispositivo de assistência ventricular pediátrica. O canal constrito é um modelo idealizado de uma cavidade nasal, que é caracterizada por canais complexos da via aérea, e também tem semelhança com uma artéria humana na presença de placas ateroscleróticas. O dispositivo de assistência ventricular pediátrica é um dispositivo real, projetado pelo grupo de pesquisa de Bioengenharia do Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo, que funciona como uma bomba que auxilia o ventrículo esquerdo dos pacientes à espera de transplante. Portanto, o objetivo desta tese é contribuir na compreensão de escoamentos em geometrias biológicas e bio-inspiradas, usando ferramentas computacionais. Análises de estabilidade linear e não linear foram feitas para um canal constrito. Três diferentes regimes de escoamento foram empregados: escoamento estacionário simétrico, que é estável para baixo número de Reynolds, escoamento assimétrico, o qual é resultado da primeira bifurcação do escoamento simétrico e escoamento pulsátil. Análise de estabilidade direta foi executada para determinar as regiões instáveis em cada regime de escoamento. Os mecanismos físicos por trás do processo de transição foram estudados por meio de simulação numérica direta para caracterizar as bifurcações. Uma vez que, as bifurcações tiveram um comportamento subcrítico, a relevância do crescimento não normal nestes escoamentos foi avaliado. Assim, dependência com a fase, número de Reynolds e número de onda do modo tridimensional foram extensivamente investigados em regiões estáveis para os três regimes de escoamento. Instabilidades convectivas foram também estudadas a fim de compreender os mecanismos físicos que conduzem os modos ótimos para seus crescimentos máximos, e diferentes mecanismos convectivos foram encontrados. O escoamento dentro do dispositivo de assistência ventricular pediátrico foi analisado por meios de simulações numéricas tridimensionais. Um modelo computacional baseado em condições de contorno especiais foi desenvolvido para modelar o escoamento pulsátil. Neste modelo, a abertura e fechamento da válvula mitral e diafragma foram representados com o uso de condições de contorno especialmente elaboradas. A força motora e o direcionamento do fluxo do diafragma foram definidos por uma distribuição de velocidades na parede do diafragma, e a abertura e fechamento da válvula mitral foram executadas por uma função de onda de velocidade que vai a zero no período sistólico. Padrões do escoamento, campos de velocidade e tensão de cisalhamento no tempo foram analisadas para avaliar o desempenho do dispositivo.

Atualmente, sabe-se que grande parte dos acidentes graves ocorridos envolvendo uma diversidade de sistemas como plataformas de petróleo, aeronaves ou plantas de processos industriais, poderiam ser evitados caso possuíssem dispositivos de controle projetados especificamente para manter a segurança durante a ocorrência de falhas no funcionamento dos mesmos. Por outro lado, observam-se complicações em realizar o controle de sistemas remotos em que é possível não haver garantia de monitoração em tempo real, como o caso de sondas espaciais ou robôs de exploração. Neste contexto, podem-se encontrar ambas as dificuldades no controle do funcionamento de um Dispositivo de Assistência Ventricular (DAV) que desempenha a função de auxiliar o bombeamento de sangue para o sistema circulatório de um paciente com insuficiência cardíaca. Este tipo de dispositivo, quando usado para terapia de destino, deve apresentar um elevado nível de segurança, pois, caso haja falha, o risco de morte é eminente. Por sua vez, o sistema deve apresentar um elevado índice de autonomia, já que as características comportamentais e fisiológicas de um paciente estão em constante mudança e afetam diretamente o modo como deve ocorrer a interação entre o DAV e o sistema cardiovascular do paciente. Sendo assim, há uma necessidade premente de aprimoramento do projeto de sistemas de controle de DAVs autônomos e seguros. A proposta do presente trabalho consiste em aplicar conceitos mecatrônicos para o projeto de um sistema de controle de DAVs e, considerando a natureza dos sinais que indicam a ocorrência de falhas, considerar a teoria de Sistemas a Eventos Discretos (SED), ferramentas de análise de risco e técnicas de diagnóstico e tratamento de falhas para a obtenção de modelos de controle considerando-se uma arquitetura modular e distribuída. Desta forma, foi desenvolvida uma arquitetura de controle supervisório para DAVs considerando características de variações de comportamento do sistema circulatório do paciente e do próprio DAV. Esta arquitetura de controle contempla o diagnóstico e tratamento de falhas desenvolvendo um método para a classificação de falhas e, de acordo com a severidade de cada uma delas é proposto um sistema de controle que atua na regeneração ou degeneração do DAV para um estado seguro, v observando, também, o cumprimento de normas médicas e técnicas de segurança. Para atingir este objetivo, propõe-se uma sistemática para o projeto do sistema de controle para DAVs considerando o aspecto multidisciplinar pertinente a este contexto. A base dessa sistemática consiste em realizar uma efetiva análise de risco do sistema utilizando a ferramenta de estudo HAZOP (Hazard and Operability Studies). A partir do conhecimento obtido sobre o comportamento do sistema em situações críticas desenvolvem-se modelos formais utilizando rede Bayesiana e rede de Petri para o diagnóstico e tratamento das possíveis falhas. O comportamento do DAV controlado pode ser analisado de duas formas: (i) a partir de ensaios in vitro utilizando técnicas de análise por simulação e ferramentas computacionais adequadas, além de testes em simuladores cardiovasculares físicos que emulam interação com o sistema circulatório humano; (ii) a partir de ensaios in vivo em animais que poderão ser utilizados para simular modelos físicos de insuficiência cardíaca e permitir uma avaliação fidedigna dos efeitos do implante do DAV. O procedimento proposto foi aplicado para um caso real de desenvolvimento de um DAV envolvendo uma equipe de pesquisadores da Escola Politécnica da USP e do Instituto Dante Pazanesse de Cardiologia. Assim, é possível obter-se um sistema de controle autônomo e seguro que atenda normas técnicas aderentes a esse assunto e os rigorosos requisitos de projeto impostos a essa classe de sistema. / Nowadays, it is kwon that the several of severe disasters compromising a great variety of systems such as oil platforms, aircrafts or industrial plants, could have been avoided if these systems had controllers designed specifically to maintain the safety levels in case of fault. On the other side, many complications are observed on performing the control of remote systems, where there is no guarantee of real time monitoring of the system, as in space probes or reconnaissance robots. In this context, both obstacles can be found on the control of ventricular assist devices (VAD), which have the role of assisting to pump the blood into the patients circulatory system, in case of irregular heartbeat or heart failure. Devices such as the VAD must possess very high safety levels, as in case of fault, the consequences are severe and might result on the dead of the patient. Nevertheless, these systems must have high degree of autonomy, as the patients physiology and behavior are constantly changing, and these changes impact directly the interactions between the VAD and the patient´s cardiovascular system. Thus, there is a pressing need to improve the design of safe and autonomous control systems for VADs. The present work proposes applying mechatronic concepts to the development of control systems for VADs, considering the nature of the fault indicating signals, as well as the Discrete Event Systems (DES) theory and through the application of tools for risk analysis, and fault diagnostic and treatment techniques aiming the development of control models based on modular and distributed architectures. Thereby, a VAD supervisory control architecture was developed, where the behavior variations of the patient´s circulatory system as well as of the VAD were taken into consideration. This control architecture features the diagnostic and treatment of faults, where methods for faults classification where developed, and according to the severity each fault is proposed a control system that performs the regeneration or degeneration of the VAD to a secure state and is according to medical standards and safety techniques. To achieve this goal is proposed a systematic for the design of the VAD control system considering the multidisciplinary context of the device. The foundation of this systematic is the performance of an effective risk analysis through the use of the toolset known vii as HAZOP (Hazard and Operability Studies). From the knowledge acquired about the system behavior during critical conditions, formal models are developed employing Bayesian Networks and Petri Nets for the diagnostic and treatment of faults. The behavior of the controlled VAD can be analyzed in two possible ways: (i) from in vitro experiments, through the use of simulation analysis tools and proper computational tools, as well as tests on real cardiovascular simulators, where the interactions between the VAD and the human circulatory system can be emulated; (ii) from in vivo experiments, animals can be used to simulate physical models of irregular heartbeat or heart failure and allow reliable valuations of the VAD implant. The proposed procedure was applied on the VAD development, which was performed by a team of researchers from the Escola Politécnica da USP and from the Instituto Dante Pazanesse de Cardiologia. Thus, is possible to achieve an autonomous and safe control system that complies with the applicable technical standards, as well as the strict project requirements for this class of system.

Numerical modelling and simulation are powerful tools for analysis and design, and with the improvement of computational power and numerical methods they are being applied on complex phenomena and systems. This work shows examples of the application of a very sophisticated numerical method, namely the Spectral/hp element method, in the study of the flow inside bioinspired complex geometries. The two topics investigated are fluid dynamic instabilities in a constricted channel and flow inside a paediatric ventricular assist device were studied by means of computational fluid mechanics. The constricted channel is an idealized model of a nasal cavity, which is characterized by complex airway channels, and also bears some resemblance to a human artery in the presence of an atherosclerotic plaques. The paediatric ventricular assist device is an actual device, designed by the Bioengineering research group of the Heart Institute of the Medicine School of the University of São Paulo, which works as a pump that assists the left ventricle of patients waiting for transplantation. Therefore, the aim of this thesis is to contribute in the understanding of biological and bio-inspired geometries flows, using computational tools. Linear and nonlinear stability were carried out for the constricted channel. Three different flow regimes were investigated: symmetric steady flow, which is stable for low Reynolds number, asymmetric steady flow, which rises as a result of the primary bifurcation of the symmetric flow and pulsatile flow. Direct stability analysis was carried out to determine the unstable regions and the critical values for each flow regime. The physical mechanisms behind the transition processes were studied by means of direct numerical simulations to characterize the bifurcations. Since the bifurcations had subcritical behaviour, the relevance of non-normal growth in these flows was assessed. Dependence on phase, Reynolds number and spanwise wavenumber of optimal modes were extensively investigated in stable regions of the three flow regimes. Convective instabilities were also studied in order to comprehend the physical mechanisms which led the optimal modes to their maxima growth, and different convective mechanisms were found. The flow inside the paediatric ventricular assist device was analyzed by means of threedimensional numerical simulations. A computational model based on special boundaries conditions was developed to model the pulsatile flow. In this model, the opening and closure of the mitral valve and diaphragm were represented with the use of specially devised boundary conditions. The driving force and the flow direction of the diaphragm were defined by velocity distribution on the diaphragm wall, and the opening and closure of the mitral valve were performed by a velocity waveform which goes to zero in the systolic period. Flow patterns, velocity fields and time-average wall shear rate were analyzed to evaluate the performance of the device. / Modelagem e simulação numéricas são ferramentas poderosas para análise e design, e com a melhoria do poder computacional e dos métodos numéricos, eles estão sendo aplicados em fenômenos e sistemas complexos. Este trabalho mostra exemplos de aplicações de um método numérico sofisticado, o método dos elementos espectrais/hp, no estudo do escoamento dentro de geometrias complexas bio-inspiradas. Os dois tópicos investigados são: instabilidades em dinâmica de fluido em um canal constrito e o escoamento dentro de um dispositivo de assistência ventricular pediátrica. O canal constrito é um modelo idealizado de uma cavidade nasal, que é caracterizada por canais complexos da via aérea, e também tem semelhança com uma artéria humana na presença de placas ateroscleróticas. O dispositivo de assistência ventricular pediátrica é um dispositivo real, projetado pelo grupo de pesquisa de Bioengenharia do Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo, que funciona como uma bomba que auxilia o ventrículo esquerdo dos pacientes à espera de transplante. Portanto, o objetivo desta tese é contribuir na compreensão de escoamentos em geometrias biológicas e bio-inspiradas, usando ferramentas computacionais. Análises de estabilidade linear e não linear foram feitas para um canal constrito. Três diferentes regimes de escoamento foram empregados: escoamento estacionário simétrico, que é estável para baixo número de Reynolds, escoamento assimétrico, o qual é resultado da primeira bifurcação do escoamento simétrico e escoamento pulsátil. Análise de estabilidade direta foi executada para determinar as regiões instáveis em cada regime de escoamento. Os mecanismos físicos por trás do processo de transição foram estudados por meio de simulação numérica direta para caracterizar as bifurcações. Uma vez que, as bifurcações tiveram um comportamento subcrítico, a relevância do crescimento não normal nestes escoamentos foi avaliado. Assim, dependência com a fase, número de Reynolds e número de onda do modo tridimensional foram extensivamente investigados em regiões estáveis para os três regimes de escoamento. Instabilidades convectivas foram também estudadas a fim de compreender os mecanismos físicos que conduzem os modos ótimos para seus crescimentos máximos, e diferentes mecanismos convectivos foram encontrados. O escoamento dentro do dispositivo de assistência ventricular pediátrico foi analisado por meios de simulações numéricas tridimensionais. Um modelo computacional baseado em condições de contorno especiais foi desenvolvido para modelar o escoamento pulsátil. Neste modelo, a abertura e fechamento da válvula mitral e diafragma foram representados com o uso de condições de contorno especialmente elaboradas. A força motora e o direcionamento do fluxo do diafragma foram definidos por uma distribuição de velocidades na parede do diafragma, e a abertura e fechamento da válvula mitral foram executadas por uma função de onda de velocidade que vai a zero no período sistólico. Padrões do escoamento, campos de velocidade e tensão de cisalhamento no tempo foram analisadas para avaliar o desempenho do dispositivo.

Atualmente, sabe-se que grande parte dos acidentes graves ocorridos envolvendo uma diversidade de sistemas como plataformas de petróleo, aeronaves ou plantas de processos industriais, poderiam ser evitados caso possuíssem dispositivos de controle projetados especificamente para manter a segurança durante a ocorrência de falhas no funcionamento dos mesmos. Por outro lado, observam-se complicações em realizar o controle de sistemas remotos em que é possível não haver garantia de monitoração em tempo real, como o caso de sondas espaciais ou robôs de exploração. Neste contexto, podem-se encontrar ambas as dificuldades no controle do funcionamento de um Dispositivo de Assistência Ventricular (DAV) que desempenha a função de auxiliar o bombeamento de sangue para o sistema circulatório de um paciente com insuficiência cardíaca. Este tipo de dispositivo, quando usado para terapia de destino, deve apresentar um elevado nível de segurança, pois, caso haja falha, o risco de morte é eminente. Por sua vez, o sistema deve apresentar um elevado índice de autonomia, já que as características comportamentais e fisiológicas de um paciente estão em constante mudança e afetam diretamente o modo como deve ocorrer a interação entre o DAV e o sistema cardiovascular do paciente. Sendo assim, há uma necessidade premente de aprimoramento do projeto de sistemas de controle de DAVs autônomos e seguros. A proposta do presente trabalho consiste em aplicar conceitos mecatrônicos para o projeto de um sistema de controle de DAVs e, considerando a natureza dos sinais que indicam a ocorrência de falhas, considerar a teoria de Sistemas a Eventos Discretos (SED), ferramentas de análise de risco e técnicas de diagnóstico e tratamento de falhas para a obtenção de modelos de controle considerando-se uma arquitetura modular e distribuída. Desta forma, foi desenvolvida uma arquitetura de controle supervisório para DAVs considerando características de variações de comportamento do sistema circulatório do paciente e do próprio DAV. Esta arquitetura de controle contempla o diagnóstico e tratamento de falhas desenvolvendo um método para a classificação de falhas e, de acordo com a severidade de cada uma delas é proposto um sistema de controle que atua na regeneração ou degeneração do DAV para um estado seguro, v observando, também, o cumprimento de normas médicas e técnicas de segurança. Para atingir este objetivo, propõe-se uma sistemática para o projeto do sistema de controle para DAVs considerando o aspecto multidisciplinar pertinente a este contexto. A base dessa sistemática consiste em realizar uma efetiva análise de risco do sistema utilizando a ferramenta de estudo HAZOP (Hazard and Operability Studies). A partir do conhecimento obtido sobre o comportamento do sistema em situações críticas desenvolvem-se modelos formais utilizando rede Bayesiana e rede de Petri para o diagnóstico e tratamento das possíveis falhas. O comportamento do DAV controlado pode ser analisado de duas formas: (i) a partir de ensaios in vitro utilizando técnicas de análise por simulação e ferramentas computacionais adequadas, além de testes em simuladores cardiovasculares físicos que emulam interação com o sistema circulatório humano; (ii) a partir de ensaios in vivo em animais que poderão ser utilizados para simular modelos físicos de insuficiência cardíaca e permitir uma avaliação fidedigna dos efeitos do implante do DAV. O procedimento proposto foi aplicado para um caso real de desenvolvimento de um DAV envolvendo uma equipe de pesquisadores da Escola Politécnica da USP e do Instituto Dante Pazanesse de Cardiologia. Assim, é possível obter-se um sistema de controle autônomo e seguro que atenda normas técnicas aderentes a esse assunto e os rigorosos requisitos de projeto impostos a essa classe de sistema. / Nowadays, it is kwon that the several of severe disasters compromising a great variety of systems such as oil platforms, aircrafts or industrial plants, could have been avoided if these systems had controllers designed specifically to maintain the safety levels in case of fault. On the other side, many complications are observed on performing the control of remote systems, where there is no guarantee of real time monitoring of the system, as in space probes or reconnaissance robots. In this context, both obstacles can be found on the control of ventricular assist devices (VAD), which have the role of assisting to pump the blood into the patients circulatory system, in case of irregular heartbeat or heart failure. Devices such as the VAD must possess very high safety levels, as in case of fault, the consequences are severe and might result on the dead of the patient. Nevertheless, these systems must have high degree of autonomy, as the patients physiology and behavior are constantly changing, and these changes impact directly the interactions between the VAD and the patient´s cardiovascular system. Thus, there is a pressing need to improve the design of safe and autonomous control systems for VADs. The present work proposes applying mechatronic concepts to the development of control systems for VADs, considering the nature of the fault indicating signals, as well as the Discrete Event Systems (DES) theory and through the application of tools for risk analysis, and fault diagnostic and treatment techniques aiming the development of control models based on modular and distributed architectures. Thereby, a VAD supervisory control architecture was developed, where the behavior variations of the patient´s circulatory system as well as of the VAD were taken into consideration. This control architecture features the diagnostic and treatment of faults, where methods for faults classification where developed, and according to the severity each fault is proposed a control system that performs the regeneration or degeneration of the VAD to a secure state and is according to medical standards and safety techniques. To achieve this goal is proposed a systematic for the design of the VAD control system considering the multidisciplinary context of the device. The foundation of this systematic is the performance of an effective risk analysis through the use of the toolset known vii as HAZOP (Hazard and Operability Studies). From the knowledge acquired about the system behavior during critical conditions, formal models are developed employing Bayesian Networks and Petri Nets for the diagnostic and treatment of faults. The behavior of the controlled VAD can be analyzed in two possible ways: (i) from in vitro experiments, through the use of simulation analysis tools and proper computational tools, as well as tests on real cardiovascular simulators, where the interactions between the VAD and the human circulatory system can be emulated; (ii) from in vivo experiments, animals can be used to simulate physical models of irregular heartbeat or heart failure and allow reliable valuations of the VAD implant. The proposed procedure was applied on the VAD development, which was performed by a team of researchers from the Escola Politécnica da USP and from the Instituto Dante Pazanesse de Cardiologia. Thus, is possible to achieve an autonomous and safe control system that complies with the applicable technical standards, as well as the strict project requirements for this class of system.

The resolution of functional mitral valve regurgitation (MR) in patients awaiting left ventricular assist device (LVAD) implantation is discussed controversially. The present study analyzed MR and echocardiographic parameters of the third-generation LVAD HeartMate 3 (HM3) over 3 years. Of 135 LVAD patients (with severe MR, n = 33; with none, mild, or moderate MR, n = 102), data of transthoracic echocardiography were included preoperatively to LVAD implantation, up to 1 month postoperatively, and at 1, 2, and 3 years after LVAD implantation. Demographic data and clinical characteristics were collected. Severe MR was reduced immediately after LVAD implantation in all patients. The echocardiographic parameters left ventricular end-diastolic diameter (P < .001), right ventricular end-diastolic diameter (P < .001), tricuspid annular plane systolic excursion (P < .001), and estimated pulmonary artery pressure (P < .001) decreased after HM3 implantation independently from the grade of MR prior to implantation and remained low during the 2 years follow-up period. Following LVAD implantation, right heart failure, ventricular arrhythmias, ischemic stroke as well as pump thrombosis and bleeding events were comparable between the groups. The incidences of death and cardiac death did not differ between the patient groups. Furthermore, the Kaplan-Meier analysis showed that survival was comparable between the groups (P = .073). HM3 implantation decreases preoperative severe MR immediately after LVAD implantation. This effect is long-lasting in most patients and reinforces the LVAD implantation without MR surgery. The complication rates and survival were comparable between patients with and without severe MR.

Patienten mit schweren Herzerkrankungen, wie z.B. Herzinsuffizienz (HI), zählen zu Risikopatienten in der zahnärztlichen Praxis und erfordern eine besondere Aufmerksamkeit in der zahnärztlichen Betreuung (Prävention, Behandlung und Nachsorge). Das Endstadium der HI führt häufig zur Notwendigkeit einer Kreislaufunterstützung im Sinne eines Herzunterstützungssystems, insbesondere eines sog. left ventricular assist devices (LVAD), und/oder zu einer Herztransplantation (HTx) [4-6] . Patienten nach HTx sind u.a. aufgrund der lebenslangen Immunsuppression als Risikopatienten einzustufen. Auch bei Patienten mit LVAD-Systemen besteht durch die Verbindung der extrakorporalen Steuereinheit nach endothorakal eine erhöhte Infektionsgefahr. In diesem Kontext wurde jedoch festgestellt, dass betroffene Patienten dieser Klientel einen hohen parodontalen Behandlungsbedarf und eine hohe Prävalenz moderater bis schwerer Parodontitis aufweisen. Zudem zeigt sich ein unzureichendes Mundgesundheitsverhalten. Parodontitis erhöht nachweislich das Risiko einer oralen Bakteriämie und schlussendlich das Risiko infektiöser Komplikationen, wie beispielsweise einer Endokarditis. Eine frühzeitige zahnärztliche Behandlung mit langfristiger präventiver Betreuung der genannten Risikopatienten ist daher zu fordern. Die vorliegende Beobachtungsstudie mit prospektiver Verlaufsbeurteilung verfolgte das Ziel festzustellen, ob eine standardisierte (bedarfsorientierte) Zuweisung zum (Haus-)Zahnarzt zu einer verbesserten Mundgesundheitssituation bei Patienten mit HI bzw. Z. n. HTx und LVAD-Implantation führt. Zudem sollten mögliche Ursachen für eine ausbleibende Verbesserung der Mundgesundheit bzw. unzureichende zahnärztliche Therapie aufgezeigt werden. Hierzu wurden zweihunderteins Patienten der Universitätsklinik für Herzchirurgie des Herzzentrums Leipzig im Rahmen einer Querschnittsstudie mit prospektiver Verlaufskontrolle zunächst (standardisiert) zahnärztlich untersucht und befragt (Baseline). Die klinisch-zahnärztliche Untersuchung umfasste die dentale und parodontale Beurteilung der Patienten. Hierfür wurden zum einen fehlende, kariöse und gefüllte Zähne (DMF-T-Index) erfasst und im Weiteren Sondierungstiefen (ST) und Attachmentverlust (AV) erhoben. Aus ST und AV wurde der Schweregrad einer vorliegenden Parodontitis ermittelt (keine/milde, moderate oder schwere Parodontitis). Zudem wurden der dentale und parodontale Behandlungsbedarf aus den vorliegenden Befunden abgeleitet: dentaler Behandlungsbedarf = Vorliegen mindestens einer behandlungsbedürftigen kariösen Läsion (D-T>0), parodontaler Behandlungsbedarf = Sondierungstiefe von ≥3.5mm in mindestens zwei Sextanten. Aus Vorliegen des dentalen und/oder parodontalen Behandlungsbedarfes wurde der gesamtheitliche zahnärztliche Behandlungsbedarf bestimmt. Weiterhin wurde das Mundgesundheits- und Inanspruchnahmeverhalten zahnärztlicher Leistungen mit einem standardisierten Fragebogen ermittelt. Zudem wurde das Mundhygieneverhalten der Patienten (Häufigkeit der täglichen Mundhygiene, Mundhygienehilfsmittel) erfasst. Anschließend erfolgte die standardisierte, zielgerichtete Zuweisung zum (Haus-)Zahnarzt mit einem Arztbrief, welcher die Information über die erfolgte zahnärztliche Untersuchung beinhaltete sowie den aktuell vorliegenden zahnärztlichen Behandlungsbedarf aufzeigte. Nach zwölf Monaten konnten achtundachtzig (HTx = 31, LVAD = 43, HI= 14) der initial untersuchten Patienten erneut unter standardisierten Bedingungen untersucht werden (Follow-up). Hierbei wurden die gleichen Parameter erfasst wie zum Zeitpunkt der Baseline- Untersuchung. Zusätzlich wurden sie in Bezug auf die Zahnarztkonsultation mittels eines standardisierten Fragebogens befragt. Dabei richtete sich die Befragung inhaltlich nach fünf thematischen Schwerpunkten aus: Auswirkung des zahnärztlichen Empfehlungsschreibens auf ein Vorstellen des Patienten beim (Haus-)Zahnarzt, Inhalt des Zahnarztbesuches (z.B. Erfragung der stattgefundenen Therapiemaßnahmen), Antibiotika-Prophylaxe beim (Haus-)Zahnarzt, Fachlicher Kenntnisstand des (Haus-)Zahnarztes in Bezug auf den Umgang mit der Grunderkrankung des Patienten (z.B. regelmäßiges Aktualisieren der Medikamentenanamnese des Patienten), Individuelles Mundgesundheitsverhalten im Zusammenhang mit der Grunderkrankung (z.B. Veränderungen in der persönlichen Mundhygiene seit Diagnosestellung) Die statistische Analyse wurde mit SPSS für Windows, Version 24.0 (SPSS, Inc., US) durchgeführt. Für metrische Parameter wurde der Mann-Whitney-U-Test angewandt. Kategorische Daten wurden mittels Chi-Quadrat- und Fischer-Test analysiert (p<0.05). Zum Zeitpunkt der Eingangsuntersuchung (Baseline) lag der parodontale Behandlungsbedarf der gesamten Patientengruppe bei 91%, die Anzahl der zerstörten Zähne (D-T) bei 0.4 ± 1.5 und die Anzahl fehlender Zähne (M-T) bei 10.7 ± 9.0. Die Auswertung der Fragebögen zeigte, dass die Mehrheit der Patienten (79,5%) der Zuweisung zum (Haus-)Zahnarzt folgte. Dabei waren keine signifikanten Unterschiede in den einzelnen Patientengruppen (HTx: 87%, LVAD: 74%, HI: 79%, p=0.41) festzustellen. Am häufigsten wurde nach Angaben der Patienten, die ihren (Haus-)Zahnarzt besucht hatten, eine professionelle Zahnreinigung (PZR) durchgeführt (53% aller Patienten). In der Gruppe der LVAD-Patienten erhielten jedoch signifikant weniger Patienten eine PZR (40%) als in der Gruppe der HTx- und HI-Patienten (68% und 64%, p=0.04). Lediglich 10% der gesamten Patientengruppe gaben trotz hohem parodontalen Behandlungsbedarf (Baseline 91%) an, dass während der letzten zwölf Monate eine Parodontitistherapie beim (Haus-)Zahnarzt eingeleitet bzw. erfolgt sei. Insbesondere HTx-Patienten gaben an, das Mundgesundheitsverhalten (Häufigkeit der täglichen Mundhygiene, Mundhygienehilfsmittel) seit Beginn der Herzerkrankung konsequenter umzusetzen (HTx: 52% vs. LVAD: 21% und HI: 36%, p=0.03). Ebenso räumten HTx-Patienten der Mundhygiene seit Beginn der Diagnosestellung einen größeren Stellenwert ein (61%), im Vergleich zu LVAD- und HI-Patienten (LVAD: 26% und HI: 21%, p˂0.01). Der Vergleich zwischen Mundgesundheit zum Zeitpunkt der Ausgangsuntersuchung (Baseline) und Kontrolluntersuchung nach zwölf Monaten (Follow-up) zeigt einige Veränderungen: Dabei war ein Anstieg der Karies (D-T; Baseline: 0.4 ± 1.5, Follow-up: 0.6 ± 1.1, p=0.03) und der fehlenden Zähne (M-T; 10.7 ± 9.0 vs. 11.1 ± 9.2, p<0.01) auffällig. Zudem war nur eine geringfügige Reduktion des parodontalen Behandlungsbedarfes der gesamten Kohorte von 91% (Baseline) zu 75% (Follow-up) festzustellen. In der Gruppe der Patienten mit HTx konnten jedoch keine bedeutenden Unterschiede der Mundgesundheits-parameter zwischen Baseline und Follow-up evaluiert werden. In der Gruppe der Patienten mit LVAD zeigte sich im Vergleich Follow-up und Baseline ein leichter Anstieg der fehlenden Zähne (M T; 13.9 ± 8.8 vs. 14.4 ± 9.0, p˂0.01) sowie ein reduzierter parodontaler Behand-lungsbedarf zum Zeitpunkt der Nachuntersuchung (88% vs. 70%, p=0.01). Die HI-Patienten-klientel fällt lediglich durch eine Zunahme der Anzahl fehlender Zähne auf (M-T; 9.8 ± 9.9 vs. 10.3 ± 9.9; p=0.03). Bei der Analyse der Mundgesundheitsparameter unter Berücksichtigung der Ergebnisse der Befragung konnten keine signifikanten Zusammenhänge gezeigt werden; so zeigte beispielsweise der parodontale Behandlungsbedarf keine Assoziationen zu einer nach Angaben der Patienten erfolgten Parodontaltherapie (p=0.69) bzw. zu einem Zahnarztbesuch im Allgemeinen (p=0.54). Des Weiteren gibt es ebenso keine Assoziationen zwischen dentalem Behandlungsbedarf und restaurativen zahnärztlichen Therapiemaßnahmen (p=0.72) sowie Zahnextraktionen (p=0.71). Die einmalige bedarfsorientierte Zuweisung zum (Haus-)Zahnarzt ist schlussendlich nicht ausreichend, um stabile mundgesunde Verhältnisse, insbesondere in Bezug auf die parodontale Behandlungsbedürftigkeit bei Patienten mit schweren Herzerkrankungen zu gewährleisten. Insgesamt liegt ein Verbesserungsbedarf sowohl im Mundgesundheitsverhalten als auch im Mundgesundheitszustand bei Patienten mit HI, LVAD und HTx vor. Obwohl der Status als Risikopatient eine intensive zahnärztliche Betreuung erfordern würde, scheinen die (Haus-)Zahnärzte unter den aktuellen Voraussetzungen nicht imstande zu sein, den derzeitigen parodontalen Versorgungsbedarf schwer Herzerkrankter abzudecken. Eine multidisziplinäre zahnmedizinische Betreuung mit Aufbau und Etablierung von „Special Care“- Einrichtungen mit spezialisierten Zahnärzten ist daher ein zu empfehlender Ansatz. Diese sollten im interdisziplinären Team mit Kardiologen/ Herzchirurgen und anderen beteiligten Fachdisziplinen eine präventionsorientierte Versorgung unter Berücksichtigung der Besonderheiten schwer herzerkrankter Patienten gewährleisten.:Inhaltsverzeichnis Abkürzungsverzeichnis Abbildungsverzeichnis 1 Einleitung 1.1 Einführung 1.2 Risikopatienten in der zahnärztlichen Praxis 1.2.1 Allgemeine Zusammenhänge 1.2.2 Patienten mit schweren Herzerkrankungen (HI, LVAD und HTx) 1.3 Mundgesundheit bei zahnmedizinischen Risikopatienten mit Schwerpunkt auf HI, LVAD und HTx 1.3.1 Bedeutung der Mundgesundheit bei Patienten mit schweren Herzerkrankungen 1.3.2 Mundgesundheitszustand bei Patienten mit schweren Herzerkrankungen (HI, LVAD und HTx/Tx) . . . 1.4 Zahnmedizinische Behandlungsempfehlungen bei Risikopatienten mit Schwerpunkt auf HI, LVAD und HTx 1.5 Ursachenforschung im Hinblick auf eine Verbesserung der Mundgesundheits-situation der Patienten mit schweren Herzerkrankungen . . . . . 1.6 Zielsetzung . . . . . . . . . . . . . 2 Publikationsmanuskript 3 Zusammenfassung der Arbeit 4 Ausblick 5 Literaturverzeichnis 6 Wissenschaftliche Präsentationen 7 Darstellung des eigenen Beitrags 8 Erklärung über die eigenständige Abfassung der Arbeit 9 Lebenslauf 10 Danksagung

A Left Ventricular Assist Device (LVAD) is a mechanical pump that helps patients with heart failure conditions. This rotary pump works in parallel to the ailing heart and provides an alternative path for blood flow from the weak left ventricle to the aorta. The LVAD is controlled by the power supplied to the pump motor. An increase in the pump motor power increases the pump speed and the pump flow. The LVAD is typically controlled at a fixed setting of pump power. This basically means that the controller does not react to any change in the activity level of the patient. An important engineering challenge is to develop an LVAD feedback controller that can automatically adjusts its pump motor power so that the resulting pump flow matches the physiological demand of the patient. To this end, the development of a mathematical model that can be used to accurately simulate the interaction between the cardiovascular system of the patient and the LVAD is essential for the controller design. The use of such a dynamic model helps engineers and physicians in testing their theories, assessing the effectiveness of prescribed treatments, and understanding in depth the characteristics of this coupled bio-mechanical system. The first contribution of this dissertation is the development of a pump power-based model for the cardiovascular-LVAD system. Previously, the mathematical models in the literature assume availability of the pump speed as an independent control variable. In reality, however, the device is controlled by pump motor power which, in turn, produces the rotational pump speed. The nonlinear relationship between the supplied power and the speed is derived, and interesting observations about the pump speed signal are documented. The second contribution is the development of a feedback controller for patients using an LVAD as either a destination therapy or a bridge to transplant device. The main objective of designing this controller is to provide a physiological demand of the patient equivalent of that of a healthy individual. Since the device is implanted for a long period of time, this objective is chosen to allow the patient to live a life as close to normal as possible. The third contribution is an analysis of the aortic valve dynamics under the support of an LVAD. The aortic valve may experiences a permanent closure when the LVAD pump power is increased too much. The permanent closure of the aortic valve can be very harmful to the patients using the device as a bridge to recovery treatments. The analysis illustrates the various changes in the hemodynamic variables of the patient as a result of aortic valve closing. The results establish the relationship between the activity level and the heart failure severity with respect to the duration of the aortic valve opening.

Background: Peripartum cardiomyopathy (PPCM) is a rare, life-threatening form of heart disease, frequently associated with gene alterations and, in some cases, presenting with advanced heart failure. Little is known about ventricular assist device (VAD) implantation in severe PPCM cases. We describe long-term follow-up of PPCM patients who were resistant to medical therapy and received mechanical circulatory support or heart transplant. Methods and results: A total of 13 patients were included with mean follow-up of eight years. Mean age of PPCM onset was 33.7 ± 7.7 years. All patients were initially treated with angiotensin-converting enzyme inhibitors and beta-blockers, and four received bromocriptine. Overall, five patients received VADs (three biventricular, two isolated left ventricular) at median 27 days (range: 3 to 150) following childbirth. Two patients developed drive line infection. Due to the short support time, none of those patients had a stroke or VAD thrombosis. In total, five patients underwent heart transplantation, of which four previously had implanted VADs. Median time to transplantation from PPCM onset was 140 days (range: 43 to 776), and time to transplantation from VAD implantation were 7, 40, 132, and 735 days, respectively. All patients survived until most recent follow up, with the exception of one patient who died following unrelated abdominal surgery two years after PPCM recovery. Conclusions: In patients with severe, life-threatening PPCM refractory to medical management, mechanical circulatory support with or without heart transplantation is a safe therapeutic option.