Various congenital heart defects (CHDs) are characterized by the existence of a single functional ventricle, which perfuses both the systemic and pulmonary circulation in parallel. A three-stage palliation procedure, including the final Fontan Completion, is often adopted by surgeons to treat patients with such CHDs. However, the most common outcome of this surgery, an extra-cardiac total cavopulmonary connection (TCPC), formed by suturing the inferior vena cava (IVC) and superior vena cava (SVC) to the pulmonary arteries (PAs), results in non-physiological flow conditions, systemic venous hypertension, reduced cardiac output, and pressure losses, which ultimately calls for a heart transplantation. A modest pressure rise of 5-6 mm Hg would correct the abnormal flow dynamics in these patients. To achieve this, a novel conceptual design of a percutaneous dual propeller pump inserted and mounted inside the TCPC is developed and studied. The designed blood pump is percutaneously inserted via the Femoral vein and deployed at the center of Total Cavopulmonary Connection (TCPC). The two propellers, each placed in the Superior Vena Cava (SVC) and the Inferior Vena Cava (IVC) are connected by a single shaft and motor, and thus rotate at same speed. The device is supported with the help of a self-expanding stent which would be anchored to the walls of the IVC and the SVC. An inverse design methodology implementing Blade Element Momentum theory and Goldstein's radial momentum loss theory was employed to generate the blade profiles for the studied propeller pumps. The propeller blade profiles generated from the inverse design optimization code were examined for hydraulic performance, blood flow pattern and potential for hemolysis inside the TCPC using 3-D computational fluid dynamics (CFD) analysis. The Lagrangian particle tracking approach in conjunction with a non-linear mathematical power law model was used for predicting the blood damage potential of the analysed blood pump designs by calculating the scalar shear stress history sustained by the red blood cells (RBC). The study demonstrated that the IVC and SVC propeller pumps could provide a pressure rise of 1-20 mm Hg at flow rates ranging from 0.5 to 5 lpm while rotating at speeds of 6,000-12,000 rpm. Moreover, the average Blood Damage Index (BDI), quantifying the level of blood trauma sustained by the RBCs for the analyzed propeller pump designs, was found to be around 3e-04% to 4e-04% which is within the acceptable limits for an axial flow heart assist device. Thus, such a dual propeller blood pump configuration could potentially provide assistance to Fontan patients by unloading the single functional ventricle thereby acting as a bridge to transplantation and recovery until a donor heart is available. / Master of Science / A single functional ventricle is a type of congenital heart defect, where either left or right ventricle is underdeveloped, resulting in a single ventricular chamber to pump blood to both the body as well as lungs. A three-stage surgical procedure called the Fontan procedure, is often adopted by the surgeons to treat this defect by disconnecting the inferior(IVC) and superior vena cava(SVC), the two main veins carrying de-oxygenated blood from the body to the heart, and connecting them to the pulmonary arteries(PAs), the vessels carrying de-oxygenated blood from heart to the lungs. This helps to bypass the underdeveloped ventricle and allows blood to flow directly from the body to the lungs. However, the absence of a pumping chamber in the newly developed blood portal system causes an increase in pressure inside the vena cava and pressure losses inside the pulmonary arteries, which results in vena cava hypertension, reduced cardiac output. A modest pressure rise of 5-6 mm Hg across the vena cava or pulmonary artery should correct the abnormal flow dynamics and should bring the cardiac output of such patients back to normal. To achieve this, a conceptual design of a dual propeller mechanical circulatory support device has been designed and developed in this thesis.

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....

Die vorliegende Untersuchung stellt sich die folgenden Fragen: Welchen Stand hat die Entwicklung von mechanischen Kreislaufunterstützungssystemen für Kinder, worin unterscheiden sich die eingesetzten Verfahren? Wie beeinflusst der Blutkontakt mit Fremdmaterial das Kapillarleck beim Kind? Welche Erfahrungen gibt es mit dem pulsatilen Ventrikelunterstützungssystem Berlin Heart beim Kind, welche Schwierigkeiten und Nebenwirkungen sind für das Kindesalter spezifisch? Wann profitieren Kinder von einer mechanischen Kreislaufunterstützung? Die bei Kindern am häufigsten eingesetzten Verfahren, Herzlungenmaschine (HLM), extrakorporale Membranoxygenierung (ECMO) und pneumatisch pulsatiles ventrikuläres Assist device (VAD) unterscheiden sich in Technik, Indikation, Nebenwirkung und möglicher Einsatzdauer erheblich. Die HLM dient der intraoperativen Kreislaufunterstützung. ECMO haben wir seit 1990 zur mittelfristigen Kreislaufunterstützung bei mehr als 70 Kindern für eine Dauer von ein bis zwei, selten bis zu drei Wochen eingesetzt. Mit VAD''s haben wir seit 1990 bei 56 Kindern die Herzfunktion teils monatelang ersetzt. Es bestehen multiple Unterschiede bei dem Einsatz von VAD zwischen Säuglingen, Kindern und Erwachsenen sowohl in der Indikation, Physiologie, Technik, Antikoagulation, der Familienbetreuung und hinsichtlich der Komplikationen. Bei jeder mechanischen Kreislaufunterstützung aktiviert der Fremdflächenkontakt des Blutes das Kontaktsystem, zu dem Gerinnungs- und Komplementsystem gehören. Klinische Äquivalente sind Thrombosen, Thrombozytenverlust und Kapillarleck. Insbesondere Säuglinge neigen zu diesen Komplikationen, weil das Verhältnis von Blutvolumen zu Fremdfläche ungünstig ist und der kontaktabhängige alternative Weg der Komplementaktivierung im jungen Alter vorherrscht. - Wir untersuchten prospektiv den prä- und postoperativen Verlauf von Kontakt- und Komplementsystem (C1q, C3, C4, C1-Inhibitor, Faktor B, Faktor XIIa) bei 11 herzoperierten Säuglingen ohne und 24 Säuglingen mit HLM. Es konnte nachgewiesen werden, dass obwohl bei allen Kindern eine Komplementaktivierung vorhanden war, diese signifikant ausgeprägter in der HLM-Gruppe stattfand. Die Kontaktaktivierung (Faktor XIIa, Präkallikrein) ließ sich nur in der HLM-Gruppe nachweisen, so dass belegt war, dass es nicht die Anästhesie oder die Operation an sich, sondern die HLM ist, die die inflammatorische Reaktion hervorruft. - Bei 27 mit HLM operierten Säuglingen untersuchten wir prospektiv die CLS-Entstehung und die Komplement- und Kontaktaktivierung. Bei den 10 Kindern, die im späteren Verlauf ein Kapillarlecksyndrom (CLS) entwickelten, waren bereits 30 Minuten nach HLM-Beginn die C1-INH-Konzentration und -Aktivität niedriger und Faktor XIIa, C3a und C5a höher als bei den 17 Kindern, die später kein CLS entwickelten. Die Aktivierung korrelierte mit dem Alter der Kinder und der HLM-Zeit, nicht mit der Tiefe der Hypothermie. - Retrospektiv untersuchten wir 28 Kinder (6 Tage - 16 Jahre alt), bei denen im terminalen Herzversagen nach Reanimation die Herzfunktion mit dem parakorporalen pneumatischen VAD Berlin Heart 1-98 Tage lang unterstützt wurde. Zwölf dieser Kinder wurden unter laufender Reanimation mit Herzdruckmassage in den Operationssaal gebracht. 13 Patienten erreichten eine Herztransplantation, 3 Kinder wurden mit dem eigenen Herzen vom System entwöhnt. 12 Kinder starben am System, Todesursachen waren Schock, Multiorganversagen, Sepsis und Blutungen. - Bei 95 herztransplantierten Kindern untersuchten wir retrospektiv die Verläufe in Abhängigkeit davon, ob die Kinder (I) vor der Transplantation in relativ stabilem Zustand zuhause waren (n=33), ob sie (II) kritisch krank hospitalisiert waren (n= 44), oder ob sie (III) nach Reanimation mit einem VAD kreislaufunterstützt wurden (n=18, Dauer 4-111 Tage). Die Überlebensraten nach 1Mo/1J/5J betrugen in Gruppe I 88/88/80 %, Gruppe II 88/82/79 %, Gruppe III 72/72/72 %. Der frühpostoperative Verlauf nach Transplantation war bei Gruppe III nur wenig komplizierter, was den Erfolg der Transplantation nicht minderte. - Retrospektiv untersuchten wir den Verlauf von 4 Kindern mit schwerer Myokarditis, die bei kardiogenem Schock mit biventrikulärem VAD kreislaufunterstützt wurden. Das schockbedingte Multiorganversagen und die Thrombozytopenie bildete sich während der Unterstützung mit dem VAD zurück. Drei Kinder konnten nach Erholung des Myokards vom VAD entwöhnt werden, eines wurde erfolgreich transplantiert. - Ausserdem untersuchten wir den Verlauf von 84 Kindern, die wegen Kardiomyopathie auf der Intensivstation behandelt wurden. Von den 69 (= 82 %), bei denen eine kreislaufstützende medikamentöse Therapie ausreichend war, konnten 32 herztransplantiert werden, 36 besserten sich und wurden nach Hause entlassen und ein Kind verstarb akut. Fünfzehn der 84 Kinder (= 18 %) ließen sich nicht stabilisieren und erhielten nach Reanimation eine mechanische Kreislaufunterstützung mit VAD (Dauer 1 – 98 Tage). Von diesen konnten 12 transplantiert werden. Die in dieser Habilitationsschrift ausgeführten Arbeiten haben weiterführende Fragestellungen und Grenzbereiche des mechanischen Kreislaufersatzes im Kindesalter aufgezeigt und neue Therapiestrategien dargestellt. Dadurch ist es möglich, die Überlebenschancen von Kindern mit terminalem Herzversagen erheblich zu verbessern. Sei es durch Zeitgewinn bis zur Erholung des Myokards oder zum Organangebot auf der HTx-Warteliste. Durch den Zeitgewinn, den die VAD`s den zur HTx gelisteten Kindern bieten, brauchen zur Transplantation freigegebene Kinderherzen seltener verworfen werden, mehr Kinder können überleben und die Ausnutzung der angebotenen Organe gelingt besser. / This scientific work addresses the following questions: what is the state of the art in mechanical circulatory support (MCS) in infants and children? How do the different techniques differ? How does mechanical circulatory support influence the systemic inflammatory response after cardiac surgery? What are the indications for use of the pneumatic pulsatile ventricular support system Berlin Heart in children and what do our experience and the results of its use show? The MCS systems most often used for children of all ages are cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), centrifugal pumps and the pneumatic pulsatile ventricular assist device (VAD). These systems vary in indications, results, side effects and potential supporting time. CPB is used to replace the circulation during cardiac surgery. ECMO has been used in our hospital since 1990 for circulatory support in cases of cardiac failure and of pulmonary failure and has been applied in more than 70 children over a period of 1 to 3 weeks. The VAD (Berlin Heart) has been used since 1990 in 56 children for long-term support, when the heart function had to be supported for up to several months. In VAD use there are multiple differences in indication, physiology, underlying disease, technique, anticoagulation and complications between infants, children and adults. In every case of MCS there is contact and complement activation as a reaction of the blood to foreign surfaces, resulting in capillary leak and activation of coagulation and anticoagulation systems with the risk of thrombosis or bleeding. In particular, young infants are prone to systemic inflammatory response in the form of capillary leak. In a prospective study we compared the complement activation after cardiac operations with or without CPB in 35 infants and measured serially the complement function and concentrations or activity of C1q, C3, C4, C1 esterase inhibitor, factor B, the activated split product C3a, prekallikrein and factor XIIa of the contact system. We found that complement activation occurs in all infants but is significantly higher in the group with CPB. Contact activation occurred only in patients who undergo CPB. Thus, the inflammatory response is caused by the use of a CPB circuit and to a lesser degree by surgical procedures and anesthesia. In 27 infants with CPB surgery we prospectively investigated the early clinical parameters that predict the development of capillary leak syndrome (CLS) and examined the relationship between CLS and complement and contact activation and C1 esterase inhibitor during and after bypass. We found that contact and complement activation occurs during CPB and contributes to CLS more frequently in infants of a younger age and with a prolonged bypass time. This activation and decrease in C1 esterase inhibitor was strongly expressed in the CLS group. Although MCS in intractable heart failure in children has normally been limited to centrifugal pumps and ECMO, we implanted 28 children with the pediatric sized pulsatile air-driven Berlin Heart VAD. Our aim was to keep the children alive and allow recovery from shock sequeale until later transplantation or myocardial recovery. Twelve children were brought to the operating room under cardiac massage. In total 12 children died on the system, but thirteen children were transplanted and three were sucessfully weaned from the system. Acute myocarditis appears to be a promising precondition for complete recovery during VAD support and in patients with cardiomyopathy support until transplantation is the goal for the future. We reviewed the course of 95 children who had undergone heart transplantation in our center to investigate whether previous VAD support has an impact on long-term outcome after transplantation. Three groups were compared and we found that bridging to transplantation with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After transplantation the overall survival rate is 86 % at 1 month, 82 % at 1 year and 75 % at 5 years. The survival of children previously supported with a VAD is similar to that of patients who were bridged with inotropes or who awaited heart transplantation electively. In 4 children with fulminant myocarditis and cardiogenic shock in whom all aggressive medical treatment failed we found that artificial replacement of the heart with complete unloading was followed by total recovery; 3 patients were successfully weaned from the device. No patient died and heart transplantation was necessary in only one child. Retrospectively we examined the course of 84 children who were treated at the ICU, presenting severe cardiac failure due to cardiomyopathy. In 15 of them medical treatment failed and the disease progressed so rapidly that they would have died during the waiting period before a suitable donor organ was found. After resuscitation these 15 children were supported with a VAD. Only 3 died during the waiting period and 12 (80%) underwent later heart transplantation. Progress has been rapid towards individualized choice of mechanical circulatory support systems for children of different ages and with different indications. With the Berlin Heart VAD prolonged circulatory support until myocardial recovery or until heart transplantation is effective in children and infants. It offers time to restore organ function, allows extubation, mobilization and neurological examination and increases the chances for successful transplantation. It can be used with low device-related morbidity and satisfactory results especially in the myocarditis and the cardiomyopathy groups. Complete recovery from secondary organ dysfunction should be achieved before heart transplantation is considered. We expect not only that children with end-stage heart failure will benefit from long-term VAD support, but also that fewer organs from young donors will be lost. Of particular importance is our experience with myocardial recovery in children with acute myocarditis in whom the devices could be explanted.

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