Objective: To document maternal and foetal morbidity and mortality in anticoagulated, pregnant patients with mechanical heart valves until 42 days postpartum. Methods: In a tertiary single-centre, prospective cohort, 178 consecutive patients at the cardiac-obstetric clinic were screened for warfarin use between 1 July 2010 and 31 December 2015. Of 33 pregnancies identified, 29 were included. Patients received intravenous unfractionated heparin from six to 12 weeks’ gestation and peripartum, and warfarin from 12 to 36 weeks. Maternal outcomes including death, major haemorrhage and thrombosis, and foetal outcomes were documented. Results: There were two maternal deaths, five returns to theatre post-delivery, eight patients transfused, six major haemorrhages, one case of infective endocarditis and three ischaemic strokes. Ten pregnancies had poor foetal outcomes (six miscarriages, three terminations, one early neonatal death). Twenty patients required more than 30 days’ hospitalisation, and 15 required three or more admissions. HIV positivity was associated with surgical delivery (p = 0.0017). Conclusions: Complication rates were high despite centralized care.

Prosthetic heart valves (PHVs) are routinely used to replace defective native heart valves in patients suffering from valvular heart diseases. While PHVs are life-saving, they have limitations in performance and durability. Therefore, it is crucial to rigorously test and evaluate their designs before their implantation. PHVs are commonly examined using cardiovascular testing equipment that measures the hemodynamic characteristics of the valves, while also providing the opportunity for their visual assessment by collecting high-quality videos. Such visual data, obtained during mechanical simulations, are typically assessed by human experts, which is a tedious and error-prone task. Automatic assessment of PHVs from video data is possible, however, there are some challenges that need to be addressed. The evolution of the valve orifice area during one cardiac cycle is one of the key quality metrics for PHV visual assessment. Very fast motion of the valve’s leaflets is one of the challenges while dealing with the visual data. Nevertheless, the more important issue lies in the orifice being partly occluded by the inner side of the leaflets or inaccurately depicted due to its transparency. This issue has not been addressed in the literature. In the first part of the thesis, a novel orifice area segmentation algorithm is proposed for automatic quantitative performance analysis of PHVs, based on the leaflet free edges to accurately extract the actual orifice area. The video frames, recorded by a high-speed digital camera during in vitro simulations, are used to obtain an initial estimate of the orifice area using active contouring methods. This initial estimate is then refined to detect leaflet free edges via a curve extension scheme and considering brightness and smoothness criteria. Both of the developed algorithms are later modified for addressing challenges related to the fast motion of leaflets, automatic detection of the beginning of a cycle, and overly bright spots and narrow areas. Evaluation on several cases including three different PHVs and with different video qualities demonstrated the effectiveness of the proposed approach and adjustments in detecting valve leaflet free edges and extraction of the actual orifice area. The proposed method significantly outperforms a baseline algorithm both in terms of valve design and computer vision evaluation metrics. It can also cope with lower quality videos and is better at processing frames with a very small opening, which is a very crucial quality for determining the malfunctions related to improper closing of the valves. In the second part of the thesis, the above-mentioned segmented orifice area is used for the durability estimation of the prosthetic heart valves. More than 50% of PHVs encounter a structural failure within 15 years post-implantation mostly because of the excessive localized forces on some areas. We perform a computer vision (CV)-based analysis of the visual symmetry of valve leaflet motion and investigate its correlation with the functional symmetry of the valve. We hypothesize that an asymmetry in the valve leaflet motion will generate an asymmetry in the flow patterns, resulting in added local stress and forces on some of the leaflets. Two pair-wise leaflet symmetry scores are proposed based on diagonals of orthogonal projection matrices (DOPM) and dynamic time warping (DTW) techniques. The proposed symmetry score profiles are compared with fluid dynamic parameters (vorticity and velocity values) at the leaflet borders, obtained from valve-specific numerical simulations. Experiments on four cases including different tricuspid PHV designs yielded promising results, with DTW scores showing good coherence with respect to the simulations, which confirms our hypothesis. The established link between visual and functional symmetry opens the door for durability estimation of prosthetic heart valves using computer vision techniques. / Graduate

The performance of the heart after a valve replacement operation will greatly depend on the flow character downstream the mitral valve thus a better understanding of the flow character is essential. Most in vitro studies of the flow downstream of a MHV have been conducted with the valve in the aortic position. Researchers reported detailed measurements most of which were obtained by Laser Doppler Velocimetry (LDV) in rigid models of the aorta. Digital Particle Image Velocimetry (DPIV) has also been utilized to reveal intricate patterns of interacting shed vortices downstream of the aortic valve. The orientation of the valves may considerably affect the flow development and slight difference may produce significant differences in the ventricular flow fields. Two orientations, respectively anatomical and anti-anatomical, of the St. Jude Medical (SJM) bileaflet valve are presented and compared with the SJM Biocor porcine valve, which served to more closely represent the natural valve. In this effort, we employ a powerful tool to monitor the velocity field in a flexible, transparent LV and study the evolution of large eddies and turbulence through a complete cardiovascular cycle. Both time average and instantaneous results of velocity, vorticity, and turbulent kinetic energy distributions are presented. The presence and location of vortical structures were deduced as well as the level of coherence of these structures. The presence of three distinct flow patterns were identified, by the location of vortical structures and level of coherence, for the three configurations corresponding to significant differences in the turbulence level distribution inside the LV. / Master of Science

Several systems of criteria have been offered for the electrocardiographic diagnosis of left ventricular hypertrophy (1,6,7,8,11,13,14,16). None is completely satisfactory since one system errs in including too many normals and at the other end of the spectrum the other system excludes too many cases of anatomically proven left ventricular hypertrophy. However, a number of patients with proven left ventricular hypertrophy have normal electrocardiograms, or show nonspecific electrocardiographic abnormalities. It has been suggested that spatial vectrocardiogram, recorded utilizing a corrected lead system, may be more sensitive in detecting left ventricular hypertrophy than routine scalar electrocardiogram (1,3,12,15,21,28,29,30). The purpose of this study is to evaluate this contention and to establish reliable vectorcardiographic criteria of left ventricular hypertrophy.

Yes / Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Im-munohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrody-namic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of a-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure.

Valvular disorders can be corrected by means of surgery, after which very comprehensive discharge planning should be implemented to prevent the occurrence of post-operative complications. Advances in medical technology and intellect instigate earlier discharge for patients after they have undergone valvular surgery. The aim of this research study is to establish the extent of discharge planning by nurses for patients who have undergone valvular surgery, so that practice guidelines in the form of an in-service educational framework can be compiled for nurses in the management of these patients post-operatively. Patients, many of whom are from rural areas, are discharged without an adequate referral system. There are, currently, no set guidelines or referral persons to direct these patients during their rehabilitation period. Based on the researcher’s personal observations, it is evident that many patients suffer from bacterial endocarditis or clotted valves due to poor post-surgery management. However, both of these conditions could be avoided if proper health education was given to these patients. The study will take the form of a quantitative, exploratory, descriptive and contextual survey. Data will be collected by means of a structured questionnaire that will be completed by the nurses working in the cardiac general ward and the cardiac clinic. Findings of the research study will be used to assist the researcher in developing an in-service educational framework for staff that are both nursing and preparing post valvular surgery patients for discharge. The goal is to prevent complications such as clot formation and endocarditis and to enable patients to deal effectively with their rehabilitation period.

No description available.

Os substitutos valvares possuem grande importância pela freqüência da sua utilização e porque de seu bom desempenho depende o sucesso do procedimento cirúrgico realizado. Vários substitutos valvares têm sido empregados, todos com complicações inerentes ao material utilizado, como trombose, calcificação, degeneração, dificuldade de esterilização, custo, complexidade de produção, etc. Buscando disponibilizar homoenxertos preservados de maneira mais simples e econômica, avaliamos uma nova forma de preservação utilizando o polietileno-glicol, método L-Hydro. Este método consiste na extração controlada de substâncias antigênicas e de incorporação de um agente antinflamatório e anti-trombótico. Em dez carneiros jovens substituímos o Tronco Pulmonar, em sete por homoenxertos pulmonares tratados pelo processo L-Hydro e em três por homoenxertos pulmonares a fresco, implantados ortotopicamente e seguidos por 320 dias. Os carneiros foram avaliados por exames laboratoriais e ecocardiográficos. Ao cabo dos 320 dias foram sacrificados, quando se procedeu à avaliação hemodinâmica, radiológica, macroscópica e por microscopia óptica e eletrônica, de varredura e transmissão. Os resultados foram analisados pelo teste t de Student de amostras independentes para os dados contínuos, pela análise de variância para as medidas repetidas e pelo teste exato de Fischer para os dados categóricos. Na evolução clínica e nos exames laboratoriais não conseguimos estabelecer diferenças significativas entre os dois grupos. O ecocardiograma revelou diferença quanto ao gradiente médio pulmonar, significativa aos 10 meses de seguimento, maior no grupo controle do que no grupo L-Hydro. A avaliação radiológica e macroscópica não estabeleceu diferenças. Na avaliação microscópica, óptica e eletrônica, células de revestimento e intersticiais foram encontradas nos dois grupos igualmente. O porcentual de revestimento celular calculado nos dois grupos foi semelhante. Nódulos de celularidade foram observados somente no grupo de homoenxertos a fresco. Em conclusão, estes dados indicam que os dois grupos apresentaram desempenho clínico e hemodinâmico semelhante. Ao ecocardiograma o grupo L-Hydro apresentou melhor desempenho; apresentou também evidências histológicas de repopulação celular intersticial e endotelial. Na análise macro e microscópica, óptica e eletrônica, o grupo L-Hydro apresentou macroscopia, estrutura histológica e ultraestrutural semelhante ao homoenxerto afresco, à exceção de nódulos de maior celularidade intersticial, presentes apenas no homoenxerto a fresco / Valve substitutes are highly important in account of their frequent use and since the success of a surgical procedure depends on their good performance. A variety of valve substitutes have been used, all presenting complications pertaining to their materials, such as thrombosis, calcification, degeneration, sterilization difficulties, cost, production complexity, etc. In an effort to make available homografts preserved in a simpler and less costly way, we evaluated a new preservation form using polyethyleneglycol, the LHydro method. This method consists in the controlled extraction of antigenic substances and the incorporation of an anti-inflammatory and anti-thrombotic agent. We substituted the pulmonary trunk in ten ovines, seven received LHydro treated pulmonary homografts and three received pulmonary homografts fresco, orthotopically implanted and followed-up for 320 days. Ovines where evaluated by means of laboratory tests and echocardiographic exams. At the end of the 320 days, they were euthanized, and hemodynamic, radiology, macroscopic, optic and electronic microscopic, scanning and transmission evaluations were performed. Results were analyzed by Student t test of independent samples for continuous data, by variance analysis of repeated measures, and by Fischer exact test for categorical data. We couldnt establish relevant differences in clinical evolution and laboratory tests between both groups. Echocardiogram revealed a difference in the pulmonary medium gradient, which was significant at the 10 months followup, higher in the control group than in the L-Hydro group. Radiologic and macroscopic evaluations didnt established differences. In the optic and electronic microscopic evaluation, liner and interstitial cells were equally found in both groups. The cell liner percent calculated in both groups was similar. Cellularity nodules were observed only in the homograft fresco group. In conclusion, these data indicate that both groups presented similar clinical and hemodynamic performances. The L-Hydro groups echocardiogram presented a better performance. It also presented histological evidences of interstitial and endothelial cell repopulation. In the macro and optic and electronic microscopic analysis, group L-Hydro presented macroscopy, histological structure and ultra-structural similar to the homograft fresco group, with the exception of nodules with higher interstitial cellularity, present only in the homograft fresco group.

Oxidative stress is associated with development and progression of cardiovascular disease. Angiotensin II produces oxidative stress and endothelial dysfunction, and its actions may be attenuated by the activity of angiotensin converting enzyme type 2 (ACE2) which converts angiotensin II to the vasoprotective peptide angiotensin (1-7). Similarly, increased oxidative stress is associated with aortic valve stenosis in humans and mice. In my thesis studies, I explore mechanisms of modulation and generation of oxidative stress in cerebral arteries and heart valves. First, I tested the hypothesis that ACE2 deficiency increases oxidative stress and vasomotor dysfunction in cerebral arteries, and examined the role of ACE2 in vascular aging. Vasomotor function was assessed in the basilar artery ex vivo of adult and old ACE2 deficient (ACE2-/y) and wild type (WT or ACE2+/y) mice. ACE2 was present, but at relatively low levels in cerebral arteries. Systolic blood pressure was similar in adult and old ACE2-/y and ACE2+/y mice. Maximal dilatation to acetylcholine was impaired in the basilar artery from adult ACE2-/y mice compared to adult ACE2+/y. In old mice, maximal vasodilatation to acetylcholine was impaired in ACE2+/y mice and severely impaired in ACE2-/y mice. The antioxidant tempol improved responses to acetylcholine in adult and old ACE2-/y and ACE2+/y mice. Nitrotyrosine staining in the basilar artery was increased in adult ACE2-/y mice and in old ACE2-/y and ACE2+/y mice relative to adult ACE2+/y, which indicates that oxidative stress was higher in cerebral arteries from ACE2 deficient mice and old mice. Expression of NADPH oxidase subunits Nox2 and p47phox, and of pro-inflammatory molecules Rcan1 and TNF alpha; was increased in cerebral arteries from old ACE2-/y and ACE2+/y mice. Additionally, I tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species (ROS). Superoxide (O2.-) was measured in heart valves from explanted human hearts that were not used for transplantation. Superoxide levels (lucigenin-enhanced chemiluminescence) were increased in homogenates of cardiac valves and pulmonary artery after incubation with serotonin. A non-specific inhibitor of flavin-oxidases (DPI), or inhibitors of monoamine oxidase-MAO (tranylcypromine and clorgyline), prevented serotonin-induced increase in O2.-. Dopamine, another MAO substrate which is increased in patients with carcinoid syndrome, also increased superoxide levels in heart valves, and this effect was attenuated by clorgyline. Apocynin did not prevent increases in O2.- during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated superoxide, and this effect was prevented by an MAO inhibitor. In conclusion, I have demonstrated that ACE2 deficiency impairs vasomotor function in cerebral arteries from adult mice and augments endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging. I have also identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

This thesis presents a stable fluid structural interaction technique to simulate the dynamics of tissue valves including bio-prosthetic heart valves and natural heart valves under physiological Reynolds numbers. A partitioned approach is implemented where the equations governing the flow and the displacement of the structure are solved using two distinct solvers. A FEAP based solid solver is strongly coupled to the p-ELAFINT flow solver using subiteration procedure. The flow solver has been massively parallelized so that the domain can be distributed among several processors. The fixed Cartesian method with adaptive mesh refinement in p-ELAFINT enables us to perform fast and efficient flow computations of problem involving moving boundaries such as heart valve leaflets. To capture the structure deformation, Enhanced Assumed Solid shell element has been implemented into the solid solver which is known for its locking free and superior bending characteristics. Aitken Relaxation method which dynamically computes the relaxation parameter is used for relaxing the solid displacement in the FSI coupling. This helps the subiteration procedure to achieve a faster convergence compared to traditional Subiterative procedures with fixed relaxation parameter. Fung type material model with experimentally derived parameters is used as the constitutive model to capture the realistic solid deformation. Opening phase of a bicuspid aortic valve (BAV) model derived from a patient specific data and a pericardial bioprosthetic valve model were simulated using the FSI algorithm with realistic material parameters under physiological flow conditions. It was observed that the valves attained its fully open position under 35 milliseconds which is similar to the physiological opening. The bioprosthetic valve attained a fully circular orifice while the BAV attained an ellipsoidal shaped orifice at its fully open position. In the BAV, strong vortical patterns were observed at peak systole and recirculation zones were observed near the sino-tubular junction. The work presented in this thesis be seen as a platform from which complex patient specific data can be modeled under physiological conditions and as a base to include contact mechanics with which complete cardiac cycle can be simulated.